(P11-025-23) Arsenic Exposure, One-Carbon Metabolism Biomarkers, and Population-Based Risk of Neural Tube Defects

Objectives: To examine the prevalence and impact of arsenic exposure on folate biomarkers and predicted risk of neural tube defects (NTD) in a population-based biomarker survey in Southern India.

Methods: Participants were 979 women (15–40 y, not pregnant or lactating). A random subset (n=250) of archived urine samples was assessed for total arsenic (ICP-MS) and creatinine (enzymatic chemistry analyzer). Red blood cells (RBC) and serum folate (WHO-recommended microbiologic assay) were evaluated. Arsenic concentrations were corrected for urinary creatinine (CRE), and elevated urinary arsenic was defined as >10 µg/g. Biomarkers were naturally logarithmically transformed. Linear regression models were used to examine associations between arsenic and folate concentrations. A previously developed Bayesian model and RBC folate and arsenic distributions in this population were used to predict NTD prevalence per 10,000 births.

Results: Urinary arsenic concentrations (geometric mean [GM]: 8.6 µg/L [95% CI: 7.7–9.5]; CRE-corrected: 14.7 µg/g [13.8–15.7]) were detectable in all samples. While < 1% of women had urinary arsenic >50 µg/L, 45% had concentrations >10 µg/L (80% after CRE-correction). Continuous CRE-corrected urinary arsenic concentrations (µg/g) were associated with lower RBC folate (β: -0.20 [SE: 0.06], p=0.001) and serum folate (β: -0.16 [SE: 0.07], p=0.026) concentrations. Women with urinary arsenic >10 µg/g had significantly lower RBC folate (GM: 522 [95% CI: 490–556] vs 626 [552–710] nmol/L; p=0.012) and serum folate (GM: 15.6 [95% CI: 14.5–16.8] vs 19.8 [17.1–23.1] nmol/L; p=0.005) concentrations, compared to women with arsenic ≤10 µg/g. The predicted NTD prevalence based on RBC folate concentrations among women with urinary arsenic >10 µg/g was 21.2 [95% UI: 16.8–26.4] NTDs per 10,000 births. Among women with arsenic ≤10 µg/g, mean RBC folate concentrations were near the optimal threshold for NTD prevention ( >748 nmol/L).

Conclusions: Findings provide preliminary evidence of low-level arsenic exposure in this folic acid-naïve population at levels similar to the United States and suggest arsenic may modify RBC folate concentrations and population-level NTD risk.

Funding Sources: US Centers for Disease Control and Prevention, University of South Carolina Disability Research and Dissemination Center; NIH T32DK007158 (HMG), 5T32HD087137 (AF)