孕前女性邻苯二甲酸酯暴露水平与生育力关联的巢式病例对照研究

Association between phthalate exposures and fecundity in preconception women:a nested case-control study

目的:探究孕前女性7种典型的邻苯二甲酸酯代谢物暴露水平与生育力的关联。方法:基于孕前队列,开展巢式病例对照研究,选取2016年至2020年在上海市嘉定区妇幼保健院招募计划备孕的孕前夫妇,其中100例妊娠等待时间(time to pregnancy,TTP)>12个月即不孕症作为病例组,随机抽取TTP≤12个月的151名女性作为对照组,比较两组邻苯二甲酸酯各类代谢物的分布特征,使用多因素二分类logistic回归模型和加权组合分位数回归模型分别评估典型的邻苯二甲酸酯7种代谢物对生育力的单独和联合影响。结果:病例组和对照组在孕前邻苯二甲酸单(2-乙基己基)酯(mono-(2-ethylhexyl)phthalate,MEHP)、邻苯二甲酸单(2-羧甲基)己基酯(mono-(2-carboxmethyl)-hexyl phthalate,MCMHP)、∑DEHP[为MEHP、MCMHP、邻苯二甲酸单(2-乙基-5-氧己基)酯、邻苯二甲酸单(2-乙基-5-羟基己基)酯和邻苯二甲酸单(2-乙基-5-羧基戊基)酯检出浓度的和]、∑PAE(7种邻苯代谢物检出浓度的和)暴露水平方面差异均有统计学意义(P=0.005,P<0.001,P=0.001,P=0.007)。多因素二分类logistic回归模型显示与处于最低四分位数水平的女性相比,MEHP、MCMHP、∑DEHP、∑PAE处于最高四分位数水平的女性不孕的风险增加(a OR=2.40,95%CI:1.12~5.15,P=0.025;a OR=7.74,95%CI:3.14~19.08,P<0.001;a OR=4.35,95%CI:1.93~9.79,P<0.001;a OR=2.04,95%CI:0.96~4.34,P=0.044)。加权组合分位数回归模型确定孕前7种邻苯二甲酸酯代谢物复合暴露是不孕的危险因素(P<0.05),其中MCMHP贡献权重较大(为61.7%)。结论:育龄女性在备孕时应当重视环境中邻苯二甲酸酯的接触,减少食用高度加工的食物以及使用塑料/聚氯乙烯材料包装的食品,以提高人群生育力。

Objective To investigate the association between exposures of seven classic phthalate metabolites and fertility among preconception women before pregnancy.MethodsBased on the preconception cohort,a nested case-control study was carried out.Preconception couples who were recruited from Shanghai Jiading District Maternal and Child Health Hospital from 2016 to 2020 with intention to conception were selected.A total of 100 women whose time to pregnancy(TTP)>12 months were selected as the case group,and 151 women with the TTP≤12 months were randomly selected as control group.The single and joint effects on fertility of phthalate metabolites were analyzed by the comparison between the two groups via the multivariate binary logistic regression model,and the weighted quantile sum regression model.ResultsThere were significant differences in mono-(2-ethylhexyl)phthalate(MEHP),mono-(2-carboxmethyl)-hexyl phthalate(MCMHP),the sum of the detected concentrations of MEHP,MCMHP,mono-(2-ethyl-5-oxohexyl)phthalate,mono-(2-ethyl-5-hydroxyhexyl)phthalate and mono-(2-ethyl-5-carboxypentyl)phthalate(∑DEHP),and the sum of the detected concentrations of the seven phthalate metabolites(∑PAE)exposure levels between the case group and control group(P=0.005,P<0.001,P=0.001,P=0.007).As shown by the multivariate binary logistic regression model,women with MEHP,MCMHP,∑DEHP,∑PAE at the highest quartile level were found to have significantly increased risk of infertility compared with women at the lowest quartile level(aOR=2.40,95%CI:1.12-5.15,P=0.025;aOR=7.74,95%CI:3.14-19.08,P<0.001;aOR=4.35,95%CI:1.93-9.79,P<0.001;aOR=2.04,95%CI:0.96-4.34,P=0.044).The weighted quantile sum regression model demonstrated that the exposure to seven phthalate metabolite mixtures in preconception was associated with an increased risk of infertility(P<0.05).Among the seven phthalate metabolites,MCMHP had the largest contribution weight(61.7%).ConclusionWomen of childbearing age should avoid the exposure to phthalates in the environment when preparing for conception,such as to reduce the consumption of highly processed foods and foods packaged with plastic/polyvinyl chloride materials to promote fertility.