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Maternal methyl nutrients, obesity programming, and neonatal anthropometric outcomes

University of British Columbia

Maternal folate, riboflavin, betaine, choline, and vitamins B-6 and B-12 (B-12) concentrations, also known as methyl nutrients, have an interrelated role in fetal growth and DNA methylation. To date, the relationship between individual maternal methyl nutrient concentrations and neonatal anthropometric outcomes have shown conflicting results, while the interrelationship of maternal methyl nutrient concentrations and their association with DNA methylation levels of fetal growth and obesity-related genes in the offspring is unknown. The overall goal of my thesis was to provide novel evidence of the interrelationship of maternal methyl nutrients during early pregnancy i.e., <20 weeks of gestation and their association with neonatal anthropometric outcomes and fetal growth and obesity programming in Canadian mother-offspring dyads. To address this goal, firstly, the relationship between concentrations of betaine, a methyl donor nutrient, and total homocysteine (tHcy), an intermediate metabolite of methylation reactions, was tested in 723 pregnant women at early pregnancy. Betaine was inversely associated with tHcy (β=-0.21µmol/L; 95%CI -0.34, -0.07µmol/L). Furthermore, the relationship between maternal methyl nutrient patterns and neonatal anthropometric outcomes was explored. Methyl nutrient patterns were mainly characterized by maternal B-12 biomarkers and betaine. Only second-trimester B-12 pattern was inversely associated with head circumference (HC) (β=-0.13cm; 95%CI -0.24, -0.03cm) and HC z-score (β=-0.09; 95%CI -0.09, -0.01). Lastly, whether DNA methylation levels of CpG sites associated with IGF-2, HIF-3α, RXRA, LEP, LEP-R, DNMT-1, DNMT-3A, and DNMT-3B genes, measured in infants, differed by maternal red blood cell (RBC) folate concentration ≤1360 nmol/L and RBC folate >1360 nmol/L was tested, and whether these CpG sites were associated with maternal methyl nutrient patterns. Infant DNA methylation levels did not significantly differ by maternal folate concentration and were not significantly associated with maternal methyl nutrient patterns. In summary, these results indicated that betaine and total B-12 were the main drivers of maternal methyl nutrients patterns in these folate-replete populations. However, the lack of association between maternal methyl nutrient patterns with neonatal anthropometric outcomes and DNA methylation levels of fetal growth and obesity-related genes in infants suggests the need for a better understanding of the role of these nutrients in fetal programming and growth.

Text

2023-09-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/75762

Human Nutrition

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/