Increased Arsenic Levels in Both Environmental Measurements and Biomonitoring Results Are Associated with Elevated Risk of Spina Bifida

BACKGROUND AND AIM: Arsenic is associated with multiple adverse reproductive outcomes, and previous studies suggested higher risk of neural tube defects among mothers exposed to higher concentration of well water arsenic in Bangladesh. We further examine the association using water arsenic as proxy for external exposure and toenail as biomarkers for internal dose. METHODS: Parental toenail and water arsenic concentrations were examined in a case-control study in National Institute of Neurosciences & Hospital, Dhaka, Bangladesh. The associations between log-transformed and percentile arsenic concentrations and physician-diagnosed spina bifida were evaluated with logistic regression and cluster analysis, adjusted for maternal age, maternal BMI, parity, educational level, folic acid use and second-hand smoke exposure during pregnancy and weighted by self-reported dietary patterns. RESULTS:Median concentration for water, maternal and paternal arsenic are 2.0 ppb, 0.4 and 0.5 microgram per gram toenail among 280 included child-parent trios (156 with spina bifida) with complete exposure data. We observed associations between highest quartile maternal arsenic levels, higher than 10 ppb arsenic in water and spina bifida risk for their children after weighted for diet (Adjusted OR for water arsenic=1.49, 95% CI=1.00-2.06; adjusted OR for maternal arsenic=1.57, 95% CI=1.10-2.24), and higher composite exposure in both hierarchical clustering and k-means clustering were also associated with increased risk after weighting. Effect heterogeneity was observed between different folic acid supplement conditions, in which dose-response was attenuated for both water and paternal concentrations. CONCLUSIONS:Prenatal inorganic arsenic exposure was associated with elevated risk of spina bifida in Bangladesh, and joint parental exposure is associated with a higher risk. Investigations and interventions to mitigate arsenic exposure during for pregnant women are warranted. KEYWORDS: Heavy metals, birth outcomes, children's environmental health