https://yk-health.org/api.php?action=feedcontributions&feedformat=atom&user=AndySGuide to YKHC Medical Practices - User contributions [en]2026-04-18T14:26:26ZUser contributionsMediaWiki 1.39.5https://yk-health.org/index.php?title=Guideline_List_(Chronological)&diff=9504Guideline List (Chronological)2025-01-11T13:50:10Z<p>AndyS: </p>
<hr />
<div>== 2024 - December ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
|-<br />
|[https://yk-health.org/images/d/d0/Stroke.pdf CVA]<br />
|12/2024<br />
|Changes to disposition, not giving aspirin w/ lytics, and monitoring parameters.<br />
|-<br />
|[https://yk-health.org/images/f/f3/Neonatal_Abstinence_Syndrome.pdf Suspected Neonatal Withdrawal]<br />
|12/2024<br />
|Brand new. Mostly for nursery.<br />
|-<br />
|[https://yk-health.org/images/3/33/UTI_adult.pdf UTI (adult)]<br />
|12/2024<br />
|Minor changes.<br />
|-<br />
|[https://yk-health.org/images/e/ec/Pneumonia_adult.pdf Pneumonia (adult)]<br />
|12/2024<br />
|Minor antibiotic changes.<br />
|-<br />
|[https://yk-health.org/images/0/03/Medevac_village_to_Bethel.pdf Medevac village to Bethel]<br />
|12/2024<br />
|Minor changes.<br />
|-<br />
|[https://yk-health.org/images/5/52/Medevac_Bethel_to_Anchorage.pdf Medevac Bethel to Anchorage]<br />
|12/2024<br />
|Minor changes including info about Guardian.<br />
|}<br />
<br />
== 2024 - October ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
|-<br />
|[https://yk-health.org/images/f/f7/Pertussis.pdf Pertussis]<br />
|10/2024<br />
|<br />
|-<br />
|[https://yk-health.org/images/8/84/TOLAC.pdf TOLAC]<br />
|10/2024<br />
|The artist formerly known as VBAC has been updated. The biggest changes are about required notifications.<br />
|-<br />
|[https://yk-health.org/images/e/e6/Intubation_adult_and_peds.pdf Intubation]<br />
|10/2024<br />
|The first page has undergone a major remodel in an effort to standardize the colors. There is a new fourth page – a checklist!<br />
|-<br />
|[https://yk-health.org/images/d/d8/MedevacTrauma.pdf Medevac/Transfer Process for Trauma]<br />
|10/2024<br />
|A brand NEW guideline that includes admission and transfer criteria for trauma patients! <br />
|}<br />
<br />
== 2024 - September ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
|-<br />
|Prenatal Care Guidelines<br />
|9/2024<br />
|<br />
|-<br />
|Fever (0-90 days)<br />
|9/2024<br />
|<br />
|-<br />
|Sepsis (Pediatric)<br />
|9/2024<br />
|<br />
|-<br />
|Lead Screening<br />
|9/2024<br />
|<br />
|-<br />
|MIS-C<br />
|9/2024<br />
|<br />
|-<br />
|Neopuff and ER warmer setup<br />
|9/2024<br />
|<br />
|-<br />
|Admissions from Clinic (pediatric)<br />
|9/2024<br />
|<br />
|-<br />
|Nirsevimab<br />
|9/2024<br />
|<br />
|}<br />
<br />
<br />
== 2024 - August ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
|-<br />
|Hypertension<br />
|8/2024<br />
|<br />
|-<br />
|Acute Cervical Lymphadenitis<br />
|8/2024<br />
|<br />
|-<br />
|Suspected Child Sexual Abuse Procedure<br />
|8/2024<br />
|<br />
|-<br />
|Failure to Thrive<br />
|8/2024<br />
|<br />
|-<br />
|mPEWS<br />
|8/2024<br />
|<br />
|-<br />
|Active Pulmonary TB (≥14y)<br />
|8/2024<br />
|<br />
|-<br />
|Latent TB Infection<br />
|8/2024<br />
|<br />
|-<br />
|Induction of Labor<br />
|8/2024<br />
|<br />
|-<br />
|Peritonsillar Abscess<br />
|8/2024<br />
|<br />
|-<br />
|TB Evaluation and Treatment (peds)<br />
|8/2024<br />
|<br />
|-<br />
|Guideline Guideline<br />
|8/2024<br />
|<br />
|-<br />
|Anemia in Adults<br />
|8/2024<br />
|<br />
|-<br />
|Fever in Underimmunized Children<br />
|8/2024<br />
|<br />
|}<br />
<br />
== 2024 - May ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[https://yk-health.org/images/5/5f/Cervical_Cancer_Screening.pdf Cervical Cancer Screening w/ hrHPV]<br />
|05/2024<br />
|Brand new. There are many training documents that go along with this.<br />
|<br />
|-<br />
|[https://yk-health.org/images/7/75/Intoxicated_ED_patient.pdf Intoxicated Patient in the ED]<br />
|05/2024<br />
|Updated "with a couple tweaks."<br />
|<br />
|-<br />
|[https://yk-health.org/images/2/20/Status_Tx_Adult.pdf Adult Status Epilepticus]<br />
|05/2024<br />
|Updated. "Not much has changed".<br />
|<br />
|-<br />
|[https://yk-health.org/images/b/bb/Osteoporosis_Screening_and_Treatment.pdf Osteoporosis]<br />
|05/2024<br />
|Not officially updated, but consent page now has more lines to sign on.<br />
|<br />
|}<br />
<br />
<br />
== 2024 - March ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[https://yk-health.org/images/7/70/Primary_prevention_CVD.pdf Primary Prevention of CVD]<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|[https://yk-health.org/images/9/9f/Hyperlipidemia.pdf Hyperlipidemia]<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/eb/Respiratory_distress.pdf Respiratory Distress and Bronchiolitis Management (<5 years)]<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|[https://yk-health.org/images/5/56/Pneumonia_peds.pdf Pneumonia Treatment (3 months – 18 years)]<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|[https://yk-health.org/images/6/65/NICU_grad_checklist.pdf Primary Care for Former Premies]<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|[https://yk-health.org/images/7/7a/Surfactant_Clinical_Resource.pdf Surfactant]<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|[https://yk-health.org/images/b/bb/Glucose_neonatal.pdf Neonatal Glucose Screening]<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/e6/Intubation_adult_and_peds.pdf Intubation]<br />
|03/2024<br />
|Updated.<br />
|<br />
|}<br />
<br />
== 2024 - February ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
|-<br />
|Seizure Evaluation (pediatric)<br />
|2/2024<br />
|<br />
|-<br />
|Status Epilepticus (pediatric)<br />
|2/2024<br />
|<br />
|-<br />
|Strangulation<br />
|2/2024<br />
|<br />
|-<br />
|Adult Critical Care Guide<br />
|2/2024<br />
|<br />
|-<br />
|Psychiatric Admissions<br />
|2/2024<br />
|<br />
|-<br />
|Neonatal Nasal CPAP<br />
|2/2024<br />
|<br />
|}<br />
<br />
== 2024 - January ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
|-<br />
|STI<br />
|1/2024<br />
|<br />
|-<br />
|Sinusitis (>4yo)<br />
|1/2024<br />
|<br />
|-<br />
|Activating the Military<br />
|1/2024<br />
|<br />
|-<br />
|Varicella<br />
|1/2024<br />
|<br />
|-<br />
|UTI (3m - 5y)<br />
|1/2024<br />
|<br />
|-<br />
|Postpartum hemorrhage<br />
|1/2024<br />
|<br />
|}</div>AndyShttps://yk-health.org/index.php?title=Guideline_List_(Chronological)&diff=9503Guideline List (Chronological)2025-01-11T13:03:08Z<p>AndyS: </p>
<hr />
<div>== 2024 - December ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
|-<br />
|[https://yk-health.org/images/d/d0/Stroke.pdf CVA]<br />
|12/2024<br />
|Changes to disposition, not giving aspirin w/ lytics, and monitoring parameters.<br />
|-<br />
|[https://yk-health.org/images/f/f3/Neonatal_Abstinence_Syndrome.pdf Suspected Neonatal Withdrawal]<br />
|12/2024<br />
|Brand new. Mostly for nursery.<br />
|-<br />
|[https://yk-health.org/images/3/33/UTI_adult.pdf UTI (adult)]<br />
|12/2024<br />
|Minor changes.<br />
|-<br />
|[https://yk-health.org/images/e/ec/Pneumonia_adult.pdf Pneumonia (adult)]<br />
|12/2024<br />
|Minor antibiotic changes.<br />
|-<br />
|[https://yk-health.org/images/0/03/Medevac_village_to_Bethel.pdf Medevac village to Bethel]<br />
|12/2024<br />
|Minor changes.<br />
|-<br />
|[https://yk-health.org/images/5/52/Medevac_Bethel_to_Anchorage.pdf Medevac Bethel to Anchorage]<br />
|12/2024<br />
|Minor changes including info about Guardian.<br />
|}<br />
<br />
== 2024 - October ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
|-<br />
|[https://yk-health.org/images/f/f7/Pertussis.pdf Pertussis]<br />
|10/2024<br />
|<br />
|-<br />
|[https://yk-health.org/images/8/84/TOLAC.pdf TOLAC]<br />
|10/2024<br />
|The artist formerly known as VBAC has been updated. The biggest changes are about required notifications.<br />
|-<br />
|[https://yk-health.org/images/e/e6/Intubation_adult_and_peds.pdf Intubation]<br />
|10/2024<br />
|The first page has undergone a major remodel in an effort to standardize the colors. There is a new fourth page – a checklist!<br />
|-<br />
|[https://yk-health.org/images/d/d8/MedevacTrauma.pdf Medevac/Transfer Process for Trauma]<br />
|10/2024<br />
|A brand NEW guideline that includes admission and transfer criteria for trauma patients! <br />
|}<br />
<br />
<br />
== 2024 - May ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[https://yk-health.org/images/5/5f/Cervical_Cancer_Screening.pdf Cervical Cancer Screening w/ hrHPV]<br />
|05/2024<br />
|Brand new. There are many training documents that go along with this.<br />
|<br />
|-<br />
|[https://yk-health.org/images/7/75/Intoxicated_ED_patient.pdf Intoxicated Patient in the ED]<br />
|05/2024<br />
|Updated "with a couple tweaks."<br />
|<br />
|-<br />
|[https://yk-health.org/images/2/20/Status_Tx_Adult.pdf Adult Status Epilepticus]<br />
|05/2024<br />
|Updated. "Not much has changed".<br />
|<br />
|-<br />
|[https://yk-health.org/images/b/bb/Osteoporosis_Screening_and_Treatment.pdf Osteoporosis]<br />
|05/2024<br />
|Not officially updated, but consent page now has more lines to sign on.<br />
|<br />
|}<br />
<br />
<br />
== 2024 - March ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[https://yk-health.org/images/7/70/Primary_prevention_CVD.pdf Primary Prevention of CVD]<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|[https://yk-health.org/images/9/9f/Hyperlipidemia.pdf Hyperlipidemia]<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/eb/Respiratory_distress.pdf Respiratory Distress and Bronchiolitis Management (<5 years)]<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|[https://yk-health.org/images/5/56/Pneumonia_peds.pdf Pneumonia Treatment (3 months – 18 years)]<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|[https://yk-health.org/images/6/65/NICU_grad_checklist.pdf Primary Care for Former Premies]<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|[https://yk-health.org/images/7/7a/Surfactant_Clinical_Resource.pdf Surfactant]<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|[https://yk-health.org/images/b/bb/Glucose_neonatal.pdf Neonatal Glucose Screening]<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/e6/Intubation_adult_and_peds.pdf Intubation]<br />
|03/2024<br />
|Updated.<br />
|<br />
|}</div>AndyShttps://yk-health.org/index.php?title=Guideline_List_(Chronological)&diff=9502Guideline List (Chronological)2025-01-11T12:34:34Z<p>AndyS: </p>
<hr />
<div>== 2024 - October ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
|-<br />
|[https://yk-health.org/images/f/f7/Pertussis.pdf Pertussis]<br />
|10/2024<br />
|<br />
|-<br />
|[https://yk-health.org/images/8/84/TOLAC.pdf TOLAC]<br />
|10/2024<br />
|The artist formerly known as VBAC has been updated. The biggest changes are about required notifications.<br />
|-<br />
|[https://yk-health.org/images/e/e6/Intubation_adult_and_peds.pdf Intubation]<br />
|10/2024<br />
|The first page has undergone a major remodel in an effort to standardize the colors. There is a new fourth page – a checklist!<br />
|-<br />
|[https://yk-health.org/images/d/d8/MedevacTrauma.pdf Medevac/Transfer Process for Trauma]<br />
|10/2024<br />
|A brand NEW guideline that includes admission and transfer criteria for trauma patients! <br />
|}<br />
<br />
<br />
== 2024 - May ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[https://yk-health.org/images/5/5f/Cervical_Cancer_Screening.pdf Cervical Cancer Screening w/ hrHPV]<br />
|05/2024<br />
|Brand new. There are many training documents that go along with this.<br />
|<br />
|-<br />
|[https://yk-health.org/images/7/75/Intoxicated_ED_patient.pdf Intoxicated Patient in the ED]<br />
|05/2024<br />
|Updated "with a couple tweaks."<br />
|<br />
|-<br />
|[https://yk-health.org/images/2/20/Status_Tx_Adult.pdf Adult Status Epilepticus]<br />
|05/2024<br />
|Updated. "Not much has changed".<br />
|<br />
|-<br />
|[https://yk-health.org/images/b/bb/Osteoporosis_Screening_and_Treatment.pdf Osteoporosis]<br />
|05/2024<br />
|Not officially updated, but consent page now has more lines to sign on.<br />
|<br />
|}<br />
<br />
<br />
== 2024 - March ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[https://yk-health.org/images/7/70/Primary_prevention_CVD.pdf Primary Prevention of CVD]<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|[https://yk-health.org/images/9/9f/Hyperlipidemia.pdf Hyperlipidemia]<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/eb/Respiratory_distress.pdf Respiratory Distress and Bronchiolitis Management (<5 years)]<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|[https://yk-health.org/images/5/56/Pneumonia_peds.pdf Pneumonia Treatment (3 months – 18 years)]<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|[https://yk-health.org/images/6/65/NICU_grad_checklist.pdf Primary Care for Former Premies]<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|[https://yk-health.org/images/7/7a/Surfactant_Clinical_Resource.pdf Surfactant]<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|[https://yk-health.org/images/b/bb/Glucose_neonatal.pdf Neonatal Glucose Screening]<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/e6/Intubation_adult_and_peds.pdf Intubation]<br />
|03/2024<br />
|Updated.<br />
|<br />
|}</div>AndyShttps://yk-health.org/index.php?title=Guideline_List_(Chronological)&diff=9501Guideline List (Chronological)2025-01-11T12:29:48Z<p>AndyS: May 2024 Guideline links</p>
<hr />
<div>== 2024 - October ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
|-<br />
|Pertussis<br />
|10/2024<br />
|<br />
|-<br />
|TOLAC<br />
|10/2024<br />
|The artist formerly known as VBAC has been updated. The biggest changes are about required notifications.<br />
|-<br />
|Intubation<br />
|10/2024<br />
|The first page has undergone a major remodel in an effort to standardize the colors. There is a new fourth page – a checklist!<br />
|-<br />
|Medevac/Transfer Process for Trauma<br />
|10/2024<br />
|A brand NEW guideline that includes admission and transfer criteria for trauma patients! <br />
|}<br />
<br />
<br />
== 2024 - May ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[[Cervical Cancer Screening w/ hrHPV]]<br />
|05/2024<br />
|Brand new. There are many training documents that go along with this.<br />
|<br />
|-<br />
|[[Intoxicated Patient in the ED]]<br />
|05/2024<br />
|Updated "with a couple tweaks."<br />
|<br />
|-<br />
|[[Adult Status Epilepticus]]<br />
|05/2024<br />
|Updated. "Not much has changed".<br />
|<br />
|-<br />
|[[Osteoporosis]]<br />
|05/2024<br />
|Not officially updated, but consent page now has more lines to sign on.<br />
|<br />
|}<br />
<br />
<br />
== 2024 - March ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[https://yk-health.org/images/7/70/Primary_prevention_CVD.pdf Primary Prevention of CVD]<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|[https://yk-health.org/images/9/9f/Hyperlipidemia.pdf Hyperlipidemia]<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/eb/Respiratory_distress.pdf Respiratory Distress and Bronchiolitis Management (<5 years)]<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|[https://yk-health.org/images/5/56/Pneumonia_peds.pdf Pneumonia Treatment (3 months – 18 years)]<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|[https://yk-health.org/images/6/65/NICU_grad_checklist.pdf Primary Care for Former Premies]<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|[https://yk-health.org/images/7/7a/Surfactant_Clinical_Resource.pdf Surfactant]<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|[https://yk-health.org/images/b/bb/Glucose_neonatal.pdf Neonatal Glucose Screening]<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/e6/Intubation_adult_and_peds.pdf Intubation]<br />
|03/2024<br />
|Updated.<br />
|<br />
|}</div>AndyShttps://yk-health.org/index.php?title=Guideline_List_(Chronological)&diff=9366Guideline List (Chronological)2024-06-20T16:10:24Z<p>AndyS: Mar 2024 Links created</p>
<hr />
<div><br />
== 2024 - May ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|Cervical Cancer Screening w/ hrHPV<br />
|05/2024<br />
|Brand new. There are many training documents that go along with this.<br />
|<br />
|-<br />
|Intoxicated Patient in the ED<br />
|05/2024<br />
|Updated "with a couple tweaks."<br />
|<br />
|-<br />
|Adult Status Epilepticus<br />
|05/2024<br />
|Updated. "Not much has changed".<br />
|<br />
|-<br />
|Osteoporosis<br />
|05/2024<br />
|Not officially updated, but consent page now has more lines to sign on.<br />
|<br />
|}<br />
<br />
<br />
== 2024 - March ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[https://yk-health.org/images/7/70/Primary_prevention_CVD.pdf Primary Prevention of CVD]<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|[https://yk-health.org/images/9/9f/Hyperlipidemia.pdf Hyperlipidemia]<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/eb/Respiratory_distress.pdf Respiratory Distress and Bronchiolitis Management (<5 years)]<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|[https://yk-health.org/images/5/56/Pneumonia_peds.pdf Pneumonia Treatment (3 months – 18 years)]<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|[https://yk-health.org/images/6/65/NICU_grad_checklist.pdf Primary Care for Former Premies]<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|[https://yk-health.org/images/7/7a/Surfactant_Clinical_Resource.pdf Surfactant]<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|[https://yk-health.org/images/b/bb/Glucose_neonatal.pdf Neonatal Glucose Screening]<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/e6/Intubation_adult_and_peds.pdf Intubation]<br />
|03/2024<br />
|Updated.<br />
|<br />
|}</div>AndyShttps://yk-health.org/index.php?title=Guideline_List_(Chronological)&diff=9365Guideline List (Chronological)2024-06-20T16:07:51Z<p>AndyS: </p>
<hr />
<div><br />
