title: Arsenic is associated with reduced effect of folic acid in myelomeningocele prevention: a case control study in Bangladesh.
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 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.
  
  
  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.
authors.affiliation: Department of Neurology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, USA. maitreyi.mazumdar@childrens.harvard.edu.|Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, USA. maitreyi.mazumdar@childrens.harvard.edu.
authors.forename: Maitreyi
authors.initials: M
authors.lastname: Mazumdar
authors.affiliation: Dhaka Community Hospital, 190/1 Baro Moghbazar, Wireless Railgate, Dhaka, 1217, Bangladesh. sharif_paed@yahoo.com.
authors.forename: Md Omar Sharif
authors.initials: MO
authors.lastname: Ibne Hasan
authors.affiliation: Bangladesh Medical College, 14/A Dhanmondi, Dhaka, 1209, Bangladesh. rezina.hamid@gmail.com.
authors.forename: Rezina
authors.initials: R
authors.lastname: Hamid
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA, USA. liv839@mail.harvard.edu.
authors.forename: Linda
authors.initials: L
authors.lastname: Valeri
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA, USA. ligi.paul_pottenplackel@tufts.edu.
authors.forename: Ligi
authors.initials: L
authors.lastname: Paul
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA, USA. jacob.selhub@tufts.edu.
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.affiliation: Department of Neurology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, USA. emarod@hsph.harvard.edu.|Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, USA. emarod@hsph.harvard.edu.
authors.forename: Ema G
authors.initials: EG
authors.lastname: Rodrigues
authors.affiliation: Department of Neurology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, USA. fareesa.silva@childrens.harvard.edu.
authors.forename: Fareesa
authors.initials: F
authors.lastname: Silva
authors.affiliation: Dhaka Community Hospital, 190/1 Baro Moghbazar, Wireless Railgate, Dhaka, 1217, Bangladesh. dch@bangla.net.bd.
authors.forename: Selim
authors.initials: S
authors.lastname: Mia
authors.affiliation: Dhaka Community Hospital, 190/1 Baro Moghbazar, Wireless Railgate, Dhaka, 1217, Bangladesh. mostofa07@gmail.com.
authors.forename: Md Golam
authors.initials: MG
authors.lastname: Mostofa
authors.affiliation: Dhaka Community Hospital, 190/1 Baro Moghbazar, Wireless Railgate, Dhaka, 1217, Bangladesh. qzaman07@gmail.com.
authors.forename: Quazi
authors.initials: Q
authors.lastname: Quamruzzaman
authors.affiliation: Dhaka Community Hospital, 190/1 Baro Moghbazar, Wireless Railgate, Dhaka, 1217, Bangladesh. dcht87@gmail.com.
authors.forename: Mahmuder
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, USA. dchris@hsph.harvard.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D001459:Bangladesh; D016022:Case-Control Studies; D019587:Dietary Supplements / Q000032:analysis; D060766:Drinking Water / Q000032:analysis*; D004781:Environmental Exposure; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008591:Meningomyelocele / Q000139:chemically induced / Q000517:prevention & control*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D060766:Drinking Water; D014874:Water Pollutants, Chemical; D005492:Folic Acid; D001151:Arsenic