Studies of the association between prenatal exposure to metal elements and risk for neural tube defects (NTDs) have produced inconsistent results. Little research has examined the joint effects and interactions of multiple elements. This study examined 273 women with NTD-affected pregnancies and 477 controls. Cadmium, cobalt, chromium, copper, iron, mercury, manganese, molybdenum, lead, and zinc were quantified in maternal serum. Single and mixed effects of these elements on NTD risk were evaluated with Bayesian kernel machine regression, and the effects of individual elements were validated using logistic regression. As a result, NTD risk increased with the concentration of the mixture of the 10 elements. NTD risk rose as the levels of the five toxic elements increased, with effect sizes larger than the overall analyses, but they decreased, albeit non-significantly, as the levels of the five essential elements increased. Lead and manganese showed risk effects on NTDs, with odds ratios (ORs) of 1.94 (1.76-2.13) and 1.25 (1.14-1.38), respectively, with the remaining nine elements remaining at their median. Molybdenum showed a protective effect against NTDs with an OR 0.87 (0.90-0.94). The single-element results were validated using logistic regression. In conclusion, NTD risk increased with concentrations of the five toxic elements, with lead and manganese being the major contributors. Essential elements showed protective effects against NTD risk.
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