孕早期邻苯二甲酸酯暴露对妊娠期亚临床甲状腺功能减退症患者妊娠结局的影响

Impact of first-trimester exposure to phthalates on pregnancy outcomes of patients with subclinical hypothyroidism during pregnancy

目的探讨孕早期邻苯二甲酸酯(phthalates,PAEs)暴露对妊娠亚临床甲状腺功能减退症(subclinical hypothyroidism,SCH)患者妊娠结局的影响。方法以2019年1月—2021年5月于南京医科大学附属苏州科技城医院孕早期检查的188例合并SCH的孕妇(胎龄0~12周)作为研究对象进行前瞻性研究。通过医院产科患者信息系统收集孕妇的一般资料并记录妊娠结局。收集产妇初次检查的尿液,采用LC-MS/MS技术测定其中10种PAEs代谢物水平并换算为PAEs的每日暴露量。采用多重线性回归分析PAEs暴露对Apgar评分影响,采用多因素logistic回归分PAEs暴露对自发早产(spontaneous preterm birth,SPTB)和小于胎龄儿(small for gestational age,SGA)等妊娠结局的影响。结果SCH患者尿液中10种PAEs代谢物的检出率均超过90%,其中邻苯二甲酸单甲酯(mono-methyl phthalate,MMP)、邻苯二甲酸单乙酯(mono-ethyl phthalate,MEP)、邻苯二甲酸单正丁酯(monon-butyl phthalate,MnBP)、邻苯二甲酸单异丁酯(monoisobutyl phthalate,MiBP)和单(2-乙基-5-羟基己基)邻苯二甲酸酯(mono-2-ethyl-5-hydroxyhexyl phthalate,MEHHP)等PAEs代谢物的检出率为100.00%。多重线性回归分析结果表明,新生儿Apgar评分与DEHP暴露呈负相关(β’=-0.331,95%CI:-0.617~-0.045);logistic回归分析显示,DMP(OR=1.445,95%CI:1.230~1.697)、DEP(OR=1.606,95%CI:1.204~2.143)、DiBP(OR=1.766,95%CI:1.301~2.399)和DEHP(OR=1.473,95%CI:1.105~1.963)是SPTB发生的危险因素,DMP(OR=1.583,95%CI:1.132~2.212)和DEHP(OR=1.627,95%CI:1.238~2.139)是SGA发生的危险因素。结论苏州地区的SCH妊娠妇女普遍暴露于PAEs,同时PAEs暴露会影响妊娠结局,影响胎儿发育、增加孕妇早产风险、降低新生儿出生体重。

Objective To explore the effect of first-trimester phthalates(PAEs)exposure on pregnancy outcomes of patients with subclinical hypothyroidism(SCH)during pregnancy.Methods From January 2019 to May 2021,188 pregnant women(a gestational age of 0-12 weeks)with SCH who underwent first-trimester screening in Suzhou Science and Technology Town Hospital Affiliated to Nanjing Medical University served as subjects for a prospective study.General information of the pregnant women was collected through the hospital information system for obstetric patients,and their pregnancy outcomes were recorded.Urine samples collected from obstetric patients undergoing prenatal diagnosis for the first time were measured by LC-MS/MS technology,and the levels of 10 PAEs metabolites were converted into the daily exposure doses of PAEs.The effects of PAEs exposure on Apgar score were analyzed by multiple linear regression.The impact of PAEs exposure on pregnancy outcomes like spontaneous preterm birth(SPTB)and small for gestational age(SGA)was analyzed by multi-factor logistic regression.Results The detection rates of 10 PAEs metabolites in urine of the SCH patients were all more than 90%,among which the detection rates of mono-methyl phthalate(MMP),mono-ethyl phthalate(MEP),mono-n-butyl phthalate(MnBP),monoisobutyl phthalate(MiBP)and mono-2-ethyl-5-hydroxyhexyl phthalate(MEHHP)were 100.00%.Multiple linear regression analysis showed that neonatal Apgar score was negatively correlated with DEHP exposure(β’=-0.331,95%CI:-0.617--0.045).Logistic regression analysis displayed that DMP(OR=1.445,95%CI:1.230-1.697),DEP(OR=1.606,95%CI:1.204-2.143),Di BP(OR=1.766,95%CI:1.301-2.399)and DEHP(OR=1.473,95%CI:1.105-1.963)were risk factors for the occurrence of SPTB,and DMP(OR=1.583,95%CI:1.132-2.212)and DEHP(OR=1.627,95%CI:1.238-2.139)were risk factors for the occurrence of SGA.Conclusion Pregnant women with SCH in Suzhou are generally exposed to PAEs,and PAEs exposure will affect pregnancy outcome and fetal development,increase the risk of premature delivery and reduce the birth weight of newborns.