上海地区辅助生殖女性孕前有机磷农药暴露对子代出生结局的影响

Birth outcomes in pregnant women with assisted reproductive technology exposure to organophosphate pesticides in Shanghai

目的阐明上海地区辅助生殖(assisted Reproduction technology,ART)女性孕前尿液有机磷农药(organophosphate pesticides,OPs)暴露水平,探讨其暴露对子代出生结局的影响。方法于2017年7月—2018年12月在上海交通大学医学院附属国际和平妇幼保健院生殖门诊招募597名ART女性,其中106名女性分娩单胎活产儿被纳入本次研究。采用气相色谱质谱串联法检测孕前尿液OPs非特异性二烷基磷酸酯(DAP)代谢物浓度[包括:磷酸二甲酯(DMP)、二甲基硫代磷酸酯(DMTP)、二甲基二硫代磷酸酯(DMDTP)、磷酸二乙酯(DEP)、二乙基硫代磷酸酯(DETP)、二乙基二硫代磷酸酯(DEDTP)]。运用广义线性回归模型(GLMs)分析孕前OPs暴露与出生结局的相关性。结果除DMDTP和DEDTP外,其余4种DAP代谢产物均高度检出,检出率为87.7%~95.3%。孕前尿液DETP浓度与新生儿分娩孕周呈负相关(β=-1.34,95%CI:-2.24^-0.45)。性别差异分析显示:孕前尿液DETP浓度与男婴分娩孕周呈负相关(β=-1.72,95%CI:-3.02^-0.43),而在女婴中无统计学关联(P>0.05)。结论上海地区ART女性孕前尿液OPs代谢物浓度远高于发达国家,且孕前OPs暴露对出生结局的影响可能存在性别差异。

Objective To investigate the association between birth outcomes and exposure levels of organophosphate pesticides(OPs)in pregnant women undergoing assisted reproduction techniques(ART).Methods The participants were recruited from the International Peace Maternity and Child Health Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China,between July 2017 and December 2018.From 597 women who met the eligibility criteria,106 singleton live born mother-neonate pairs were included in this study.Preconception exposure to OPs was assessed by measuring six non-specific dialkylphosphate(DAP)metabolites in urine[dimethylphosphate(DMP),dimethyldithiophosphate(DMTP),dimethyldithiophosphate(DMDTP),diethylphosphate(DEP),diethylthiophosphate(DETP)and diethyldithiophosphate(DEDTP)].Generalized linear models(GLMs)were used to explore the relationship between OP exposures and birth outcomes.Results The detection frequencies of DAP metabolites were high for DEP(91.5%),DETP(95.3%),DMP(91.5%)and DMTP(87.7%),were low for DMDTP(12.1%)and DEDTP(2.0%).We found that DETP metabolite levels were negatively associated with gestational age(β=-1.34,95%CI:-2.24^-0.45).When stratified by neonatal gender,we found the similar results among male neonates(β=-1.72,95%CI:-3.02^-0.43),but not among female neonates.Conclusion The OP exposure levels in Shanghai were much higher than those reported in developed countries,and the adverse effects of OPs on gestational age were more pronounced among male than female neonates.