Metabolic Networks and Metabolites Underlie Associations Between Maternal Glucose During Pregnancy and Newborn Size at Birth.
Open accessAbstract
Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and nontargeted gas chromatography/mass spectrometry metabolomics on maternal serum collected at fasting and 1 h following glucose beverage consumption during an oral glucose tolerance test (OGTT) for 400 northern European mothers at ∼28 weeks' gestation in the Hyperglycemia and Adverse Pregnancy Outcome Study. Amino acids, fatty acids, acylcarnitines, and products of lipid metabolism decreased and triglycerides increased during the OGTT. Analyses of individual metabolites indicated limited maternal glucose associations at fasting, but broader associations, including amino acids, fatty acids, carbohydrates, and lipids, were found at 1 h. Network analyses modeling metabolite correlations provided context for individual metabolite associations and elucidated collective associations of multiple classes of metabolic fuels with newborn size and adiposity, including acylcarnitines, fatty acids, carbohydrates, and organic acids. Random forest analyses indicated an improved ability to predict newborn size outcomes by using maternal metabolomics data beyond traditional risk factors, including maternal glucose. Broad-scale association of fuel metabolites with maternal glucose is evident during pregnancy, with unique maternal metabolites potentially contributing specifically to newborn birth weight and adiposity.
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In earlier studies, adjusting for maternal BMI attenuated the associations between gestational diabetes and childhood obesity.
“Adjusting for maternal BMI attenuated the associations between gestational diabetes and childhood obesity in earlier studies, 30,31”
From Association of Gestational Diabetes With Maternal Disorders of Glucose Metabolism and Childhood Adiposity (2018) · cites this paper as [31]
The Introduction says offspring of mothers with gestational diabetes are at risk for childhood obesity, but it does not say whether adjusting for maternal BMI attenuates that association. The Methods describe BMI adjustment for analyses of newborn birth weight and skinfolds, not childhood obesity. Searches for BMI adjustment and attenuation found no passage addressing the claimed finding. (LLM, conf=0.76)
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References 49 · Cited by 69
Research works printed but not linked: 1
- [22]Freinkel N, Metzger BE, Nitzan M, Daniel R, Surmaczynska B, Nagel T. Facilitated anabolism in late pregnancy: some novel maternal compensations for accelerated starvation. In Diabetes: Proceedings of the Eighth Congress of the International Diabetes Federation, Brussels, Belgium, 1973. Amsterdam, The Netherlands, Excerpta Medica International Congress Series, p. 474–488
- Authors
- Scholtens, D. M., Bain, J. R., Reisetter, A. C., Muehlbauer, M. J., Nodzenski, M., Stevens, R. D., Ilkayeva, O., Lowe, L. P., Metzger, B. E., Newgard, C. B., & Lowe, W. L.
- Affiliations
- Northwestern University (US)
- Duke University (US)
- Corresponding author
- Scholtens, Denise M.
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2016-04-05
- Volume
- 65
- Issue
- 7
- Pages
- 2039-2050
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC4915585
- OpenAlex
- W2333237904
- Cited by
- 69
- References
- 49
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 11 · 2021: 4 · 2020: 5 · 2019: 9 · 2018: 10 · 2017: 9 · 2016: 2
- FWCI
- 12.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-095963)
- National Institute of Child Health and Human Development (R01-HD-34242, R01-HD-34243)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- maternal blood glucose, pregnancy, newborn birth weight, neonatal adiposity, metabolic networks, oral glucose tolerance test, acylcarnitines, fatty acids, amino acids, triglycerides, lipid metabolism, carbohydrate metabolism, organic acids
- MeSH terms
- Adult, Birth Weight, Blood Glucose, Female, Glucose Tolerance Test, Humans, Infant, Newborn, Gas Chromatography-Mass Spectrometry, Pregnancy, Pregnancy Outcome, Triglycerides, Body Mass Index, Metabolic Networks and Pathways
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