Arsenic Exposure, Periconceptional Folic Acid Supplementation, and the Risk for Neural Tube Defects: A Case–Control Study

Arsenic induces neural tube defects (NTDs) in laboratory animals, but evidence in human populations is scarce. We examined the association between arsenic exposure and the risk for NTDs and explored whether folic acid supplementation could attenuate the risk posed by arsenic exposure. Based on a population-based birth defects surveillance program, this case–control study of 408 women with NTD-affected pregnancies and 593 women with healthy pregnancies was recruited in northern China between 2003 and 2016. Arsenic concentrations in placental tissues were quantified by inductively coupled plasma–mass spectrometers. The odds ratio (OR) with 95% confidence interval (95% CI) was calculated with logistic regression to evaluate the association between arsenic exposure and the occurrence of NTDs while adjusting for confounding factors. Potential modification effects of folic acid supplementation on the association between arsenic exposure and NTD risk were examined. Placental median arsenic concentrations were higher in NTD cases (13.32 ng/g) than in controls (10.51 ng/g). An arsenic concentration above the median of all participants was associated with an increased risk for NTDs with an OR of 1.63 (95% CI 1.13–2.35). Among women who reported not taking folic acid supplements during the periconceptional period, arsenic exposure showed an NTD risk of 1.68 (95% CI 1.09–2.58), while there was no association between arsenic exposure and NTD risk among women who reported taking folic acid supplements [adjusted OR (95% CI) 1.30 (0.58–2.92)]. Arsenic exposure is a risk factor for NTDs, but this risk could be alleviated by folic acid supplementation.