== 2024 - May ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|Cervical Cancer Screening w/ hrHPV<br />
|05/2024<br />
|Brand new. There are many training documents that go along with this.<br />
|<br />
|-<br />
|Intoxicated Patient in the ED<br />
|05/2024<br />
|Updated "with a couple tweaks."<br />
|<br />
|-<br />
|Adult Status Epilepticus<br />
|05/2024<br />
|Updated. "Not much has changed".<br />
|<br />
|-<br />
|Osteoporosis<br />
|05/2024<br />
|Not officially updated, but consent page now has more lines to sign on.<br />
|<br />
|}<br />
<br />
<br />
== 2024 - March ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[https://yk-health.org/images/7/70/Primary_prevention_CVD.pdf Primary Prevention of CVD]<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|[https://yk-health.org/images/9/9f/Hyperlipidemia.pdf Hyperlipidemia]<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|[https://yk-health.org/images/e/eb/Respiratory_distress.pdf Respiratory Distress and Bronchiolitis Management (<5 years)]<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|[https://yk-health.org/images/5/56/Pneumonia_peds.pdf Pneumonia Treatment (3 months – 18 years)]<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|[[Primary Care for Former Premies]]<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|[[Surfactant]]<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|[[Neonatal Glucose Screening Evaluation and Treatment|Neonatal Glucose Screening]]<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|[[Intubation – Adult and Peds|Intubation]]<br />
|03/2024<br />
|Updated.<br />
|<br />
|}</div>AndyShttps://yk-health.org/index.php?title=Guideline_List_(Chronological)&diff=9364Guideline List (Chronological)2024-06-20T16:02:09Z<p>AndyS: </p>
<hr />
<div><br />
== 2024 - May ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|Cervical Cancer Screening w/ hrHPV<br />
|05/2024<br />
|Brand new. There are many training documents that go along with this.<br />
|<br />
|-<br />
|Intoxicated Patient in the ED<br />
|05/2024<br />
|Updated "with a couple tweaks."<br />
|<br />
|-<br />
|Adult Status Epilepticus<br />
|05/2024<br />
|Updated. "Not much has changed".<br />
|<br />
|-<br />
|Osteoporosis<br />
|05/2024<br />
|Not officially updated, but consent page now has more lines to sign on.<br />
|<br />
|}<br />
<br />
<br />
== 2024 - March ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|[[Primary Prevention of CVD]]<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|[[Hyperlipidemia]]<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|[[Respiratory distress|Respiratory Distress and Bronchiolitis Management (<5 years)]]<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|[[Pneumonia Treatment (3 months – 18 years)]]<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|[[Primary Care for Former Premies]]<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|[[Surfactant]]<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|[[Neonatal Glucose Screening Evaluation and Treatment|Neonatal Glucose Screening]]<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|[[Intubation – Adult and Peds|Intubation]]<br />
|03/2024<br />
|Updated.<br />
|<br />
|}</div>AndyShttps://yk-health.org/index.php?title=Guideline_List_(Chronological)&diff=9363Guideline List (Chronological)2024-06-20T15:54:29Z<p>AndyS: /* 2024 - May */</p>
<hr />
<div><br />
== 2024 - May ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|Cervical Cancer Screening w/ hrHPV<br />
|05/2024<br />
|Brand new. There are many training documents that go along with this.<br />
|<br />
|-<br />
|Intoxicated Patient in the ED<br />
|05/2024<br />
|Updated "with a couple tweaks."<br />
|<br />
|-<br />
|Adult Status Epilepticus<br />
|05/2024<br />
|Updated. "Not much has changed".<br />
|<br />
|-<br />
|Osteoporosis<br />
|05/2024<br />
|Not officially updated, but consent page now has more lines to sign on.<br />
|<br />
|}<br />
<br />
<br />
== 2024 - March ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|Primary Prevention of CVD<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|Hyperlipidemia<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|Respiratory Distress and Bronchiolitis Management (<5 years)<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|Pneumonia Treatment (3 months – 18 years)<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|Primary Care for Former Premies<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|Surfactant<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|Neonatal Glucose Screening<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|Intubation<br />
|03/2024<br />
|Updated.<br />
|<br />
|}</div>AndyShttps://yk-health.org/index.php?title=Guideline_List_(Chronological)&diff=9362Guideline List (Chronological)2024-06-20T15:50:47Z<p>AndyS: /* 2024 - March */</p>
<hr />
<div><br />
== 2024 - May ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|Primary Prevention of CVD<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|Hyperlipidemia<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|Respiratory Distress and Bronchiolitis Management (<5 years)<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|Pneumonia Treatment (3 months – 18 years)<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|Primary Care for Former Premies<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|Surfactant<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|Neonatal Glucose Screening<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|Intubation<br />
|03/2024<br />
|Updated.<br />
|<br />
|}<br />
<br />
<br />
== 2024 - March ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|Primary Prevention of CVD<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|Hyperlipidemia<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|Respiratory Distress and Bronchiolitis Management (<5 years)<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|Pneumonia Treatment (3 months – 18 years)<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|Primary Care for Former Premies<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|Surfactant<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|Neonatal Glucose Screening<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|Intubation<br />
|03/2024<br />
|Updated.<br />
|<br />
|}</div>AndyShttps://yk-health.org/index.php?title=Guideline_List_(Chronological)&diff=9329Guideline List (Chronological)2024-03-18T22:57:35Z<p>AndyS: Created page with " == 2024 - March == {| class="wikitable" |+ !Topic !Date !Comment ! |- |Primary Prevention of CVD |03/2024 |Overhauled and expanded the aspirin guideline into something bigger and better! | |- |Hyperlipidemia |03/2024 |Brand-new | |- |Respiratory Distress and Bronchiolitis Management (<5 years) |03/2024 |Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis | |- |P..."</p>
<hr />
<div><br />
== 2024 - March ==<br />
{| class="wikitable"<br />
|+<br />
!Topic<br />
!Date<br />
!Comment<br />
!<br />
|-<br />
|Primary Prevention of CVD<br />
|03/2024<br />
|Overhauled and expanded the aspirin guideline into something bigger and better!<br />
|<br />
|-<br />
|Hyperlipidemia<br />
|03/2024<br />
|Brand-new<br />
|<br />
|-<br />
|Respiratory Distress and Bronchiolitis Management (<5 years)<br />
|03/2024<br />
|Revamped “wheezing & bronchiolitis” into a more inclusive guideline that begins with the management of respiratory distress and then moves into bronchiolitis<br />
|<br />
|-<br />
|Pneumonia Treatment (3 months – 18 years)<br />
|03/2024<br />
|Vastly simplified with all redundancy removed. Meant to be used along with the above respiratory distress guideline.<br />
|<br />
|-<br />
|Primary Care for Former Premies<br />
|03/2024<br />
|Updated.<br />
|<br />
|-<br />
|Surfactant<br />
|03/2024<br />
|Small updates, including mention of RSI.<br />
|<br />
|-<br />
|Neonatal Glucose Screening<br />
|03/2024<br />
|Small updates and some reorganization<br />
|<br />
|-<br />
|Intubation<br />
|03/2024<br />
|Updated.<br />
|<br />
|}</div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=9012Transcutaneous paCO2 Monitoring2023-03-14T23:04:55Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref name="Nassar2017">Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
[[File:Sentec.PNG|left]]<br />
<br clear=all><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of monitoring paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO<sub>2</sub> monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> is '''substantially more accurate''' than peripheral venous CO<sub>2</sub> for estimating paCO<sub>2</sub>.<ref name="Nassar2017"/><br />
# Because CO<sub>2</sub> takes several minutes to diffuse out of the skin, the displayed TC-CO<sub>2</sub> reading at any given time reflects the paCO<sub>2</sub> from 2-4 minutes prior.<br />
# The tracing is a flat line (rather than the waveform created by exhaled air).<br />
# TC-CO<sub>2</sub> is used to follow paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> '''IS NOT''' an acceptable substitute for ET-CO<sub>2</sub> in situations such as:<br />
## Confirmation of ET-tube placement.<br />
## CPR (neither for CPR adequacy nor ROSC identification).<br />
## Respiratory monitoring during sedation.<br />
## Any situation where monitoring for apnea or any rapid changes in paCO<sub>2</sub>.<br />
# The accuracy of end-tidal CO<sub>2</sub> as an estimate of paCO<sub>2</sub> is largely dependent upon how closely a patient's lung function matches an ideal lung. For patients who are intubated for non-respiratory issues, their lung function should pretty closely approximate an ideal lung, and thus end-tidal CO<sub>2</sub> should estimate paCO<sub>2</sub> with reasonable accuracy. But for patients with lung processes which create V/Q mismatches, end-tidal CO<sub>2</sub> is not a good estimate of paCO<sub>2</sub>. In such situations, TC-CO<sub>2</sub> provides a MUCH MORE ACCURATE estimate paCO<sub>2</sub>.<ref name="Nassar2017"/> Thus, if paCO<sub>2</sub> requires monitoring in patients with ARDS, bronchiolitis, pneumonia, etc., TC-CO<sub>2</sub> should be considered regardless of the type of respiratory support the patient is receiving (i.e. none, high-flow, or intubated). In such a situation, an intubated patient might be monitored with end-tidal CO<sub>2</sub> to watch for apnea and TC-CO<sub>2</sub> to assess adequacy of ventilation over time.<br />
<br><br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry (with an adjustable duration trend line)<br />
# Instantaneous heart rate (with an adjustable duration trend line)<br />
# Delayed paCO<sub>2</sub> (with an adjustable duration trend line)<br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
'''PubMed Searches:'''<br />
: [https://pubmed.ncbi.nlm.nih.gov/?term=(%22transcutaneous%20co2%22%5BTitle%5D%20OR%20%22transcutaneous%20carbon%20dioxide%22%5BTitle%5D)%20AND%20(infant%5BTitle%5D%20OR%20neonat*%5BTitle%5D%20OR%20child*%5BTitle%5D) ("transcutaneous co2"[Title<nowiki>]</nowiki> OR "transcutaneous carbon dioxide"[Title<nowiki>]</nowiki>) AND (infant[Title<nowiki>]</nowiki> OR neonat*[Title<nowiki>]</nowiki> OR child*[Title<nowiki>]</nowiki>)]<br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=9011Transcutaneous paCO2 Monitoring2023-03-14T21:52:27Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref name="Nassar2017">Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
[[File:Sentec.PNG|left]]<br />
<br clear=all><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of monitoring paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO<sub>2</sub> monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> is '''substantially more accurate''' than peripheral venous CO<sub>2</sub> for estimating paCO<sub>2</sub>.<ref name="Nassar2017"/><br />
# Because CO<sub>2</sub> takes several minutes to diffuse out of the skin, the displayed TC-CO<sub>2</sub> reading at any given time reflects the paCO<sub>2</sub> from 2-4 minutes prior.<br />
# The tracing is a flat line (rather than the waveform created by exhaled air).<br />
# TC-CO<sub>2</sub> is used to follow paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> '''IS NOT''' an acceptable substitute for ET-CO<sub>2</sub> in situations such as:<br />
## Confirmation of ET-tube placement.<br />
## CPR (neither for CPR adequacy nor ROSC identification).<br />
## Respiratory monitoring during sedation.<br />
## Any situation where monitoring for apnea or any rapid changes in paCO<sub>2</sub>.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry (with an adjustable duration trend line)<br />
# Instantaneous heart rate (with an adjustable duration trend line)<br />
# Delayed paCO<sub>2</sub> (with an adjustable duration trend line)<br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
'''PubMed Searches:'''<br />
: [https://pubmed.ncbi.nlm.nih.gov/?term=(%22transcutaneous%20co2%22%5BTitle%5D%20OR%20%22transcutaneous%20carbon%20dioxide%22%5BTitle%5D)%20AND%20(infant%5BTitle%5D%20OR%20neonat*%5BTitle%5D%20OR%20child*%5BTitle%5D) ("transcutaneous co2"[Title<nowiki>]</nowiki> OR "transcutaneous carbon dioxide"[Title<nowiki>]</nowiki>) AND (infant[Title<nowiki>]</nowiki> OR neonat*[Title<nowiki>]</nowiki> OR child*[Title<nowiki>]</nowiki>)]<br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=File:Sentec.PNG&diff=9010File:Sentec.PNG2023-03-14T21:42:12Z<p>AndyS: </p>
<hr />
<div></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=9009Transcutaneous paCO2 Monitoring2023-03-13T18:38:09Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref name="Nassar2017">Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of monitoring paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO<sub>2</sub> monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> is '''substantially more accurate''' than peripheral venous CO<sub>2</sub> for estimating paCO<sub>2</sub>.<ref name="Nassar2017"/><br />
# Because CO<sub>2</sub> takes several minutes to diffuse out of the skin, the displayed TC-CO<sub>2</sub> reading at any given time reflects the paCO<sub>2</sub> from 2-4 minutes prior.<br />
# The tracing is a flat line (rather than the waveform created by exhaled air).<br />
# TC-CO<sub>2</sub> is used to follow paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> '''IS NOT''' an acceptable substitute for ET-CO<sub>2</sub> in situations such as:<br />
## Confirmation of ET-tube placement.<br />
## CPR (neither for CPR adequacy nor ROSC identification).<br />
## Respiratory monitoring during sedation.<br />
## Any situation where monitoring for apnea or any rapid changes in paCO<sub>2</sub>.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry (with an adjustable duration trend line)<br />
# Instantaneous heart rate (with an adjustable duration trend line)<br />
# Delayed paCO<sub>2</sub> (with an adjustable duration trend line)<br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
'''PubMed Searches:'''<br />
: [https://pubmed.ncbi.nlm.nih.gov/?term=(%22transcutaneous%20co2%22%5BTitle%5D%20OR%20%22transcutaneous%20carbon%20dioxide%22%5BTitle%5D)%20AND%20(infant%5BTitle%5D%20OR%20neonat*%5BTitle%5D%20OR%20child*%5BTitle%5D) ("transcutaneous co2"[Title<nowiki>]</nowiki> OR "transcutaneous carbon dioxide"[Title<nowiki>]</nowiki>) AND (infant[Title<nowiki>]</nowiki> OR neonat*[Title<nowiki>]</nowiki> OR child*[Title<nowiki>]</nowiki>)]<br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=9008Transcutaneous paCO2 Monitoring2023-03-13T18:36:11Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref name="Nassar2017">Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of monitoring paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO<sub>2</sub> monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> is '''substantially more accurate''' than peripheral venous CO<sub>2</sub> for estimating paCO<sub>2</sub>.<ref name="Nassar2017"/><br />
