Cord blood metabolomic profiling in high risk newborns born to diabetic, obese, and overweight mothers: preliminary report

Özlem Ünal Uzun; Duygu Eneş; Müge Çınar; Ayla Günlemez Adugit; Büşra Uçar; Ali Duranoğlu; Ufuk Bozkurt Obuz; Mustafa Çelebier; İncilay Lay

doi:10.1515/jpem-2024-0605

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Article

Cord blood metabolomic profiling in high risk newborns born to diabetic, obese, and overweight mothers: preliminary report

Özlem Ünal Uzun , Duygu Eneş , Müge Çınar , Ayla Günlemez Adugit , Büşra Uçar , Ali Duranoğlu , Ufuk Bozkurt Obuz , Mustafa Çelebier and İncilay Lay

Published/Copyright: April 8, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 6

Abstract

Objectives

Newborns of diabetic and obese/overweight mothers face long-term metabolic risks. Untargeted cord blood metabolomic analysis using quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS) was performed to explore metabolic alterations and pathways in these high-risk infants.

Methods

Cord blood samples were collected from 46 newborns born to mothers with gestational diabetes (10), obesity (14), overweight (18), type 2 diabetes mellitus (3), type 1 diabetes mellitus (1), and 20 newborns born to healthy mothers. Q-TOF LC/MS was used to investigate the alterations in cord blood metabolomic profiles. Data processing was conducted using MZmine 2.53. Putative metabolites were idendtified using MetaboAnalyst 6.0.

Results

Distinct metabolite profiles were observed between diabetes and control groups. Significant identical trend in 19 metabolites were determined in both diabetes and obesity + overweight group vs. control group. Key pathways included steroid and bile acid biosynthesis. Upregulated oxidative stress, clues to sphingophospholipid metabolism, high levels of dihomo-gamma-linolenic acid (DGLA), pantothenic acid, and TRH were detected. The kynurenine pathway was prominent in the diabetes group.

Conclusions

Estrogen metabolites from the 16- and 2-pathways may indicate metabolic risk, with increased downstream flux under diabetic conditions. Accelerated bile acid synthesis may alter fetal metabolic programming, since bile acids play crucial roles in cellular energy regulation and signaling. Elevated pantothenic acid, essential for the production of coenzyme-A, suggests significant alterations in carbohydrate, protein, and fat metabolism. High serum DGLA levels emerge as a potential biomarker for metabolic abnormalities. Increased plasma kynurenines could predict cardiovascular risks. Larger targeted studies are required to validate these metabolic profiles and pathways.

Keywords: metabolomics; maternal diabetes; maternal obesity; high-risk newborn; quadrupole flight time mass spectrometer

Corresponding author: Prof. Dr. Özlem Ünal Uzun, Department of Pediatrics, Division of Metabolism, Faculty of Medicine, Kocaeli University, Umuttepe Yerleşkesi 41000, İzmit-Kocaeli, Türkiye, E-mail: unalozlem@gmail.com

Research ethics: Ethical approval for all materials used in the study was obtained from the Kocaeli University Non-Interventional Clinical Research Ethics Committee (E-80418770-020-222989) on 25th April 2022.
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. ÖÜU: Contributed to the planning and design of the study, data collection, analysis, interpretation, and manuscript preparation. DE: Contributed to data analysis and interpretation. MÇ: Contributed to data collection. AGA: Contributed to data collection. BU: Contributed to data analysis and interpretation. AD: Contributed to data collection. UOB: Contributed to data interpretation. MÇ: Contributed to data analysis, interpretation, and manuscript preparation. İL: Contributed to the planning and design of the study, data analysis, interpretation, and manuscript preparation.
Use of Large Language Models, AI and Machine Learning Tools: ChatGPT was used solely for improving the English language of the manuscript.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: The data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Received: 2024-12-15

Accepted: 2025-03-23

Published Online: 2025-04-08

Published in Print: 2025-06-26

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https://doi.org/10.1515/jpem-2024-0605

Keywords for this article

metabolomics; maternal diabetes; maternal obesity; high-risk newborn; quadrupole flight time mass spectrometer