First Evidence on the Adverse Effect of Maternal Germanium Exposure on Fetal Neural Tube Defects

Germanium (Ge) can induce certain neurotoxic effects and may affect the fetal neural tube development. We aimed to investigate its association with the risk of neural tube defects (NTDs) by adopting integrated evidence. The potential associations between maternal hair Ge concentrations were explored using a relatively large case-control study of 285 NTD cases (women delivering a birth affected by NTDs) and 543 controls (those delivering healthy fetus without NTDs). The potential toxicological pathways and the reliability of the exposure biomarker of hair Ge were confirmed using additional population study and rat model, respectively. The epidemiological study showed that there was a significantly positive association between maternal hair Ge and NTD risk, with odds ratios (95% confidence interval) of 1.91 (1.24- 2.94) and 1.42 (1.00-2.00) for two concerned time-windows covering the early pregnancy period. Likewise, we found a significantly positive dose-response relationship between Ge intake and its concentration in rats' fur sample. By using a birth cohort, we found that maternal Ge exposure may increase oxidation stress and the likelihood of fever or flu among pregnant women, which were both related to NTD risk. We first concluded that maternal Ge exposure was positively associated with NTD risk with integrated evidence.