出生队列研究揭示：胎盘金属负荷影响子代认知发育

Prenatal metals and offspring cognitive development: Insights from a large-scale placental bioassay study

产前金属暴露与子代认知发育：大规模胎盘生物检测研究的见解

Authors: Jixing Zhou, Juan Tong, Chunmei Liang, Penggui Wu, Jiajun Ouyang, Wenjin Cai, Lu Cheng, Yuzhu Teng, Jie Sheng, Guopeng Gao, Shuangqin Yan, Fangbiao Tao, Shilu Tong, Kun Huang

Source: Environmental Research

DOI: 10.1016/j.envres.2024.120684.

Abstract

The developing foetus is particularly sensitive to neurotoxic metals. The placenta is considered an ideal tissue for biomonitoring prenatal cumulative metal exposure. Based on the Ma’anshan Birth Cohort study (MABC) in China, this study investigated associations of non-essential metals and essential metals in placenta, including arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), cobalt (Co), selenium (Se) and zinc (Zn), with cognitive development in children among 1586 mother-child pairs. Also, we explored potential interactions between the metals and modifying role of the sex. Children’s cognitive development was tested at preschool age using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Analyses used multiple linear regression, Bayesian kernel machine regression (BKMR), the quantile g-computation (Qgcomp), interaction and marginal effects models, and restricted cubic spline in R and STATA. In this study, the geometric means [GMs (SD)] for placental metal concentrations were 8.10 (7.54) ng/g for As, 32.32 (29.20) ng/g for Cd, 11.89 (13.33) ng/g for Hg, 32.21 (28.24) ng/g for Pb, 15.05 (8.91) ng/g for Co, 508.82 (192.35) ng/g for Se, 18481.60 (14030.61) ng/g for Zn. In individual models, placental As levels were negatively associated with the Fluent Reasoning Index (FRI) in the overall sample. Cd levels were negatively associated with the full-scale intelligence quotient (FSIQ), the Verbal Comprehension Index (VCI) and the Visual Spatial Index (VSI). The four metal mixture (As, Cd, Hg and Pb) was negatively associated with FSIQ, VCI, VSI and FRI. Placental Cd and As were the largest contributors to the negative mixture association on the FSIQ. The negative associations of placental As, Cd and Hg with FSIQ in children were gradually attenuated with increasing Zn and Se. After stratifying by sex, the individual and mixture associations between elevated placental non-essential metal exposures and reduced cognitive scores were significant only in boys. Zn and Se were the major contributors to the positive mixture associations on the FSIQ. In summary, prenatal exposure to As, Cd and Hg has sex-specific adverse associations on children’s cognitive development. A more accurate assessment of the necessity of prenatal supplementation of micronutrients including Zn and Se is needed.

Keywords: Placenta; Metal; Cognition; Cohort.

摘要

发育中的胎儿对神经毒性金属特别敏感。胎盘被认为是产前累积金属暴露生物监测的理想组织。本研究以马鞍山优生优育队列研究（the Ma’anshan Birth Cohort study，MABC）为基础，在1 586母子对中调查了胎盘中的非必需金属和必需金属，包括砷（As）、镉（Cd）、汞（Hg）、铅（Pb）、钴（Co）、硒（Se）和锌（Zn）与儿童认知发展的关系。此外，我们还探讨了金属之间的潜在相互作用以及性别的调节作用。本研究采用韦氏幼儿智力量表第四版（WPPSI-IV）中文版评估学龄前儿童认知发育。分析使用了 R 和 STATA 中的多元线性回归、贝叶斯核机器回归（Bayesian kernel machine regression，BKMR）、基于分位数的g计算（the quantile g-computation，Qgcomp）、交互作用和边际效应模型以及限制性三次样条（restricted cubic spline，RCS）。本研究中，胎盘金属水平的几何平均数[GMs (SD)] 分别为：As 8.10 (7.54) ng/g、Cd 32.32 (29.20) ng/g、Hg 11.89 (13.33) ng/g、Pb 32.21 (28.24) ng/g、Co 15.05 (8.91) ng/g、Se 508.82 (192.35) ng/g、Zn 18481.60 (14030.61) ng/g。研究发现胎盘As水平与总体样本的流体推理指数（the Fluent Reasoning Index，FRI）呈负相关。Cd水平与总智商（the full-scale intelligence quotient，FSIQ）、言语理解指数（the Verbal Comprehension Index，VCI）和视觉空间指数（the Visual Spatial Index，VSI）呈负相关。四种金属混合物（As、Cd、Hg和Pb）与FSIQ、VCI、VSI和FRI呈负相关。胎盘Cd和As是造成 FSIQ 负相关的最大因素。胎盘As、Cd和Hg水平与儿童 FSIQ 的负向关联随着胎盘Zn和Se水平的增加而逐渐减弱。按性别分层后，胎盘非必需金属暴露量升高与儿童认知分数降低之间的单一和混合物关联仅在男童中显著。Zn和Se是造成 FSIQ 混合正相关的主要因素。总之，产前接触As、Cd和Hg对儿童的认知发展有性别特异性的不利影响。需要对产前补充包括Zn和Se在内的微量营养素的必要性进行更准确的评估。

关键词：胎盘；金属；认知；队列。