Sex-specific associations between maternal exposure to metal mixtures and fetal growth trajectories: A prospective birth cohort study.

BACKGROUND

The associations of prenatal metals exposure with birth outcomes have been widely assessed. However, evidence on the associations between metal mixtures and fetal intrauterine growth trajectories is scarce.

OBJECTIVES

This study aimed to explore the associations of metal mixtures with fetal intrauterine growth trajectories overall and by sex.

METHODS

We analyzed data from the Ma'anshan birth cohort, which included a total of 1041 pregnant woman. The concentrations of 12 metals in maternal blood were measured during early pregnancy, and fetal intrauterine growth indicators were standardized and assessed at 16, 23, 30, 34, and 38 weeks of gestation. We used generalized linear regression and linear mixed models to identify the key fetal growth indicator (biparietal diameter (BPD)), and applied GBTM to characterize BPD SD-scores trajectories. To further assess the individual and combined effects of metals, we conducted multivariable logistic regression and repeated holdouts weighted quantile sum (WQS) regression analyses, respectively. Finally, we performed a sex-stratified analysis to explore sex-specific associations.

RESULTS

The sex-stratified multivariable logistic regression analysis indicated that in male fetal, cobalt (Co) (OR: 0.60, 95 % CI: 0.38, 0.92) was negatively associated with the high-growth BPD-SD scores trajectory. In contrast, Co (OR: 2.39, 95 % CI: 1.40, 4.45) showed a positive association in female fetal. Results from the WQS showed that early pregnancy metal mixture exposure was associated with BPD-SD scores at 16, 34, and 38 weeks in female fetal. The results highlighted Zn and Co as key metals associated with high-growth BPD SD-scores trajectory. We also identified a significant interaction between early pregnancy metal mixtures and sex on high-growth BPD SD-scores trajectories. The WQS*sex interaction term had a mean odds ratio of 1.271 (95 % CI: 1.027, 1.619).

CONCLUSION

This study suggests that exposure to prenatal metal mixtures affects fetal intrauterine growth trajectories with sexual dimorphism.