| Objective:This study aims to evaluate effects of exposure to perfluoroalkyl and polyfluoroalkyl substances(PFASs)in early pregnant women on thyroid hormones and the relationship between thyroid hormones and fetal growth.At the same time,to investigate whether thyroid hormone were intermediate variables among the associations between PFASs and fetal growth.Methods:This study was based on the birth cohort of Zhuang nationality in Guangxi,pregnant women with thyroid hormone testing data and their newborns were selected as the subjects of this study.The peripheral venous blood samples from pregnant women were collected in early pregnancy.UPLC-MS was performed to determine the serum concentrations of 11 kinds of PFASs,including PFPe A,PFHx A,PFHp A,PFOA,PFNA,PFDA,PFUn DA,PFDo DA,PFBS,PFHx S,PFOS.We obtained maternal thyroid hormones from the electronic medical records in the study hospital,including T3,FT3,T4,FT4 and TSH.We analyzed the relationship between PFASs and thyroid hormones in 905subjects.Nonparametric test was used to analyze the difference of thyroid hormone levels in serum of pregnant women with different characteristics.So experimental data were grouped according to thyroid hormone tests weeks,including early pregnancy(<13 weeks)and middle pregnancy(13～27 weeks).The PFASs concentrations were divided into four groups with the 25th,50th,75th percentile,and the lowest concentration group as the reference group to analyze the association of different PFASs exposure levels with thyroid hormone.We also included the exposure groups as ordered variables into the regression model for p-trend testing.The association of PFASs exposure to early and middle thyroid hormone was analyzed by multiple linear regression model.To facilitate interpretation of the results,the percentage of changes(Change%)and 95%CI were calculated from(e~β-1)×100.The relationships between PFASs exposure,gestational thyroid function and fetal growth were analyzed in 727 mothers and infants,and researched the possible intermediary role of thyroid hormone in PFASs and fetal growth.The associations between thyroid hormone,PFASs and gestational weeks,birth weight and birth length were analyzed by multiple linear regression models.The mediation effect analysis was used in approach which meet the intermediary effect analysis conditions.SPSS 23.0 and R3.6.3 were used for statistical analysis.A two-tailed and P<0.05 was used as the statistical significance level.Results:1.Relationship between serum PFASs and thyroid hormones:multiple linear regressionIn the first trimester,PFOS was negatively associated with T3,T4 and positively associated with FT3.Each IQR increase in the level of PFOS,T3decreased by 2.261%(95%CI:-4.472%,-0.069%,P=0.045);FT3 increased by4.102%(95%CI:1.537%,6.807%,P=0.002);T4 decreased by 3.473%(95%CI:-6.567%,-0.208%,P=0.035).PFBS was positively associated with FT3 and TSH.Each IQR increase in the level of PFBS,FT3 increased by 1.396%(95%CI:0.069%,2.740%,P=0.038);TSH increased by 6.069%(95%CI:1.045%,11.342%,P=0.017).In the second trimester,PFUn DA was positively associated with T3,FT4.Each IQR increase in the level of PFUn DA,T3 increased 4.102%(95%CI:1.326%,6.955%,P=0.004);FT4 increased 4.174%(95%CI:0.835%,7.549%,P=0.014).PFDA was positively associated with T3,FT4.Each IQR increase in the level of PFDA,T3 increased 2.456%(95%CI:0.556%,4.391%,P=0.011);FT4increased 2.385%(95%CI:0.139%,4.681%,P=0.036).PFOS was negatively associated with T3.Each IQR increase in the level of PFOS,T3 decreased by2.869%(95%CI:-5.263%,-0.484%,P=0.020).PFBS was negatively associated with T3.Each IQR increase in the level of PFBS,T3 decreased by 1.240%(95%CI:-2.329%,-0.069%,P=0.040).The results of categorized PFASs models showed that in the first trimester,PFOS was inversely associated with the T3 levels(quartile 4 vs 1:-2.585%,95%CI:-4.943%,-0.168%,P=0.036)and positively associated with the FT3levels(quartile 4 