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

Maitreyi Mazumdar,Ema G Rodrigues,Md Omar Sharif Ibne Hasan,Mahmuder Rahman,Quazi Quamruzzaman,Jacob Selhub,David C Christiani,Fareesa Silva,Linda Valeri,Selim Mia,Ligi Paul,Md Golam Mostofa,Rezina Hamid

doi:10.1186/s12940-015-0020-0

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.

Highlights

Arsenic induces neural tube defects in several animal models, but its potential to cause neural tube defects in humans is unknown
This study aimed to identify whether environmental arsenic exposure is associated with higher risk of neural tube defects, and whether environmental arsenic exposure modifies the protective effect of folic acid supplementation
39.4% of the study population reported periconceptional folic acid use, which is similar to other studies in Bangladesh [21]

Summary

Introduction

Arsenic induces neural tube defects in several animal models, but its potential to cause neural tube defects in humans is unknown. The potential mechanisms of arsenic-induced neural tube defects include direct toxicity from reactive oxygen species to the developing neural plate [8], and disruption of maternal glucose metabolism [10]. Mice with specific defects in folate transport had higher rates of neural tube defects after in utero arsenic exposure than wild-type mice exposed [5,11]. Understanding the associations between arsenic and folate is important for public health practitioners as folic acid supplementation and fortification is the primary strategy for neural tube defect prevention. In addition to preventing neural tube defects, folic acid is recognized to reduce the risk of other congenital anomalies, with the strongest evidence supporting folic acid’s role in reduction of cardiac malformations [12]

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