Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years

Abstract

Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated. As outcomes, serum concentrations of antibodies against tetanus and diphtheria vaccines were determined at age 5. Data from a previous cohort born eight years earlier were available for pooled analyses. Prenatal exposure showed inverse associations with the antibody concentrations five years later, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months showed the strongest inverse associations with antibody concentrations at age 5 years, particularly for tetanus. Joint analyses showed statistically significant decreases in tetanus antibody concentrations by 19% to 29% at age 5 for each doubling of the PFAS exposure in early infancy. These findings support the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy. This vulnerability appears to be the greatest during the first 6 months after birth, where PFAS exposures are affected by breast-feeding.

Developmental Exposures to Perfluoroalkyl Substances (PFASs): An Update of Associated Health Outcomes

“…In the birth cohorts, higher maternal concentrations of PFASs during pregnancy were associated with lower anti-vaccine antibody levels for rubella [58], diphtheria [51] and tetanus [55] in their children at ages 3 to 5 years. No consistent associations were found however between prenatal concentrations of PFASs and vaccine antibody levels for influenza and measles among the children [58].…”

“…No consistent associations were found however between prenatal concentrations of PFASs and vaccine antibody levels for influenza and measles among the children [58]. Childhood and infancy exposure to PFASs has also been shown to decrease vaccine antibody levels for diphtheria and tetanus in children aged 5 to 13 years in longitudinal studies from the Faroe Islands [51, 53–55]. Finally, cross-sectional measures of PFASs and rubella and mumps titers in adolescents aged 12 to 19 years in NHANES showed lower levels for these antibodies in relation to higher PFAS concentrations [48].…”

Environmental exposures during pregnancy: Mechanistic effects on immunity

“…Well-known cohort studies in the Faroe Islands have associated autoantibodies with prenatal and childhood exposure to environmental chemicals such as methylmercury, PCBs, and PFASs in Faroese children (Osuna, Grandjean, Weihe, & El-Fawal, 2014). In contrast, vaccine-elicited antibody responses against diphtheria (Grandjean et al, 2012) and tetanus (Grandjean et al, 2017) were reduced upon prenatal exposure to PCB and PFASs as previously discussed in the immunosuppression section. Evaluated autoantibodies were specific to both neural (neurofilaments, choline acetyltransferase, astrocyte glial fibrillary acidic protein, and myelin basic protein) and nonneural (actin, desmin, and keratin) antigens (Osuna et al, 2014).…”

Application of benchmark analysis for mixed contaminant exposures: Mutual adjustment of two perfluoroalkylate substances associated with immunotoxicity

“…However, in a recent study, we modeled serum concentrations during infancy and found that levels at ages 3 and 6 months appeared to be at least as strong predictors of decreased vaccine responses at age 5 years as was the maternal concentrations [17]. The time dependence is difficult to explore in detail due to the complexity of obtaining blood samples from small children.…”

“…We prospectively followed birth cohorts in the Faroe Islands and showed that developmental PFAS exposures constitute a major determinant for antibody concentrations directed against tetanus and diphtheria toxoids at ages 5 and 7 years, i.e., after three or four routine vaccinations [16,17]. Our most recent findings suggest that elevated serum-PFAS concentrations in infancy are particularly associated with lower antibody concentrations at age 5 [17]. In contrast, at age 7 years, the postnatal PFAS accumulation seems to play a major role [16].…”