Preconception and Early-Pregnancy Serum Metal(loid) Concentrations in Relation to Gestational Glucose Regulation: A Prospective Cohort Study.

Although metal(loid) exposure during pregnancy has been increasingly studied, evidence remains limited on whether serum metal(loid) concentrations measured before conception are related to glucose regulation during pregnancy. In this prospective cohort study, serum concentrations of multiple metal(loid)s were measured during the preconception period and early pregnancy. Gestational diabetes mellitus (GDM) was diagnosed using a 75-g oral glucose tolerance test at 24-28 gestational weeks, and fasting, 1-h, and 2-h plasma glucose (PG) levels were assessed as continuous outcomes. Generalized linear regression, restricted cubic spline analysis, Bayesian kernel machine regression, and a multiple informant model were used to characterize individual, nonlinear, joint, and period-specific associations. During the preconception period, higher nickel (Ni) and lead (Pb) concentrations were associated with higher 2-h PG, whereas strontium (Sr) was inversely associated with fasting PG. During early pregnancy, cadmium (Cd) and titanium (Ti) were positively associated with 1-h PG, whereas Sr was inversely associated with 2-h PG. BKMR analyses were broadly consistent with several element-specific associations identified in the single-metal analyses. The multiple informant model also indicated that associations differed between the preconception and early-pregnancy measurement periods for some metal(loid)s. Overall, serum metal(loid) concentrations measured during the preconception and early-pregnancy periods showed period- and element-specific patterns of association with gestational glucose measures, supporting the need to consider preconception exposure in future studies.