孕期重金属元素和微量元素水平与子代先天性心脏病相关性的前瞻性队列研究

Association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects in offspring:a prospective cohort study

摘要:

目的 探讨孕期重金属元素和微量元素水平与子代先天性心脏病（简称先心病）的相关性，并建立孕期重金属元素和微量元素水平与子代先心病发生概率的预测模型。 方法 基于2010~2012年在甘肃省妇幼保健院开展的前瞻性出生队列研究，采用巢式病例对照研究方法，对14 359名孕妇进行随访观察，以随访观察期内其子代确诊先心病的97名孕妇为先心病组，从队列人群中以1∶2的比例匹配194名子代未患先心病的孕妇为对照组。采用电感耦合等离子体质谱测定孕母孕20~24周时血液样本和胎儿脐血样本中的重金属元素和微量元素水平。采用多因素logistic回归分析评估重金属元素和微量元素水平与子代先心病之间的关联，并构建孕期重金属元素和微量元素水平与子代先心病发生概率的列线图预测模型。 结果 与对照组相比，先心病组孕妇血液样本中铝（aluminium，Al）、钠（natrium，Na）、钙（calcium，Ca）、钛（titanium，Ti）、硒（selenium，Se）、锶（strontium，Sr）、锡（stannum，Sn）、锑（stibium，Sb）、钡（barium，Ba）、钍（thorium，Th）水平较高，差异有统计学意义（P<0.05）；先心病组脐血样本中Al、锌（zinc，Zn）、镁（magnesium，Mg）、钾（kalium，K）、Ca、Ti、铬（chromium，Cr）、铜（copper，Cu）、砷（arsenic，As）、Se、Sr、银（argentum，Ag）、镉（cadmium，Cd）、Sn、铅（plumbum，Pb）水平显著高于对照组（P<0.05）。多因素logistic回归分析显示，孕妇血液样本中Sb水平升高，其子代患先心病的风险显著增加（^aOR=4.81，P=0.004）；而在脐血样本中，高浓度水平的Al（^aOR=4.22，P=0.013）、Mg（^aOR=8.00，P=0.014）、Pb（^aOR=3.82，P=0.049）与先心病的发生风险增加存在关联。孕期重金属元素和微量元素水平与子代先心病的预测模型中纳入的变量有：孕妇血Al、Th、Sb水平和脐血Al、Mg、Pb水平，绘制的列线图预测模型的校正曲线趋近于理想曲线。 结论 孕期Al、Th、Sb、Mg、Pb水平升高提示子代罹患先心病的风险增加，联合以上指标构建的列线图预测模型可以预测子代先心病的发生概率。

Abstract:

Objective To study the association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects(CHD)in offspring,and to establish a model for predicting the probability of CHD based on the levels of heavy metals and trace elements during pregnancy.Methods Based on the prospective birth cohort study in Gansu Provincial Maternal and Child Health Hospital in 2010-2012,a nested case-control study was conducted for the follow-up observation of 14359 pregnant women.Among the pregnant women,97 pregnant women whose offspring were diagnosed with CHD during follow-up were enrolled as the CHD group,and 194 pregnant women whose offspring had no CHD were selected as the control group.Inductively coupled plasma mass spectrometry was used to measure the levels of heavy metals and trace elements in maternal blood samples and fetal umbilical cord blood samples.A multivariate logistic regression analysis was used to evaluate the association between heavy metal and trace elements and CHD in offspring.A nomogram model for predicting the probability of CHD in offspring was established based on the levels of heavy metals and trace elements during pregnancy.Results Compared with the control group,the CHD group had significantly higher levels of aluminum(Al),natrium(Na),calcium(Ca),titanium(Ti),selenium(Se),strontium(Sr),stannum(Sn),stibium(Sb),barium(Ba),and thorium(Th)in maternal blood samples(P<0.05),as well as significantly higher levels of Al,zinc(Zn),magnesium(Mg),kalium(K),Ca,Ti,chromium(Cr),copper(Cu),arsenic(As),Se,Sr,argentum(Ag),cadmium(Cd),Sn,and plumbum(Pb)in umbilical cord blood(P<0.05).The multivariate logistic regression analysis showed that the increase in the Sb level in maternal blood was associated with the increase in the risk of CHD in offspring[adjusted odds ratio(a OR)=4.81,95%confidence interval(CI):1.65-14.07,P=0.004],while in umbilical cord blood,the high levels of Al(a OR=4.22,95%CI:1.35-13.16,P=0.013),Mg(a OR=8.00,95%CI:1.52-42.08,P=0.014),and Pb(a OR=3.82,95%CI:0.96-15.23,P=0.049)were significantly associated with the risk of CHD in offspring.The levels of Al,Th,and Sb in maternal blood and levels of Al,Mg,and Pb in umbilical cord blood were included in the predictive model for CHD in offspring based on the levels of heavy metals and trace elements during pregnancy,and the calibration curve of the nomogram predictive model was close to the ideal curve.Conclusions Increases in the levels of Al,Th,Sb,Mg,and Pb during pregnancy may indicate the increase in the risk of CHD in offspring,and the nomogram predictive model based on these indices can be used to predict the probability of CHD in offspring.