Association between maternal antimony exposure and offspring congenital heart defects: findings from a large birth cohort study

Background: This nested case-control study aimed to investigate the association between maternal blood antimony concentrations and the risk of congenital heart defects (CHDs) in offspring, identify potential risk factors for CHDs, and inform prevention strategies. Method: The study was conducted within a birth cohort established jointly by Gansu Provincial Maternity and Child Care Hospital and Yale University. A total of 291 women were enrolled, including 97 women who gave birth to infants with CHDs (case group) and 194 controls. Controls were selected from the same cohort using a 1:2 matching ratio and matched to cases by age and community. Maternal whole blood samples were collected during prenatal hospitalization before delivery, and antimony concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Receiver operating characteristic (ROC) curve analysis was used to determine an antimony exposure cutoff and classify participants into high and low exposure groups. Conditional multivariable logistic regression was performed to assess the association between maternal blood antimony concentrations and the risk of CHDs in offspring. Results: The mean maternal blood antimony concentration was 13.05 μg/L in the control group and 20.30 μg/L in the CHDs group, and the difference between the two groups was statistically significant. Compared with the low exposure group, the high exposure group was associated with a significantly higher risk of CHDs in offspring (OR = 4.455, 95% CI: 2.029-9.782). Similar associations were observed for the subgroups of isolated CHDs, great arteries malformation, septal defects, and atrial septal defects (ASDs). For each 6 μg/L increment in maternal blood antimony, a 38.9% higher risk of CHDs in offspring (OR = 1.389, 95% CI: 1.110-1.735), with consistent findings in the isolated CHDs, septal defects, and ASDs subgroups. Restricted cubic spline (RCS) analysis showed that when maternal blood antimony exceeded 18.409 μg/L, CHDs risk in offspring increased with rising antimony levels. Conclusion: Higher maternal blood antimony concentrations were associated with an increased risk of CHDs in offspring. These findings suggest that the prenatal living environment may be a modifiable target for CHD prevention and warrant efforts to minimize exposure to potential environmental sources of antimony.