Associations between early pregnancy essential metals and birth outcomes: Exploration of effect modification by...

Inconsistent evidence exists on the association between maternal essential metals exposure and birth outcomes. We aim to investigate these associations and explore potential effect modification by maternal thyroid hormones (THs). We collected data from the Ma'anshan birth cohort, including 953 mother-infant pairs. Metals and THs were measured in early pregnancy. Multiple regression and restricted cubic spline (RCS) models were used to evaluate associations between individual metals and outcomes. Bayesian Kernel Machine Regression (BKMR) was applied to assess mixture effects. Stratified analyses with interaction tests were performed to evaluate effect modification by THs. Multiple regression models showed that higher manganese (Mn) and zinc (Zn) concentrations were associated with higher birth weight z-score (BWZ) (Mn: β = 0.44, 95% CI: 0.17, 0.72; Zn: β = 0.38, 95% CI: 0.09, 0.68) and increased large for gestational age (LGA) risk (Mn: OR = 2.82, 95% CI: 1.28, 6.21; Zn: OR = 2.50, 95% CI: 1.08, 5.80). Copper (Cu) was inversely associated with small for gestational age (SGA) risk (OR = 0.27, 95% CI: 0.08, 0.97). RCS analyses revealed significant non-linear associations with LGA for both Se and Zn, with a more clearly inverted U-shaped pattern for Se. BKMR showed a monotonic increasing association of the metal mixture with both BWZ and LGA, with the trend significant at lower-to-moderate concentrations. Mn was the primary contributor for both outcomes, whereas no significant associations were observed for SGA. Interaction and stratified analyses showed that Cu was positively associated with BWZ and LGA in the overall population, with stronger effects in the high FT4 subgroup (BWZ: β = 0.35, 95% CI: 0.05, 0.80; LGA: OR = 2.14, 95% CI: 1.01, 8.20), whereas no associations were found in the low FT4 subgroup, indicating a potential modifying role of FT4. Other stratified findings lacked interaction evidence and were considered exploratory.