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Cited by 23Folate and B Vitamins ResearchBirth, Development, and HealthGestational Diabetes Research and Management

Associations between Nutrients in One-Carbon Metabolism and Fetal DNA Methylation in Pregnancies with or without Gestational Diabetes Mellitus

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Kadam, Isma’il, Dalloul, Mudar, Hausser, Jeanette, Huntley, Monique, Hoepner, Lori, Fordjour, Lawrence, Hittelman, Joan, Saxena, Anjana +4 more·2023·Clinical Epigenetics
DOI 10.1186/s13148-023-01554-1PMC PMC10464204
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Abstract

Background: Gestational diabetes mellitus (GDM), characterized by hyperglycemia that develops during pregnancy, increases the risk of fetal macrosomia, childhood obesity and cardiometabolic disorders later in life. This process has been attributed partly to DNA methylation modifications in growth and stress-related pathways. Nutrients involved with one-carbon metabolism (OCM), such as folate, choline, betaine, and vitamin B 12, provide methyl groups for DNA methylation of these pathways. Therefore, this study aimed to determine whether maternal OCM nutrient intakes and levels modified fetal DNA methylation and in turn altered fetal growth patterns in pregnancies with and without GDM. Results: In this prospective study at a single academic institution from September 2016 to June 2019, we recruited 76 pregnant women with and without GDM at 25–33 weeks gestational age and assessed their OCM nutrient intake by diet recalls and measured maternal blood OCM nutrient levels. We also collected placenta and cord blood samples at delivery to examine fetal tissue DNA methylation of the genes that modify fetal growth and stress response such as insulin-like growth factor 2 (IGF2) and corticotropin-releasing hormone (CRH). We analyzed the association between maternal OCM nutrients and fetal DNA methylation using a generalized linear mixed model. Our results demonstrated that maternal choline intake was positively correlated with cord blood CRH methylation levels in both GDM and non-GDM pregnancies (r = 0.13, p = 0.007). Further, the downstream stress hormone cortisol regulated by CRH was inversely associated with maternal choline intake (r = − 0.36, p = 0.021). Higher maternal betaine intake and serum folate levels were associated with lower cord blood and placental IGF2 DNA methylation (r = − 0.13, p = 0.049 and r = − 0.065, p = 0.034, respectively) in both GDM and non-GDM pregnancies. Further, there was an inverse association between maternal betaine intake and birthweight of infants (r = − 0.28, p = 0.015). Conclusions: In conclusion, we observed a complex interrelationship between maternal OCM nutrients and fetal DNA methylation levels regardless of GDM status, which may, epigenetically, program molecular pathways related to fetal growth and stress response.

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  • These micronutrient deficiencies contribute not only to immediate pregnancy complications but also to persistent alterations in fetal growth, neurodevelopment, and metabolic programming, often mediated through epigenetic mechanisms.

    “These deficiencies contribute not only to immediate pregnancy complications but also to persistent alterations in fetal growth, neurodevelopment, and metabolic programming, often mediated through epigenetic mechanisms [89,90].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [90]

    The Discussion (page unavailable) reports associations between maternal methyl-nutrient levels and fetal DNA methylation, with possible consequences for fetal growth. The Background discusses lasting obesity and cardiometabolic risks, but attributes those risks to gestational diabetes; this paper does not establish that micronutrient deficiencies cause immediate pregnancy complications or persistent neurodevelopmental and metabolic changes. (LLM, conf=0.87)

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Cited by

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Authors
Kadam, I., Dalloul, M., Hausser, J., Huntley, M., Hoepner, L., Fordjour, L., Hittelman, J., Saxena, A., Liu, J., Futterman, I. D., Minkoff, H., & Jiang, X.
Affiliations
  • City University of New York (US)
  • SUNY Downstate Health Sciences University (US)
  • The Graduate Center, CUNY (US)
  • Maimonides Medical Center (US)
Corresponding author
Jiang, Xinyin
ORCID
Venue
Clinical Epigenetics
Publisher
Springer Science and Business Media LLC
Published
2023-08-26
Volume
15
Issue
1
Pages
137-137
ISSN
  • 1868-7075 (ISSN-L)
  • 1868-7083
DOI
10.1186/s13148-023-01554-1
PMC
PMC10464204
OpenAlex
W4386189443
Cited by
23
References
7
Citations by year
2026: 6 · 2025: 7 · 2024: 8 · 2023: 2
FWCI
4.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Epigenetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • SUNY Digital Repository Support (State University of New York System) (submittedVersion, cc-by)
Funders
  • City University of New York (Interdisciplinary Research Grant)
  • American Egg Board/Egg Nutrition Center
Topics
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
Keywords
gestational diabetes mellitus, one-carbon metabolism, maternal nutrient intake, choline, betaine, folic acid, vitamin B12, insulin-like growth factor II, corticotropin-releasing factor, cortisol, fetal growth, birth weight, placenta, umbilical cord blood, epigenetic programming, stress response
MeSH terms
Female, Fetus, Folic Acid, Humans, Insulin-Like Growth Factor II, Pregnancy, Promoter Regions, Genetic, Prospective Studies, Diabetes, Gestational, DNA Methylation

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