孕早期邻苯二甲酸酯暴露与孕晚期空腹血糖水平关联的队列研究

A cohort study on association between the first trimester phthalates exposure and fasting blood glucose level in the third trimester

目的分析孕妇孕早期邻苯二甲酸酯（PAE）暴露与孕晚期FPG水平的关联及患妊娠糖尿病（GDM）的风险。方法选取2013年5月至2014年9月在马鞍山市妇幼保健院产前检查的3474名孕妇为研究对象，于孕早、中、晚期分别随访，采用问卷调查收集研究对象的社会人口学资料，记录临床相关信息；收集孕妇晨尿样本，运用固相萃取-高效液相色谱-串联质谱法（SPE—HPLC—MS／MS）检测尿液样本中7种PAE代谢物浓度；在孕早、晚期测定FPG，在孕中期进行75g口服糖耐量试验（OGTT）。运用线性回归模型分析尿PAE代谢物与孕晚期FPG间的关联性，运用logistic模型分析孕早期PAE暴露水平与孕晚期患GDM的风险。结果GDM检出率为12．8％；孕早期邻苯二甲酸单甲酯（MMP）、邻苯二甲酸单乙酯（MEP）、邻苯二甲酸单丁酯（MBP）、邻苯二甲酸单苄酯（MBzP）、邻苯二甲酸单（2-乙基-5-羟基己基）酯（MEHHP）暴露水平与孕晚期FPG呈正相关（P〈0．05），邻苯二甲酸单（2-乙基己基）酯（MEHP）、邻苯二甲酸单（2-乙基-5-酮基己基）酯（MEOHP）暴露水平与孕晚期空腹血糖水平呈负相关（P〈0．05）。孕早期MEHHP暴露增加正常组和GDM组FPG水平，MMP、MEP、MBP、MBzP、MEHP和MEOHP暴露只影响正常组的FPG水平，对GDM组的FPG水平无影响。孕早期MMP和MBP暴露增加孕晚期患GDM的风险，MEOHP暴露降低孕晚期患GDM的风险。结论孕早期PAE暴露与孕晚期FPG水平存在关联，不同种类PAE代谢物与孕晚期FPG水平关联性存在差异，PAE代谢物对正常孕妇FPG水平的影响较GDM孕妇更为显著。不同种类PAE代谢物可能增高或降低孕妇孕晚期患GDM的风险性。

Objective To examine the association between the phthalate exposure in the first trimester and fasting blood glucose level or gestational diabetes mellitus （GDM） in the third trimester in pregnant women. Methods A total of 3 474 pregnant women, receiving their prenatal examination in Ma＇ anshan Maternal and Child Health-Care Hospital of Anhui province, were selected from May 2013 to September 2014. Questionnaires were used to collect the information about their socio- demographic characteristics, clinical characteristics and GDM diagnostic results in the first, second and third trimesters. Urine samples and fasting venous blood samples were collected. Concentrations of 7 kinds of phthalate metabolites in urine samples were detected by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry （SPE-HPLC-MS/MS）, and multiple linear regression model was used for statistical analyses. Logistic regression analysis on the risk of the first trimester phthalate exposure for GDM in the third trimester was conducted. Results The prevalence of GDM in this study was 12.8%, monomethyl phthalate （MMP）, monoethyl phthalate （MEP）, mono-n-butyl phthalate （MBP）, rnonobenzyl phthalate （MBzP） and mono-（2-ethyl-5- oxohexyl） phthalate （MEHHP） exposure levels were positively correlated with the fasting blood glucose level in the third trimester （P〈0.05）, but mono-（2-ethylhexyl） phthalate （MEHP） and mono-（2-ethyl-5-hydroxylhexyl） phthalate （MEOHP） exposure levels were negatively correlated with the fasting blood glucose level in the third trimester （P〈0.05）. Stratified analysis showed a positive correlation between MEHHP exposure and the third trimester fasting blood glucose level in both normal group and GDM group. However, MMP, MEP, MBP, MBzP, MEHP and MEOHP exposure levels had influences on the third trimester fasting blood glucose level in normal group but not in GDM group. MMP and MBP exposure might increase the risk of GDM, but MEOHP exposure might reduce the risk of GDM. Conclusion The phthalate exposure in the first trimester might be associated with the fasting blood glucose level in the third trimester, MMP, MEP, MBP, MBzP and MEHHP concentrations were positively associated with the third trimester blood glucose level, MEHP and MEOHP concentrations were negatively associated with the third trimester blood glucose level. Moreover, the effects of different kinds of phthalates might be different.