# Because CO<sub>2</sub> takes several minutes to diffuse out of the skin, the displayed TC-CO<sub>2</sub> reading at any given time reflects the paCO<sub>2</sub> from 2-4 minutes prior.<br />
# The tracing is a flat line (rather than the waveform created by exhaled air).<br />
# TC-CO<sub>2</sub> is used to follow paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> '''IS NOT''' an acceptable substitute for ET-CO<sub>2</sub> in situations such as:<br />
## Confirmation of ET-tube placement.<br />
## CPR (neither for CPR adequacy nor ROSC identification).<br />
## Respiratory monitoring during sedation.<br />
## Any situation where monitoring for apnea or any rapid changes in paCO<sub>2</sub>.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry (with an adjustable duration trend line)<br />
# Instantaneous heart rate (with an adjustable duration trend line)<br />
# Delayed paCO<sub>2</sub> (with an adjustable duration trend line)<br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=9007Transcutaneous paCO2 Monitoring2023-03-13T18:31:48Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref name="Nassar2017">Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of monitoring paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO<sub>2</sub> monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> is '''substantially more accurate''' than peripheral venous CO<sub>2</sub> for estimating paCO<sub>2</sub>.<ref name="Nassar2017"/><br />
# Because CO<sub>2</sub> takes several minutes to diffuse out of the skin, the displayed TC-CO<sub>2</sub> reading at any given time reflects the paCO<sub>2</sub> from 2-4 minutes prior.<br />
# The tracing is a flat line (rather than the waveform created by exhaled air).<br />
# TC-CO<sub>2</sub> is used to follow paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> '''IS NOT''' an acceptable substitute for ET-CO<sub>2</sub> in situations such as:<br />
## Confirmation of ET-tube placement.<br />
## CPR (neither for CPR adequacy nor ROSC identification).<br />
## Respiratory monitoring during sedation.<br />
## Any situation where monitoring for apnea or any rapid changes in paCO<sub>2</sub>.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry (with an adjustable duration trend line)<br />
# Instantaneous heart rate <br />
# Trending of paCO<sub>2</sub> (with an adjustable duration trend line)<br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=9006Transcutaneous paCO2 Monitoring2023-03-13T18:29:57Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref name="Nassar2017">Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of monitoring paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO<sub>2</sub> monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> is '''substantially more accurate''' than peripheral venous CO<sub>2</sub> for estimating paCO<sub>2</sub>.<ref name="Nassar2017"/><br />
# Because CO<sub>2</sub> takes several minutes to diffuse out of the skin, the displayed TC-CO<sub>2</sub> reading at any given time reflects the paCO<sub>2</sub> from 2-4 minutes prior.<br />
# The tracing is a flat line (rather than the waveform created by exhaled air).<br />
# TC-CO<sub>2</sub> is used to follow paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> '''IS NOT''' an acceptable substitute for ET-CO<sub>2</sub> in situations such as:<br />
## Confirmation of ET-tube placement.<br />
## CPR (neither for CPR adequacy nor ROSC identification).<br />
## Respiratory monitoring during sedation.<br />
## Any situation where monitoring for apnea or any rapid changes in paCO<sub>2</sub>.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry<br />
# Instantaneous heart rate (with an adjustable duration trend line)<br />
# Trending of paCO<sub>2</sub> (with an adjustable duration trend line)<br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=9005Transcutaneous paCO2 Monitoring2023-03-13T17:15:02Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref>Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of following paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO<sub>2</sub> monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# The TC-CO<sub>2</sub> reading at any given time reflects the paCO<sub>2</sub> from several minutes prior.<br />
# TC-CO<sub>2</sub> measures paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> '''IS NOT''' an acceptable substitute for ET-CO<sub>2</sub> in these situations:<br />
## Confirmation of ET-tube placement.<br />
## CPR (neither for CPR adequacy nor ROSC identification).<br />
## Respiratory monitoring during sedation.<br />
## Any situation where monitoring for apnea or any rapid changes in paCO<sub>2</sub>.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry<br />
# Instantaneous heart rate<br />
# Trending of paCO<sub>2</sub><br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=File:Sentec_TCCO2.png&diff=9004File:Sentec TCCO2.png2023-03-13T13:43:50Z<p>AndyS: </p>
<hr />
<div></div>AndyShttps://yk-health.org/index.php?title=Trancutaneous_paCO2_Monitoring&diff=9003Trancutaneous paCO2 Monitoring2023-03-13T13:28:30Z<p>AndyS: AndyS moved page Trancutaneous paCO2 Monitoring to Transcutaneous paCO2 Monitoring</p>
<hr />
<div>#REDIRECT [[Transcutaneous paCO2 Monitoring]]</div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=9002Transcutaneous paCO2 Monitoring2023-03-13T13:28:30Z<p>AndyS: AndyS moved page Trancutaneous paCO2 Monitoring to Transcutaneous paCO2 Monitoring</p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref>Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of following paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO<sub>2</sub> monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> measures paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> is NOT an acceptable substitute for ET-CO<sub>2</sub> in these situations:<br />
## Confirmation of ET-tube placement.<br />
## Respiratory monitoring during sedation.<br />
## Any situation where apnea is a concern.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry<br />
# Instantaneous heart rate<br />
# Trending of paCO<sub>2</sub><br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Trancutaneous_pCO2_Monitoring&diff=9001Trancutaneous pCO2 Monitoring2023-03-13T13:25:07Z<p>AndyS: AndyS moved page Trancutaneous pCO2 Monitoring to Trancutaneous paCO2 Monitoring</p>
<hr />
<div>#REDIRECT [[Trancutaneous paCO2 Monitoring]]</div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=9000Transcutaneous paCO2 Monitoring2023-03-13T13:25:07Z<p>AndyS: AndyS moved page Trancutaneous pCO2 Monitoring to Trancutaneous paCO2 Monitoring</p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref>Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of following paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO<sub>2</sub> monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> measures paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> is NOT an acceptable substitute for ET-CO<sub>2</sub> in these situations:<br />
## Confirmation of ET-tube placement.<br />
## Respiratory monitoring during sedation.<br />
## Any situation where apnea is a concern.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry<br />
# Instantaneous heart rate<br />
# Trending of paCO<sub>2</sub><br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=8999Transcutaneous paCO2 Monitoring2023-03-13T13:24:22Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref>Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of following paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO<sub>2</sub> monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> measures paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> is NOT an acceptable substitute for ET-CO<sub>2</sub> in these situations:<br />
## Confirmation of ET-tube placement.<br />
## Respiratory monitoring during sedation.<br />
## Any situation where apnea is a concern.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry<br />
# Instantaneous heart rate<br />
# Trending of paCO<sub>2</sub><br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=8998Transcutaneous paCO2 Monitoring2023-03-13T13:22:59Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref>Nassar BS, Schmidt GA. [https://doi.org/10.1513/AnnalsATS.201701-034FR '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?'''] Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of following paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO2 monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> measures paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> is NOT an acceptable substitute for ET-CO<sub>2</sub> in these situations:<br />
## Confirmation of ET-tube placement.<br />
## Respiratory monitoring during sedation.<br />
## Any situation where apnea is a concern.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry<br />
# Instantaneous heart rate<br />
# Trending of paCO<sub>2</sub><br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=8997Transcutaneous paCO2 Monitoring2023-03-13T13:20:21Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref>Nassar BS, Schmidt GA. '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?''' Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: [https://doi.org/10.1513/AnnalsATS.201701-034FR 10.1513/AnnalsATS.201701-034FR]. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
YKDRH obtained TC-CO<sub>2</sub> monitors for the purpose of following paCO<sub>2</sub> <u>trends</u> in patients receiving high-flow nasal cannula or non-invasive ventilation (i.e. CPAP/BiPAP). This was necessary because end-tidal CO2 monitoring is not compatible with these interventions.<br />
<br />
<br />
== Important Points ==<br />
# Applicable for all age groups (including extremely premature neonates).<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> measures paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> is NOT an acceptable substitute for ET-CO<sub>2</sub> in these situations:<br />
## Confirmation of ET-tube placement.<br />
## Respiratory monitoring during sedation.<br />
## Any situation where apnea is a concern.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry<br />
# Instantaneous heart rate<br />
# Trending of paCO<sub>2</sub><br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=8996Transcutaneous paCO2 Monitoring2023-03-13T12:48:49Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref>Nassar BS, Schmidt GA. '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?''' Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: [https://doi.org/10.1513/AnnalsATS.201701-034FR 10.1513/AnnalsATS.201701-034FR]. PMID: 28570147.</ref><br><br />
<br><br />
<br />
== Primary Purpose ==<br />
Monitoring paCO<sub>2</sub> <u>trends</u> in patients receiving ventilatory assistance with high-flow nasal cannula or non-invasive ventilation.<br />
<br />
<br />
== Important Points ==<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> measures paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> is NOT an acceptable substitute for ET-CO<sub>2</sub> in these situations:<br />
## Confirmation of ET-tube placement.<br />
## Respiratory monitoring during sedation.<br />
## Any situation where apnea is a concern.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry<br />
# Instantaneous heart rate<br />
# Trending of paCO<sub>2</sub><br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=8995Transcutaneous paCO2 Monitoring2023-03-13T12:42:24Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref>Nassar BS, Schmidt GA. '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?''' Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: [https://doi.org/10.1513/AnnalsATS.201701-034FR 10.1513/AnnalsATS.201701-034FR]. PMID: 28570147.</ref><br><br />
<br />
== Important Points ==<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> measures paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> is NOT an acceptable substitute for ET-CO<sub>2</sub> in these situations:<br />
## Confirmation of ET-tube placement.<br />
## Respiratory monitoring during sedation.<br />
## Any situation where apnea is a concern.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry<br />
# Instantaneous heart rate<br />
# Trending of paCO<sub>2</sub><br />
<br />
== Resources ==<br />
: [https://yk-health.org/wiki/File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf Sentec Instruction Manual]<br />
'''Instructional Videos:'''<br />
: [https://www.youtube.com/watch?v=7d7XNtQNllA Neonatal Sensor Application for the Sentec Digital Transcutaneous Monitoring System]<br />
: [https://www.youtube.com/watch?v=7HX7dgqieaM Sensor Application Adult Cheek for the Sentec Digital Transcutaneous Monitoring System]<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=File:Transcutaneous_CO2_monitor_SDMS_InstructionManual_EN.pdf&diff=8994File:Transcutaneous CO2 monitor SDMS InstructionManual EN.pdf2023-03-13T12:29:52Z<p>AndyS: </p>
<hr />
<div></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=8993Transcutaneous paCO2 Monitoring2023-03-13T12:29:16Z<p>AndyS: </p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are a highly accurate, non-invasive method for estimating paCO<sub>2</sub>.<ref>Nassar BS, Schmidt GA. '''Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?''' Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: [https://doi.org/10.1513/AnnalsATS.201701-034FR 10.1513/AnnalsATS.201701-034FR]. PMID: 28570147.</ref><br><br />
<br />
== Important Points ==<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO<sub>2</sub> measures paCO<sub>2</sub> trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO<sub>2</sub> is NOT an acceptable substitute for ET-CO<sub>2</sub> in these situations:<br />
## Confirmation of ET-tube placement.<br />
## Respiratory monitoring during sedation.<br />
## Any situation where apnea is a concern.<br />
<br />
== Device ==<br />
YKDRH has acquired the '''Sentec''' Digital Monitoring System.<br><br />
The Sentec devices provides monitoring of:<br />
# Instantaneous oximetry<br />
# Instantaneous heart rate<br />
# Trending of paCO<sub>2</sub><br />
<br />
== Resources ==<br />
: Instruction Manual<br />
: Instructional Video<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=Transcutaneous_paCO2_Monitoring&diff=8992Transcutaneous paCO2 Monitoring2023-03-13T12:19:56Z<p>AndyS: Created page with "Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are highly..."</p>
<hr />
<div>Transcutaneous CO<sub>2</sub> (TC-CO<sub>2</sub>) monitors function by measuring the CO<sub>2</sub> which diffuses out the skin. Modern TC-CO<sub>2</sub> monitors are highly accurate for measuring paCO<sub>2</sub>.<ref>Nassar BS, Schmidt GA. Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures? Ann Am Thorac Soc. 2017 Jun;14(6):1005-1014. doi: 10.1513/AnnalsATS.201701-034FR. PMID: 28570147.</ref><br><br />
<br />
== Important Points ==<br />
# Initial reading requires approximately five minutes to establish.<br />
# TC-CO2 measures paCO2 trends; it DOES NOT measure instantaneous levels. Therefore, TC-CO2 is NOT an acceptable substitute for ET-CO2 in these situations:<br />
## Confirmation of ET-tube placement.<br />
## Respiratory monitoring during sedation.<br />
## Any situation where apnea is a concern.<br />
<br />
== REFERENCES ==<br />
<references /></div>AndyShttps://yk-health.org/index.php?title=H_Pylori_Guideline_Revision_Supplement_2022&diff=8739H Pylori Guideline Revision Supplement 20222022-03-22T13:39:22Z<p>AndyS: </p>
<hr />
<div>This guideline revision page addresses only the methods and results of the 2022 guideline update. For a broader review of the topic of H. pylori in Alaska Natives and for prior and/or ANMC guidelines, see the [[Helicobacter_pylori_in_Alaska_Natives|'''Helicobacter pylori in Alaska Natives''']] page.<br />
<br><br />
<br><br />
<br />
== Reason[s] for update ==<br />
Routine review/update.<br />
<br><br />
<br><br />
<br />
== Methods ==<br />
* Review of latest ANMC H. pylori treatment guideline ([https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf Feb 19, 2020 ][https://web.archive.org/web/20201024034528/https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf , Archive])<br><br />
* Updated literature search (PubMed, [https://pubmed.ncbi.nlm.nih.gov/?term=%28alaska%5BTitle%5D+OR+polar%5BTitle%5D+OR+arctic%5BTitle%5D%29+AND+helicobacter%5BTitle%2FAbstract%5D&sort=date (alaska[Title<nowiki>]</nowiki> OR polar[Title<nowiki>]</nowiki> OR arctic[Title<nowiki>]</nowiki>) AND helicobacter[Title/Abstract<nowiki>]</nowiki>]). This is a broader search than previously in that it looks for "helicobacter" in the abstract as well as the title.<br />
* Attendance at the 2019 Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium<br />
:: >Hosted by the CDC in Anchorage, Alaska<br />
:: >Experts were longstanding, world-renown researchers<br />
:: >Results were published in ''Gastroenterology'' in April 2020<ref name="Nolen2020">Nolen LD, Vindigni SM, Parsonnet J; Symposium leaders. Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium. Gastroenterology. 2020 Apr;158(5):1197-1201. doi: 10.1053/j.gastro.2019.11.299. PMID: 31836529; PMCID: [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7103478/ PMC7103478]. DOI:[https://doi.org/10.1053/j.gastro.2019.11.299 10.1053/j.gastro.2019.11.299]</ref><br />
* Pediatric H. pylori literature review: <br />
:: >PUBMED, [https://pubmed.ncbi.nlm.nih.gov/?term=pylori%5BTitle%5D+AND+%28pediatric*%5BTitle%5D+OR+child*%5BTitle%5D%29+AND+%28review%5BTitle%5D+OR+overview%5BTitle%5D+OR+guideline*%5BTitle%5D%29 pylori[Title<nowiki>]</nowiki> AND (pediatric*[Title<nowiki>]</nowiki> OR child*[Title<nowiki>]</nowiki>) AND (review[Title<nowiki>]</nowiki> OR overview[Title<nowiki>]</nowiki> OR guideline*[Title<nowiki>]</nowiki>)]<br />
<br><br />
<br />
==Results==<br />
# ANMC H. Pylori Treatment Guideline has no significant changes pertinent to the YKHC guideline. Of note, ANMC has started a study of offering EGD for gastric cancer screening for patients with a first-degree relative (parent, sibling, or child) with gastric cancer; they are treating to eradicate H. pylori in this group regardless of findings; but this treatment is limited to the study patients and thus is not applicable to our practice in Bethel.<br />
# PubMed search returned 49 articles, 12 of which were published since the last literature review. Only one of these articles addresses treatment in our setting, which is the CDC conference summary,<ref name="Nolen2020"/> which continues to explicitly advocate the current algorithm/guideline (which was originally published by an international, circumpolar expert group in 2016<ref name=mcmahon2016>McMahon BJ, Bruce MG, Koch A, et al. The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary. Epidemiology and Infection. 2016;144(2):225-233. PMID:[https://pubmed.ncbi.nlm.nih.gov/26094936/ 26094936]. PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4697284/ PMC4697284]. doi:[https://doi.org/10.1017/s0950268815001181 10.1017/S0950268815001181].</ref>) <br />
# Pediatric PubMed search returned 50 results, the most pertinent being the ''Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016)''<ref name=NASPGHAN>Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, Czinn S, Gold BD, Guarner J, Elitsur Y, Homan M, Kalach N, Kori M, Madrazo A, Megraud F, Papadopoulou A, Rowland M; ESPGHAN, NASPGHAN. Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016). J Pediatr Gastroenterol Nutr. 2017 Jun;64(6):991-1003. doi: 10.1097/MPG.0000000000001594. PMID: 28541262.</ref><br />
<br><br />
<br />
== Discussion ==<br />
* The YKHC H. pylori guideline continues to be consistent with the ANMC H. pylori guideline.<br />
* For adults, the YKHC guideline is very different than the standard of care in the remainder of the U.S. which endorsed the "test-and-treat" strategy. The prevalence of H. pylori in the Alaska Native population is far too high for such a strategy.<br />
* For pediatrics, the YKHC guideline (which treats pediatrics identical to adults) is consistent with national guidelines (i.e. NASPGHAN<ref name="Nolen2020"/>)<br />
* The only minor issue with the YKHC guideline is that it does not address recent recommendations regarding new, commercially available, rapid H. pylori culture and sensitivities to guide initial antimicrobial choice.<br />
