Placental transfer efficiency of metals and its association with cognitive development in offspring: Roles of placental inflammatory cytokines and oxidative stress markers.

Prenatal heavy metal exposure has developmental neurotoxicity. However, current understanding of the association between placental transfer efficiency (PTE) of metals and offspring cognitive development remains limited. Based on 1418 mother-child pairs in Ma'anshan Birth Cohort Study, we investigated the association between the PTE of fourteen metals and offspring cognitive development, and examined the mediating and modulating roles of placental inflammation and oxidative stress factors. Results showed that both individual and mixed exposure to PTEs of metals were negatively associated with children's full-scale intelligence quotient (FSIQ). Cu (copper), Hg (mercury), and V (vanadium) were the largest three negative contributors. After stratifying by placental metal levels, negative associations between the PTEs of Hg and Molybdenum (Mo) with FSIQ were only observed in children with placental Hg and Mo levels above the median. Further mediation analyses showed that approximately 7.8-17.5 % of the effects of high PTEs to Cu, Hg, V, and Mo on the decrease in FSIQ were mediated by the placental inflammatory cytokines [interleukin (IL)-8, IL-6] and oxidative stress factor [hypoxia inducible factor-1alpha (HIF-1α)]. the marginal effect of the negative associations of the PTE of Cu and PTE of Mo with FSIQ decreased with decreasing placental inflammatory cytokines [IL-8, IL-6, tumor necrosis factor-α (TNF-α), IL-4]. These findings indicated that the high transfer property of metals at the maternal - fetal interface can trigger placental inflammation and oxidative stress, and thus the long-term effects on cognitive development in children.