Arsenic Exposure Affects Plasma Insulin-Like Growth Factor 1 (IGF-1) in Children in Rural Bangladesh

BACKGROUND: Exposure to inorganic arsenic (As) through drinking water during pregnancy is associated with lower birth size and child growth. The aim of the study was to assess the effects of As exposure on child growth parameters to evaluate causal associations. METHODOLOGY/FINDINGS: Children born in a longitudinal mother-child cohort in rural Bangladesh were studied at 4.5 years (n=640) as well as at birth (n=134). Exposure to arsenic was assessed by concurrent and prenatal (maternal) urinary concentrations of arsenic metabolites (U-As). Associations with plasma concentrations of insulin-like growth factor 1 (IGF-1), calcium (Ca), vitamin D (Vit-D), bone-specific alkaline phosphatase (B-ALP), intact parathyroid hormone (iPTH), and phosphate (PO(4)) were evaluated by linear regression analysis, adjusted for socioeconomic factor, parity and child sex. Child U-As (per 10 µg/L) was significantly inversely associated with concurrent plasma IGF-1 (β=-0.27; 95% confidence interval: -0.50, -0.0042) at 4.5 years. The effect was more obvious in girls (β=-0.29; -0.59, 0.021) than in boys, and particularly in girls with adequate height (β=-0.491; -0.97, -0.02) or weight (β=-0.47; 0.97, 0.01). Maternal U-As was inversely associated with child IGF-1 at birth (r=-0.254, P=0.003), but not at 4.5 years. There was a tendency of positive association between U-As and plasma PO(4) in stunted boys (β=0.27; 0.089, 0.46). When stratified by % monomethylarsonic acid (MMA, arsenic metabolite) (median split at 9.7%), a much stronger inverse association between U-As and IGF-1 in the girls (β=-0.41; -0.77, -0.03) was obtained above the median split. CONCLUSION: The results suggest that As-related growth impairment in children is mediated, at least partly, through suppressed IGF-1 levels.