<br><br />
<br />
==Guideline Changes==<br />
# Under treatment indications, "Intestinal Metaplasia" is changed to "Gastric Intestinal Metaplasia" (to prevent any confusion with Barrett's esophagus).<br />
# Addition of box specifying test-of-cure details:<br />
:::* ≥4wks after COMPLETION of treatment.<br />
:::* Either urea breath test (UBT), stool antigen test, or endoscopic biopsy (if indicated for other reasons; using either pathology or CLO-test).<br />
:::* Regardless of test, no antibiotics or bismuth for FOUR weeks prior.<br />
:::* Regardless of test, no PPI for TWO weeks prior.<br />
<br><br />
<br />
==Topics for Exploration==<br />
Commercial (i.e. non-CDC) rapid H. pylori culture/sensitivities which can be used to guide antimicrobial therapy for primary treatment.<br />
<br><br />
<br><br />
<br><br />
<br />
Author: Andrew W. Swartz, MD<br />
<br><br />
<br><br />
<br />
==References==<br />
----</div>AndyShttps://yk-health.org/index.php?title=H_Pylori_Guideline_Revision_Supplement_2022&diff=8738H Pylori Guideline Revision Supplement 20222022-03-22T13:36:39Z<p>AndyS: </p>
<hr />
<div>This guideline revision page addresses only the methods and results of the 2022 guideline update. For a broader review of the topic of H. pylori in Alaska Natives and for prior and/or ANMC guidelines, see the [[Helicobacter_pylori_in_Alaska_Natives|'''Helicobacter pylori in Alaska Natives''']] page.<br />
<br><br />
<br><br />
<br />
== Reason[s] for update ==<br />
Routine review/update.<br />
<br><br />
<br><br />
<br />
== Methods ==<br />
* Review of latest ANMC H. pylori treatment guideline ([https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf Feb 19, 2020 ][https://web.archive.org/web/20201024034528/https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf , Archive])<br><br />
* Updated literature search (PubMed, [https://pubmed.ncbi.nlm.nih.gov/?term=%28alaska%5BTitle%5D+OR+polar%5BTitle%5D+OR+arctic%5BTitle%5D%29+AND+helicobacter%5BTitle%2FAbstract%5D&sort=date (alaska[Title<nowiki>]</nowiki> OR polar[Title<nowiki>]</nowiki> OR arctic[Title<nowiki>]</nowiki>) AND helicobacter[Title/Abstract<nowiki>]</nowiki>]). This is a broader search than previously in that it looks for "helicobacter" in the abstract as well as the title.<br />
* Attendance at the 2019 Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium<br />
:: >Hosted by the CDC in Anchorage, Alaska<br />
:: >Experts were longstanding, world-renown researchers<br />
:: >Results were published in ''Gastroenterology'' in April 2020<ref name="Nolen2020">Nolen LD, Vindigni SM, Parsonnet J; Symposium leaders. Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium. Gastroenterology. 2020 Apr;158(5):1197-1201. doi: 10.1053/j.gastro.2019.11.299. PMID: 31836529; PMCID: [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7103478/ PMC7103478]. DOI:[https://doi.org/10.1053/j.gastro.2019.11.299 10.1053/j.gastro.2019.11.299]</ref><br />
* Pediatric H. pylori literature review: <br />
:: >PUBMED, [https://pubmed.ncbi.nlm.nih.gov/?term=pylori%5BTitle%5D+AND+%28pediatric*%5BTitle%5D+OR+child*%5BTitle%5D%29+AND+%28review%5BTitle%5D+OR+overview%5BTitle%5D+OR+guideline*%5BTitle%5D%29 pylori[Title<nowiki>]</nowiki> AND (pediatric*[Title<nowiki>]</nowiki> OR child*[Title<nowiki>]</nowiki>) AND (review[Title<nowiki>]</nowiki> OR overview[Title<nowiki>]</nowiki> OR guideline*[Title<nowiki>]</nowiki>)]<br />
<br><br />
<br />
==Results==<br />
# ANMC H. Pylori Treatment Guideline has no significant changes pertinent to the YKHC guideline. Of note, ANMC has started a study of offering EGD for gastric cancer screening for patients with a first-degree relative (parent, sibling, or child) with gastric cancer; they are treating to eradicate H. pylori in this group regardless of findings; but this treatment is limited to the study patients and thus is not applicable to our practice in Bethel.<br />
# PubMed search returned 49 articles, 12 of which were published since the last literature review. Only one of these articles addresses treatment in our setting, which is the CDC conference summary,<ref name="Nolen2020"/> which continues to explicitly advocate the current algorithm/guideline (which was originally published by an international, circumpolar expert group in 2016<ref name=mcmahon2016>McMahon BJ, Bruce MG, Koch A, et al. The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary. Epidemiology and Infection. 2016;144(2):225-233. PMID:[https://pubmed.ncbi.nlm.nih.gov/26094936/ 26094936]. PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4697284/ PMC4697284]. doi:[https://doi.org/10.1017/s0950268815001181 10.1017/S0950268815001181].</ref>) <br />
# Pediatric PubMed search returned 50 results, the most pertinent being the ''Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016)''<ref name=NASPGHAN>Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, Czinn S, Gold BD, Guarner J, Elitsur Y, Homan M, Kalach N, Kori M, Madrazo A, Megraud F, Papadopoulou A, Rowland M; ESPGHAN, NASPGHAN. Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016). J Pediatr Gastroenterol Nutr. 2017 Jun;64(6):991-1003. doi: 10.1097/MPG.0000000000001594. PMID: 28541262.</ref><br />
<br><br />
<br />
== Discussion ==<br />
* The YKHC H. pylori guideline continues to be consistent with the ANMC H. pylori guideline.<br />
* For adults, the YKHC guideline is very different than the standard of care in the remainder of the U.S. which endorsed the "test-and-treat" strategy. The prevalence of H. pylori in the Alaska Native population is far too high for such a strategy.<br />
* For pediatrics, the local guideline (which treats pediatrics identical to adults) is consistent with national guidelines (i.e. NASPGHAN<ref name="Nolen2020"/>)<br />
* The only minor issue with the YKHC guideline is that it does not address recent recommendations to utilize newly developed, commercially available, rapid H. pylori culture and sensitivities to guide initial H. pylori antimicrobial choice.<br />
<br><br />
<br />
==Guideline Changes==<br />
# Under treatment indications, "Intestinal Metaplasia" is changed to "Gastric Intestinal Metaplasia" (to prevent any confusion with Barrett's esophagus).<br />
# Addition of box specifying test-of-cure details:<br />
:::* ≥4wks after COMPLETION of treatment.<br />
:::* Either urea breath test (UBT), stool antigen test, or endoscopic biopsy (if indicated for other reasons; using either pathology or CLO-test).<br />
:::* Regardless of test, no antibiotics or bismuth for FOUR weeks prior.<br />
:::* Regardless of test, no PPI for TWO weeks prior.<br />
<br><br />
<br />
==Topics for Exploration==<br />
Commercial (i.e. non-CDC) rapid H. pylori culture/sensitivities which can be used to guide antimicrobial therapy for primary treatment.<br />
<br><br />
<br><br />
<br><br />
<br />
Author: Andrew W. Swartz, MD<br />
<br><br />
<br><br />
<br />
==References==<br />
----</div>AndyShttps://yk-health.org/index.php?title=H_Pylori_Guideline_Revision_Supplement_2022&diff=8737H Pylori Guideline Revision Supplement 20222022-03-22T13:34:24Z<p>AndyS: </p>
<hr />
<div>This guideline revision page addresses only the methods and results of the 2022 guideline update. For a broader review of the topic of H. pylori in Alaska Natives and for prior and/or ANMC guidelines, see the [[Helicobacter_pylori_in_Alaska_Natives|'''Helicobacter pylori in Alaska Natives''']] page.<br />
<br><br />
<br><br />
<br />
== Reason[s] for update ==<br />
Routine review/update.<br />
<br><br />
<br><br />
<br />
== Methods ==<br />
* Review of latest ANMC H. pylori treatment guideline ([https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf Feb 19, 2020 ][https://web.archive.org/web/20201024034528/https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf , Archive])<br><br />
* Updated literature search (PubMed, [https://pubmed.ncbi.nlm.nih.gov/?term=%28alaska%5BTitle%5D+OR+polar%5BTitle%5D+OR+arctic%5BTitle%5D%29+AND+helicobacter%5BTitle%2FAbstract%5D&sort=date (alaska[Title<nowiki>]</nowiki> OR polar[Title<nowiki>]</nowiki> OR arctic[Title<nowiki>]</nowiki>) AND helicobacter[Title/Abstract<nowiki>]</nowiki>]). This is a broader search than previously in that it looks for "helicobacter" in the abstract as well as the title.<br />
* Attendance at the 2019 Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium<br />
:: >Hosted by the CDC in Anchorage, Alaska<br />
:: >Experts were longstanding, world-renown researchers<br />
:: >Results were published in ''Gastroenterology'' in April 2020<ref name="Nolen2020">Nolen LD, Vindigni SM, Parsonnet J; Symposium leaders. Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium. Gastroenterology. 2020 Apr;158(5):1197-1201. doi: 10.1053/j.gastro.2019.11.299. PMID: 31836529; PMCID: [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7103478/ PMC7103478]. DOI:[https://doi.org/10.1053/j.gastro.2019.11.299 10.1053/j.gastro.2019.11.299]</ref><br />
* Pediatric H. pylori literature review: <br />
:: >PUBMED, [https://pubmed.ncbi.nlm.nih.gov/?term=pylori%5BTitle%5D+AND+%28pediatric*%5BTitle%5D+OR+child*%5BTitle%5D%29+AND+%28review%5BTitle%5D+OR+overview%5BTitle%5D+OR+guideline*%5BTitle%5D%29 pylori[Title<nowiki>]</nowiki> AND (pediatric*[Title<nowiki>]</nowiki> OR child*[Title<nowiki>]</nowiki>) AND (review[Title<nowiki>]</nowiki> OR overview[Title<nowiki>]</nowiki> OR guideline*[Title<nowiki>]</nowiki>)]<br />
<br><br />
<br />
==Results==<br />
# ANMC H. Pylori Treatment Guideline has no significant changes pertinent to the YKHC guideline. Of note, ANMC has started a study of offering EGD for gastric cancer screening for patients with a first-degree relative (parent, sibling, or child) with gastric cancer; they are treating to eradicate H. pylori in this group regardless of findings; but this treatment is limited to the study patients and thus is not applicable to our practice in Bethel.<br />
# PubMed search returned 49 articles, 12 of which were published since the last literature review. Only one of these articles addresses treatment in our setting, which is the CDC conference summary,<ref name="Nolen2020"/> which continues to explicitly advocate the current algorithm/guideline (which was originally published by an international, circumpolar expert group in 2016<ref name=mcmahon2016>McMahon BJ, Bruce MG, Koch A, et al. The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary. Epidemiology and Infection. 2016;144(2):225-233. PMID:[https://pubmed.ncbi.nlm.nih.gov/26094936/ 26094936]. PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4697284/ PMC4697284]. doi:[https://doi.org/10.1017/s0950268815001181 10.1017/S0950268815001181].</ref>) <br />
# Pediatric PubMed search returned 50 results, the most pertinent being the ''Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016)''<ref name=NASPGHAN>Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, Czinn S, Gold BD, Guarner J, Elitsur Y, Homan M, Kalach N, Kori M, Madrazo A, Megraud F, Papadopoulou A, Rowland M; ESPGHAN, NASPGHAN. Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016). J Pediatr Gastroenterol Nutr. 2017 Jun;64(6):991-1003. doi: 10.1097/MPG.0000000000001594. PMID: 28541262.</ref><br />
<br><br />
<br />
== Discussion ==<br />
* The YKHC H. pylori guideline continues to be consistent with the ANMC H. pylori guideline.<br />
* For adults, the local guideline is very different than the standard of care in the remainder of the U.S. which endorsed the "test-and-treat" strategy. The prevalence of H. pylori in the Alaska Native population far to high for such a strategy.<br />
* For pediatrics, the local guideline (which treats pediatrics identical to adults) is consistent with national guidelines (i.e. NASPGHAN<ref name="Nolen2020"/>)<br />
* The only minor issue with the local guideline is that it does address recent recommendations to utilize newly developed, commercially available, rapid H. pylori culture and sensitivities to guide initial H. pylori antimicrobial choice.<br />
<br><br />
<br />
==Guideline Changes==<br />
# Under treatment indications, "Intestinal Metaplasia" is changed to "Gastric Intestinal Metaplasia" (to prevent any confusion with Barrett's esophagus).<br />
# Addition of box specifying test-of-cure details:<br />
:::* ≥4wks after COMPLETION of treatment.<br />
:::* Either urea breath test (UBT), stool antigen test, or endoscopic biopsy (if indicated for other reasons; using either pathology or CLO-test).<br />
:::* Regardless of test, no antibiotics or bismuth for FOUR weeks prior.<br />
:::* Regardless of test, no PPI for TWO weeks prior.<br />
<br><br />
<br />
==Topics for Exploration==<br />
Commercial (i.e. non-CDC) rapid H. pylori culture/sensitivities which can be used to guide antimicrobial therapy for primary treatment.<br />
<br><br />
<br><br />
<br><br />
<br />
Author: Andrew W. Swartz, MD<br />
<br><br />
<br><br />
<br />
==References==<br />
----</div>AndyShttps://yk-health.org/index.php?title=H_Pylori_Guideline_Revision_Supplement_2022&diff=8736H Pylori Guideline Revision Supplement 20222022-03-22T13:08:22Z<p>AndyS: </p>
<hr />
<div>This guideline revision page addresses only the methods and results of the 2022 guideline update. For a broader review of the topic of H. pylori in Alaska Natives and for prior and/or ANMC guidelines, see the [[Helicobacter_pylori_in_Alaska_Natives|'''Helicobacter pylori in Alaska Natives''']] page.<br />
<br><br />
<br><br />
<br />
== Reason[s] for update ==<br />
Routine 2-year review/update.<br />
<br><br />
<br><br />
<br />
== Methods ==<br />
* Review of latest ANMC H. pylori treatment guideline ([https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf Feb 19, 2020 ][https://web.archive.org/web/20201024034528/https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf , Archive])<br><br />
* Updated literature search (PubMed, [https://pubmed.ncbi.nlm.nih.gov/?term=%28alaska%5BTitle%5D+OR+polar%5BTitle%5D+OR+arctic%5BTitle%5D%29+AND+helicobacter%5BTitle%2FAbstract%5D&sort=date (alaska[Title<nowiki>]</nowiki> OR polar[Title<nowiki>]</nowiki> OR arctic[Title<nowiki>]</nowiki>) AND helicobacter[Title/Abstract<nowiki>]</nowiki>]). This is a broader search than previously in that it looks for "helicobacter" in the abstract as well as the title.<br />
* Attendance at the 2019 Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium<br />
:: >Hosted by the CDC in Anchorage, Alaska<br />
:: >Experts were longstanding, world-renown researchers<br />
:: >Results were published in ''Gastroenterology'' in April 2020<ref name="Nolen2020">Nolen LD, Vindigni SM, Parsonnet J; Symposium leaders. Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium. Gastroenterology. 2020 Apr;158(5):1197-1201. doi: 10.1053/j.gastro.2019.11.299. PMID: 31836529; PMCID: [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7103478/ PMC7103478]. DOI:[https://doi.org/10.1053/j.gastro.2019.11.299 10.1053/j.gastro.2019.11.299]</ref><br />
* Pediatric H. pylori literature review: <br />
:: >PUBMED, [https://pubmed.ncbi.nlm.nih.gov/?term=pylori%5BTitle%5D+AND+%28pediatric*%5BTitle%5D+OR+child*%5BTitle%5D%29+AND+%28review%5BTitle%5D+OR+overview%5BTitle%5D+OR+guideline*%5BTitle%5D%29 pylori[Title<nowiki>]</nowiki> AND (pediatric*[Title<nowiki>]</nowiki> OR child*[Title<nowiki>]</nowiki>) AND (review[Title<nowiki>]</nowiki> OR overview[Title<nowiki>]</nowiki> OR guideline*[Title<nowiki>]</nowiki>)]<br />
<br><br />
<br />
==Results==<br />
# ANMC H. Pylori Treatment Guideline has no significant changes pertinent to the YKHC guideline. Of note, ANMC has started a study of offering EGD for gastric cancer screening for patients with a first-degree relative (parent, sibling, or child) with gastric cancer; they are treating to eradicate H. pylori in this group regardless of findings; but this treatment is limited to the study patients and thus is not applicable to our practice in Bethel.<br />
# PubMed search returned 49 articles, 12 of which were published since the last literature review. Only one of these articles addresses treatment in our setting, which is the CDC conference summary,<ref name="Nolen2020"> which continues to explicitly advocate the current algorithm/guideline (which was originally published by an international, circumpolar expert group in 2016<ref name=mcmahon2016>McMahon BJ, Bruce MG, Koch A, et al. The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary. Epidemiology and Infection. 2016;144(2):225-233. PMID:[https://pubmed.ncbi.nlm.nih.gov/26094936/ 26094936]. PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4697284/ PMC4697284]. doi:[https://doi.org/10.1017/s0950268815001181 10.1017/S0950268815001181].</ref>) <br />
# Pediatric PubMed search returned 50 results, the most pertinent being the ''Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016)''<ref name=NASPGHAN>Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, Czinn S, Gold BD, Guarner J, Elitsur Y, Homan M, Kalach N, Kori M, Madrazo A, Megraud F, Papadopoulou A, Rowland M; ESPGHAN, NASPGHAN. Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016). J Pediatr Gastroenterol Nutr. 2017 Jun;64(6):991-1003. doi: 10.1097/MPG.0000000000001594. PMID: 28541262.</ref><br />
<br><br />
<br />
== Discussion ==<br />
* The YKHC H. pylori guideline continues to be consistent with the ANMC H. pylori guideline.<br />
* For adults, the local guideline is very different than the standard of care in the remainder of the U.S. which endorsed the "test-and-treat" strategy. The prevalence of H. pylori in the Alaska Native population far to high for such a strategy.<br />
* For pediatrics, the local guideline (which treats pediatrics identical to adults) is consistent with national guidelines (i.e. NASPGHAN<ref name="Nolen2020"/>)<br />
* The only minor issue with the local guideline is that it does address recent recommendations to utilize newly developed, commercially available, rapid H. pylori culture and sensitivities to guide initial H. pylori antimicrobial choice.<br />
<br><br />
