| Objective: Antimony(Sb),cadmium(Cd),lead(Pb),barium(Ba),etc.are considered having endocrine disruption characteristics as their estrogenic activity.It has been reported that exposure of these endocrine disruptors may increase the risk of type 2 diabetes and other diseases related to insulin resistance,but whether they have an effect on gestational diabetes mellitus(GDM)remains unclear.This study was designed to analyze the association between exposure of metals with strong estrogenic activity as Sb,tin(Sn),Cd,Ba,Pb,selenium(Se)and chromium(Cr)during early pregnancy and the risk of GDM.Methods: The subjects were pregnant women enrolled from July 2014 to July 2016 in Tongji Maternal and Child Health Cohort(TMCHC),with single live birth,without pregestational diabetes mellitus,and provided urine samples before 20 weeks of gestation.Interview based on the questionnaire was conducted at enrollment before 16 weeks of pregnancy to collect information on demographic indicators,diseases,and lifestyles of the pregnant women.The height and weight of them were measured at the same time.Pre-pregnancy weight was reported and pre-pregnancy body mass index(BMI)was calculated.Oral glucose tolerance test of 75 g was performed during 24-28 weeks of gestation to diagnose GDM.After delivery,information about the birth outcome was obtained from hospital records.Concentrations of metals in urine samples were measured by inductively coupled plasma mass spectrometry(ICP-MS).Urinary creatinine concentration was determined by the modified Jaffrey method.A robust Poisson regression was used to analyze the association between every single element concentration and the risk of GDM.The mixed exposure level was evaluated using a comprehensive score based on the concentration of 7 metals and the relative estrogenic activity,and the correlation between the comprehensive scores of 7 elements and the risk of GDM was analyzed by robust Poisson regression.The combined exposure level of 7 elements was further evaluated by Weighted Quantile Sum(WQS),and the association between WQS and the risk of GDM was analyzed using robust Poisson regression.Result: The study included 2093 pregnant women eligible.The median(M)age of pregnant women was 28.3 and interquartile range(IQR)were 26.6-30.5 years.The proportion of pregnant women with a normal BMI(18.5-23.9)was 67.51%,83.37% of them had higher education and 9.51% were unemployed.241(11.5%)pregnant women were diagnosed with GDM.Compared with pregnant women without GDM,women with GDM were elder(M(IQR)): 29.1(27.1,32.3)vs.28.3(26.6,30.3),more classified overweight and obese: 26.97% vs.11.93%,more with family history of type 2 diabetes: 12.03% vs.6.86%,less proportion of primigravid pregnant women: 48.55% vs.57.56%,more were unemployed 14.52% vs.8.86%,all P < 0.01.No significant difference in other characters as education,smoking exposure,fetal sex,etc.between groups(all P > 0.05).The median(IQR)of concentrations of seven elements in urine samples of GDM pregnant women and those without GDM were antimony: 0.49(0.31,0.83)vs.0.38(0.24,0.59),tin: 0.70(0.45,1.11)vs.0.58(0.39,0.89),barium: 2.55(1.31,2.55)vs.2.09(0.93,4.29),chromium: 0.50(0.37,0.87)vs.0.46(0.31,0.69),selenium: 47.82(35.71,67.21)vs.42.24(31.71,57.33),cadmium: 0.89(0.59,1.32)vs.0.84(0.55,1.25),lead: 2.16(1.44,3.06)vs.2.02(1.46,2.80),respectively.Among them,the concentrations of antimony,tin,barium,chromium,and selenium were significantly higher in pregnant women with GDM than those without(all P < 0.01).After adjusting for known confounding factors,robust Poisson regression showed that the risk of GDM increased in a dose-dependent manner with antimony and tin in the urine.Compared with the lowest tertile of urinary concentration,the relative risk(RR)of GDM in the highest tertile group was 1.71(95% confidence interval(CI): 1.21,2.42)for Sb and 1.44(95% CI: 1.04,2.01)for Sn respectively.Stratified analyses according to the age median,fetal sex,and pre-pregnancy BMI showed that the relationship between Sb or Sn and the risk of GDM remained statistical significance in all group.The interaction of Sb or Sn and each stratification factor with GDM risk were no statistically significant.The relative risk of GDM in pregnant women with the highest tertile of urinaryselenium was 1.42(95% CI: 1.01,2.01)compared with the lowest tertile.The correlation between chromium,barium and the increased risk of GDM was on the edge of statistical significance;no statistical correlation was observed between lead,cadmium and the risk of GDM.Compared with the lowest tertile of the comprehensive score based on 7 metal concentrations and their relative estrogenic activities,the RR of GDM in the highest tertile was 1.64(95% CI: 1.17,2.28).The risk of GDM increased by 80%(RR: 1.80;95% CI: 1.40,2.33)for each unit of WQS,and Sb,Ba,and Sn accounted for 38.5%,14.6%,and 13.9% respectively.Conclusions: Under the exposure level of this population,higher exposure to Sb or Sn leads to a higher risk of GDM,which remained in the stratified analysis by age,fetal sex,pre-pregnancy BMI.The higher level of urinary Se or Cr was found associated with a higher risk of GDM,but the relationships between need further studied in combination with a nutritional assessment.Higher exposure to barium was at the edge of statistical significance;no statistical correlation between urinary Pb,Cd and the risk of GDM had been observed.Assessing the association of mixed exposure of the seven metals with the risk of GDM using comprehensive scores,higher comprehensive scores were associated with increased risk of GDM.Increased WQS of mixed exposure of seven elements significantly increased the risk of GDM,among which Sb,Ba,and Sn were the main sources of risk. |
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