孕期邻苯二甲酸酯复合暴露与双胞胎出生体重差异的关联研究

Association of mixed-exposure to phthalates during pregnancy with birth weight difference between twins

目的探讨孕期邻苯二甲酸酯(phthalates,PAEs)复合暴露与双胞胎出生体重差异的关联。方法采用前瞻性队列研究设计,在2013年1月至2016年12月,招募了来自武汉双胞胎出生队列(The Wuhan Twin Birth Cohort,WTBC)的289名双胞胎妊娠孕妇,使用高效液相色谱串联质谱检测孕妇孕早期、中期和晚期尿液中8种PAEs代谢物浓度,包括邻苯二甲酸单乙酯(monoethyl phthalate,MEP)、邻苯二甲酸单异丁酯(monoisobutyl phthalate,MiBP)、邻苯二甲酸单丁酯(monobutyl phthalate,MBP)、邻苯二甲酸单苄基酯(monobenzyl phthalate,MBzP)、邻苯二甲酸单(2-乙基己基)酯[mono(2-ethylhexyl)phthalate,MEHP]、邻苯二甲酸单(2-乙基-5-氧己基)酯[mono(2-ethyl-5-oxohexyl)phthalate,MEOHP]、邻苯二甲酸单(2-乙基-5-羧基戊基)酯[mono(2-ethyl-5-hydroxyhexyl)phthalate,MEHHP]、邻苯二甲酸单(2-乙基-5-羧基戊基)酯[mono(2-ethyl-5carboxypentyl)phthalate,MECPP]。采用多重线性回归分析这8种PAEs代谢物暴露与双胞胎出生体重差的关系,分位数g计算回归(quantile g-computation,qgcomp)和加权分位数和回归(weighted quantile sum regression,WQS)来评估PAEs复合暴露与双胞胎出生体重差异的关系。结果研究对象尿液中PAEs代谢物检出率均超过80.00%,其中MBP检出率最高为97.00%,整个孕期的浓度中位数是42.08μg/L;检出率最低的是MBzP为84.43%,整个孕期的浓度中位数是0.46μg/L。双胞胎体重差的中位数为210 g。校正多个潜在混杂因素后,多重线性回归结果表明,整个妊娠期,MEP、MBP、MEHP暴露与双胞胎出生体重差正相关。基于WQS的分析结果显示,整个孕期PAEs复合暴露与双胞胎体重差间存在正相关,qgcomp分析结果表明8种PAEs混合物每增加一个四分位数,双胞胎出生体重差增加3.88%(95%CI:0.25%~7.64%)。结论整个孕期PAEs的复合暴露可增大双胞胎出生体重差。

Objective To explore the association between mixed-exposure to phthalates(PAEs)during pregnancy and birth weight difference between twins.Methods A prospective cohort study was conducted.From January 2013 to December 2016,289 women with twin pregnancy from the Wuhan Twin Birth Cohort were recruited.The concentrations of eight PAEs metabolites in the urine of pregnant women in the first,second,and third trimesters were measured by high performance liquid chromatography-tandem mass spectrometry.These PAEs included monoethyl phthalate(MEP),monoisobutyl phthalate(MiBP),monobutyl phthalate(MBP),monobenzyl phthalate(MBzP),mono(2-ethylhexyl)phthalate(MEHP),mono(2-ethyl-5-oxohexyl)phthalate(MEOHP),mono(2-ethyl-5-hydroxyhexyl)phthalate(MEHHP),and mono(2-ethyl-5-carboxypentyl)phthalate(MECPP).Multiple linear regression was used to analyze the relationships between mixed-exposure to these PAEs and weight difference between twins.Quantile g-computation and weighted quantile sum regression were used to evaluate the association between mixed-exposure to these PAEs and weight difference between twins.Results The detection rates of all PAEs in urine were more than 80.00%.The highest detection rate was 97.00%for MBP,with a median concentration of 42.08μg/L throughout the entire pregnancy.The lowest detection rate was 84.43%for MBzP,with a median concentration of 0.46μg/L over the entire pregnancy.The median of birth weight difference between twins was 210 g.After adjustment for multiple confounders,multiple linear regression showed that the mixed-exposure to MEP,MBP,and MEHP throughout pregnancy was positively associated with the birth weight difference between twins.Weighted quantile sum regression results showed a positive correlation between mixed-exposure to PAEs and birth weight difference between twins during pregnancy.Moreover,quantile g-computation results showed that the birth weight difference between twins increased by 3.88%(95%CI:0.25%-7.64%)with each quartile increase in the mixture of eight PAEs.Conclusion The mixed-exposure to PAEs during the entire pregnancy could increase the birth weight difference between twins.