<br />
==Guideline Changes==<br />
# Under treatment indications, "Intestinal Metaplasia" is changed to "Gastric Intestinal Metaplasia" (to prevent any confusion with Barrett's esophagus).<br />
# Addition of box specifying test-of-cure details:<br />
:::* ≥4wks after COMPLETION of treatment.<br />
:::* Either urea breath test (UBT), stool antigen test, or endoscopic biopsy (if indicated for other reasons; using either pathology or CLO-test).<br />
:::* Regardless of test, no antibiotics or bismuth for FOUR weeks prior.<br />
:::* Regardless of test, no PPI for TWO weeks prior.<br />
<br><br />
<br />
==Topics for Exploration==<br />
Commercial (i.e. non-CDC) rapid H. pylori culture/sensitivities which can be used to guide antimicrobial therapy for primary treatment.<br />
<br><br />
<br><br />
<br><br />
<br />
Author: Andrew W. Swartz, MD<br />
<br><br />
<br><br />
<br />
==References==<br />
----</div>AndyShttps://yk-health.org/index.php?title=H_Pylori_Guideline_Revision_Supplement_2022&diff=8735H Pylori Guideline Revision Supplement 20222022-03-22T12:43:44Z<p>AndyS: </p>
<hr />
<div>This guideline revision page addresses only the methods and results of the 2022 guideline update. For a broader review of the topic of H. pylori in Alaska Natives and for prior and/or ANMC guidelines, see the [[Helicobacter_pylori_in_Alaska_Natives|'''Helicobacter pylori in Alaska Natives''']] page.<br />
<br><br />
<br><br />
<br />
== Reason[s] for update ==<br />
Routine 2-year review/update.<br />
<br><br />
<br><br />
<br />
== Methods ==<br />
* Review of latest ANMC H. pylori treatment guideline ([https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf Feb 19, 2020 ][https://web.archive.org/web/20201024034528/https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf , Archive])<br><br />
* Updated literature search (PubMed, [https://pubmed.ncbi.nlm.nih.gov/?term=%28alaska%5BTitle%5D+OR+polar%5BTitle%5D+OR+arctic%5BTitle%5D%29+AND+helicobacter%5BTitle%2FAbstract%5D&sort=date (alaska[Title<nowiki>]</nowiki> OR polar[Title<nowiki>]</nowiki> OR arctic[Title<nowiki>]</nowiki>) AND helicobacter[Title/Abstract<nowiki>]</nowiki>]). This is a broader search than previously in that it looks for "helicobacter" in the abstract as well as the title.<br />
* Attendance at the 2019 Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium<br />
:: >Hosted by the CDC in Anchorage, Alaska<br />
:: >Experts were longstanding, world-renown researchers<br />
:: >Results were published in ''Gastroenterology'' in April 2020<ref name="Nolen2020">Nolen LD, Vindigni SM, Parsonnet J; Symposium leaders. Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium. Gastroenterology. 2020 Apr;158(5):1197-1201. doi: 10.1053/j.gastro.2019.11.299. PMID: 31836529; PMCID: [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7103478/ PMC7103478]. DOI:[https://doi.org/10.1053/j.gastro.2019.11.299 10.1053/j.gastro.2019.11.299]</ref><br />
* Pediatric H. pylori literature review: <br />
:: >PUBMED, [https://pubmed.ncbi.nlm.nih.gov/?term=pylori%5BTitle%5D+AND+%28pediatric*%5BTitle%5D+OR+child*%5BTitle%5D%29+AND+%28review%5BTitle%5D+OR+overview%5BTitle%5D+OR+guideline*%5BTitle%5D%29 pylori[Title<nowiki>]</nowiki> AND (pediatric*[Title<nowiki>]</nowiki> OR child*[Title<nowiki>]</nowiki>) AND (review[Title<nowiki>]</nowiki> OR overview[Title<nowiki>]</nowiki> OR guideline*[Title<nowiki>]</nowiki>)]<br />
<br><br />
<br />
==Results==<br />
# ANMC H. Pylori Treatment Guideline has no significant changes pertinent to the YKHC guideline. Of note, ANMC has started a study of offering EGD for gastric cancer screening for patients with a first-degree relative (parent, sibling, or child) with gastric cancer; they are treating to eradicate H. pylori in this group regardless of findings; but this treatment is limited to the study patients and thus is not applicable to our practice in Bethel.<br />
# PubMed search returned 49 articles, 12 of which were published since the last literature review. Only one of these articles addresses treatment in our setting, which is the CDC conference summary,<ref name="Nolen2020"/> which continues to explicitly advocate the current algorithm/guideline (which was originally published by an international, circumpolar expert group in 2016<ref name=mcmahon2016>McMahon BJ, Bruce MG, Koch A, et al. The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary. Epidemiology and Infection. 2016;144(2):225-233. PMID:[https://pubmed.ncbi.nlm.nih.gov/26094936/ 26094936]. PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4697284/ PMC4697284]. doi:[https://doi.org/10.1017/s0950268815001181 10.1017/S0950268815001181].</ref>) <br />
# Pediatric PubMed search returned 50 results, the most pertinent being the ''Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016)''<ref>Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, Czinn S, Gold BD, Guarner J, Elitsur Y, Homan M, Kalach N, Kori M, Madrazo A, Megraud F, Papadopoulou A, Rowland M; ESPGHAN, NASPGHAN. Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016). J Pediatr Gastroenterol Nutr. 2017 Jun;64(6):991-1003. doi: 10.1097/MPG.0000000000001594. PMID: 28541262.</ref><br />
<br><br />
<br />
==Guideline Changes==<br />
# Under treatment indications, "Intestinal Metaplasia" is changed to "Gastric Intestinal Metaplasia" (to prevent any confusion with Barrett's esophagus).<br />
# Addition of box specifying test-of-cure details:<br />
:::* ≥4wks after COMPLETION of treatment.<br />
:::* Either urea breath test (UBT), stool antigen test, or endoscopic biopsy (if indicated for other reasons; using either pathology or CLO-test).<br />
:::* Regardless of test, no antibiotics or bismuth for FOUR weeks prior.<br />
:::* Regardless of test, no PPI for TWO weeks prior.<br />
<br><br />
<br />
==Topics for Exploration==<br />
Commercial (i.e. non-CDC) rapid H. pylori culture/sensitivities which can be used to guide antimicrobial therapy for primary treatment.<br />
<br><br />
<br><br />
<br><br />
<br />
Author: Andrew W. Swartz, MD<br />
<br><br />
<br><br />
<br />
==References==<br />
----</div>AndyShttps://yk-health.org/index.php?title=H_Pylori_Guideline_Revision_Supplement_2022&diff=8734H Pylori Guideline Revision Supplement 20222022-03-22T12:35:57Z<p>AndyS: </p>
<hr />
<div>This guideline revision page addresses only the methods and results of the 2022 guideline update. For a broader review of the topic of H. pylori in Alaska Natives and for prior and/or ANMC guidelines, see the [[Helicobacter_pylori_in_Alaska_Natives|'''Helicobacter pylori in Alaska Natives''']] page.<br />
<br><br />
<br><br />
<br />
== Reason[s] for update ==<br />
Routine 2-year review/update.<br />
<br><br />
<br><br />
<br />
== Methods ==<br />
* Review of latest ANMC H. pylori treatment guideline ([https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf Feb 19, 2020 ][https://web.archive.org/web/20201024034528/https://anmc.org/files/CG_HelicobacterPyloriGuideline.pdf , Archive])<br><br />
* Updated literature search (PubMed, [https://pubmed.ncbi.nlm.nih.gov/?term=%28alaska%5BTitle%5D+OR+polar%5BTitle%5D+OR+arctic%5BTitle%5D%29+AND+helicobacter%5BTitle%2FAbstract%5D&sort=date (alaska[Title<nowiki>]</nowiki> OR polar[Title<nowiki>]</nowiki> OR arctic[Title<nowiki>]</nowiki>) AND helicobacter[Title/Abstract<nowiki>]</nowiki>]). This is a broader search than previously in that it looks for "helicobacter" in the abstract as well as the title.<br />
* Attendance at the 2019 Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium<br />
:: >Hosted by the CDC in Anchorage, Alaska<br />
:: >Experts were longstanding, world-renown researchers<br />
:: >Results were published in ''Gastroenterology'' in April 2020<ref name="Nolen2020">Nolen LD, Vindigni SM, Parsonnet J; Symposium leaders. Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium. Gastroenterology. 2020 Apr;158(5):1197-1201. doi: 10.1053/j.gastro.2019.11.299. PMID: 31836529; PMCID: [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7103478/ PMC7103478]. DOI:[https://doi.org/10.1053/j.gastro.2019.11.299 10.1053/j.gastro.2019.11.299]</ref><br />
* Pediatric H. pylori literature review: <br />
:: >PUBMED, [https://pubmed.ncbi.nlm.nih.gov/?term=pylori%5BTitle%5D+AND+%28pediatric*%5BTitle%5D+OR+child*%5BTitle%5D%29+AND+%28review%5BTitle%5D+OR+overview%5BTitle%5D+OR+guideline*%5BTitle%5D%29 pylori[Title<nowiki>]</nowiki> AND (pediatric*[Title<nowiki>]</nowiki> OR child*[Title<nowiki>]</nowiki>) AND (review[Title<nowiki>]</nowiki> OR overview[Title<nowiki>]</nowiki> OR guideline*[Title<nowiki>]</nowiki>)]<br />
:: >Review of the ''Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016)''<ref>Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, Czinn S, Gold BD, Guarner J, Elitsur Y, Homan M, Kalach N, Kori M, Madrazo A, Megraud F, Papadopoulou A, Rowland M; ESPGHAN, NASPGHAN. Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016). J Pediatr Gastroenterol Nutr. 2017 Jun;64(6):991-1003. doi: 10.1097/MPG.0000000000001594. PMID: 28541262.</ref><br />
<br><br />
<br />
==Results==<br />
# ANMC H. Pylori Treatment Guideline has no significant changes pertinent to the YKHC guideline. Of note, ANMC has started a study of offering EGD for gastric cancer screening for patients with a first-degree relative (parent, sibling, or child) with gastric cancer; they are treating to eradicate H. pylori in this group regardless of findings; but this treatment is limited to the study patients and thus is not applicable to our practice in Bethel.<br />
# PubMed search returned 49 articles, 12 of which were published since the last literature review. Only one of these articles addresses treatment in our setting, which is the CDC conference summary,<ref name="Nolen2020"/> which continues to explicitly advocate the current algorithm/guideline (which was originally published by an international, circumpolar expert group in 2016<ref name=mcmahon2016>McMahon BJ, Bruce MG, Koch A, et al. The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary. Epidemiology and Infection. 2016;144(2):225-233. PMID:[https://pubmed.ncbi.nlm.nih.gov/26094936/ 26094936]. PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4697284/ PMC4697284]. doi:[https://doi.org/10.1017/s0950268815001181 10.1017/S0950268815001181].</ref>) <br />
<br><br />
<br />
==Guideline Changes==<br />
# Under treatment indications, "Intestinal Metaplasia" is changed to "Gastric Intestinal Metaplasia" (to prevent any confusion with Barrett's esophagus).<br />
# Addition of box specifying test-of-cure details:<br />
:::* ≥4wks after COMPLETION of treatment.<br />
:::* Either urea breath test (UBT), stool antigen test, or endoscopic biopsy (if indicated for other reasons; using either pathology or CLO-test).<br />
:::* Regardless of test, no antibiotics or bismuth for FOUR weeks prior.<br />
:::* Regardless of test, no PPI for TWO weeks prior.<br />
<br><br />
<br><br />
<br />
Author: Andrew W. Swartz, MD<br />
<br><br />
<br />
==References==<br />
----</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8717Cardiac Biomarkers in Pediatrics2022-02-12T08:36:41Z<p>AndyS: /* hs-cTnT */</p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle.<br><br />
<br />
Troponin "leaks" from cardiomyocytes when cell membrane permeability is increased; this condition is termed myocardial "injury," and it can be caused by both ischemic and non-ischemic processes. Ischemic processes include acute coronary syndrome and chronic coronary ischemia (such as ischemic cardiomyopathy), while non-ischemic processes include a multitude of diverse conditions (such as inflammation, apoptosis, cytotoxicity, infiltrative diseases, hypoxemia, shock, ventricular strain, trauma, etc).<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref> Clinical decisions regarding elevated troponin must incorporate an understanding <u>non-ischemic</u> myocardial injury. Indeed, while ischemic causes of myocardial injury predominate in older adults, <u>non-ischemic causes vastly predominate in all pediatric age groups</u>.<ref name=Wang2021/><br />
<br><br />
<br />
=== Normal Range[s] in Pediatric Age Groups ===<br />
Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).<br />
<br><br />
<br><br />
<br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 <u>healthy</u>, term <u>newborns</u> in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several notable findings:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Bohn et al (2019)<ref name=Bohn2019>Bohn MK, Higgins V, Kavsak P, Hoffman B, Adeli K. High-Sensitivity Generation 5 Cardiac Troponin T Sex- and Age-Specific 99th Percentiles in the CALIPER Cohort of Healthy Children and Adolescents. Clin Chem. 2019 Apr;65(4):589-591. doi:[https://doi.org/10.1373/clinchem.2018.299156 10.1373/clinchem.2018.299156]. Epub 2019 Feb 8. PMID:[https://pubmed.ncbi.nlm.nih.gov/30737206/ 30737206]. [http://web.archive.org/web/20220121142237/https://watermark.silverchair.com/clinchem0589.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtgwggLUBgkqhkiG9w0BBwagggLFMIICwQIBADCCAroGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMl4zG0GFTLFsAxQlSAgEQgIICi9rtEHt0uQdmISjuSqNplYMUPPB2BYgbGVmyTaXZCCBLN7trLTiIoyta3WQgX29Or77tWs5ehXEXxDOcDbihDW-7vNziCRnzM_fs6hEbx7xOaWWy0YnGxX8gtsBgYTZMmHu2BD9gkV4ZJTO6Y26yR2pxB320Uq5aCNyvmrTl_gJx6XeVAUrAKQJ-qRgbPcxu8jC-BtUK3cxHW183n6k9-Sq0o1bjy1kJCUVZhGoLJasd6KuY9EhabfNvVrhnc5E3boLF-lNoof8pChLa-b9MHHg01m334zOpSyAdXSa8yUpEr3fyBoPk_A_EoshIfwEpu4nGGwhe8M8hwiOulBtlUp-oQt8neYVyqCobZcr2De8SHQoaeGSUXAK_Fv4XXACdl_C3NcyPJglzTvV67-Vfszd-4owWEuHDVUcv9UvtE21xJzuHGteyEbM67f1yjQ2uP0MJLNWtPNuEj-yj3S4PC8F4SeWUWV0y2bosDKsbU5KlYE5c65giuFvZQOLTtarmeXohElWPZHEe5GN2ekDEkvuUpQ57T8szWd7-LH1CG-jPrYSLEgf-8QI0MmV9zRm7rXYcpsVAvR0LHCm6DJU8ko-Ktjn9iAgp4Nq25ez3ZhrmlR-cZ78iTB3qi48imUEXDlitUEeo4nz1SoFMo0QokNrNc1D0sihRyoUcd4C_mkjU16tfLesK8Xr9gGgrdX2iYHGQVI7bsErMVjUVn-LdSctjFPWDCH67Yh3SRMFBQLsdGnzm9Uru5PXC_4mJg7WUirlQ_HQuY17dg3ImamMekHiRVxvkToTRtB9mbCMHiYsfc87iQm-QxYMcNYHj3YiD4EOVeBIUkEjx-al-r3jDMe_Qn3xF6nM4hPHEog Archived]</ref><br />
::Unclear if retrospective or prospective; samples from "apparently" healthy infants (<1y) obtained from local maternity wards and outpatient clinics in Toronto, Canada; samples from >1 obtained from the "CALIPER biobank." Table-1 shows the reported 99th percentiles. Additionally, the authors report several notable observations:<br />
:::*''"hs-cTnT concentrations were markedly increased from 0 to <6 months and subsequently decreased and narrowed at 1 year."''<br />
:::*''"Although hs-cTnT concentrations from 0 to <1 year were normally distributed, hs-cTnT concentrations for both sexes of age 1 to <19 years were highly skewed."''<br />
:::*The authors comment about their 1y to 19y age group having 99th percentile cut-offs of 11 (F) and 14 (M) and this differing from the manufacturer package insert. They astutely note that the major cause for this difference is likely their use of a different reference population, and they highlight that neither reference population had imaging done (i.e. structural and coronary cardiac evaluations) to show that they were truly healthy with regard to establishing a distribution in "healthy" individuals.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0 – <6m || style="text-align:center;" | 55 || style="text-align:center;" | 93<br />
|-<br />
| 6m – <1y || style="text-align:center;" | 44 || style="text-align:center;" | 21<br />
|-<br />
| 1 – <19y F || style="text-align:center;" | 249 || style="text-align:center;" | 11<br />
|-<br />
| 1 – <19y M || style="text-align:center;" | 249 || style="text-align:center;" | 14<br />
|}<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-2. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-3 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-3.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
:;Guo et al (2021)<ref>Guo Q, Yang D, Zhou Y, Zhang S, Zhu T, Wang A, Lei M, Yang X. Establishment of the reference interval for high-sensitivity cardiac troponin T in healthy children of Chongqing Nan'an district. Scand J Clin Lab Invest. 2021 Nov;81(7):579-584. doi:[https://doi.org/10.1080/00365513.2021.1979245 10.1080/00365513.2021.1979245]. Epub 2021 Sep 28. PMID:[https://pubmed.ncbi.nlm.nih.gov/34581638/ 34581638]. (obtained through the Alaska Medical Library)</ref><br />
::From January 2017 to February 2020, 4,617 questionnaires distributed to children from Chongqing Southeast Hospital (China), pediatricians physically examined respondents to confirm no health issues, 3,463 children included in the study, ages 0-14y, analyzed by sex. Results are presented in Table-4. <br />
:::*The combination of large sample size and pediatrician physical exams to confirm no underlying health problems makes this undoubtedly the most robust data available at the time of this writing (January 2022). <br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-4.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 1d(UCB) || style="text-align:center;" | 34 || style="text-align:center;" | 60.8<br />
|-<br />
| 1d(VB) || style="text-align:center;" | 253 || style="text-align:center;" | 78.8<br />
|-<br />
| 2–28d || style="text-align:center;" | 236 || style="text-align:center;" | 96.6<br />
|-<br />
| 29d–<3m || style="text-align:center;" | 178 || style="text-align:center;" | 58.6<br />
|-<br />
| 3–<6m || style="text-align:center;" | 177 || style="text-align:center;" | 34.2<br />
|-<br />
| 6m–<1y || style="text-align:center;" | 377 || style="text-align:center;" | 16.2<br />
|-<br />
| 1–<3y || style="text-align:center;" | 899 || style="text-align:center;" | 11.4<br />
|-<br />
| 3–<6y (M) || style="text-align:center;" | 361 || style="text-align:center;" | 8<br />
|-<br />
| 3–<6y (F) || style="text-align:center;" | 327 || style="text-align:center;" | 7.8<br />
|-<br />
| 6–14y (M) || style="text-align:center;" | 373 || style="text-align:center;" | 7.8<br />
|-<br />
| 6–14y (F) || style="text-align:center;" | 248 || style="text-align:center;" | 7.3<br />
|}<br />
<br><br />
:::*Figure-1 is an adaptation of Guo et al's figure illustrating the distribution of hs-cTnT versus age:<br />
