The link between prenatal exposure to a chemical mixture, cord blood hormones, and birth weight: an epidemiologic study

Prenatal chemical exposure has frequently been associated with fetal growth, although the underlying molecular mechanisms remain unclear. This study aims to explore the potential mediating role of hormones in the association between prenatal chemical mixture exposure and birth weight. We used data of 432 newborns from two Flemish birth cohorts. The common set of available and detectable exposure biomarkers and hormones analyzed in cord plasma are: 6 metals/trace elements, 3 polychlorinated biphenyl (PCB) congeners, hexachlorobenzene, dichlorodiphenyldichloroethylene and 2 perfluoroalkyl substances; and 3 thyroid, 3 reproductive and 2 metabolic hormones. Mixtures analyses were performed to assess each of the bilateral associations in the path exposures-hormones-birth weight, including mediation analysis. Combining all exposures, we found an inverse association between PCB 180 and birth weight. PCB 180 was positively associated with sex hormone-binding globulin (SHBG) and negatively associated with leptin and insulin. Similarly, thallium was positively associated with testosterone, estradiol, and SHBG, and negatively with insulin. Lead was positively associated with insulin. Higher free thyroxine (FT4), insulin, and leptin were associated with higher birth weight, whereas higher SHBG was associated with lower birth weight. Mediation analysis for PCB 180 indicated that 94% of the effect of this exposure on birth weight is mediated by FT4, SHBG, leptin, and insulin. Assessing the health risk of chemical mixture exposure reflects better real-world situations, thereby allowing more effective risk assessment. Our results suggest that hormonal markers are on the causal path in the association between environmental exposure and birth weight, adding interesting insights for mechanistic research.