| Objectives Gestational diabetes mellitus(GDM)is a common obstetric complication with adverse effects on both mothers and their children.Previous studies revealed the link between metal exposure and incidence of diabetes mellitus(DM),but the data on the associations of maternal metal exposure with GDM are scarce.We examined the association between metal exposure and risks of GDM among a population-based birth cohort.There are three objectives in our study: 1)to explore the association between levels of arsenic and chromium and the risk of GDM at different gestational stages in a birth cohort;2)to assess whether prepregnancy BMI and maternal age affect these associations and to evaluate the critical period;3)to explore the association between serum arsenic levels and chromium levels and the expression of placental inflammatory factors and to evaluate the possible effect of placental inflammatory factors on the association between levels of arsenic and chromium and the risk of GDM.Methods The Ma’anshan Birth Cohort(MABC)Study,conducted between May 2013 and September 2014 in the City of Ma’anshan,Anhui province in China,is a prospective cohort study.3474 women were enrolled in total.After losses due to miscarriage and stillbirth(n=155),loss to follow-up(n=7)and the exclusion of twins(n=39)and pre-gestational diabetes mellitus(PGDM)(n=13),3260 pregnant women were eligible and followed up in this study.Blood samples were collected from participants and face-to-face interview were conducted.2969 and 3099 maternal blood samples were provided in the first and second trimester of pregnancy,respectively,and 2712 cord blood samples and 2508 placental samples were collected at delivery.Oral and written consents were collected from all participants.Among the confirmed participants,the GDM screening used a 75 g oral glucose tolerance test(OGTT)at weeks 24-28 of gestation based on the criteria from Chinese Medical Association.Arsenic and Chromium concentrations were determined at multiple time points during pregnancy by ICP-MS.The mRNA expression of 14 placental inflammatory cytokines(IL-1β,IL-10,MCP-1,CRP,HO-1,HIF1α,GRP78,TNF-α,IL-4,IL-6,IL-8,IFNγ,CD206 and CD68)were determined by RT-PCR.To compare the differences between GDM and normal groups,we applied independent sample t-test and independent non-parametric test for normally and non-normally distributed continuous variables,respectively.For categorical variables,we used Pearson Chi-square test to compare them.Quartile cutoff points at 25%,50% and 75% were used to transform arsenic and chromiun levels into categorical variables.We used binary logistic regressions model to study the correlation between arsenic,chromium levels and GDM risk.Adjustments were made for maternal age,prepregnancy body mass index(BMI),monthly income,gestational age and parity,because those factors may contribute to GDM risk.The effects of combination of arsenic and chromium in early pregnancy on GDM were also analyzed.A product variable,arenic*chromium,was set in logistic regression model.Statistical interaction was analyzed and evaluated by odds ratio of product variable and Excel.Multivariable linear regression analyses were used to explore that whether arsenic or chromium in early pregnancy associated with inflammatory factors after the levels of 14 inflammatory factors and concentrations of arsenic and chromium have been natural log transformed.All statistical analysis were done using SPSS statistical software(v.16)and p<0.05 was considered to be statistically significant.Results A total of 419(12.85%)women were diagnosed with GDM.Maternal age,prepregnancy BMI,gestational age,parity and monthly income were significant difference(p<0.05)between GDM and normal groups,with higher maternal age,higher prepregnancy BMI,lower gestational age in GDM group.The incidences of GDM gradually increased with increasing quartiles of As levels with significant trend.As levels were associated with the GDM(OR:1.77,95%CI: 1.29-2.43)at only the 4th quartile in the first trimester.After adjustment for maternal age,prepregnancy BMI,monthly income,gestational age and parity,the association remains significant(OR:1.71,95%CI: 1.23-2.38).Stratified analyses showed the associations were largely limited to normal maternal age and normal weight women.Cr levels were associated with the GDM(95%CI: 1.29-2.43)at the 2nd quartile in the first trimester and at the 3nd quartile in the second trimester.After adjustment for maternal age,prepregnancy BMI,monthly income,gestational age and parity,the association remain significant(95%CI: 1.22-2.38).Stratified analyses showed the associations were largely limited to maternal age of ≥30y group and normal weight women in the second trimester.There was statistical interaction between arsenic and chromium in early pregnancy and GDM risks.The expression of placental inflammatory factors were significant difference(p<0.05)between GDM and normal groups,with higher HIF1α and GRP-78 levels,lower IL-4 and CD206 levels in GDM group.In the multivariable linear regression models,As levels in the first trimester were related with increased expression of placental inflammatory factor CRP,and with decreased expression of placental inflammatory factor IL-4,Cr levels in the first trimester were related with decreased expression of placental inflammatory factor GRP78 and IL-4.Conclusion Our study showed an association between As and GDM in a birth cohort and explored first trimester may be the critical period for As associated GDM.This association was universal in the general pregnant population of normal age and of normal weight.Lower chromium level related to GDM risk in the first and second trimester.This association was limited to maternal age of ≥30y group and normal weight women in the second trimester.There was interaction between arsenic and chromium in early pregnancy and GDM odds.Inflammatory factor involved in the pathogenesis of GDM,As and Cr of early pregnancy may affected the placental expression of inflammatory factor.Inflammatory factor may involved in the pathogenesis of As,Cr and GDM. |
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