Maternal Biomarkers of Nutritional Status Prior to Pregnancy and Newborn Epigenetic Aging

Abstract Objectives Maternal diet prior to and during pregnancy has been related to child health across the lifespan; however, mechanisms remain unclear. Gestational age acceleration (GAA), a measure of epigenetic aging relative to clinically estimated gestational age (GA), has emerged as a potential biomarker predictive of childhood BMI and atopic diseases. Few studies have evaluated the associations of maternal nutrient biomarkers, including methyl donors and fatty acids (FA), with GAA. Methods We evaluated associations among 391 mother-child dyads in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. Women were randomized to low-dose aspirin (LDA) or placebo, both containing 400 μg folic acid, prior to and through 36 weeks pregnancy. Maternal folate, homocysteine, vitamin B-12, vitamin D, carotenoids, tocopherols, and plasma FAs were quantified from blood samples obtained ≤6 months prior to conception and at 8 weeks gestation. DNA methylation was measured with the Infinium MethylationEPIC BeadChip using cord blood DNA. Epigenetic GA was calculated using the Knight and Bohlin clocks. GAA was defined as the residual from a model regressing GA on epigenetic GA. We assessed associations between nutritional biomarkers and GAA using robust linear regression, controlling for maternal age, race, education, employment status, total cholesterol, and child sex. A false discovery rate (FDR) correction was applied to account for multiple comparisons using the Benjamini-Hochberg method. Results Mean (SD, range) clinically estimated GA at delivery was 38.9 (1.5, 31.1–44.9) weeks and was positively correlated with epigenetic age (Knight clock r = 0.51, Bohlin clock r = 0.76). Being female was positively related to GAAKnight. Maternal age was positively associated with GAABohlin. In multivariable regression models, preconception folate was inversely related to GAABohlin (β = −0.004, 95% CI: −0.007–0.000, P = 0.04); however, this was not significant after adjustment for multiple comparisons (FDR P = 0.82). Other nutritional biomarkers and LDA were not related to GAA. Conclusions Maternal nutritional biomarkers prior to conception and during early pregnancy were not related to newborn epigenetic age acceleration in predominantly term deliveries among women supplemented with folic acid. Funding Sources Supported by the Intramural Research Program of the NICHD.