Association of Chromosomal Abnormalities with Prenatal Exposure to Heavy Metals: A Nested Case-Control Study in High-Risk Pregnant Women in China

Prenatal exposure to heavy metals causes multiple hazards to fetal growth and development. Epidemiological studies on the association between heavy metals and fetal chromosomal abnormalities (CAs) are lacking. We conducted a nested case-control study in a cohort of high-risk pregnant women in China from September 2018 to June 2021. A total of 387 participants were diagnosed with fetal CAs in the case group and 699 were diagnosed with a normal karyotype in the control group. Amniotic fluid concentrations of 10 metals (barium, cobalt, antimony, manganese, ferrum, copper, selenium, strontium, vanadium, and chromium) were measured using inductively coupled plasma-mass spectrometry. We applied quantile g-computation and weighted quantile sum regression to assess the overall effect of metal mixtures and identify metals with significant weight. Logistic and Poisson regression analyses were used to estimate the effects of metals on CAs and CAs subtypes. Our results showed that the metal mixture concentrations were positively associated with the risk of fetal CAs. In adjusted logistic models, Sb was associated with fetal CAs (OR=1.15, 95% CI: 1.02-1.30), and revealed a linear dose-response relationship between Sb level and the risk of fetal CAs. Additionally, the exploratory analysis revealed that Sb levels were associated with Klinefelter syndrome (OR=1.452, 95% CI: 1.063-1.984) and Turner syndrome (OR=1.698; 95% CI,1.048-2.751). Our study revealed that metal mixtures are associated with a higher risk of fetal CAs and that this association may be driven primarily by Sb. Moreover, we provide a genetic perspective on the effects of heavy metals on sexual development in humans.