Free Cortisol Mediates Associations of Maternal Urinary Heavy Metals with Neonatal Anthropometric Measures: A Cross-Sectional Study

Prenatal exposure to heavy metals is known to be associated with adverse birth outcomes and oxidative stress biomarkers. In this study, we examined whether maternal free cortisol or 8-Hydroxy-2-Deoxyguanosine (8-OHdG) could mediate associations between maternal heavy metal exposure and birth outcomes. A total of 182 healthy pregnant women were recruited. Heavy metals (including Pb, Hg, and Cd), free-cortisol, and 8-OHdG were analyzed in urine at delivery. Birth outcomes including birth weight, length, Ponderal index, and head circumference were measured. To examine associations of maternal urinary heavy metals with biomarkers and birth outcomes, generalized linear models were employed. Birth length was positively associated with Pb (beta = 0.78, 95% CI: 0.09-1.46) and Hg (beta = 0.84, 95% CI: 0.23-1.45) (both p < 0.05). The Ponderal index, a measure of a newborn's leanness, was negatively associated with maternal urinary Pb (beta = -0.23, 95% CI: -0.46--0.07) and Hg (beta = -0.26, 95% CI: -0.44--0.08) (both p < 0.05). No association between maternal Cd and birth outcomes was observed. Most heavy metals showed positive associations with free cortisol and 8-OHdG. Free cortisol was identified as a mediator underlying the observed relationship between Hg and birth length or Ponderal index. This study observed adverse birth outcomes from maternal exposures to Pb and Hg. Increased free cortisol related to Hg exposure was suggested as a possible causal pathway from Hg exposure to birth outcomes such as the Ponderal index.