[[File:Guo et al Fig-2.PNG|frameless|center|526px]]<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=File:Guo_et_al_Fig-2.PNG&diff=8716File:Guo et al Fig-2.PNG2022-02-12T08:29:16Z<p>AndyS: </p>
<hr />
<div></div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8689Cardiac Biomarkers in Pediatrics2022-01-22T02:00:30Z<p>AndyS: /* Biochemistry */</p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle.<br><br />
<br />
Troponin "leaks" from cardiomyocytes when cell membrane permeability is increased; this condition is termed myocardial "injury," and it can be caused by both ischemic and non-ischemic processes. Ischemic processes include acute coronary syndrome and chronic coronary ischemia (such as ischemic cardiomyopathy), while non-ischemic processes include a multitude of diverse conditions (such as inflammation, apoptosis, cytotoxicity, infiltrative diseases, hypoxemia, shock, ventricular strain, trauma, etc).<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref> Clinical decisions regarding elevated troponin must incorporate an understanding <u>non-ischemic</u> myocardial injury. Indeed, while ischemic causes of myocardial injury predominate in older adults, <u>non-ischemic causes vastly predominate in all pediatric age groups</u>.<ref name=Wang2021/><br />
<br><br />
<br />
=== Normal Range[s] in Pediatric Age Groups ===<br />
Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).<br />
<br><br />
<br><br />
<br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 <u>healthy</u>, term <u>newborns</u> in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several notable findings:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Bohn et al (2019)<ref name=Bohn2019>Bohn MK, Higgins V, Kavsak P, Hoffman B, Adeli K. High-Sensitivity Generation 5 Cardiac Troponin T Sex- and Age-Specific 99th Percentiles in the CALIPER Cohort of Healthy Children and Adolescents. Clin Chem. 2019 Apr;65(4):589-591. doi:[https://doi.org/10.1373/clinchem.2018.299156 10.1373/clinchem.2018.299156]. Epub 2019 Feb 8. PMID:[https://pubmed.ncbi.nlm.nih.gov/30737206/ 30737206]. [http://web.archive.org/web/20220121142237/https://watermark.silverchair.com/clinchem0589.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtgwggLUBgkqhkiG9w0BBwagggLFMIICwQIBADCCAroGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMl4zG0GFTLFsAxQlSAgEQgIICi9rtEHt0uQdmISjuSqNplYMUPPB2BYgbGVmyTaXZCCBLN7trLTiIoyta3WQgX29Or77tWs5ehXEXxDOcDbihDW-7vNziCRnzM_fs6hEbx7xOaWWy0YnGxX8gtsBgYTZMmHu2BD9gkV4ZJTO6Y26yR2pxB320Uq5aCNyvmrTl_gJx6XeVAUrAKQJ-qRgbPcxu8jC-BtUK3cxHW183n6k9-Sq0o1bjy1kJCUVZhGoLJasd6KuY9EhabfNvVrhnc5E3boLF-lNoof8pChLa-b9MHHg01m334zOpSyAdXSa8yUpEr3fyBoPk_A_EoshIfwEpu4nGGwhe8M8hwiOulBtlUp-oQt8neYVyqCobZcr2De8SHQoaeGSUXAK_Fv4XXACdl_C3NcyPJglzTvV67-Vfszd-4owWEuHDVUcv9UvtE21xJzuHGteyEbM67f1yjQ2uP0MJLNWtPNuEj-yj3S4PC8F4SeWUWV0y2bosDKsbU5KlYE5c65giuFvZQOLTtarmeXohElWPZHEe5GN2ekDEkvuUpQ57T8szWd7-LH1CG-jPrYSLEgf-8QI0MmV9zRm7rXYcpsVAvR0LHCm6DJU8ko-Ktjn9iAgp4Nq25ez3ZhrmlR-cZ78iTB3qi48imUEXDlitUEeo4nz1SoFMo0QokNrNc1D0sihRyoUcd4C_mkjU16tfLesK8Xr9gGgrdX2iYHGQVI7bsErMVjUVn-LdSctjFPWDCH67Yh3SRMFBQLsdGnzm9Uru5PXC_4mJg7WUirlQ_HQuY17dg3ImamMekHiRVxvkToTRtB9mbCMHiYsfc87iQm-QxYMcNYHj3YiD4EOVeBIUkEjx-al-r3jDMe_Qn3xF6nM4hPHEog Archived]</ref><br />
::Unclear if retrospective or prospective; samples from "apparently" healthy infants (<1y) obtained from local maternity wards and outpatient clinics in Toronto, Canada; samples from >1 obtained from the "CALIPER biobank." Table-1 shows the reported 99th percentiles. Additionally, the authors report several notable observations:<br />
:::*''"hs-cTnT concentrations were markedly increased from 0 to <6 months and subsequently decreased and narrowed at 1 year."''<br />
:::*''"Although hs-cTnT concentrations from 0 to <1 year were normally distributed, hs-cTnT concentrations for both sexes of age 1 to <19 years were highly skewed."''<br />
:::*The authors comment about their 1y to 19y age group having 99th percentile cut-offs of 11 (F) and 14 (M) and this differing from the manufacturer package insert. They astutely note that the major cause for this difference is likely their use of a different reference population, and they highlight that neither reference population had imaging done (i.e. structural and coronary cardiac evaluations) to show that they were truly healthy with regard to establishing a distribution in "healthy" individuals.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0 – <6m || style="text-align:center;" | 55 || style="text-align:center;" | 93<br />
|-<br />
| 6m – <1y || style="text-align:center;" | 44 || style="text-align:center;" | 21<br />
|-<br />
| 1 – <19y F || style="text-align:center;" | 249 || style="text-align:center;" | 11<br />
|-<br />
| 1 – <19y M || style="text-align:center;" | 249 || style="text-align:center;" | 14<br />
|}<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-2. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-3 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-3.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
:;Guo et al (2021)<ref>Guo Q, Yang D, Zhou Y, Zhang S, Zhu T, Wang A, Lei M, Yang X. Establishment of the reference interval for high-sensitivity cardiac troponin T in healthy children of Chongqing Nan'an district. Scand J Clin Lab Invest. 2021 Nov;81(7):579-584. doi:[https://doi.org/10.1080/00365513.2021.1979245 10.1080/00365513.2021.1979245]. Epub 2021 Sep 28. PMID:[https://pubmed.ncbi.nlm.nih.gov/34581638/ 34581638]. (obtained through the Alaska Medical Library)</ref><br />
::From January 2017 to February 2020, 4,617 questionnaires distributed to children from Chongqing Southeast Hospital (China), pediatricians physically examined respondents to confirm no health issues, 3,463 children included in the study, ages 0-14y, analyzed by sex. Results are presented in Table-4. <br />
:::*The combination of large sample size and pediatrician physical exams to confirm no underlying health problems makes this undoubtedly the most robust data available at the time of this writing (January 2022). <br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-4.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 1d(UCB) || style="text-align:center;" | 34 || style="text-align:center;" | 60.8<br />
|-<br />
| 1d(VB) || style="text-align:center;" | 253 || style="text-align:center;" | 78.8<br />
|-<br />
| 2–28d || style="text-align:center;" | 236 || style="text-align:center;" | 96.6<br />
|-<br />
| 29d–<3m || style="text-align:center;" | 178 || style="text-align:center;" | 58.6<br />
|-<br />
| 3–<6m || style="text-align:center;" | 177 || style="text-align:center;" | 34.2<br />
|-<br />
| 6m–<1y || style="text-align:center;" | 377 || style="text-align:center;" | 16.2<br />
|-<br />
| 1–<3y || style="text-align:center;" | 899 || style="text-align:center;" | 11.4<br />
|-<br />
| 3–<6y (M) || style="text-align:center;" | 361 || style="text-align:center;" | 8<br />
|-<br />
| 3–<6y (F) || style="text-align:center;" | 327 || style="text-align:center;" | 7.8<br />
|-<br />
| 6–14y (M) || style="text-align:center;" | 373 || style="text-align:center;" | 7.8<br />
|-<br />
| 6–14y (F) || style="text-align:center;" | 248 || style="text-align:center;" | 7.3<br />
|}<br />
<br><br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8688Cardiac Biomarkers in Pediatrics2022-01-22T01:41:40Z<p>AndyS: </p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle.<br><br />
<br />
Troponin I and T "leak" from cardiomyocytes when cell membrane permeability is increased; this condition is referred to as myocardial "injury," and can be caused by both ischemic and non-ischemic processes. Ischemic processes include acute coronary syndrome and chronic coronary ischemia (such as ischemic cardiomyopathy), while a multitude of non-ischemic processes can yield myocardial cell "injury" (including inflammation, apoptosis, cytotoxicity, infiltrative diseases, hypoxemia, shock, ventricular strain, trauma, etc).<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref> Clinical decisions regarding elevated troponin must incorporate an understanding <u>non-ischemic</u> myocardial injury. Indeed, while ischemic causes of myocardial injury predominate in older adults, non-ischemic causes vastly predominate in the pediatric age groups.<ref name=Wang2021/><br />
<br><br />
<br />
=== Normal Range[s] in Pediatric Age Groups ===<br />
Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).<br />
<br><br />
<br><br />
<br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 <u>healthy</u>, term <u>newborns</u> in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several notable findings:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Bohn et al (2019)<ref name=Bohn2019>Bohn MK, Higgins V, Kavsak P, Hoffman B, Adeli K. High-Sensitivity Generation 5 Cardiac Troponin T Sex- and Age-Specific 99th Percentiles in the CALIPER Cohort of Healthy Children and Adolescents. Clin Chem. 2019 Apr;65(4):589-591. doi:[https://doi.org/10.1373/clinchem.2018.299156 10.1373/clinchem.2018.299156]. Epub 2019 Feb 8. PMID:[https://pubmed.ncbi.nlm.nih.gov/30737206/ 30737206]. [http://web.archive.org/web/20220121142237/https://watermark.silverchair.com/clinchem0589.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtgwggLUBgkqhkiG9w0BBwagggLFMIICwQIBADCCAroGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMl4zG0GFTLFsAxQlSAgEQgIICi9rtEHt0uQdmISjuSqNplYMUPPB2BYgbGVmyTaXZCCBLN7trLTiIoyta3WQgX29Or77tWs5ehXEXxDOcDbihDW-7vNziCRnzM_fs6hEbx7xOaWWy0YnGxX8gtsBgYTZMmHu2BD9gkV4ZJTO6Y26yR2pxB320Uq5aCNyvmrTl_gJx6XeVAUrAKQJ-qRgbPcxu8jC-BtUK3cxHW183n6k9-Sq0o1bjy1kJCUVZhGoLJasd6KuY9EhabfNvVrhnc5E3boLF-lNoof8pChLa-b9MHHg01m334zOpSyAdXSa8yUpEr3fyBoPk_A_EoshIfwEpu4nGGwhe8M8hwiOulBtlUp-oQt8neYVyqCobZcr2De8SHQoaeGSUXAK_Fv4XXACdl_C3NcyPJglzTvV67-Vfszd-4owWEuHDVUcv9UvtE21xJzuHGteyEbM67f1yjQ2uP0MJLNWtPNuEj-yj3S4PC8F4SeWUWV0y2bosDKsbU5KlYE5c65giuFvZQOLTtarmeXohElWPZHEe5GN2ekDEkvuUpQ57T8szWd7-LH1CG-jPrYSLEgf-8QI0MmV9zRm7rXYcpsVAvR0LHCm6DJU8ko-Ktjn9iAgp4Nq25ez3ZhrmlR-cZ78iTB3qi48imUEXDlitUEeo4nz1SoFMo0QokNrNc1D0sihRyoUcd4C_mkjU16tfLesK8Xr9gGgrdX2iYHGQVI7bsErMVjUVn-LdSctjFPWDCH67Yh3SRMFBQLsdGnzm9Uru5PXC_4mJg7WUirlQ_HQuY17dg3ImamMekHiRVxvkToTRtB9mbCMHiYsfc87iQm-QxYMcNYHj3YiD4EOVeBIUkEjx-al-r3jDMe_Qn3xF6nM4hPHEog Archived]</ref><br />
::Unclear if retrospective or prospective; samples from "apparently" healthy infants (<1y) obtained from local maternity wards and outpatient clinics in Toronto, Canada; samples from >1 obtained from the "CALIPER biobank." Table-1 shows the reported 99th percentiles. Additionally, the authors report several notable observations:<br />
:::*''"hs-cTnT concentrations were markedly increased from 0 to <6 months and subsequently decreased and narrowed at 1 year."''<br />
:::*''"Although hs-cTnT concentrations from 0 to <1 year were normally distributed, hs-cTnT concentrations for both sexes of age 1 to <19 years were highly skewed."''<br />
:::*The authors comment about their 1y to 19y age group having 99th percentile cut-offs of 11 (F) and 14 (M) and this differing from the manufacturer package insert. They astutely note that the major cause for this difference is likely their use of a different reference population, and they highlight that neither reference population had imaging done (i.e. structural and coronary cardiac evaluations) to show that they were truly healthy with regard to establishing a distribution in "healthy" individuals.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0 – <6m || style="text-align:center;" | 55 || style="text-align:center;" | 93<br />
|-<br />
| 6m – <1y || style="text-align:center;" | 44 || style="text-align:center;" | 21<br />
|-<br />
| 1 – <19y F || style="text-align:center;" | 249 || style="text-align:center;" | 11<br />
|-<br />
| 1 – <19y M || style="text-align:center;" | 249 || style="text-align:center;" | 14<br />
|}<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-2. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-3 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-3.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
:;Guo et al (2021)<ref>Guo Q, Yang D, Zhou Y, Zhang S, Zhu T, Wang A, Lei M, Yang X. Establishment of the reference interval for high-sensitivity cardiac troponin T in healthy children of Chongqing Nan'an district. Scand J Clin Lab Invest. 2021 Nov;81(7):579-584. doi:[https://doi.org/10.1080/00365513.2021.1979245 10.1080/00365513.2021.1979245]. Epub 2021 Sep 28. PMID:[https://pubmed.ncbi.nlm.nih.gov/34581638/ 34581638]. (obtained through the Alaska Medical Library)</ref><br />
::From January 2017 to February 2020, 4,617 questionnaires distributed to children from Chongqing Southeast Hospital (China), pediatricians physically examined respondents to confirm no health issues, 3,463 children included in the study, ages 0-14y, analyzed by sex. Results are presented in Table-4. <br />
:::*The combination of large sample size and pediatrician physical exams to confirm no underlying health problems makes this undoubtedly the most robust data available at the time of this writing (January 2022). <br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-4.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 1d(UCB) || style="text-align:center;" | 34 || style="text-align:center;" | 60.8<br />
|-<br />
| 1d(VB) || style="text-align:center;" | 253 || style="text-align:center;" | 78.8<br />
|-<br />
| 2–28d || style="text-align:center;" | 236 || style="text-align:center;" | 96.6<br />
|-<br />
| 29d–<3m || style="text-align:center;" | 178 || style="text-align:center;" | 58.6<br />
|-<br />
| 3–<6m || style="text-align:center;" | 177 || style="text-align:center;" | 34.2<br />
|-<br />
| 6m–<1y || style="text-align:center;" | 377 || style="text-align:center;" | 16.2<br />
|-<br />
| 1–<3y || style="text-align:center;" | 899 || style="text-align:center;" | 11.4<br />
|-<br />
| 3–<6y (M) || style="text-align:center;" | 361 || style="text-align:center;" | 8<br />
|-<br />
| 3–<6y (F) || style="text-align:center;" | 327 || style="text-align:center;" | 7.8<br />
|-<br />
| 6–14y (M) || style="text-align:center;" | 373 || style="text-align:center;" | 7.8<br />
|-<br />
| 6–14y (F) || style="text-align:center;" | 248 || style="text-align:center;" | 7.3<br />
|}<br />
<br><br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8687Cardiac Biomarkers in Pediatrics2022-01-22T01:35:08Z<p>AndyS: /* Biochemistry */</p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle.<br><br />
<br />
Troponin I and T "leak" from cardiomyocytes when cell membrane permeability is increased; this condition is referred to as myocardial "injury," and can be caused by both ischemic and non-ischemic processes. Ischemic processes include acute coronary syndrome and chronic coronary ischemia (such as ischemic cardiomyopathy), while a multitude of non-ischemic processes can yield myocardial cell "injury" (including inflammation, apoptosis, cytotoxicity, infiltrative diseases, hypoxemia, shock, ventricular strain, trauma, etc).<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref> Clinical decisions regarding elevated troponin must incorporate an understanding <u>non-ischemic</u> myocardial injury.<br />
<br><br />
<br />
=== Normal Range[s] ===<br />
Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).<br />
<br><br />
<br><br />
<br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 <u>healthy</u>, term <u>newborns</u> in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several notable findings:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Bohn et al (2019)<ref name=Bohn2019>Bohn MK, Higgins V, Kavsak P, Hoffman B, Adeli K. High-Sensitivity Generation 5 Cardiac Troponin T Sex- and Age-Specific 99th Percentiles in the CALIPER Cohort of Healthy Children and Adolescents. Clin Chem. 2019 Apr;65(4):589-591. doi:[https://doi.org/10.1373/clinchem.2018.299156 10.1373/clinchem.2018.299156]. Epub 2019 Feb 8. PMID:[https://pubmed.ncbi.nlm.nih.gov/30737206/ 30737206]. [http://web.archive.org/web/20220121142237/https://watermark.silverchair.com/clinchem0589.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtgwggLUBgkqhkiG9w0BBwagggLFMIICwQIBADCCAroGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMl4zG0GFTLFsAxQlSAgEQgIICi9rtEHt0uQdmISjuSqNplYMUPPB2BYgbGVmyTaXZCCBLN7trLTiIoyta3WQgX29Or77tWs5ehXEXxDOcDbihDW-7vNziCRnzM_fs6hEbx7xOaWWy0YnGxX8gtsBgYTZMmHu2BD9gkV4ZJTO6Y26yR2pxB320Uq5aCNyvmrTl_gJx6XeVAUrAKQJ-qRgbPcxu8jC-BtUK3cxHW183n6k9-Sq0o1bjy1kJCUVZhGoLJasd6KuY9EhabfNvVrhnc5E3boLF-lNoof8pChLa-b9MHHg01m334zOpSyAdXSa8yUpEr3fyBoPk_A_EoshIfwEpu4nGGwhe8M8hwiOulBtlUp-oQt8neYVyqCobZcr2De8SHQoaeGSUXAK_Fv4XXACdl_C3NcyPJglzTvV67-Vfszd-4owWEuHDVUcv9UvtE21xJzuHGteyEbM67f1yjQ2uP0MJLNWtPNuEj-yj3S4PC8F4SeWUWV0y2bosDKsbU5KlYE5c65giuFvZQOLTtarmeXohElWPZHEe5GN2ekDEkvuUpQ57T8szWd7-LH1CG-jPrYSLEgf-8QI0MmV9zRm7rXYcpsVAvR0LHCm6DJU8ko-Ktjn9iAgp4Nq25ez3ZhrmlR-cZ78iTB3qi48imUEXDlitUEeo4nz1SoFMo0QokNrNc1D0sihRyoUcd4C_mkjU16tfLesK8Xr9gGgrdX2iYHGQVI7bsErMVjUVn-LdSctjFPWDCH67Yh3SRMFBQLsdGnzm9Uru5PXC_4mJg7WUirlQ_HQuY17dg3ImamMekHiRVxvkToTRtB9mbCMHiYsfc87iQm-QxYMcNYHj3YiD4EOVeBIUkEjx-al-r3jDMe_Qn3xF6nM4hPHEog Archived]</ref><br />
::Unclear if retrospective or prospective; samples from "apparently" healthy infants (<1y) obtained from local maternity wards and outpatient clinics in Toronto, Canada; samples from >1 obtained from the "CALIPER biobank." Table-1 shows the reported 99th percentiles. Additionally, the authors report several notable observations:<br />
:::*''"hs-cTnT concentrations were markedly increased from 0 to <6 months and subsequently decreased and narrowed at 1 year."''<br />
:::*''"Although hs-cTnT concentrations from 0 to <1 year were normally distributed, hs-cTnT concentrations for both sexes of age 1 to <19 years were highly skewed."''<br />
