Association between perfluoroalkyl substance exposure and asthma and allergic disease in children as modified by MMR vaccination

Abstract

Perfluoroalkyl substances (PFAS) are highly persistent chemicals that might be associated with asthma and allergy, but the associations remain unclear. Therefore, this study examined whether pre- and post-natal PFAS exposure was associated with childhood asthma and allergy. Measles, mumps and rubella (MMR) vaccination in early life may have a protective effect against asthma and allergy and is therefore taken into account when evaluating these associations. In a cohort of Faroese children whose mothers were recruited during pregnancy, serum concentrations of five PFAS were measured: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) at three timepoints (maternal serum in pregnancy week 34–36 and child serum at ages 5 and 13 years) and determined their association with immunoglobulin E (IgE) (cord blood and at age 7 years) and asthma/allergic diseases (questionnaires at ages 5 and 13 years and skin prick test at age 13 years). A total of 559 children were included in the analyses. Interactions with MMR vaccination were evaluated. Among 22 MMR-unvaccinated children, higher levels of the five PFAS at age 5 years were associated with increased odds of asthma at ages 5 and 13. The associations were reversed among MMR-vaccinated children. Pre-natal PFAS exposure was not associated with childhood asthma or allergic diseases regardless of MMR vaccination status. In conclusion, PFAS exposure at age 5 was associated with increased risk of asthma among a small subgroup of MMR-unvaccinated children but not among MMR-vaccinated children. While PFAS exposure may impact immune system functions, this study suggests that MMR vaccination might be a potential effect-modifier.

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

“…In regard to T H 2-related allergy, increased odds of asthma in children were reported at elevated PFAS exposures (Dong et al 2013), although this finding has not been replicated (Humblet et al 2014). Our own studies (i.e., Timmermann et al 2017) suggested that serum-PFAS concentrations at age 5 years were associated with increased odds of asthma only among the children who had not yet been vaccinated against measles, mumps, and rubella (MMR), while the association was reversed among MMR-vaccinated children. Although inhibition of antibody responses, perhaps associated with increased risk of allergy development, could represent a change in the T H 1/T H 2 balance (Dong et al 2011), the relative role of the immune system components is complex.…”

“…The Faroese Cohort 5 of 490 children was recruited from births at the National Hospital in Tórshavn, Faroe Islands, during 2007–2009 (Kim et al 2014; Timmermann et al 2017). A maternal serum sample was collected about two weeks after the expected term date.…”

“…In order to increase the statistical power, this study included data from the earlier Cohort 3 (born 1997–2000), which had formed the basis of previous reports (Grandjean et al 2012; Grandjean and Budtz-Jorgensen 2013; Mogensen et al 2015a). Apart from being about eight years apart and therefore differing in exposure levels and profiles (median concentrations of PFHxS, PFOS, PFOA, and perfluorodecanoate (PFDA) were lower in Cohort 5, while the concentrations of perfluorononanoate (PFNA) were slightly higher compared to Cohort 3), the two cohorts are highly similar, and methods were virtually identical (Cohort 3 sampled maternal blood in late pregnancy) (Dalgard et al 2016; Timmermann et al 2017). …”

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

“…Only one prospective study investigated both prenatal and childhood exposures to PFASs and hypersensitivity outcomes, and reported increased odds of asthma at ages 5 and 13 with higher levels of PFASs at age 5, but only among children not vaccinated for measles, mumps and rubella. The same study found no associations between maternal prenatal PFASs concentrations and IgE levels, childhood asthma or allergic diseases [57] at ages 5 and 13.…”

“…Thirteen studies reported on autoimmunity/hypersensitivity endpoints in eight prospective birth cohorts from Canada [45], Japan [61, 62, 63], Taiwan [65], Faroe Islands [57], Greenland, Ukraine [60], Norway [58] and from four cross-sectional studies in Taiwan [66] and the USA (NHANES) [46–48]. Higher IgE levels in 2-year-old Taiwanese children were observed with higher cord blood PFOS and PFOA concentrations, but no associations were found for atopic dermatitis at the same age [65].…”