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Arsenic exposure and serum antibody concentrations to diphtheria and tetanus toxoid in children at age 5: A prospective birth cohort in Bangladesh.

ABSTRACT: 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.

SUBMITTER: Welch BM

PROVIDER: S-EPMC6513691 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Arsenic exposure and serum antibody concentrations to diphtheria and tetanus toxoid in children at age 5: A prospective birth cohort in Bangladesh.

Welch Barrett M BM Branscum Adam A Ahmed Sharia M SM Hystad Perry P Smit Ellen E Afroz Sakila S Megowan Meghan M Golam Mostofa M Ibne Hasan Md Omar Sharif MOS Rahman Mohammad L ML Quamruzzaman Quazi Q Christiani David C DC Kile Molly L ML

Environment international 20190430

<h4>Background</h4>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).<h4>Methods</h4>A prospective cohort of pregnant women was recruited in Bangladesh (2008-2011). Avera ...[more]

PMID: 31051324

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Project description:ObjectiveTetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt. Data on reactogenicity and immunogenicity, particularly after repeated Tdap, are limited. We compared local injection-site and systemic reactions and serologic response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant women by self-reported prior Tdap receipt.Study designPregnant women (gestational age 20-34 weeks) and nonpregnant women receiving Tdap were enrolled in this observational study. Injection-site and systemic reactions were assessed for one week post-vaccination. Pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae, tetanus and diphtheria specific IgG antibody titers were determined by standardized enzyme-linked immunosorbent assay at baseline and 28 days post-vaccination. Reactogenicity and serologic responses were compared by pregnancy status, and within pregnant women by self-reported prior Tdap receipt.Results374 pregnant and 225 nonpregnant women were vaccinated. Severe local or systemic reactions or "any" fever were uncommon (≤3% for both groups). Moderate/severe injection-site pain was significantly higher in pregnant (17.9%) versus nonpregnant (11.1%) women, but did not prompt a healthcare visit. Proportions of other moderate/severe or any severe reactions were not significantly higher in pregnant compared to nonpregnant women. Moderate/severe (including pain) and severe reactions were not significantly higher in pregnant women receiving repeat versus first-time Tdap. Antibody titers increased from baseline to post-vaccination for all vaccine antigens in pregnant and nonpregnant women; post-vaccination titers against pertussis toxin and filamentous hemagglutinin were significantly higher in nonpregnant versus pregnant women (p < 0.01).ConclusionTdap was well-tolerated in pregnant and nonpregnant women. Pregnant women were more likely to report moderate/severe pain at the Tdap injection-site compared with nonpregnant women, but did not necessitate medical visits. Prior Tdap receipt did not increase occurrence of moderate/severe local or systemic reactions in pregnant women. Serologic responses to all vaccine antigens were robust. Clinical Trial Registration@ClinicalTrials.gov. NCT02209623. https://clinicaltrials.gov/ct2/show/NCT02209623.

Project description:BACKGROUND:Preterm birth is a disease of multifactorial etiologies that has environmental, social, and maternal health components. Individual studies have shown that exposure to arsenic contaminated drinking water, child marriage, and low maternal weight gain during pregnancy contribute to preterm birth. These factors are highly prevalent and often co-exist in Bangladesh, a country in South Asia with one of the world's highest prevalences of preterm birth. OBJECTIVE:To evaluate the individual and interactive effects of prenatal arsenic exposure, child marriage, and pregnancy weight gain on preterm birth in a prospective birth cohort in Bangladesh. METHODS:During 2008-2011, we recruited 1613 pregnant women aged ?18years at ?16weeks of gestation and followed them until 1-month post-partum. We measured total arsenic in drinking water (n=1184) and in maternal toenails (n=1115) collected at enrollment and ?1-month post-partum, respectively using inductively coupled plasma mass spectrometry. Child marriage (<18years old) was defined using self-report, and 2nd and 3rd trimester pregnancy weight gain was calculated using monthly records. Gestational age was determined at enrollment by ultrasound. RESULTS:In multivariate adjusted Poisson regression models, the risk ratios (RR) for preterm birth were 1.12 (95% CI: 1.07-1.18) for a unit change in natural log water arsenic exposure, 2.28 (95% CI: 1.76-2.95) for child marriage, and 0.64 (95% CI: 0.42-0.97) for a pound per week increase in maternal weight during the 2nd and 3rd trimesters. In stratified analysis by child marriage, pregnancy weight gain was inversely associated with preterm birth among women with a history of child marriage (RR=0.58; 95% CI: 0.37-0.92), but not among women with no history of child marriage (RR=86; 95% CI: 0.37-2.01). Mediation analysis revealed that both arsenic exposure and child marriage had small but significant associations with preterm birth via lowering pregnancy weight gain. Similar associations were observed when arsenic exposure was assessed using maternal toenail arsenic concentrations. CONCLUSIONS:Reducing arsenic exposure and ending child marriage could reduce the risk of preterm birth in Bangladesh. Furthermore, enhancing nutritional support to ensure adequate weight gain during pregnancy may provide additional benefits especially for women with a history of child marriage.

Dataset Information

Arsenic exposure and serum antibody concentrations to diphtheria and tetanus toxoid in children at age 5: A prospective birth cohort in Bangladesh.

Publications

Arsenic exposure and serum antibody concentrations to diphtheria and tetanus toxoid in children at age 5: A prospective birth cohort in Bangladesh.

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