By David Richards
Welch poses for a quick photo during field work.
(Photo courtesy of Barrett Welch)
Prenatal exposure to arsenic may detrimentally impact early childhood immunologic development in Bangladesh, according to a recent NIEHS-funded study from Oregon State University (OSU). The findings, published June 2019, in Environment International, also show that females and children with lower nutritional status are more likely at risk of arsenic-related effects.
“Arsenic, and in particular exposure to arsenic though drinking water, has a diverse set of effects on the developing immune system,” said study lead author Barrett Welch, Ph.D., formerly of OSU and current fellow with the Perinatal and Early Life Epidemiology Group at NIEHS. “This study builds on previous evidence that arsenic is immunotoxic. These results indicate that arsenic may be adversely influencing children’s humoral immunity, unfortunately reducing children’s capacity to sustain protective antibodies years after vaccination.”
Arsenic, a heavy metal, naturally occurs in groundwater in Bangladesh and has been a particularly pervasive issue since the majority of the country’s population switched its public drinking water source from surface water to groundwater. As of 2012, an estimated 19 million to 39 million people were exposed to concentrations above the country’s national standard. Since the country declared arsenic a public health crisis, research from global institutions like NIEHS focusing on pregnant women and their children has been particularly vital.
Health Effects in Young Children
Welch with colleagues from Dhaka Community Hospital in Bangladesh. Welch is currently a fellow with the Perinatal and Early Life Epidemiology Group at NIEHS.
(Photo courtesy of Barrett Welch)
Data for the study were collected from a prospective birth cohort led by Welch’s advisor, Molly Kile, Sc.D., at OSU and in close collaboration with colleagues at the Dhaka Community Hospital Trust (DCH) and Harvard University. “Kile’s leadership and DCH’s remarkable dedication to their communities were critical to the success of this project,” Welch explained. Welch and co-authors assessed the associations of arsenic concentrations measured in household drinking water with children’s immune functions at age 5, as indicated by antibody levels following diphtheria and tetanus vaccinations.
Because inactivated diphtheria and tetanus toxoids are both contained in the same vaccine and given at standardized age intervals, a child’s immune response to vaccination can provide a useful biomarker of immune function. “We decided to use vaccine antibodies because it is considered a relative indicator of humoral immunity for people who have been vaccinated,” Welch said. “It is a relatively simple way to gather a picture of overall humoral immune function in a large population setting.”
The research team analyzed children’s blood samples to assess whether protective levels of each antibody were associated with arsenic levels. They found that arsenic concentration in drinking water was negatively associated with the diphtheria antibody, while no association was found with the tetanus antibody. This shows a relationship between arsenic exposure and the body’s ability to produce those antibodies to protect against effects of exposure. “The results we see in this study are consistent with results seen in other epidemiological studies, which show that relevant concentrations of environmental contaminants like arsenic can influence a child’s immune status,” Welch said.
The study also analyzed the timing of when the mother and child were exposed to the arsenic-contaminated drinking water. Welch and his team found that pregnancy is the most susceptible time of arsenic-related immunotoxicity. “Pregnancy is an incredibly sensitive period for immunological development as there are many critical processes occurring in a short period of time,” Welch explained. After birth, for example, exposures may be lessened during breastfeeding because arsenic does not readily cross into breast milk.
Risk Factors Among Child Sex and Nutrition
Adjusted odds ratios of clinically insufficient tetanus or diphtheria antibodies (<0.1 IU/mL) for a doubling in drinking water arsenic during pregnancy, toddlerhood (12-40 weeks), or early childhood (5 years). Results show that females and kids with stunted growth or underweight status had lower diphtheria antibody at age 5 with higher pregnancy arsenic levels.
(Photo courtesy of Barrett Welch)
The study also finds the sex and nutritional status of children are modifying factors for environmental influence on immune function. Significantly lower diphtheria and tetanus antibody levels in females, but not males, were associated with higher arsenic concentrations in drinking water. “This might be due to the fact that arsenic can influence hormone action and hormones are closely involved with immune function,” Welch added. “I believe the potential interplay between hormones, immune function, and environmental exposures deserves additional attention.” In unrelated studies, arsenic has been shown to influence hormones as an endocrine disruptor.
Children with potentially lower nutritional status, as indicated by being underweight or having stunted growth, also showed negative associations between antibody and arsenic levels, while children with adequate weight or height did not.
Implications for Public Health
The observational study provides new insights into the roles of the timing of exposure and the different susceptible subgroups when evaluating the effects of arsenic in drinking water on early childhood immunologic development. “From a broader community health standpoint, we hope this research can help encourage additional conversations about current drinking water standards and ways to mitigate arsenic exposures for susceptible communities,” Welch said.
Citation: Arsenic exposure and serum antibody concentrations to diphtheria and tetanus toxoid in children at age 5: A prospective birth cohort in Bangladesh. Welch BM, Branscum A, Ahmed SM, Hystad P, Smit E, Afroz S, Megowan M, Golam M, Ibne Hasan MOS, Rahman ML, Quamruzzaman Q, Christiani DC, Kile ML. Environ Int. 2019 Jun;127:810-818. doi: 10.1016/j.envint.2019.04.015. Epub 2019 Apr 30.
