Joint associations among prenatal metal mixtures and nutritional factors on birth weight z-score: Evidence from an urban U.S. population

The benefits of nutritional factors on birth outcomes have been recognized, however, limited studies have examined the role of nutritional factors in mitigating the detrimental effects of metals exposure during gestation. We used data collected from 526 mother-infant dyads enrolled in the Programming of Intergenerational Stress Mechanisms longitudinal pregnancy cohort to examine the joint effects of prenatal exposure to metals and maternal nutrition on birth weight for gestational age (BWGA) z-scores. We measured concentrations of twelve metals and trace elements in urine samples collected during pregnancy. Maternal nutritional intake was measured using the Block98 Food Frequency Questionnaire and converted into energy-adjusted consumption of individual nutrients. Using multivariable linear regression and Bayesian Kernel Machine Regression, we found that three metals [cobalt (Co), nickel (Ni), and lead (Pb)] and five metals [barium (Ba), caesium (Cs), copper (Cu), Ni, and zinc (Zn)] were associated with BWGA z-score in male and female infants, respectively. When examining the sex-specific interactions between these metals and nutrient groups [macro nutrients, minerals, A vitamins, B vitamins, anti-oxidant, methyl-donor nutrients, and inflammatory (pro- and anti-)] using a Cross-validated Kernel Ensemble model, we identified significant interactions between the macro nutrients and Co (p = 0.05), minerals and Pb (p = 0.04), and A vitamins and Ni (p = 0.001) in males. No significant interactions were found in females. Furthermore, three minerals (phosphorus, iron, potassium) and vitamin A were found to be more crucial than other nutrients in modifying the association between each respective metal and BWGA z-score in males. A better understanding of the sex-specific interactions between nutrients and metals on birth weight can guide pregnant women to protect their neonates from the adverse health impacts of metal exposures by optimizing nutrient intakes accordingly.