Arsenic is associated with reduced effect of folic acid in myelomeningocele prevention: a case control study in Bangladesh

Abstract

BackgroundArsenic induces neural tube defects in several animal models, but its potential to cause neural tube defects in humans is unknown. Our objective was to investigate the associations between maternal arsenic exposure, periconceptional folic acid supplementation, and risk of posterior neural tube defect (myelomeningocele) among a highly exposed population in rural Bangladesh.MethodsWe performed a case–control study that recruited physician-confirmed cases from community health clinics served by Dhaka Community Hospital in Bangladesh, as well as local health facilities that treat children with myelomeningocele. Controls were selected from pregnancy registries in the same areas. Maternal arsenic exposure was estimated from drinking water samples taken from wells used during the first trimester of pregnancy. Periconceptional folic acid use was ascertained by self-report, and maternal folate status was further assessed by plasma folate levels measured at the time of the study visit.ResultsFifty-seven cases of myelomeningocele were identified along with 55 controls. A significant interaction was observed between drinking water inorganic arsenic and periconceptional folic acid use. As drinking water inorganic arsenic concentrations increased from 1 to 25 μg/L, the estimated protective effect of folic acid use declined (OR 0.22 to 1.03), and was not protective at higher concentrations of arsenic. No main effect of arsenic exposure on myelomeningocele risk was identified.ConclusionsOur study found a significant interaction between drinking water inorganic arsenic concentration from wells used during the first trimester of pregnancy and reported intake of periconceptional folic acid supplements. Results suggest that environmental arsenic exposure reduces the effectiveness of folic acid supplementation in preventing myelomeningocele.

Does arsenic increase the risk of neural tube defects among a highly exposed population? A new case–control study in Bangladesh

“…Myelomeningocele was the neural tube defect identified most often and most reliably in our pilot studies (Mazumdar et al, , ) and, therefore, is the focus of this current study. There is currently no surveillance system in Bangladesh to identify all pregnancies affected by neural tube defect; a surveillance system following all pregnancies might be able to identify a more severe phenotype, such as those who die during gestation or are otherwise undiscovered.…”

Arsenic trioxide targets MTHFD1 and SUMO-dependent nuclear de novo thymidylate biosynthesis

“…Exposure to low doses of arsenic from contaminated drinking water and food can cause cancer, skin lesions (41, 51), cardiovascular disease, diabetes, neurotoxicity, and developmental effects, and can decrease the efficacy of folic acid in NTD prevention (11,37,41). Despite mitigation efforts, chronic exposure to low-dose arsenic persists as a global public health issue affecting an estimated 200 million people worldwide (38,41,51).…”

“…Arsenic is one of the environmental factors that may contribute to reduced efficacy of folic acid supplementation in NTD prevention (37).…”

Safety of folic acid

“…NTDs are generally recognized to result from complex gene–nutrient–environment interactions . Environmental toxins also contribute to risk in limited and specific contexts, such as the contamination of corn‐based products with the mycotoxin fumonisin or arsenic exposure . Current knowledge does not allow a priori identification of women who are at risk of folic acid–responsive NTDs.…”