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Curr Dev Nutr. 2019 Jun 13;3(Suppl 1). pii: nzz048.P11-036-19. doi: 10.1093/cdn/nzz048.P11-036-19. eCollection 2019 Jun.

Effects of Maternal Vitamin D3 Supplementation on Offspring Epigenetic Gestational Age Acceleration at Birth: A Randomized Controlled Trial (P11-036-19).

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Augusta University.
Medical University of South Carolina.



We have previously found that vitamin D supplementation may slow down epigenetic aging in young adults. Recently, new epigenetic clocks have been developed to estimate gestational age in newborn babies. We tested the hypothesis that vitamin D supplementation would slow down the epigenetic gestational aging.


A total of 92 participants (51% whites, 21% blacks, 28% Hispanics) were randomly selected from 450 pregnant women who were enrolled in a randomized controlled trial. Each mother was randomized to receive either 4000 IU/day vitamin D3 or placebo plus the standard prenatal vitamins containing 400 IU vitamin D3. Cord blood genome-wide methylation analyses were performed on the Illumina Infinium MethylationEPIC Beadchip. DNA methylation gestational age (DNAmGA) was calculated based on two methods developed by Knight and Bohlin. The effects of vitamin D3 supplementation on DNA methylation-based gestational age acceleration (∆DNAmGA) were estimated in linear regressions adjusted for maternal age, race, smoking status and sex of the babies.


Gestational age was highly correlated with DNAmGAKnight and DNAmGABohlin having the same correlation coefficients of 0.88 (ps < 0.001). Both DNAmGAKnight and DNAmGABohlin clocks also performed well in black and Hispanic populations with correlation coefficients ranging from 0.80 to 0.98 (ps < 0.001). Vitamin D3 supplementation decreased ∆DNAmGA by both Knight's clock (β = -0.89, P = 0.047) and Bohlin's clock (β = -0.71, P = 0.005) only in the black participants.


Both Knight's and Bohlin's epigenetic gestational clocks were highly correlated with gestational age in this multiethnic cohort. Vitamin D3 supplementation decreased epigenetic gestational age acceleration at birth, but only in black babies. A follow-up study is warranted to evaluate the role of accelerated gestational aging in offspring growth and development.

Funding Sources:

W. K. Kellogg Foundation and the South Carolina Clinical & Translational Research (SCTR) Institute, at the Medical University of South Carolina, NIH/NCAT Grant UL1TR000062. YD and HZ are also supported by AHA 14GRANT20480211.

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