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Meta-Analysis
. 2025 Jun;117(6):e2494.
doi: 10.1002/bdr2.2494.

Comparing Folic Acid Interventions and Arsenic Reduction Strategies for Neural Tube Defect Prevention in Bangladesh: A Systematic Review and Decision Analysis

Chih-Fu Wei  1   2 , Ernani F Choma  1 , Xingyan Wang  3 , Carrie G Wade  4 , Ya Luan Hsiao  5 , Diane Bao  6 , Sudipta K Mukherjee  7 , David C Christiani  1   8 , Marc G Weisskopf  1 , Liming Liang  3 , Maitreyi Mazumdar  1   6
Affiliations
Meta-Analysis

Comparing Folic Acid Interventions and Arsenic Reduction Strategies for Neural Tube Defect Prevention in Bangladesh: A Systematic Review and Decision Analysis

Chih-Fu Wei et al. Birth Defects Res. 2025 Jun.

Abstract

Background: Maternal intake of folic acid prevents most cases of neural tube defects (NTDs), and arsenic exposure may increase NTD risk. In Bangladesh, where arsenic exposures are high, understanding the potential impacts of arsenic reduction and folic acid-based interventions can guide decision-making.

Methods: We conducted a systematic review and meta-analysis to estimate the prevalence of NTDs in Bangladesh. We searched PubMed, Embase, Web of Science, Global Health, and Bangladesh Journals Online and extracted data using standardized forms. We used forest plots and random effects models to estimate the prevalence of all NTDs and spina bifida. Decision analysis used assumptions from the literature to compare expected NTD prevalence under strategies incorporating combinations of folic acid supplementation, fortification, and arsenic filters. Sensitivity analyses aimed to quantify the influence of adherence to supplements on estimates.

Results: Eleven studies were included. Prevalences of NTD and spina bifida were 27.4 and 11.2 per 10,000 births, respectively; however, when estimated from population red blood cell folate concentrations, NTD prevalence was higher in both high arsenic exposure (drinking water ≥ 50 μg/L) and lower arsenic exposure groups (34.3 and 25.3 per 10,000 births, respectively). Folic acid fortification reduced the prevalence of NTDs to 11.1 and 9.1 per 10,000 births among high exposure and low exposure groups, respectively. Arsenic filters provided little marginal benefit. Benefits of supplements equaled those of fortification when adherence to supplements exceeded 90%.

Conclusions: Bangladesh has high rates of NTDs and high arsenic exposures. Folic acid fortification is projected to be the most effective strategy for NTD prevention.

Keywords: arsenic; decision analysis; folic acid; neural tube defects; spina bifida.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Decision tree for impacts of different folic acid provision and arsenic reduction strategies. (a) Population with high arsenic exposure and (b) population with low arsenic exposure.
FIGURE 2
FIGURE 2
Forest plot for prevalence of (a) neural tube defects and (b) spina bifida in Bangladesh.
FIGURE 3
FIGURE 3
Estimated mean red blood cell (RBC) folate concentrations in population with (a) high arsenic exposure and (b) low arsenic exposure under different combinations of folic acid fortification, supplementation, and arsenic filtration strategies. We assumed 100% adherence with folic acid supplements. NTDs, neural tube defects.
FIGURE 4
FIGURE 4
Estimated prevalence of neural tube defects (NTD) in population with (a) high arsenic exposure and (b) low arsenic exposure under different combinations of folic acid fortification, supplementation, and arsenic filtration strategies.
FIGURE 5
FIGURE 5
Estimated prevalence of neural tube defects under different rates of adherence to folic acid supplementation in a population with high (≥ 50 μg/L) arsenic exposure.
See this image and copyright information in PMC

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