Metabolomic fingerprints of clustered preterm and term neonates – a pilot study

IntroductionAdrenal steroidogenesis plays a pivotal role in neonatal adaptation, and advanced steroid profiling offers novel insights into disease risks and personalized management strategies. This study aimed to identify adrenal steroid metabolomic clusters in neonates and to correlate them with cl...

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Main Authors: Miłosz Lorek, Teresa Joanna Stradomska, Anna Siejka, Janusz Fuchs, Dominika Januś, Aneta Gawlik-Starzyk
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1569355/full
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author Miłosz Lorek
Miłosz Lorek
Teresa Joanna Stradomska
Anna Siejka
Janusz Fuchs
Dominika Januś
Aneta Gawlik-Starzyk
author_facet Miłosz Lorek
Miłosz Lorek
Teresa Joanna Stradomska
Anna Siejka
Janusz Fuchs
Dominika Januś
Aneta Gawlik-Starzyk
author_sort Miłosz Lorek
collection DOAJ
description IntroductionAdrenal steroidogenesis plays a pivotal role in neonatal adaptation, and advanced steroid profiling offers novel insights into disease risks and personalized management strategies. This study aimed to identify adrenal steroid metabolomic clusters in neonates and to correlate them with clinical outcomes.MethodsIn a prospective observational design (June 2021–July 2022), 50 neonates (12 early preterm, 18 late preterm, and 20 full-term) admitted with respiratory distress underwent continuous 24-hour urine collection via an urinary catheter. Steroid profiles were analyzed by gas chromatography–mass spectrometry. K-means clustering was employed to classify the metabolomic data, which were subsequently correlated with mortality, bronchopulmonary dysplasia (BPD), small for gestational age (SGA), and intraventricular hemorrhage (IVH).ResultsK-means analysis delineated three distinct metabolic clusters. Cluster 1 displayed a profoundly suppressed steroidogenesis (low C19 and C21 excretion, diminished 3β-hydroxysteroid dehydrogenase and 5α-reductase activities), correlating with an increased incidence of BPD, high mortality risk scores, and significant rates of SGA/intrauterine growth restriction. Cluster 2 exhibited adrenal hyperactivation with elevated cortisol/cortisone derivatives, moderately increased C19/C21 metabolites, and partial 3β-HSD deficits, associated with a heightened risk of IVH and mortality. Cluster 3 showed robust steroidogenesis (high C19/C21 excretion and high 3β-HSD/5α-reductase activities), accompanied by the lowest mortality rates and absence of BPD or SGA/IUGR.ConclusionsSuppressed steroidogenesis increased BPD, SGA, and mortality, while excessive cortisol output in Cluster 2 was associated with a higher risk of IVH. Robust steroidogenesis supported favorable outcomes, highlighting the potential for metabolome-guided interventions.
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spelling doaj-art-2c657388a1504ed69963f99341bcdd692025-08-20T03:10:05ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-05-011610.3389/fendo.2025.15693551569355Metabolomic fingerprints of clustered preterm and term neonates – a pilot studyMiłosz Lorek0Miłosz Lorek1Teresa Joanna Stradomska2Anna Siejka3Janusz Fuchs4Dominika Januś5Aneta Gawlik-Starzyk6Department of Neonatal and Pediatric Intensive Care, John Paul II Center for Child and Family Health, Sosnowiec, PolandDepartment of Pediatrics and Pediatric Endocrinology, Medical University of Silesia, Katowice, PolandLaboratory for the Diagnosis of Metabolic Disorders and Steroidogenesis, The Children's Memorial Health Institute, Warsaw, PolandLaboratory for the Diagnosis of Metabolic Disorders and Steroidogenesis, The Children's Memorial Health Institute, Warsaw, PolandDepartment of Neonatal and Pediatric Intensive Care, John Paul II Center for Child and Family Health, Sosnowiec, PolandDepartment of Paediatric and Adolescent Endocrinology, Jagiellonian University Medical College, University Children's Hospital, Krakow, PolandDepartment of Pediatrics and Pediatric Endocrinology, Medical University of Silesia, Katowice, PolandIntroductionAdrenal steroidogenesis plays a pivotal role in neonatal adaptation, and advanced steroid profiling offers novel insights into disease risks and personalized management strategies. This study aimed to identify adrenal steroid metabolomic clusters in neonates and to correlate them with clinical outcomes.MethodsIn a prospective observational design (June 2021–July 2022), 50 neonates (12 early preterm, 18 late preterm, and 20 full-term) admitted with respiratory distress underwent continuous 24-hour urine collection via an urinary catheter. Steroid profiles were analyzed by gas chromatography–mass spectrometry. K-means clustering was employed to classify the metabolomic data, which were subsequently correlated with mortality, bronchopulmonary dysplasia (BPD), small for gestational age (SGA), and intraventricular hemorrhage (IVH).ResultsK-means analysis delineated three distinct metabolic clusters. Cluster 1 displayed a profoundly suppressed steroidogenesis (low C19 and C21 excretion, diminished 3β-hydroxysteroid dehydrogenase and 5α-reductase activities), correlating with an increased incidence of BPD, high mortality risk scores, and significant rates of SGA/intrauterine growth restriction. Cluster 2 exhibited adrenal hyperactivation with elevated cortisol/cortisone derivatives, moderately increased C19/C21 metabolites, and partial 3β-HSD deficits, associated with a heightened risk of IVH and mortality. Cluster 3 showed robust steroidogenesis (high C19/C21 excretion and high 3β-HSD/5α-reductase activities), accompanied by the lowest mortality rates and absence of BPD or SGA/IUGR.ConclusionsSuppressed steroidogenesis increased BPD, SGA, and mortality, while excessive cortisol output in Cluster 2 was associated with a higher risk of IVH. Robust steroidogenesis supported favorable outcomes, highlighting the potential for metabolome-guided interventions.https://www.frontiersin.org/articles/10.3389/fendo.2025.1569355/fullneonatesadrenalssteroidogenesismetabolomicsK-means clustering
spellingShingle Miłosz Lorek
Miłosz Lorek
Teresa Joanna Stradomska
Anna Siejka
Janusz Fuchs
Dominika Januś
Aneta Gawlik-Starzyk
Metabolomic fingerprints of clustered preterm and term neonates – a pilot study
Frontiers in Endocrinology
neonates
adrenals
steroidogenesis
metabolomics
K-means clustering
title Metabolomic fingerprints of clustered preterm and term neonates – a pilot study
title_full Metabolomic fingerprints of clustered preterm and term neonates – a pilot study
title_fullStr Metabolomic fingerprints of clustered preterm and term neonates – a pilot study
title_full_unstemmed Metabolomic fingerprints of clustered preterm and term neonates – a pilot study
title_short Metabolomic fingerprints of clustered preterm and term neonates – a pilot study
title_sort metabolomic fingerprints of clustered preterm and term neonates a pilot study
topic neonates
adrenals
steroidogenesis
metabolomics
K-means clustering
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1569355/full
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