Sequential Mediation by Maternal Weight Gain and Late Blood Metal Concentration in the Association Between Heavy Metal Exposure in Early Pregnancy and Fetal Growth.

BACKGROUND: To assess the mediation effect of gestational weight gain (GWG) and blood heavy metal levels in the late pregnancy affecting the association between early pregnancy metal exposure and fetal growth. METHODS: We analyzed data from Korean Children's Environmental Health Study cohort comprising 4,712 full-term births. Blood levels of lead (Pb), mercury (Hg), and cadmium (Cd) during pregnancy, and newborn birthweights were retrieved. We applied single-exposure model to assess the association between heavy metal levels and newborn anthropometric measures and conducted path analyses to examine the direct and indirect effects of heavy metal levels in early pregnancy on newborn measures. RESULTS: Exposure to Pb (β = -15.470, P = 0.036) and Cd (β = -24.150, P = 0.004) during late pregnancy were associated with lower birthweight. Early exposure to Pb was not directly associated with lower birthweight, however, mediation of late exposure to Pb (β = -7.417, P = 0.049) resulted in lower birthweight (β = -14.787, P = 0.036). Early exposure to Hg was associated with higher birthweight, however, indirect paths via GWG (β = 3.626, P = 0.048) and late Hg levels (β = -12.929, P = 0.111) countered each other, resulting in the nullification of the total effect (β = -8.519, P = 0.301). CONCLUSION: The effect of Pb exposure in early pregnancy on birthweight was mediated by GWG and Pb exposures during late pregnancy. When assessing the impact of heavy metal exposure on birthweight, it is important to note that GWG and late heavy metal levels act as mediators, rather than confounders.