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 during the first trimester. Birth outcomes, including gestational age, birthweight, birth length, head circumference, and ponderal index, were ascertained through physical measurement at birth and abstraction from medical records. Beta 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 among metals identified as significant in the single-metal analyses. Results: Sex-specific associations were observed for lead; a positive association with gestational age was observed among male infants, while inverse associations with birth weight, birth length, head circumference, and gestational age were observed among female infants. Sex-specific associations were also observed for selenium; a positive association with ponderal index and an inverse association with birth length were observed among female infants. Overall, total mercury was inversely associated with birthweight and ponderal index. 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 with birthweight among female infants. Conclusions: Our findings suggest that prenatal exposure to metals may be related to birth outcomes, and infant sex may modify these associations.