【摘要】 目的 研究行体外受精（IVF）助孕治疗的女性尿液中邻苯二甲酸酯（PAEs）代谢产物浓度与子代出生体重的相关性。方法 自2015年10月至2016年12月期间从华中科技大学同济医学院附属同济医院生殖中心招募行IVF助孕治疗的553名女性，最终314名成功分娩新生儿的女性被纳入本研究。在采卵当天对研究对象进行问卷调查并收集其尿液。采用固相萃取-高效液相色谱-串联质谱联用技术（HPLC-MS/MS）检测8种PAEs代谢产物的浓度：邻苯二甲酸单甲酯（MMP）、邻苯二甲酸单乙酯（MEP）、邻苯二甲酸单丁酯（MBP）、邻苯二甲酸单苄基酯（MBzP）、邻苯二甲酸单（2-乙基己基）酯（MEHP）、邻苯二甲酸单（2-乙基-5-羟己基）酯（MEHHP）、邻苯二甲酸单（2-乙基-5-氧己基）酯（MEOHP）和邻苯二甲酸单辛酯（MOP）。采用广义线性模型（GLMs）分别分析PAEs代谢物水平与单胎和双胎新生儿出生体重之间的关联。结果 校正了潜在协变量后，孕前尿液中的MEP和MEHHP浓度与双胎新生儿出生体重存在剂量-反应负相关(P_趋势<0.05),MEHHP浓度与单胎新生儿出生体重存在剂量-反应正相关(P_趋势<0.05)。PAEs代谢物浓度为连续变量建立回归模型时，MEP、MEHHP、MEHP和∑DEHP浓度与双胎新生儿出生体重呈负相关（P<0.05）。性别分层分析发现，PAEs暴露对出生体重的影响存在一定的性别差异。结论 接受IVF助孕的女性孕前普遍暴露于PAEs,且其PAEs暴露可能影响单胎和双胎新生儿的出生体重。更多还原

【Abstract】 Objective To research the associations between urinary phthalate metabolite concentrations and the birth weights of singletons and twins among women who had undergone in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Methods We recruited 557 women who had undergone IVF between October 2015 and December 2016.Finally, 314 women who successfully gave birth to singletons or twins were included in this study.On the day of oocytes retrieved, the questionnaires were required to be finished, the urine was collected.The concentrations of eight kinds of PAEs metabolites in urine were detected by solid phase extraction high performance liquid chromatography tandem mass spectrometry, including monomethyl phthalate(MMP),mono-ethyl phthalate(MEP),mono-n-butyl phthalate(MBP),mono-benzyl phthalate(MBzP),mono(2-ethylhexyl)phthalate(MEHP),mono(2-ethyl-5-hydroxyhexyl)phthalate(MEHHP),mono(2-ethyl-5-oxohexyl)phthalate(MEOHP),mono-n-octyl phthalate(MOP).ΣDEHP,the molar concentration of the MEOHP,MEHHP and MEHP,was calculated.The associations between phthalate metabolites in urine and birth weights of the singleton and twin groups were evaluated using generalized linear models(GLMs).Results After adjusting for relevant confounders, we found that birth weight in the twin group had negative dose-response correlations with maternal preconception MEP and MEHHP in urine(both P for trends<0.05)and that birth weight in the singleton group had positive dose-response correlations with MEHHP in urine(P for trends<0.05).When the phthalate metabolites were modeled as continuous variables, we observed association between decreased twin birth weight and MEP,MEHHP,MEHP and ∑DEHP(P<0.05).The sex-stratified analyses indicated a sex difference in effects of exposure to PAEs on birth weight.Conclusion The infertile women undergoing IVF are widely exposed to PAEs.Preconception phthalate metabolites in maternal urine may affect the birth weights of both singleton and twin newborns.更多还原