Relationships Between Blood Metal Exposure And Thyroid Hormones In Pregnant Women

Part Ⅰ Environment-wide association study on the associations of blood metal exposure with thyroid hormones in pregnant womenObjective:To investigate the associations of exposure to multiple metals with thyroid hormone homeostasis among pregnant women using the method of environment-wide association study(EWAS).Methods:Among all the 1644 participants enrolled in Hangzhou Birth Cohort Study(HBCS)at baseline,a total of 915 pregnant women with complete data of interest were analyzed.Eleven metals were measured in blood samples collected around 25 weeks gestation.Serum levels of thyroid hormones including free triiodothyronine(FT3),total triiodothyronine(TT3),free thyroxine(FT4),total thyroxine(TT4)and thyroid-stimulating hormone(TSH)were extracted from the medical records.Relationships between tertiles of metal levels(setting the lowest tertile as the reference)and percent changes in thyroid hormones were estimated by multivariable adjusted linear regression models.Results:Five metals[arsenic(As),selenium(Se),manganese(Mn),nickel(Ni),antimony(Sb)]were significantly linked to decreased levels of one or more thyroid hormones based on trend tests in the single-metal models.Percent changes[95%confidence intervals(CIs)]in thyroid hormones for the third tertiles of metals remained significant between FT3 and As[-3.53%(-5.48%,-1.54%)];and between TT3 and As[-4.19%(-7.00%,-1.31%)];and between FT4 and Mn[-2.05%(-3.49%,-0.58%)],Sb[-1.99%(-3.44%,-0.52%)]in the multiple-metal models.Conclusions:Thyroid hormone concentrations were reversely related to the levels of blood metals of As,Mn and Sb among Chinese pregnant women.Due to the cross-sectional nature of the present study,additional prospective studies are warranted to confirm the causality.Part Ⅱ Associations between environmental risk scores of metal mixtures and thyroid hormones in pregnant womenObjective:To estimate the environmental risk scores(ERS)of co-exposure metals,and to explore the associations between ERS and thyroid hormones among Chinese pregnant women.Methods:There were 11 blood metals and 5 serum thyroid hormones had been examined among 915 pregnant women from Hangzhou Birth Cohort Study(HBCS)at baseline.All the subjects were randomly splitted into training(n=641)and testing(n=274)sets.Based on the training set,four candidate adaptive elastic net(AENET)models were separately constructed for each thyroid hormone,when using the thyroid hormones as dependent variables and different combinations of metal terms plus adjustments as independent variables.The optimal AENET models were regarded as those with the minimum root-mean-square error(RMSE)in the testing sets.ERS values of co-exposure metals were calculated as the weighted sum of metal terms with weights equal to the coefficients from the optimal AENET models.Associations between ERS and thyroid hormones were investigated by the crude and adjusted linear regression models.Results:The optimal AENET models were constructed with the metal main effects for free triiodothyronine(FT3)and free thyroxine(FT4),and with the metal main effects plus squared terms for total triiodothyronine(TT3),respectively.The differences of ERS levels between the training and testing sets were not statistically significant.Compared with the first tertile(T1,reference)of ERS,percent changes[95%confidence intervals(CIs)]of FT3 were significantly increased in the second[2.21%(0.17%,4.29%)]and third tertiles[4.58%(2.46%,6.73%)]among all the subjects(p trend<0.001).Similar positive associations of ERS levels with TT3 and FT4 were observed.When the ERS levels were treated as continuous variables,the positive associations were kept robust.Conclusions:The optimal AENET models were thyroid-hormone-specific.The ERS levels of co-exposure metals were positively associated with thyroid hormones among pregnant women.