A Prospective Cohort Study Examining the Association Between Maternal Arsenic Exposure, Fetal Loss, and Neonatal Mortality

Abstract

Arsenic crosses the placenta, possibly increasing the risk of adverse reproductive outcomes. We aimed to examine the association between maternal arsenic exposure and fetal/neonatal survival using a prospective cohort of 1,616 maternal-infant pairs recruited at ≤ 16 weeks gestational age in Bangladesh (2008-2011). Arsenic concentration was measured in maternal drinking water at enrollment. Extended Cox regression (both time-dependent coefficients and step functions) was used to estimate the time-varying association between maternal arsenic exposure and fetal/neonatal death (all mortality between enrollment and one month after birth). A sensitivity analysis assessed gestational arsenic exposure using maternal urine at enrollment. We observed 203 fetal losses and 20 neonatal deaths. Higher arsenic exposure was associated with a slightly increased mortality rate through the second trimester, and then switched directions around 32 weeks gestation. In the step function model, the hazard ratios (HR) of mortality for each unit increase in natural log drinking water arsenic (μg/L) ranged from HR=1.7 in weeks 25-28 (95% CI: 1.3, 2.1), to HR=0.9 in weeks 33-36 (95% CI: 0.6, 1.2). This non-linear association suggests that arsenic may exert survival pressure on developing fetuses, potentially contributing to survival bias, and may also indicate that arsenic toxicity differs by fetal developmental stage.