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

Zhen-Hua Li; Cheng-Yang Hu; Si-Wei Dai; Hui-Ya Ma; Si-Yu Zhang; Chen Sun; Jia-Hui Li; Kai Huang; Mao-Lin Chen; Guo-Peng Gao; Xiu-Jun Zhang

doi:10.1016/j.scitotenv.2024.178291

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

Sci Total Environ. 2024 Dec 28:959:178291. doi: 10.1016/j.scitotenv.2024.178291. Online ahead of print.

Authors

Zhen-Hua Li¹, Cheng-Yang Hu², Si-Wei Dai¹, Hui-Ya Ma³, Si-Yu Zhang¹, Chen Sun¹, Jia-Hui Li¹, Kai Huang⁴, Mao-Lin Chen⁵, Guo-Peng Gao⁶, Xiu-Jun Zhang⁷

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China.
² Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China; Department of Humanistic Medicine, School of Humanistic Medicine, Anhui Medical University, 81 Meishan Road, Hefei 230032, China.
³ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China; Management & Checkup Center, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei 230022, Anhui, China.
⁴ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China; Department of Hospital Infection Prevention and Control, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei 230601, China.
⁵ Department of Gynecology and Obstetrics, Ma'anshan Maternal and Child Health Hospital, Ma'anshan 243000, China.
⁶ Department of Child Health Care, Ma'anshan Maternal and Child Health Hospital, Ma'anshan 243000, China.
⁷ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China; MOE Key Laboratory of Population Health Across Life Cycle, 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address: zhangxiujun@ahmu.edu.cn.

PMID: 39733573
DOI: 10.1016/j.scitotenv.2024.178291

Abstract

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.

Keywords: Fetal growth; Metals; Mixture exposure; Trajectory.