Abstract
Many gestational exposures influence birth outcomes, yet the joint contribution of toxicant and psychosocial factors is understudied. Moreover, associated gestational epigenetic mechanisms are unknown. Lead (Pb) and depression independently influence birth outcomes and offspring NR3C1 (glucocorticoid receptor) DNA methylation. We hypothesized that gestational Pb and depression would jointly influence birth outcomes and NR3C1 methylation. Pregnancy exposure information, DNA methylation, and birth outcome data were collected prospectively from n = 272 mother–infant pairs. Factor analysis was used to reduce the dimensionality of NR3C1. Multivariable linear regressions tested for interaction effects between gestational Pb and depression exposures with birth outcomes and NR3C1. Interaction effects indicated that higher levels of Pb and depression jointly contributed to earlier gestations, smaller infant size at birth, and asymmetric fetal growth. Pb and depression were also jointly associated with the two primary factor scores explaining the most variability in NR3C1 methylation; NR3C1 scores were associated with some infant outcomes, including gestational age and asymmetric fetal growth. Pb and depression can cumulatively influence birth outcomes and epigenetic mechanisms, which may lay the foundation for later health risk. As toxicants and social adversities commonly co-occur, research should consider the life course consequences of these interconnected exposures.
Highlights
We found that depression during pregnancy and prenatal Pb exposure synergistically contributed to earlier gestational age and smaller infant body size at birth
Prenatal depression and Pb exposures jointly contributed to some gestational NR3C1 methylation signatures; NR3C1 methylation signatures were in turn associated with infant outcomes
We found support for our hypothesis that maternal depression in conjunction with prenatal Pb exposure would lead to worse birth outcomes than either exposure independently
Summary
Several studies have shown maternal depression during pregnancy to be prospectively associated with gestational NR3C1 methylation [30,31,32], with a recent meta-analysis (n = 977 individuals) suggesting a small positive association between prenatal psychosocial adversity and NR3C1 methylation [35] Despite these parallel sets of studies, researchers have not considered gestational Pb and depression exposures as jointly modulating NR3C1 methylation. We examined the joint contribution of Pb and depression occurring during gestation in relation to birth outcomes, and considered NR3C1 methylation as a potential shared biological mechanism that may help explain how these environmental and psychosocial factors influence infant health. We test these hypotheses using data from a prospective birth cohort study while controlling for a range of maternal and infant factors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
