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

Authors: MAZUMDAR, MAITREYI - Boston Children'S Hospital; IBNE HASAN, MD OMAR SHARIF - Dhaka Community Hospital; HAMID, REZINA - Bangladesh Medical College; VALERI, LINDA - Harvard University; PAUL POTTENPLACKEL, LIGI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SELHUB, JACOB - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RODRIGUES, EMA - Harvard University; SILVA, FAREESA - Boston Children'S Hospital; MIA, SELIM - Dhaka Community Hospital; MOSTOFA, MD GOLAM - Dhaka Community Hospital; QUAMRUZZAMAN, QUAZI - Dhaka Community Hospital; RAHMAN, MAHMUDER - Dhaka Community Hospital; CHRISTIANI, DAVID - Harvard University

Submitted to: Environmental Health
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/20/2015
Publication Date: 4/10/2015
Citation: Mazumdar, M., Ibne Hasan, M., Hamid, R., Valeri, L., Paul Pottenplackel, L., Selhub, J., Rodrigues, E.G., Silva, F., Mia, S., Mostofa, M., Quamruzzaman, Q., Rahman, M., Christiani, D.C. 2015. Arsenic is associated with reduced effect of folic acid in myelomeningocele prevention: a case control study in Bangladesh. Environmental Health. 14:34. https://doi.org/10.1186/s12940-015-0020-0.

Interpretive Summary: Exposure to arsenic is a public health concern in areas where drinking water is contaminated with naturally occurring arsenic or in areas where residual lead arsenate from pesticides is still present in the soil. Arsenic detoxification potentially involves addition of methyl chemical groups to arsenic. Arsenic induces neural tube defects in many animal models, but it is unknown whether arsenic exposure in human mothers increases the risk for neural tube defects in children. Since folate is a precursor for the methyl groups, folate nutrition can influence the outcomes of arsenic exposure. Adequate folate nutrition may reduce toxicity due to arsenic exposure. Exposure to arsenic through drinking water sources from groundwater is a global public health emergency. We determined whether folate nutritional status of mothers exposed to naturally occurring arsenic in drinking water was associated with neural tube defects in their children in rural Bangladesh. Periconceptional folic acid use protected against neural tube defects due to arsenic in drinking water. However, the estimated protective effect of folic acid use declined when drinking water arsenic concentrations increased from 1 to 25 micrograms/L, and folic acid was not protective at higher concentrations of arsenic. Exposure to arsenic itself was not associated with increased risk for neural tube defects. The results of this study suggest that environmental arsenic exposure reduces the effectiveness of folic acid supplementation in preventing neural tube defects.

Technical Abstract: Background: Arsenic 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. Methods: We 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. Results: Fifty-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 (mu)g/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. Conclusions: Our 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.