Serum Poly-and Prefluoroalkyl Exposure In Pregnant Women And Risk Of Gestational Diabetes Mellitus In The Zhuang Area

ObjectiveThis study aims to evaluate the levels of poly-and perfluoroalkyl substances（PFASs）in pregnant women and analyze their influencing factors,and to examine the relationship between pregnant women exposure to PFASs and the risk of gestational diabetes mellitus（GDM）.MethodThe participants were extracted from the Guangxi Zhuang Birth Cohort.The cohort was established in September 2015 and now still going on.The cohort has set up six survey sites in Guangxi where the Zhuang people live.The pregnant women whose gestational age is less than 22 weeks are included in the cohort.The basic information of pregnant women is collected through a face-to-face questionnaire survey by professional investigators.The information includes basic demographic information,previous pregnancy history,family history,behavior,lifestyle,and other information.Through Guangxi Women and Children Health Service Information Management system,follow-up pregnant women’s birth inspection data,delivery conditions,newborn conditions and other information.Pregnant women collect fasting peripheral venous blood during the first inspection,and placenta,fetal umbilical cord blood,and oropharynx during delivery.Then liquid-liquid extraction,UPLC-MS was used to detect the levels of 11 PFASs（PFBS,PFPe A,PFHx A,PFHx S,PFHp A,PFOA,PFOS,PFNA,PFDA,PFUn A,PFDo A）.A cross-sectional study was used to analyze the factors influencing the exposure level of PFASs in pregnant women.Since the concentration of PFASs were non-normal distributed,the median and quartile were used for statistical description.Nonparametric rank sum test was used to analyze the difference in the concentration of PFASs in pregnant women.After the log10 logarithm conversion of PFASs,multiple linear regression was used to analyze the factors influencing the exposure level of PFASs.A nested case-control study was used to analyzed the relationship between the risk of GDM and the exposure of PFASs.For every case selected,three consecutive controls were randomly selected and matched by maternal age（within 3-year interval）.Rank sum test and LASSO regression analysis were used to construct a multi-compound compound exposure model.Restricted cubic spline regression was used to analyze the dose-response relationship between single compound and GDM risk.SPSS 22.0 and R 3.6.3 were used for statistical analysis.A two-tailed and P<0.05 was used as the statistical significance level.ResultsPart I:Pregnant women’s exposure to PFASs and its influencing factors1.A total of 1583 pregnant women were included in this study.The average gestational age of pregnant women at the time of inclusion was 10.8±2.6 weeks,and the average age was 28.2±6.0 years.The average BMI was20.9±3.0 kg/m2.The median concentration and the detection rate of PFOA was 2.15 ng/m L and 100%respectively;that of PFBS was 1.74 ng/m L and99.2%;that of PFHp A was 1.71 ng/m L and 93.4%;that of PFOS was 1.08ng/m L and 100%;that of PFNA was 0.58 ng/m L and 99.9%;that of PFDA was0.41 ng/m L and 99.8%;that of PFUn A was 0.37 ng/m L and 100%;that of PFDo A was 0.11 ng/m L and 98.0%;PFHx A and PFPe A,the median concentration were less than the detection limit,the detection rate is 24.0%and8.4%,respectively.2.Correlation between different PFASs:there was a strong correlation between long-chain perfluoroalkyl carboxylates（PFCAs）PFOA PFNA PFDA PFUn A PFDo A;there was a strong correlation between long-chain perfluoroalkyl sulfonates（PFSAs）PFOS and PFHx S;PFOS is also strongly correlated with long-chain PFCAs;short-chain PFBS is not related to other substances.3.Factors affecting the exposure level of PFASs in the serum of pregnant women:there is no collinearity among various confounding factors,and the results of multiple linear regression analysis showed that the influencing factors of PFDo A were mark up,types of energy used and residential ventilation;that of PFUn A were age,ethic and types of energy used;that of PFDA were occupation;smoking habits and residential ventilation;that of PFNA were age and smoking habits;that of PFOA were age;parity and the presence of factories near their home;that of PFHp A were residential ventilation and types of energy used;that of PFBS were parity,smoking habits and residential ventilation;that of PFHx S were age,parity and occupation;that of PFOS were age,parity,alcohol intake and residential ventilation.PartⅡ:The association between PFASs and gestational diabetes mellitusThe second section included 768 pregnant women,192 were in the case group and 576 were in the control group.Regression models were analyzed using maternal serum PFASs levels as categorical variables,based on the tertile distribution of PFASs concentrations in the controls,and the lowest tertile was assigned as the reference group.Adjusted maternal BMI,smoking habits,sporting habits.1.Five compounds of PFHp A,PFOA,PFNA,PFBS,PFHx S were screened by the Mann-Whitney U test to construct a multi-pollutant model.Compared with the traditional method,the LASSO regression analysis method increased PFDA PFUn A,with a total of seven compounds.2.In the five-compound model,after adjusting for BMI,smoking and exercise,compared with low exposure,serum PFHp A(adjusted OR=4.84,95%CI:2.49～8.25,P_trend<0.001)was statistically significant with increased risk of GDM,while PFOA(adjusted OR=0.27,95%CI:0.14～0.49,P_trend<0.001)and PFBS(adjusted OR=0.44,95%CI:0.27～0.72,P_trend=0.001)was associated with a reduced risk of GDM.3.In the seven-compound model,after adjusting for BMI smoking and exercise,the risk of GDM increased with the increase of PFHp A exposure level(adjusted OR=4.71,95%CI:2.74～8.04,P_trend<0.001),PFOA(adjusted OR=0.26,95%CI:0.14～0.49,P_trend<0.001)andPFBS(adjusted OR=0.45,95%CI:0.28～0.74,P_trend=0.002)was associated with a reduced risk of GDM.4.There was an inverted s-type nonlinear relationship between increased serum PFHp A concentration and increased risk of GDM(P_Nolinear=0.017),in a stable state after rapid rise.Increased serum PFOA concentration was statistically correlated with decreased risk of GDM overall(P_overall=0.01,P_Nolinear=0.707).There was a s-type nonlinear relationship between increase in PFBS concentration and reduced risk of GDM(P_Nolinear=0.002).5.While for PFNA,PFDA,PFUn A,PFDo A and PFOS,no significant associations with GDM were found（all P>0.05）.Conclusions1.The zhuang pregnant women were exposed to a variety of PFASs,of which PFBS and PFHp A exposure levels were higher,and PFOA,PFDA,PFNA,PFDo A,PFUn A,PFHx S,and PFOS were at lower exposure levels.2.Various factors affect the exposure level of PFASs.It is found that the exposure of pregnant women to PFASs is related to factors such as age,smoking habits,residential ventilation,and use of non-clean energy.3.PFASs exposure during pregnancy is closely related to GDM,and PFHp A is a risk factor for the development of GDM during pregnancy...