Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.
Pompeu Fabra University, Barcelona, Spain.
JAMA Netw Open. 2024 May 1;7(5):e2412040. doi: 10.1001/jamanetworkopen.2024.12040.
Prenatal exposure to ubiquitous endocrine-disrupting chemicals (EDCs) may increase the risk of metabolic syndrome (MetS) in children, but few studies have studied chemical mixtures or explored underlying protein and metabolic signatures.
To investigate associations of prenatal exposure to EDC mixtures with MetS risk score in children and identify associated proteins and metabolites.
DESIGN, SETTING, AND PARTICIPANTS: This population-based, birth cohort study used data collected between April 1, 2003, and February 26, 2016, from the Human Early Life Exposome cohort based in France, Greece, Lithuania, Norway, Spain, and the UK. Eligible participants included mother-child pairs with measured prenatal EDC exposures and complete data on childhood MetS risk factors, proteins, and metabolites. Data were analyzed between October 2022 and July 2023.
Nine metals, 3 organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 5 perfluoroalkyl substances (PFAS), 10 phthalate metabolites, 3 phenols, 4 parabens, and 4 organophosphate pesticide metabolites measured in urine and blood samples collected during pregnancy.
At 6 to 11 years of age, a composite MetS risk score was constructed using z scores of waist circumference, systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and insulin levels. Childhood levels of 44 urinary metabolites, 177 serum metabolites, and 35 plasma proteins were quantified using targeted methods. Associations were assessed using bayesian weighted quantile sum regressions applied to mixtures for each chemical group.
The study included 1134 mothers (mean [SD] age at birth, 30.7 [4.9] years) and their children (mean [SD] age, 7.8 [1.5] years; 617 male children [54.4%] and 517 female children [45.6%]; mean [SD] MetS risk score, -0.1 [2.3]). MetS score increased per 1-quartile increase of the mixture for metals (β = 0.44; 95% credible interval [CrI], 0.30 to 0.59), organochlorine pesticides (β = 0.22; 95% CrI, 0.15 to 0.29), PBDEs (β = 0.17; 95% CrI, 0.06 to 0.27), and PFAS (β = 0.19; 95% CrI, 0.14 to 0.24). High-molecular weight phthalate mixtures (β = -0.07; 95% CrI, -0.10 to -0.04) and low-molecular weight phthalate mixtures (β = -0.13; 95% CrI, -0.18 to -0.08) were associated with a decreased MetS score. Most EDC mixtures were associated with elevated proinflammatory proteins, amino acids, and altered glycerophospholipids, which in turn were associated with increased MetS score.
This cohort study suggests that prenatal exposure to EDC mixtures may be associated with adverse metabolic health in children. Given the pervasive nature of EDCs and the increase in MetS, these findings hold substantial public health implications.
产前暴露于普遍存在的内分泌干扰化学物质（EDCs）可能会增加儿童患代谢综合征（MetS）的风险，但很少有研究研究化学混合物或探索潜在的蛋白质和代谢特征。
研究产前暴露于 EDC 混合物与儿童代谢综合征风险评分的相关性，并确定相关的蛋白质和代谢物。
设计、地点和参与者：这是一项基于人群的出生队列研究，使用了 2003 年 4 月 1 日至 2016 年 2 月 26 日期间在法国、希腊、立陶宛、挪威、西班牙和英国的人类早期生活暴露组队列中收集的数据。合格的参与者包括母婴对子，他们的产前 EDC 暴露量可测量，且有完整的儿童代谢综合征危险因素、蛋白质和代谢物数据。数据分析于 2022 年 10 月至 2023 年 7 月进行。
尿液和血液样本中测量了 9 种金属、3 种有机氯农药、5 种多氯联苯、2 种多溴二苯醚（PBDEs）、5 种全氟烷基物质（PFAS）、10 种邻苯二甲酸代谢物、3 种酚类、4 种对羟基苯甲酸酯和 4 种有机磷酸酯农药代谢物。
在 6 至 11 岁时，使用腰围、收缩压和舒张压、甘油三酯、高密度脂蛋白胆固醇和胰岛素水平的 z 分数构建了一个复合代谢综合征风险评分。使用靶向方法定量测定了 44 种尿代谢物、177 种血清代谢物和 35 种血浆蛋白的水平。使用贝叶斯加权分位数总和回归评估了每个化学物质组混合物的相关性。
该研究包括 1134 位母亲（出生时的平均[标准差]年龄，30.7[4.9]岁）及其子女（平均[标准差]年龄，7.8[1.5]岁；617 名男性儿童[54.4%]和 517 名女性儿童[45.6%]；平均[标准差]代谢综合征评分，-0.1[2.3]）。每增加一个四分位数，金属（β=0.44；95%可信区间[CrI]，0.30 至 0.59）、有机氯农药（β=0.22；95%CrI，0.15 至 0.29）、PBDEs（β=0.17；95%CrI，0.06 至 0.27）和 PFAS（β=0.19；95%CrI，0.14 至 0.24）混合物的代谢综合征评分均增加。高分子量邻苯二甲酸酯混合物（β=-0.07；95%CrI，-0.10 至 -0.04）和低分子量邻苯二甲酸酯混合物（β=-0.13；95%CrI，-0.18 至 -0.08）与代谢综合征评分降低相关。大多数 EDC 混合物与促炎蛋白、氨基酸和甘油磷脂的升高有关，而这些又与代谢综合征评分的升高有关。
这项队列研究表明，产前暴露于 EDC 混合物可能与儿童不良代谢健康有关。鉴于 EDC 的普遍存在和代谢综合征的增加，这些发现具有重要的公共卫生意义。
