Environmental Exposure and Biomarker Lab

Highlights

• Drinking water arsenic was negatively associated with vaccine-related diphtheria antibody.
• Null associations were observed between tetanus antibody titers and drinking water arsenic.
• Pregnancy appeared to be the most susceptible period for arsenic-related immunotoxicity.
• Arsenic-related effects were most pronounced in females, or children that were stunted growth or underweight.

Background

Arsenic can impair immune function. Timing of exposure can influence potential immunotoxicity of arsenic exposure. We examined the association between drinking water arsenic concentrations (W-As) measured repeatedly during different exposure windows in early life and serum concentrations of IgG antibodies against diphtheria and tetanus toxoids (diphtheria and tetanus antibody).

Methods

A prospective cohort of pregnant women was recruited in Bangladesh (2008–2011). Averaged W-As levels were calculated for: pregnancy (W-Aspregnancy): ≤16 weeks gestation and <1 month; toddlerhood (W-Astoddlerhood): 12 and 20–40 months; and early childhood (W-Aschildhood): 4–5 years. Serum was collected from 502 vaccinated children at age 5 and concentrations of diphtheria and tetanus toxoid IgG (i.e. antibody) were quantified. Antibody concentrations >0.1 IU/mL were considered clinically sufficient for protection. Associations were estimated using linear and logistic regression models.

Results

Inverse associations were observed between W-Aspregnancy and serum diphtheria antibody levels, while null associations were observed between W-As and tetanus antibody. Children within the highest versus lowest tertile of W-Aspregnancy had 91% greater odds of having clinically insufficient concentrations of diphtheria antibody (Odds ratio:1.91, 95% confidence interval (CI): 1.03, 3.56). Among females, a doubling in W-Aspregnancy was associated with 12.3% (95%CI: −20.1%, −4.5%) lower median concentrations of diphtheria antibody. Tetanus antibody was only associated with W-Aspregnancy among females (percent change in median: −9.5%, 95%CI: −17.6%, −1.3%). Among children who were stunted or underweight, a doubling in W-Aspregnancy was associated with decreased diphtheria antibody of 19.8% (95%CI: −32%, −7.5%) and 14.3% (95%CI: −26.7%, −2%), respectively.

Conclusions

Among vaccinated children, W-As measured during pregnancy was associated with decreased diphtheria antibody levels, but not tetanus antibody. However, W-As measured during toddlerhood and early childhood were not associated with either antibody outcome. Children's sex and malnutrition status were important effect modifiers of W-As for both diphtheria and tetanus antibody levels, highlighting the importance of these factors and the timing of the exposure when evaluating the effect of arsenic on humoral immunity.