Arsenic modifies the effect of folic acid in spina bifida prevention, a large hospital-based case-control study in Bangladesh
Journal
Environmental Health
Journal Volume
23
Journal Issue
1
Start Page
Article number 51
ISSN
1476-069X
Date Issued
2024-06-03
Author(s)
Mukherjee, Sudipta Kumer
Ekramullah, Sheikh Muhammad
Arman, D. M.
Islam, Md Joynul
Azim, Mubinul
Rahman, Asifur
Rahman, Md Nafaur
Ziauddin, Md
Tindula, Gwen
Suchanda, Hafiza Sultana
Gomberg, Diana F.
Weisskopf, Marc G.
Liang, Liming
Warf, Benjamin C.
Christiani, David C.
Mazumdar, Maitreyi
Abstract
Background: Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother's arsenic exposure, folic acid, and spina bifida risk in Bangladesh.
Methods: We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure.
Results: We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother's arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52-2.29, p = 0.82).
Conclusions: Mother's arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.
Subjects
Arsenic
Bangladesh
Folic acid
Spina bifida
Publisher
Springer Science and Business Media LLC
Type
journal article