A nested case-control study on zinc levels in maternal whole blood and fetal cord blood and risk of congenital heart disease in offspring

BackgroundZinc is a trace element essential for normal fetal heart development, and excess zinc can be toxic. The relationship between maternal and fetal zinc levels and the development of congenital heart disease (CHD) in the offspring is unclear.ObjectiveTo study the effects of maternal and neonatal zinc exposure levels on the risk of developing CHD in the offspring.MethodsThe data and biological samples of the study subjects were derived from the birth cohort established by Gansu Provincial Maternity and Child Care Hospital in Lanzhou from 2010 to 2012. Questionnaire surveys were conducted at baseline in the first trimester and at follow-up visits in the second trimester, the third trimester, and 42 d after delivery. Maternal venous blood during the third trimester and neonatal umbilical venous blood at delivery were collected, and information on their birth outcomes was extracted from medical records. Ninety-seven children with CHD diagnosed by echocardiography at birth and confirmed at the follow-up after 42 d were selected as the case group, and 194 healthy full-term infants were selected as the control group, 1∶2 matched for maternal age and geographical location from the database. The zinc concentrations in whole blood of pregnant mothers and umbilical cord blood of fetuses in both groups were measured by inductively coupled plasma mass spectrometry. According to the quartiles P25 and P75 of zinc levels in the whole blood of pregnant mothers and neonatal cord blood in the control group, zinc exposure was divided into three groups: low, medium, and high. After adjusting for maternal vaginal bleeding in early pregnancy, pre-pregnancy folic acid and vitamin supplementation, birth weight, and umbilical cerclage confounders, a multiple conditional logistic regression model was applied to analyze the associations between maternal whole blood and fetal umbilical cord blood zinc levels and the risk of CHD in the offspring, and a further subgroup analysis was performed by disease classification.ResultsThe medians (P25, P75) of maternal whole blood zinc levels in the case group and the control group were 5.034 (3.456, 6.644) and 4.693 (3.411, 5.646) mg·L−1, respectively, with significant differences between the two groups (P=0.029). The medians (P25, P75) of neonatal cord blood zinc level was 2.153 (1.479, 2.405) mg·L−1 in the case group and 1.636 (1.304, 1.979) mg·L−1 in the control group, with significant differences between the two groups (P5.65 mg·L−1) (OR=2.225, 95%CI: 1.017-4.868). Compared with the neonatal medium zinc exposure level group (1.30-1.98 mg·L−1), the neonatal high exposure level group (>1.98 mg·L−1) also had an increased risk of CHD (OR=4.132, 95%CI: 1.801-9.480). The subgroup analysis results showed that compared with corresponding medium exposure level groups, the risk of simple CHD in the offspring of the maternal high zinc exposure level group was increased (OR=4.081, 95%CI: 1.427-11.669), and the risks of simple CHD (OR=7.122, 95%CI: 2.126-23.854) and complex CHD (OR=5.165, 95%CI: 1.859-14.346) of neonates of the neonatal high zinc exposure level group were increased.ConclusionUnder the exposure levels of the study population, high concentrations of zinc exposure in pregnant mothers and neonates may be associated with the incidence of CHD.