Prenatal Lead and Depression Exposures Jointly Influence Birth Outcomes and NR3C1 DNA Methylation

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.