:::*The authors comment about their 1y to 19y age group having 99th percentile cut-offs of 11 (F) and 14 (M) and this differing from the manufacturer package insert. They astutely note that the major cause for this difference is likely their use of a different reference population, and they highlight that neither reference population had imaging done (i.e. structural and coronary cardiac evaluations) to show that they were truly healthy with regard to establishing a distribution in "healthy" individuals.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0 – <6m || style="text-align:center;" | 55 || style="text-align:center;" | 93<br />
|-<br />
| 6m – <1y || style="text-align:center;" | 44 || style="text-align:center;" | 21<br />
|-<br />
| 1 – <19y F || style="text-align:center;" | 249 || style="text-align:center;" | 11<br />
|-<br />
| 1 – <19y M || style="text-align:center;" | 249 || style="text-align:center;" | 14<br />
|}<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-2. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-3 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-3.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
:;Guo et al (2021)<ref>Guo Q, Yang D, Zhou Y, Zhang S, Zhu T, Wang A, Lei M, Yang X. Establishment of the reference interval for high-sensitivity cardiac troponin T in healthy children of Chongqing Nan'an district. Scand J Clin Lab Invest. 2021 Nov;81(7):579-584. doi:[https://doi.org/10.1080/00365513.2021.1979245 10.1080/00365513.2021.1979245]. Epub 2021 Sep 28. PMID:[https://pubmed.ncbi.nlm.nih.gov/34581638/ 34581638]. (obtained through the Alaska Medical Library)</ref><br />
::From January 2017 to February 2020, 4,617 questionnaires distributed to children from Chongqing Southeast Hospital (China), pediatricians physically examined respondents to confirm no health issues, 3,463 children included in the study, ages 0-14y, analyzed by sex. Results are presented in Table-4. <br />
:::*The combination of large sample size and pediatrician physical exams to confirm no underlying health problems makes this undoubtedly the most robust data available at the time of this writing (January 2022). <br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-4.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 1d(UCB) || style="text-align:center;" | 34 || style="text-align:center;" | 60.8<br />
|-<br />
| 1d(VB) || style="text-align:center;" | 253 || style="text-align:center;" | 78.8<br />
|-<br />
| 2–28d || style="text-align:center;" | 236 || style="text-align:center;" | 96.6<br />
|-<br />
| 29d–<3m || style="text-align:center;" | 178 || style="text-align:center;" | 58.6<br />
|-<br />
| 3–<6m || style="text-align:center;" | 177 || style="text-align:center;" | 34.2<br />
|-<br />
| 6m–<1y || style="text-align:center;" | 377 || style="text-align:center;" | 16.2<br />
|-<br />
| 1–<3y || style="text-align:center;" | 899 || style="text-align:center;" | 11.4<br />
|-<br />
| 3–<6y (M) || style="text-align:center;" | 361 || style="text-align:center;" | 8<br />
|-<br />
| 3–<6y (F) || style="text-align:center;" | 327 || style="text-align:center;" | 7.8<br />
|-<br />
| 6–14y (M) || style="text-align:center;" | 373 || style="text-align:center;" | 7.8<br />
|-<br />
| 6–14y (F) || style="text-align:center;" | 248 || style="text-align:center;" | 7.3<br />
|}<br />
<br><br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8686Cardiac Biomarkers in Pediatrics2022-01-21T21:04:06Z<p>AndyS: </p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle. Troponin I and T are released from cardiomyocytes due to multiple types of myocardial cell "injury" (including ischemia, necrosis, apoptosis, cytotoxicity, inflammation, etc). Clinical decision making must incorporate the understanding that troponin I and T can undergo <u>non-ischemic</u> release (such as during non-ischemic heart failure, non-ischemic inflammation, and other conditions which injure the cardiomyocites without associated ischemia.<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref><br />
<br><br />
=== Normal Range[s] ===<br />
Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).<br />
<br><br />
<br><br />
<br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 <u>healthy</u>, term <u>newborns</u> in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several notable findings:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Bohn et al (2019)<ref name=Bohn2019>Bohn MK, Higgins V, Kavsak P, Hoffman B, Adeli K. High-Sensitivity Generation 5 Cardiac Troponin T Sex- and Age-Specific 99th Percentiles in the CALIPER Cohort of Healthy Children and Adolescents. Clin Chem. 2019 Apr;65(4):589-591. doi:[https://doi.org/10.1373/clinchem.2018.299156 10.1373/clinchem.2018.299156]. Epub 2019 Feb 8. PMID:[https://pubmed.ncbi.nlm.nih.gov/30737206/ 30737206]. [http://web.archive.org/web/20220121142237/https://watermark.silverchair.com/clinchem0589.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtgwggLUBgkqhkiG9w0BBwagggLFMIICwQIBADCCAroGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMl4zG0GFTLFsAxQlSAgEQgIICi9rtEHt0uQdmISjuSqNplYMUPPB2BYgbGVmyTaXZCCBLN7trLTiIoyta3WQgX29Or77tWs5ehXEXxDOcDbihDW-7vNziCRnzM_fs6hEbx7xOaWWy0YnGxX8gtsBgYTZMmHu2BD9gkV4ZJTO6Y26yR2pxB320Uq5aCNyvmrTl_gJx6XeVAUrAKQJ-qRgbPcxu8jC-BtUK3cxHW183n6k9-Sq0o1bjy1kJCUVZhGoLJasd6KuY9EhabfNvVrhnc5E3boLF-lNoof8pChLa-b9MHHg01m334zOpSyAdXSa8yUpEr3fyBoPk_A_EoshIfwEpu4nGGwhe8M8hwiOulBtlUp-oQt8neYVyqCobZcr2De8SHQoaeGSUXAK_Fv4XXACdl_C3NcyPJglzTvV67-Vfszd-4owWEuHDVUcv9UvtE21xJzuHGteyEbM67f1yjQ2uP0MJLNWtPNuEj-yj3S4PC8F4SeWUWV0y2bosDKsbU5KlYE5c65giuFvZQOLTtarmeXohElWPZHEe5GN2ekDEkvuUpQ57T8szWd7-LH1CG-jPrYSLEgf-8QI0MmV9zRm7rXYcpsVAvR0LHCm6DJU8ko-Ktjn9iAgp4Nq25ez3ZhrmlR-cZ78iTB3qi48imUEXDlitUEeo4nz1SoFMo0QokNrNc1D0sihRyoUcd4C_mkjU16tfLesK8Xr9gGgrdX2iYHGQVI7bsErMVjUVn-LdSctjFPWDCH67Yh3SRMFBQLsdGnzm9Uru5PXC_4mJg7WUirlQ_HQuY17dg3ImamMekHiRVxvkToTRtB9mbCMHiYsfc87iQm-QxYMcNYHj3YiD4EOVeBIUkEjx-al-r3jDMe_Qn3xF6nM4hPHEog Archived]</ref><br />
::Unclear if retrospective or prospective; samples from "apparently" healthy infants (<1y) obtained from local maternity wards and outpatient clinics in Toronto, Canada; samples from >1 obtained from the "CALIPER biobank." Table-1 shows the reported 99th percentiles. Additionally, the authors report several notable observations:<br />
:::*''"hs-cTnT concentrations were markedly increased from 0 to <6 months and subsequently decreased and narrowed at 1 year."''<br />
:::*''"Although hs-cTnT concentrations from 0 to <1 year were normally distributed, hs-cTnT concentrations for both sexes of age 1 to <19 years were highly skewed."''<br />
:::*The authors comment about their 1y to 19y age group having 99th percentile cut-offs of 11 (F) and 14 (M) and this differing from the manufacturer package insert. They astutely note that the major cause for this difference is likely their use of a different reference population, and they highlight that neither reference population had imaging done (i.e. structural and coronary cardiac evaluations) to show that they were truly healthy with regard to establishing a distribution in "healthy" individuals.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0 – <6m || style="text-align:center;" | 55 || style="text-align:center;" | 93<br />
|-<br />
| 6m – <1y || style="text-align:center;" | 44 || style="text-align:center;" | 21<br />
|-<br />
| 1 – <19y F || style="text-align:center;" | 249 || style="text-align:center;" | 11<br />
|-<br />
| 1 – <19y M || style="text-align:center;" | 249 || style="text-align:center;" | 14<br />
|}<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-2. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-3 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-3.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
:;Guo et al (2021)<ref>Guo Q, Yang D, Zhou Y, Zhang S, Zhu T, Wang A, Lei M, Yang X. Establishment of the reference interval for high-sensitivity cardiac troponin T in healthy children of Chongqing Nan'an district. Scand J Clin Lab Invest. 2021 Nov;81(7):579-584. doi:[https://doi.org/10.1080/00365513.2021.1979245 10.1080/00365513.2021.1979245]. Epub 2021 Sep 28. PMID:[https://pubmed.ncbi.nlm.nih.gov/34581638/ 34581638]. (obtained through the Alaska Medical Library)</ref><br />
::From January 2017 to February 2020, 4,617 questionnaires distributed to children from Chongqing Southeast Hospital (China), pediatricians physically examined respondents to confirm no health issues, 3,463 children included in the study, ages 0-14y, analyzed by sex. Results are presented in Table-4. <br />
:::*The combination of large sample size and pediatrician physical exams to confirm no underlying health problems makes this undoubtedly the most robust data available at the time of this writing (January 2022). <br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-4.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 1d(UCB) || style="text-align:center;" | 34 || style="text-align:center;" | 60.8<br />
|-<br />
| 1d(VB) || style="text-align:center;" | 253 || style="text-align:center;" | 78.8<br />
|-<br />
| 2–28d || style="text-align:center;" | 236 || style="text-align:center;" | 96.6<br />
|-<br />
| 29d–<3m || style="text-align:center;" | 178 || style="text-align:center;" | 58.6<br />
|-<br />
| 3–<6m || style="text-align:center;" | 177 || style="text-align:center;" | 34.2<br />
|-<br />
| 6m–<1y || style="text-align:center;" | 377 || style="text-align:center;" | 16.2<br />
|-<br />
| 1–<3y || style="text-align:center;" | 899 || style="text-align:center;" | 11.4<br />
|-<br />
| 3–<6y (M) || style="text-align:center;" | 361 || style="text-align:center;" | 8<br />
|-<br />
| 3–<6y (F) || style="text-align:center;" | 327 || style="text-align:center;" | 7.8<br />
|-<br />
| 6–14y (M) || style="text-align:center;" | 373 || style="text-align:center;" | 7.8<br />
|-<br />
| 6–14y (F) || style="text-align:center;" | 248 || style="text-align:center;" | 7.3<br />
|}<br />
<br><br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8685Cardiac Biomarkers in Pediatrics2022-01-21T15:45:42Z<p>AndyS: </p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle. Troponin I and T are released from cardiomyocytes due to multiple types of myocardial cell "injury" (including ischemia, necrosis, apoptosis, cytotoxicity, inflammation, etc). Clinical decision making must incorporate the understanding that troponin I and T can undergo <u>non-ischemic</u> release (such as during non-ischemic heart failure, non-ischemic inflammation, and other conditions which injure the cardiomyocites without associated ischemia.<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref><br />
<br><br />
=== Normal Range[s] ===<br />
Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).<br />
<br><br />
<br><br />
<br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 <u>healthy</u>, term <u>newborns</u> in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several notable findings:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Bohn et al (2019)<ref name=Bohn2019>Bohn MK, Higgins V, Kavsak P, Hoffman B, Adeli K. High-Sensitivity Generation 5 Cardiac Troponin T Sex- and Age-Specific 99th Percentiles in the CALIPER Cohort of Healthy Children and Adolescents. Clin Chem. 2019 Apr;65(4):589-591. doi:[https://doi.org/10.1373/clinchem.2018.299156 10.1373/clinchem.2018.299156]. Epub 2019 Feb 8. PMID:[https://pubmed.ncbi.nlm.nih.gov/30737206/ 30737206]. [http://web.archive.org/web/20220121142237/https://watermark.silverchair.com/clinchem0589.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtgwggLUBgkqhkiG9w0BBwagggLFMIICwQIBADCCAroGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMl4zG0GFTLFsAxQlSAgEQgIICi9rtEHt0uQdmISjuSqNplYMUPPB2BYgbGVmyTaXZCCBLN7trLTiIoyta3WQgX29Or77tWs5ehXEXxDOcDbihDW-7vNziCRnzM_fs6hEbx7xOaWWy0YnGxX8gtsBgYTZMmHu2BD9gkV4ZJTO6Y26yR2pxB320Uq5aCNyvmrTl_gJx6XeVAUrAKQJ-qRgbPcxu8jC-BtUK3cxHW183n6k9-Sq0o1bjy1kJCUVZhGoLJasd6KuY9EhabfNvVrhnc5E3boLF-lNoof8pChLa-b9MHHg01m334zOpSyAdXSa8yUpEr3fyBoPk_A_EoshIfwEpu4nGGwhe8M8hwiOulBtlUp-oQt8neYVyqCobZcr2De8SHQoaeGSUXAK_Fv4XXACdl_C3NcyPJglzTvV67-Vfszd-4owWEuHDVUcv9UvtE21xJzuHGteyEbM67f1yjQ2uP0MJLNWtPNuEj-yj3S4PC8F4SeWUWV0y2bosDKsbU5KlYE5c65giuFvZQOLTtarmeXohElWPZHEe5GN2ekDEkvuUpQ57T8szWd7-LH1CG-jPrYSLEgf-8QI0MmV9zRm7rXYcpsVAvR0LHCm6DJU8ko-Ktjn9iAgp4Nq25ez3ZhrmlR-cZ78iTB3qi48imUEXDlitUEeo4nz1SoFMo0QokNrNc1D0sihRyoUcd4C_mkjU16tfLesK8Xr9gGgrdX2iYHGQVI7bsErMVjUVn-LdSctjFPWDCH67Yh3SRMFBQLsdGnzm9Uru5PXC_4mJg7WUirlQ_HQuY17dg3ImamMekHiRVxvkToTRtB9mbCMHiYsfc87iQm-QxYMcNYHj3YiD4EOVeBIUkEjx-al-r3jDMe_Qn3xF6nM4hPHEog Archived]</ref><br />
::Unclear if retrospective or prospective; samples from "apparently" healthy infants (<1y) obtained from local maternity wards and outpatient clinics in Toronto, Canada; samples from >1 obtained from the "CALIPER biobank." Table-1 shows the reported 99th percentiles. Additionally, the authors report several notable observations:<br />
:::*''"hs-cTnT concentrations were markedly increased from 0 to <6 months and subsequently decreased and narrowed at 1 year."''<br />
:::*''"Although hs-cTnT concentrations from 0 to <1 year were normally distributed, hs-cTnT concentrations for both sexes of age 1 to <19 years were highly skewed."''<br />
:::*The authors comment about their 1y to 19y age group having 99th percentile cut-offs of 11 (F) and 14 (M) and this differing from the manufacturer package insert. They astutely note that the major cause for this difference is likely their use of a different reference population, and they highlight that neither reference population had imaging done (i.e. structural and coronary cardiac evaluations) to show that they were truly healthy with regard to establishing a distribution in "healthy" individuals.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0 – <6m || style="text-align:center;" | 55 || style="text-align:center;" | 93<br />
|-<br />
| 6m – <1y || style="text-align:center;" | 44 || style="text-align:center;" | 21<br />
|-<br />
| 1 – <19y F || style="text-align:center;" | 249 || style="text-align:center;" | 11<br />
|-<br />
| 1 – <19y M || style="text-align:center;" | 249 || style="text-align:center;" | 14<br />
|}<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-2. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-3 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-3.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
<br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8684Cardiac Biomarkers in Pediatrics2022-01-21T15:35:50Z<p>AndyS: </p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle. Troponin I and T are released from cardiomyocytes due to multiple types of myocardial cell "injury" (including ischemia, necrosis, apoptosis, cytotoxicity, inflammation, etc). Clinical decision making must incorporate the understanding that troponin I and T can undergo <u>non-ischemic</u> release (such as during non-ischemic heart failure, non-ischemic inflammation, and other conditions which injure the cardiomyocites without associated ischemia.<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. ([https://web.archive.org/web/20220121152936/https://jcp.bmj.com/content/jclinpath/57/10/1025.full.pdf Archived])</ref><br />
<br><br />
=== Normal Range[s] ===<br />
Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).<br />
<br><br />
<br><br />
<br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 <u>healthy</u>, term <u>newborns</u> in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several notable findings:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Bohn et al (2019)<ref name=Bohn2019>Bohn MK, Higgins V, Kavsak P, Hoffman B, Adeli K. High-Sensitivity Generation 5 Cardiac Troponin T Sex- and Age-Specific 99th Percentiles in the CALIPER Cohort of Healthy Children and Adolescents. Clin Chem. 2019 Apr;65(4):589-591. doi:[https://doi.org/10.1373/clinchem.2018.299156 10.1373/clinchem.2018.299156]. Epub 2019 Feb 8. PMID:[https://pubmed.ncbi.nlm.nih.gov/30737206/ 30737206]. [http://web.archive.org/web/20220121142237/https://watermark.silverchair.com/clinchem0589.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtgwggLUBgkqhkiG9w0BBwagggLFMIICwQIBADCCAroGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMl4zG0GFTLFsAxQlSAgEQgIICi9rtEHt0uQdmISjuSqNplYMUPPB2BYgbGVmyTaXZCCBLN7trLTiIoyta3WQgX29Or77tWs5ehXEXxDOcDbihDW-7vNziCRnzM_fs6hEbx7xOaWWy0YnGxX8gtsBgYTZMmHu2BD9gkV4ZJTO6Y26yR2pxB320Uq5aCNyvmrTl_gJx6XeVAUrAKQJ-qRgbPcxu8jC-BtUK3cxHW183n6k9-Sq0o1bjy1kJCUVZhGoLJasd6KuY9EhabfNvVrhnc5E3boLF-lNoof8pChLa-b9MHHg01m334zOpSyAdXSa8yUpEr3fyBoPk_A_EoshIfwEpu4nGGwhe8M8hwiOulBtlUp-oQt8neYVyqCobZcr2De8SHQoaeGSUXAK_Fv4XXACdl_C3NcyPJglzTvV67-Vfszd-4owWEuHDVUcv9UvtE21xJzuHGteyEbM67f1yjQ2uP0MJLNWtPNuEj-yj3S4PC8F4SeWUWV0y2bosDKsbU5KlYE5c65giuFvZQOLTtarmeXohElWPZHEe5GN2ekDEkvuUpQ57T8szWd7-LH1CG-jPrYSLEgf-8QI0MmV9zRm7rXYcpsVAvR0LHCm6DJU8ko-Ktjn9iAgp4Nq25ez3ZhrmlR-cZ78iTB3qi48imUEXDlitUEeo4nz1SoFMo0QokNrNc1D0sihRyoUcd4C_mkjU16tfLesK8Xr9gGgrdX2iYHGQVI7bsErMVjUVn-LdSctjFPWDCH67Yh3SRMFBQLsdGnzm9Uru5PXC_4mJg7WUirlQ_HQuY17dg3ImamMekHiRVxvkToTRtB9mbCMHiYsfc87iQm-QxYMcNYHj3YiD4EOVeBIUkEjx-al-r3jDMe_Qn3xF6nM4hPHEog Archived]</ref><br />
::Unclear if retrospective or prospective; samples from "apparently" healthy infants (<1y) obtained from local maternity wards and outpatient clinics in Toronto, Canada; samples from >1 obtained from the "CALIPER biobank." Table-1 shows the reported 99th percentiles. Additionally, the authors report several notable observations:<br />
:::*''"hs-cTnT concentrations were markedly increased from 0 to <6 months and subsequently decreased and narrowed at 1 year."''<br />
:::*''"Although hs-cTnT concentrations from 0 to <1 year were normally distributed, hs-cTnT concentrations for both sexes of age 1 to <19 years were highly skewed."''<br />
:::*The authors comment about their 1y to 19y age group having 99th percentile cut-offs of 11 (F) and 14 (M) and this differing from the manufacturer package insert. They astutely note that the major cause for this difference is likely their use of a different reference population, and they highlight that neither reference population had imaging done (i.e. structural and coronary cardiac evaluations) to show that they were truly healthy with regard to establishing a distribution in "healthy" individuals.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0 – <6m || style="text-align:center;" | 55 || style="text-align:center;" | 93<br />
