Transgenerational associations between newborn metabolic profiles and bronchopulmonary dysplasia in neonates born to mothers with an obese phenotype

Abstract Maternal obesity increases risk for bronchopulmonary dysplasia (BPD) by up to 42%. Identifying metabolic features that may contribute to the association between maternal pre-pregnancy body mass index (BMI) and BPD is critical in defining the molecular relationship between these conditions....

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Main Authors: Jonathan D. Reiss, Wei Yang, Alan L. Chang, Jonathan Z. Long, Ivana Marić, Jochen Profit, Karl G. Sylvester, David K. Stevenson, Nima Aghaeepour, Gary M. Shaw
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-85252-3
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author Jonathan D. Reiss
Wei Yang
Alan L. Chang
Jonathan Z. Long
Ivana Marić
Jochen Profit
Karl G. Sylvester
David K. Stevenson
Nima Aghaeepour
Gary M. Shaw
author_facet Jonathan D. Reiss
Wei Yang
Alan L. Chang
Jonathan Z. Long
Ivana Marić
Jochen Profit
Karl G. Sylvester
David K. Stevenson
Nima Aghaeepour
Gary M. Shaw
author_sort Jonathan D. Reiss
collection DOAJ
description Abstract Maternal obesity increases risk for bronchopulmonary dysplasia (BPD) by up to 42%. Identifying metabolic features that may contribute to the association between maternal pre-pregnancy body mass index (BMI) and BPD is critical in defining the molecular relationship between these conditions. We investigated the association between maternal obesity and BPD using newborn screen metabolites as an explanatory variable. We hypothesized that elevated pre-pregnancy BMI compared to a normal BMI referent group, is associated with increased circulating short and long-chain acylcarnitines and subsequent development of BPD. This was a retrospective study with linkage of maternal pre-pregnancy BMI, with newborn screen metabolites obtained from the California Newborn Screening Program and further linked with neonatal outcomes. Results demonstrated elevated levels of phenylalanine and proline associated with an increased risk for BPD (OR 5.3, 95% CI 1.2–23.8 and OR 5.4, 95% CI 1.3–22.3) in the obesity group compared to the referent group. Short- and long-chain acylcarnitines demonstrated a mildly increased risk for BPD in neonates of mothers with severe obesity compared to controls. The findings suggest that specific metabolites may influence the molecular conditioning that increases susceptibility to BPD.
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spelling doaj-art-e4d9034f8c2744ada3f792994768b7562025-01-12T12:15:21ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-85252-3Transgenerational associations between newborn metabolic profiles and bronchopulmonary dysplasia in neonates born to mothers with an obese phenotypeJonathan D. Reiss0Wei Yang1Alan L. Chang2Jonathan Z. Long3Ivana Marić4Jochen Profit5Karl G. Sylvester6David K. Stevenson7Nima Aghaeepour8Gary M. Shaw9Stanford Department of Pediatrics, Division of NeonatologyStanford Department of Pediatrics, Division of NeonatologyStanford Department of Anesthesiology, Perioperative and Pain MedicineDepartment of Pathology and Stanford, Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University School of MedicineStanford Department of Pediatrics, Division of NeonatologyStanford Department of Pediatrics, Division of NeonatologyStanford Department of Surgery, Division of Pediatric SurgeryStanford Department of Pediatrics, Division of NeonatologyStanford Department of Pediatrics, Division of NeonatologyStanford Department of Pediatrics, Division of NeonatologyAbstract Maternal obesity increases risk for bronchopulmonary dysplasia (BPD) by up to 42%. Identifying metabolic features that may contribute to the association between maternal pre-pregnancy body mass index (BMI) and BPD is critical in defining the molecular relationship between these conditions. We investigated the association between maternal obesity and BPD using newborn screen metabolites as an explanatory variable. We hypothesized that elevated pre-pregnancy BMI compared to a normal BMI referent group, is associated with increased circulating short and long-chain acylcarnitines and subsequent development of BPD. This was a retrospective study with linkage of maternal pre-pregnancy BMI, with newborn screen metabolites obtained from the California Newborn Screening Program and further linked with neonatal outcomes. Results demonstrated elevated levels of phenylalanine and proline associated with an increased risk for BPD (OR 5.3, 95% CI 1.2–23.8 and OR 5.4, 95% CI 1.3–22.3) in the obesity group compared to the referent group. Short- and long-chain acylcarnitines demonstrated a mildly increased risk for BPD in neonates of mothers with severe obesity compared to controls. The findings suggest that specific metabolites may influence the molecular conditioning that increases susceptibility to BPD.https://doi.org/10.1038/s41598-025-85252-3
spellingShingle Jonathan D. Reiss
Wei Yang
Alan L. Chang
Jonathan Z. Long
Ivana Marić
Jochen Profit
Karl G. Sylvester
David K. Stevenson
Nima Aghaeepour
Gary M. Shaw
Transgenerational associations between newborn metabolic profiles and bronchopulmonary dysplasia in neonates born to mothers with an obese phenotype
Scientific Reports
title Transgenerational associations between newborn metabolic profiles and bronchopulmonary dysplasia in neonates born to mothers with an obese phenotype
title_full Transgenerational associations between newborn metabolic profiles and bronchopulmonary dysplasia in neonates born to mothers with an obese phenotype
title_fullStr Transgenerational associations between newborn metabolic profiles and bronchopulmonary dysplasia in neonates born to mothers with an obese phenotype
title_full_unstemmed Transgenerational associations between newborn metabolic profiles and bronchopulmonary dysplasia in neonates born to mothers with an obese phenotype
title_short Transgenerational associations between newborn metabolic profiles and bronchopulmonary dysplasia in neonates born to mothers with an obese phenotype
title_sort transgenerational associations between newborn metabolic profiles and bronchopulmonary dysplasia in neonates born to mothers with an obese phenotype
url https://doi.org/10.1038/s41598-025-85252-3
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