Altered metabolites in newborns with persistent pulmonary hypertension

Martina A Steurer; Scott Oltman; Rebecca J Baer; Sky Feuer; Liang Liang; Randi A Paynter; Larry Rand; Kelli K Ryckman; Roberta L Keller; Laura L Jelliffe-Pawlowski

doi:10.1038/s41390-018-0023-y

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Altered metabolites in newborns with persistent pulmonary hypertension

Journal article

Open access

Peer reviewed

Altered metabolites in newborns with persistent pulmonary hypertension

Martina A Steurer, Scott Oltman, Rebecca J Baer, Sky Feuer, Liang Liang, Randi A Paynter, Larry Rand, Kelli K Ryckman, Roberta L Keller and Laura L Jelliffe-Pawlowski

Pediatric research, Vol.84(2), pp.272-278

08/2018

DOI: 10.1038/s41390-018-0023-y

PMCID: PMC7691760

PMID: 29895840

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Abstract

There is an emerging evidence that pulmonary hypertension is associated with amino acid, carnitine, and thyroid hormone aberrations. We aimed to characterize metabolic profiles measured by the newborn screen (NBS) in infants with persistent pulmonary hypertension of the newborn (PPHN) METHODS: Nested case-control study from population-based database. Cases were infants with ICD-9 code for PPHN receiving mechanical ventilation. Controls receiving mechanical ventilation were matched 2:1 for gestational age, sex, birth weight, parenteral nutrition administration, and age at NBS collection. Infants were divided into derivation and validation datasets. A multivariable logistic regression model was derived from candidate metabolites, and the area under the receiver operator characteristic curve (AUROC) was generated from the validation dataset. We identified 1076 cases and 2152 controls. Four metabolites remained in the final model. Ornithine (OR 0.32, CI 0.26-0.41), tyrosine (OR 0.48, CI 0.40-0.58), and TSH 0.50 (0.45-0.55) were associated with decreased odds of PPHN; phenylalanine was associated with increased odds of PPHN (OR 4.74, CI 3.25-6.90). The AUROC was 0.772 (CI 0.737-0.807). In a large, population-based dataset, infants with PPHN have distinct, early metabolic profiles. These data provide insight into the pathophysiology of PPHN, identifying potential therapeutic targets and novel biomarkers to assess the response.

Multivariate Analysis

Ornithine - blood

Area Under Curve

Humans

Logistic Models

Male

Treatment Outcome

Tyrosine - blood

Neonatal Screening

Gestational Age

Respiration, Artificial

Case-Control Studies

Birth Weight

Female

Phenylalanine - blood

Persistent Fetal Circulation Syndrome - blood

Infant, Newborn

Persistent Fetal Circulation Syndrome - physiopathology

Thyrotropin - blood

Details

Title: Subtitle: Altered metabolites in newborns with persistent pulmonary hypertension
Creators: Martina A Steurer - California Preterm Birth Initiative, University of California San Francisco, San Francisco, CA, USA. SteurerMullerM@peds.ucsf.edu
Scott Oltman - Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
Rebecca J Baer - Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
Sky Feuer - California Preterm Birth Initiative, University of California San Francisco, San Francisco, CA, USA
Liang Liang - Department of Genetics, Stanford University, Palo Alto, CA, USA
Randi A Paynter - California Preterm Birth Initiative, University of California San Francisco, San Francisco, CA, USA
Larry Rand - Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA
Kelli K Ryckman - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA
Roberta L Keller - Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
Laura L Jelliffe-Pawlowski - California Preterm Birth Initiative, University of California San Francisco, San Francisco, CA, USA
Resource Type: Journal article
Publication Details: Pediatric research, Vol.84(2), pp.272-278
DOI: 10.1038/s41390-018-0023-y
PMID: 29895840
PMCID: PMC7691760
NLM abbreviation: Pediatr Res
ISSN: 1530-0447
eISSN: 1530-0447
Publisher: United States
Grant note: U01 HL101456 / NHLBI NIH HHS R21 HD087864 / NICHD NIH HHS
Language: English
Date published: 08/2018
Academic Unit: Stead Family Department of Pediatrics; Epidemiology
Record Identifier: 9983995174202771

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