The Association between Prenatal Selenium-Related DNA Methylation Modifications in Placenta and Newborn Neurobehavioral Development: An Epigenome-Wide Study of Two U.S. Birth Cohorts

Abstract

Background/Aim: As a micronutrient, selenium (Se) levels in pregnancy have been linked with the neurobehavioral development of the offspring. DNA methylation is a potential mediator of the effect of Se on neurobehavioral development; however, very few studies have investigated the role of DNA methylation in relation to prenatal Se and child neurobehavior. We aimed to investigate the associations between placental Se and epigenome-wide DNA methylation in two U.S. cohorts and to assess the association between Se-related DNA methylation modifications and children’s neurobehavioral development.Methods: We measured placental Se concentration of 343 newborns enrolled in the New Hampshire Birth Cohort Study and of 141 infants in the Rhode Island Child Health Study. Genome-wide placental DNA methylation was measured by HumanMethylation450 Bead Chip, and the newborn neurobehavioral development was assessed by the NICU Network Neurobehavioral Scales. We meta-analyzed the associations between placental Se concentration and DNA methylation in each cohort, adjusting for confounders (P < 1× 10-5). We also fit multiple linear regression to assess the associations between DNA methylation and newborn neurobehavioral development.Results: We identified 25 Se-related differentially methylated CpG sites. 18 of the 25 CpG sites were positively associated with placental Se concentration. Among the 18 CpG sites, increased DNA methylation of cg19730691 (OR [95% Confidence Interval, CI] = 0.92 [0.86, 1.00], P = 0.05) and cg09674502 (OR [95%CI] = 0.89 [0.81 0.99], P = 0.03) were also associated with lower risk of high-level hypertonic responses of infants. The nearest genes to the cg19730691 and cg09674502 are TBX15 and GFI1.Conclusions: The Se-related increase of TBXI5 and GFI1 DNA methylation were associated with beneficial motor development in infants. Future work will assess the relationship of the identified CpG sites methylation levels with childhood motor development.