vs 1:3.698%,95%CI:0.898%,6.575%,P=0.009,P-trend=0.044).PFBS was positively associated with the T3 levels(quartile 2 vs 1:3.382%,95%CI:1.027%,5.793%,P=0.005).PFNA was positively associated with the FT3levels(quartile 3 vs 1:3.353%,95%CI:0.703%,6.074%,P=0.013)and inversely associated with the T4 levels(quartile 3 vs 1:-5.000%,95%CI:-8.127%,-1.766%,P=0.003).In the second trimester,PFUn DA was positively associated with the T3,FT4levels(T3,quartile 3 vs 1:2.678%,95%CI:0.341%,5.070%,P=0.025;quartile 4vs 1:3.865%,95%CI:1.286%,6.510%,P=0.003,P-trend=0.001;FT4,quartile 4vs 1:3.319%,95%CI:0.261%,6.470%,P=0.033,P-trend=0.011).PFDA was positively associated with the T3 levels(quartile 4 vs 1:2.467%,95%CI:0.049%,4.945%,P=0.046,P-trend=0.010).PFOS was inversely associated with the T3,FT3 and FT4 levels(T3,quartile 3 vs 1:-3.787%,95%CI:-6.202%,-1.309%,P=0.003,P-trend=0.034;FT3,quartile 4 vs 1:-2.680%,0.049,95%CI:-5.275%,-0.014%,P=0.049;FT4,quartile 3 vs 1:-3.420%,95%CI:-6.305%,-0.447%,P=0.025).PFOA was positively associated with the FT3 levels(quartile 3 vs 1:3.095%,95%CI:0.370%,5.894%,P=0.026).No statistical differences between PFASs and TSH concentrations were found,but PFBS and TSH had linear trend(P-trend=0.048).2.The association between thyroid hormone and fetal growthIn the first trimester,T3 was negatively associated with birth length(P=0.021,β=-1.598,95%CI:-2.949,-0.247);FT3 was positively associated with birth length(P=0.008,β=1.599,95%CI:0.420,2.779);T4 was negatively associated with birth length(P=0.005,β=-1.296,95%CI:-2.205,-0.387).In the second trimester,FT3 was positively associated with birth weight(P=0.042,β=284.192,95%CI:10.543,557.840).Neonatal gender stratification results revealed that in the first trimester,T3,FT3,T4 were significantly associated with birth length only in boys.T3 and T4were negatively associated with male birth length(T3,P=0.025,β=-2.106,95%CI:-3.942,-0.270;T4,P=0.011,β=-1.431,95%CI:-2.536,-0.327);FT3 was positively associated with male birth length(P=0.010,β=1.870,95%CI:0.458,3.282).In the second trimester,maternal T3 concentrations were positively associated with male gestational week(P=0.028,β=2.435,95%CI:0.269,4.600).3.The association between PFASs and fetal growthPFUn DA was positively associated with birth weight and gestational weeks(P=0.042,β=88.576,95%CI:3.388,173.763;P=0.027,β=0.440,95%CI:0.051,0.829).PFNA was negatively associated with birth weight(P=0.021,β=-76.920,95%CI:-142.137,-11.702).PFHp A was negatively associated with gestational weeks(P=0.007,β=-0.219,95%CI:-0.377,-0.060).4.Intermediation role of thyroid hormone in PFASs and fetal growthMediation analysis results showed that the indirect effect of T3-PFUn DA-birth length did not reach the statistical significance level,and the effect of PFASs exposure on the gestational week may not be mediated by T3.Conclusion:1.PFASs exposure may affect thyroid hormones in pregnant women,where PFOS affected the T3,FT3,T4 levels in the first trimester.PFBS affected the FT3and TSH levels in early maternal pregnancy.PFUn DA,PFDA,PFOS,PFBS affected the T3 levels in the second trimester.PFUn DA and PFDA affected the FT4 levels in the second trimester.2.Thyroid hormone levels were associated with fetal growth and have gender differences.The main performance was that the T3,FT3,T4 levels were statistically related to the birth length in the first trimester,which was obvious in boys.Maternal FT3 levels were statistically associated with birth weight and T3levels were statistically associated with gestational week in boys.3.Maternal PFASs exposure affected fetal growth,PFUn DA was positively association with birth weight and birth week;PFNA was negatively associated with birth weight,and PFHp A was negatively associated with birth week.4.This study found no mediated role of thyroid hormone in PFASs in association with growth and development. |
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