Prenatal exposure to multiple metals and birth outcomes: An observational study within the National Children's Study cohort

Background: Prenatal exposure to metals may play an important role in fetal growth. However, the epidemiologic evidence for certain metals is sparse, and most of the existing research has focused on evaluating single metals in highly exposed target populations. Objectives: We evaluated associations of cadmium, lead, manganese, selenium, and total mercury exposures during pregnancy with fetal growth using data from mother-infant pairs participating in the National Children's Study. Methods: Prenatal metal exposures were measured using maternal blood collected from 6 to 32 weeks of gestation. Birth outcomes, including gestational age, birthweight, birth length, head circumference, and ponderal index, were ascertained through physical measurement at birth or abstraction from medical records. Regression coefficients and their 95% confidence intervals were estimated from multivariable linear regression models in the overall study population as well as among male and female infants. We further evaluated pairwise metal–metal interactions. Results: Sex-specific associations were observed for lead, with inverse associations for birthweight, birth length, head circumference, and gestational age observed only among female infants. Sex-specific associations were also observed for selenium, with a positive association for birthweight observed among male infants; selenium was also positively associated with ponderal index and inversely associated with birth length among female infants. Overall, total mercury was inversely associated with birthweight and ponderal index, and the association with birthweight was stronger among female infants. No significant associations were observed with cadmium and manganese. In the metal–metal interaction analyses, we found evidence of a synergistic interaction between lead and total mercury and antagonistic interaction between selenium and total mercury with selected birth outcomes. Conclusions: Our findings suggest that prenatal exposure to metals may be related to birth outcomes, and infant sex may modify these associations.