|-<br />
| 6m – <1y || style="text-align:center;" | 44 || style="text-align:center;" | 21<br />
|-<br />
| 1 – <19y F || style="text-align:center;" | 249 || style="text-align:center;" | 11<br />
|-<br />
| 1 – <19y M || style="text-align:center;" | 249 || style="text-align:center;" | 14<br />
|}<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-2. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-3 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-3.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
<br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8683Cardiac Biomarkers in Pediatrics2022-01-21T15:12:09Z<p>AndyS: </p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
Released due to multiple types of myocardial injury (ischemia, necrosis, apoptosis, cytotoxicity, inflammation). Certain levels, ''in the proper context'', constitute the definition of myocardial infarction. However, troponin can undergo ''non-ischemic'' release during heart failure, inflammation, and other conditions (such as infiltrative diseases).'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH).<br />
<br><br />
<br><br />
<br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 <u>healthy</u>, term <u>newborns</u> in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several notable findings:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Bohn et al (2019)<ref name=Bohn2019>Bohn MK, Higgins V, Kavsak P, Hoffman B, Adeli K. High-Sensitivity Generation 5 Cardiac Troponin T Sex- and Age-Specific 99th Percentiles in the CALIPER Cohort of Healthy Children and Adolescents. Clin Chem. 2019 Apr;65(4):589-591. doi:[https://doi.org/10.1373/clinchem.2018.299156 10.1373/clinchem.2018.299156]. Epub 2019 Feb 8. PMID:[https://pubmed.ncbi.nlm.nih.gov/30737206/ 30737206]. [http://web.archive.org/web/20220121142237/https://watermark.silverchair.com/clinchem0589.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtgwggLUBgkqhkiG9w0BBwagggLFMIICwQIBADCCAroGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMl4zG0GFTLFsAxQlSAgEQgIICi9rtEHt0uQdmISjuSqNplYMUPPB2BYgbGVmyTaXZCCBLN7trLTiIoyta3WQgX29Or77tWs5ehXEXxDOcDbihDW-7vNziCRnzM_fs6hEbx7xOaWWy0YnGxX8gtsBgYTZMmHu2BD9gkV4ZJTO6Y26yR2pxB320Uq5aCNyvmrTl_gJx6XeVAUrAKQJ-qRgbPcxu8jC-BtUK3cxHW183n6k9-Sq0o1bjy1kJCUVZhGoLJasd6KuY9EhabfNvVrhnc5E3boLF-lNoof8pChLa-b9MHHg01m334zOpSyAdXSa8yUpEr3fyBoPk_A_EoshIfwEpu4nGGwhe8M8hwiOulBtlUp-oQt8neYVyqCobZcr2De8SHQoaeGSUXAK_Fv4XXACdl_C3NcyPJglzTvV67-Vfszd-4owWEuHDVUcv9UvtE21xJzuHGteyEbM67f1yjQ2uP0MJLNWtPNuEj-yj3S4PC8F4SeWUWV0y2bosDKsbU5KlYE5c65giuFvZQOLTtarmeXohElWPZHEe5GN2ekDEkvuUpQ57T8szWd7-LH1CG-jPrYSLEgf-8QI0MmV9zRm7rXYcpsVAvR0LHCm6DJU8ko-Ktjn9iAgp4Nq25ez3ZhrmlR-cZ78iTB3qi48imUEXDlitUEeo4nz1SoFMo0QokNrNc1D0sihRyoUcd4C_mkjU16tfLesK8Xr9gGgrdX2iYHGQVI7bsErMVjUVn-LdSctjFPWDCH67Yh3SRMFBQLsdGnzm9Uru5PXC_4mJg7WUirlQ_HQuY17dg3ImamMekHiRVxvkToTRtB9mbCMHiYsfc87iQm-QxYMcNYHj3YiD4EOVeBIUkEjx-al-r3jDMe_Qn3xF6nM4hPHEog Archived]</ref><br />
::Unclear if retrospective or prospective; samples from "apparently" healthy infants (<1y) obtained from local maternity wards and outpatient clinics in Toronto, Canada; samples from >1 obtained from the "CALIPER biobank." Table-1 shows the reported 99th percentiles. Additionally, the authors report several notable observations:<br />
:::*''"hs-cTnT concentrations were markedly increased from 0 to <6 months and subsequently decreased and narrowed at 1 year."''<br />
:::*''"Although hs-cTnT concentrations from 0 to <1 year were normally distributed, hs-cTnT concentrations for both sexes of age 1 to <19 years were highly skewed."''<br />
:::*The authors comment about their 1y to 19y age group having 99th percentile cut-offs of 11 (F) and 14 (M) and this differing from the manufacturer package insert. They astutely note that the major cause for this difference is likely their use of a different reference population, and they highlight that neither reference population had imaging done (i.e. structural and coronary cardiac evaluations) to show that they were truly healthy with regard to establishing a distribution in "healthy" individuals.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0 – <6m || style="text-align:center;" | 55 || style="text-align:center;" | 93<br />
|-<br />
| 6m – <1y || style="text-align:center;" | 44 || style="text-align:center;" | 21<br />
|-<br />
| 1 – <19y F || style="text-align:center;" | 249 || style="text-align:center;" | 11<br />
|-<br />
| 1 – <19y M || style="text-align:center;" | 249 || style="text-align:center;" | 14<br />
|}<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-2. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-3 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-3.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
<br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8682Cardiac Biomarkers in Pediatrics2022-01-21T15:02:07Z<p>AndyS: </p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
Released due to multiple types of myocardial injury (ischemia, necrosis, apoptosis, cytotoxicity, inflammation). Certain levels, ''in the proper context'', constitute the definition of myocardial infarction. However, troponin can undergo ''non-ischemic'' release during heart failure, inflammation, and other conditions (such as infiltrative diseases).'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH).<br />
<br><br />
<br><br />
<br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 healthy, term newborn in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several findings worthy of presenting:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Bohn et al (2019)<ref name=Bohn2019>Bohn MK, Higgins V, Kavsak P, Hoffman B, Adeli K. High-Sensitivity Generation 5 Cardiac Troponin T Sex- and Age-Specific 99th Percentiles in the CALIPER Cohort of Healthy Children and Adolescents. Clin Chem. 2019 Apr;65(4):589-591. doi:[https://doi.org/10.1373/clinchem.2018.299156 10.1373/clinchem.2018.299156]. Epub 2019 Feb 8. PMID:[https://pubmed.ncbi.nlm.nih.gov/30737206/ 30737206]. [http://web.archive.org/web/20220121142237/https://watermark.silverchair.com/clinchem0589.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtgwggLUBgkqhkiG9w0BBwagggLFMIICwQIBADCCAroGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMl4zG0GFTLFsAxQlSAgEQgIICi9rtEHt0uQdmISjuSqNplYMUPPB2BYgbGVmyTaXZCCBLN7trLTiIoyta3WQgX29Or77tWs5ehXEXxDOcDbihDW-7vNziCRnzM_fs6hEbx7xOaWWy0YnGxX8gtsBgYTZMmHu2BD9gkV4ZJTO6Y26yR2pxB320Uq5aCNyvmrTl_gJx6XeVAUrAKQJ-qRgbPcxu8jC-BtUK3cxHW183n6k9-Sq0o1bjy1kJCUVZhGoLJasd6KuY9EhabfNvVrhnc5E3boLF-lNoof8pChLa-b9MHHg01m334zOpSyAdXSa8yUpEr3fyBoPk_A_EoshIfwEpu4nGGwhe8M8hwiOulBtlUp-oQt8neYVyqCobZcr2De8SHQoaeGSUXAK_Fv4XXACdl_C3NcyPJglzTvV67-Vfszd-4owWEuHDVUcv9UvtE21xJzuHGteyEbM67f1yjQ2uP0MJLNWtPNuEj-yj3S4PC8F4SeWUWV0y2bosDKsbU5KlYE5c65giuFvZQOLTtarmeXohElWPZHEe5GN2ekDEkvuUpQ57T8szWd7-LH1CG-jPrYSLEgf-8QI0MmV9zRm7rXYcpsVAvR0LHCm6DJU8ko-Ktjn9iAgp4Nq25ez3ZhrmlR-cZ78iTB3qi48imUEXDlitUEeo4nz1SoFMo0QokNrNc1D0sihRyoUcd4C_mkjU16tfLesK8Xr9gGgrdX2iYHGQVI7bsErMVjUVn-LdSctjFPWDCH67Yh3SRMFBQLsdGnzm9Uru5PXC_4mJg7WUirlQ_HQuY17dg3ImamMekHiRVxvkToTRtB9mbCMHiYsfc87iQm-QxYMcNYHj3YiD4EOVeBIUkEjx-al-r3jDMe_Qn3xF6nM4hPHEog Archived]</ref><br />
::Unclear if retrospective or prospective; samples from "apparently" healthy infants (<1y) obtained from local maternity wards and outpatient clinics in Toronto, Canada; samples from >1 obtained from the "CALIPER biobank." Table-1 shows the reported 99th percentiles. Additionally, the authors report several notable observations:<br />
:::*''"hs-cTnT concentrations were markedly increased from 0 to <6 months and subsequently decreased and narrowed at 1 year."''<br />
:::*''"Although hs-cTnT concentrations from 0 to <1 year were normally distributed, hs-cTnT concentrations for both sexes of age 1 to <19 years were highly skewed."''<br />
:::*The authors comment about their 1y to 19y age group having 99th percentile cut-offs of 11 (F) and 14 (M) and this differing from the manufacturer package insert. They astutely note that the major cause for this difference is likely their use of a different reference population, and they highlight that neither reference population had imaging done (i.e. structural and coronary cardiac evaluations) to show that they were truly healthy with regard to establishing a distribution in "healthy" individuals.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0 – <6m || style="text-align:center;" | 55 || style="text-align:center;" | 93<br />
|-<br />
| 6m – <1y || style="text-align:center;" | 44 || style="text-align:center;" | 21<br />
|-<br />
| 1 – <19y F || style="text-align:center;" | 249 || style="text-align:center;" | 11<br />
|-<br />
| 1 – <19y M || style="text-align:center;" | 249 || style="text-align:center;" | 14<br />
|}<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-2. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-3 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-3.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
<br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8681Cardiac Biomarkers in Pediatrics2022-01-21T05:50:49Z<p>AndyS: </p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
Released due to multiple types of myocardial injury (ischemia, necrosis, apoptosis, cytotoxicity, inflammation). Certain levels, ''in the proper context'', constitute the definition of myocardial infarction. However, troponin can undergo ''non-ischemic'' release during heart failure, inflammation, and other conditions (such as infiltrative diseases).'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 healthy, term newborn in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several findings worthy of presenting:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-1. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-2 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
<br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8680Cardiac Biomarkers in Pediatrics2022-01-21T05:00:05Z<p>AndyS: </p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-PRO-TERMINAL BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
Released due to multiple types of myocardial injury (ischemia, necrosis, apoptosis, cytotoxicity, inflammation). Certain levels, ''in the proper context'', constitute the definition of myocardial infarction. However, troponin can undergo ''non-ischemic'' release during heart failure, inflammation, and other conditions (such as infiltrative diseases).'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 healthy, term newborn in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several findings worthy of presenting:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-1. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-2 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
<br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Newborn Infant Toddler Child Adolescent<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyShttps://yk-health.org/index.php?title=Cardiac_Biomarkers_in_Pediatrics&diff=8679Cardiac Biomarkers in Pediatrics2022-01-21T04:59:10Z<p>AndyS: /* METHODS */</p>
<hr />
<div><br><br />
'''Bottom Line Up Front (BLUF):'''<br><br />
<br />
#Compared to healthy adults, the serum troponin and BNP levels in <u>healthy</u> neonates and infants less than 1 year have normal ranges with 99th percentiles nearly <u>two orders of magnitude</u> greater.<br />
#HIGH-SENSITIVITY TROPONIN-T (hs-cTnT)<br />
##As a biomarker, troponin occupies a relatively unique position in medicine. Unlike most biomarker cut-offs, which are based upon a desired sensitivity/specificity for diagnosis of a condition, troponin cut-offs are an arbitrarily chosen percentile of the values observed in a healthy population. A troponin value above the 99th percentile in healthy persons is the DEFINITION of "myocardial injury" (regardless of the clinical situation of the individual patient). Therefore, the troponin cut-off does not have a sensitivity/specificity for "myocardial injury," it simply IS myocardial injury. This is a relatively unique role for a serum biomarker, outranking even the concept of "gold standard".<br />
## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).<br />
## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref><br />
#N-PRO-TERMINAL BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.<br />
#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.<br />
#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:<br />
#* Evidence that the marker can distinguish disease from non-disease (as represented by the [https://en.wikipedia.org/wiki/Receiver_operating_characteristic AUROC]) in the age group in question.<br />
#* Knowledge of the diagnostic cut-off for the disease in question, as well as the sensitivity and specificity associated with that cut-off.<br />
#False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).<br />
#If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the diagnostic cut-off,<sup>†</sup> the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.<br />
#This page is not applicable to the following topics:<br />
#* Following cardiac biomarker trends for an already-diagnosed condition.<br />
#* Use cardiac biomarkers in preterm infants.<br />
<br><br />
<br><br />
__TOC__<br />
<br><br />
<br><br />
<br />
== hs-cTnT ==<br />
=== Biochemistry ===<br />
Released due to multiple types of myocardial injury (ischemia, necrosis, apoptosis, cytotoxicity, inflammation). Certain levels, ''in the proper context'', constitute the definition of myocardial infarction. However, troponin can undergo ''non-ischemic'' release during heart failure, inflammation, and other conditions (such as infiltrative diseases).'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref><br />
::Prospective, single-cohort study of cord blood of 241 healthy, term newborn in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several findings worthy of presenting:<br />
:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''<br />
:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''<br />
:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''<br />
:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''<br />
<br><br />
:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref><br />
::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-1. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-1.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| Cord || style="text-align:center;" | 105 || style="text-align:center;" | 88<br />
|-<br />
| 2-5d || style="text-align:center;" | 73 || style="text-align:center;" | 664<br />
|}<br />
<br><br />
<br />
:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref><br />
::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-2 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.<br />
{| class="wikitable" style="margin: auto;"<br />
|+ Table-2.<br />
|-<br />
! Age !! n !! 99th percentile<br />
|-<br />
| 0–<6 m || style="text-align:center;" | 64 || style="text-align:center;" | 87<br />
|-<br />
| 6 m–<1y || style="text-align:center;" | 45 || style="text-align:center;" | 39<br />
|-<br />
| 1–<19 years || style="text-align:center;" | 131 || style="text-align:center;" | 11<br />
|}<br />
<br><br />
<br />
<br />
<br />
=== Diagnostic Cutoff[s] ===<br />
99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
<br />
== N-Pro-BNP ==<br />
=== Biochemistry ===<br />
Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.'''[REF]'''<br />
<br><br />
=== Normal Range[s] ===<br />
<br><br />
=== Diagnostic Cutoff[s] ===<br />
<br><br />
=== Validated Clinical Use[s] ===<br />
<br><br />
<br><br />
<br />
== METHODS ==<br />
Literature searches were performed for the specific test types available at YKDRH:<br />
# high-sensitivity Troponin T<br />
# N-Terminal pro-BNP<br />
Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.<br />
<br><br />
<br />
;Troponin-T PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29&size=200 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infan*[Title] OR child*[Title] or adolescen*[Title]) AND ("high-sensitiv*"[Title] AND "troponin T"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infan*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22high-sensitiv*%22%5BTitle%5D+AND+%22troponin+T%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
;BNP PubMed Search<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29&sort=date&size=100 Search]<br />
<br><br />
:: ''with diagnostic outcomes:''<br />
:(pediatric*[Title] OR neonat*[Title] OR newborn*[Title] OR infant*[Title] OR child*[Title] or adolescen*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("receiver operating characteristic"[Title/Abstract] OR "ROC curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract] OR cut-off[Title/Abstract] OR cutoff[Title/Abstract] OR "Diagnostic accuracy"[Title/Abstract]) [https://pubmed.ncbi.nlm.nih.gov/?term=%28pediatric*%5BTitle%5D+OR+neonat*%5BTitle%5D+OR+newborn*%5BTitle%5D+OR+infant*%5BTitle%5D+OR+child*%5BTitle%5D+or+adolescen*%5BTitle%5D%29+AND+%28%22N-Terminal+pro-B-Type+Natriuretic+Peptide%22%5BTitle%5D%29+AND+%28%22receiver+operating+characteristic%22%5BTitle%2FAbstract%5D+OR+%22ROC+curve%22%5BTitle%2FAbstract%5D+OR+AUROC%5BTitle%2FAbstract%5D+OR+specificity%5BTitle%2FAbstract%5D+OR+cut-off%5BTitle%2FAbstract%5D+OR+cutoff%5BTitle%2FAbstract%5D+OR+%22Diagnostic+accuracy%22%5BTitle%2FAbstract%5D%29&size=200 Search]<br />
<br><br />
<br><br />
<br />
== NOTES ==<br />
'''†''' A percentile cutoff in a healthy population is NOT the same as a diagnostic cutoff; a percentile is an observation detached from clinical implication, whereas diagnostic cut-off has an associated sensitivity and specificity for diagnosing a particular disease/condition.<br />
<br><br />
<br />
<br><br />
<br><br />
<br />
== REFERENCES ==<br />
<references /><br />
<br><br />
<br><br />
<br />
;Keywords:<br />
:Cardiac Biomarker Troponin BNP Pediatric Neonate Infant Toddler Child Adolescant<br />
<br />
;Author[s]:<br />
:Andrew W. Swartz, MD<br />
<br />
;Reviewer[s]:<br />
:Leslie Herrmann, MD</div>AndyS