Prenatal metal mixtures and child blood pressure in the Rhea mother-child cohort in Greece.

BACKGROUND: Child blood pressure (BP) is predictive of future cardiovascular risk. Prenatal exposure to metals has been associated with higher BP in childhood, but most studies have evaluated elements individually and measured BP at a single time point. We investigated impacts of prenatal metal mixture exposures on longitudinal changes in BP during childhood and elevated BP at 11 years of age. METHODS: The current study included 176 mother-child pairs from the Rhea Study in Heraklion, Greece and focused on eight elements (antimony, arsenic, cadmium, cobalt, lead, magnesium, molybdenum, selenium) measured in maternal urine samples collected during pregnancy (median gestational age at collection: 12 weeks). BP was measured at approximately 4, 6, and 11 years of age. Covariate-adjusted Bayesian Varying Coefficient Kernel Machine Regression and Bayesian Kernel Machine Regression (BKMR) were used to evaluate metal mixture impacts on baseline and longitudinal changes in BP (from ages 4 to 11) and the development of elevated BP at age 11, respectively. BKMR results were compared using static versus percentile-based cutoffs to define elevated BP. RESULTS: Molybdenum and lead were the mixture components most consistently associated with BP. J-shaped relationships were observed between molybdenum and both systolic and diastolic BP at age 4. Similar associations were identified for both molybdenum and lead in relation to elevated BP at age 11. For molybdenum concentrations above the inflection points (~ 40-80 µg/L), positive associations with BP at age 4 were stronger at high levels of lead. Lead was positively associated with BP measures at age 4, but only at high levels of molybdenum. Potential interactions between molybdenum and lead were also identified for BP at age 11, but were sensitive to the cutoffs used to define elevated BP. CONCLUSIONS: Prenatal exposure to high levels of molybdenum and lead, particularly in combination, may contribute to higher BP at age 4. These early effects appear to persist throughout childhood, contributing to elevated BP in adolescence. Future studies are needed to identify the major sources of molybdenum and lead in this population.