A Nested Case-Control Study On The Relationship Between Nickel,Barium,Lead,and Titanium Exposure During Pregnancy And Congenital Heart Disease In Offspring

ObjectiveBased on the Lanzhou birth cohort in China,this study aims to understand the concentration of nickel,barium,lead,and titanium in the blood of pregnant women,and explore the relationship between their exposure alone and combined exposure and the risk of fetal congenital heart disease(CHD).MethodsA prospective nested case-control design was used to investigate the association between body exposure to nickel,barium,lead,and titanium during pregnancy and fetal CHD risk.The study population was recruited from 2010 to 2012 at Gansu Maternal and Child Health Hospital in Lanzhou,China.The pregnant women who agreed to be enrolled in the cohort underwent fetal CHD screening by fetal heart color ultrasound during the second trimester.The children and their mothers who were diagnosed with CHD after birth and were still clearly diagnosed with CHD at the follow-up 42 days later were included in the case group.The matching conditions were that the mothers of the children were 2 years older than the case group and lived in the same street as the case group.Healthy newborns and their mothers were selected from the cohort as controls.Fasting venous blood was collected from pregnant women before hospitalization for exposure analysis of nickel,barium,lead,and titanium.The concentrations of nickel,barium,lead,and titanium in the blood of pregnant women were measured by inductively coupled plasma mass spectrometry.A conditional Logistic regression model was used to explore the relationship between single and combined exposure levels of nickel,barium,lead,and titanium during pregnancy and fetal CHD and subtypes.Results1.A total of 291 maternal and infant pairs were included in the study,including 97 maternal and infant pairs in the case group,including 43 infants with simple CHD and 54 infants with complex CHD,and 194 infants in the control group.The median concentrations of nickel,barium,lead,and titanium in pregnant women were 25.58μg/L,84.38μg/L,69.67μg/L,and 304.65μg/L,respectively.2.The logistic regression model showed that the exposure levels of nickel,lead,and titanium in the blood of pregnant women were correlated with the risk of CHD in their offspring.Compared with a low exposure level,a high exposure level of nickel in maternal blood(≥189.29μg/L)increased the risk of CHD in offspring by 2.098 times(OR = 3.098,95%CI:1.322-7.260).The high blood lead exposure level of pregnant women(≥86.70μg/L)increased the risk of CHD by 1.192 times(OR = 2.192,95%CI: 1.021-4.707).High blood exposure to titanium in pregnant women(≥ 404.22μg/L)increased the risk of CHD in offspring by 3.065 times(OR = 4.065,95%CI: 1.887-8.758).Increased blood exposure to nickel,barium,lead,and titanium in pregnant women also increased the risk of CHD in offspring(high vs.low exposure: OR = 5.946,95%CI: 2.872-12.309).3.The logistic regression model showed that the blood exposure level of titanium and the combined exposure level of the four target substances in pregnant women were associated with the risk of different types of CHD.High blood nickel exposure in pregnant women increased the risk of complex CHD(high vs.low exposure: OR = 4.321,95%CI:1.646-11.348).Conclusions1.The exposure level of nickel,lead,and titanium in the blood of pregnant women is positively correlated with the risk of CHD in their offspring,and the risk increases gradually with the increase of the exposure level of nickel,lead,and titanium.2.The exposure level of nickel and titanium in the blood of pregnant women is correlated with the type of CHD in their offspring.3.The combined exposure levels of nickel,barium,lead,and titanium in the blood of pregnant women are correlated with the increased risk of CHD and different types of congenital heart disease in their offspring.