Prenatal exposure to phthalates, bisphenol A and perfluoroalkyl substances and cord blood levels of IgE, TSLP and IL-33

Abstract

The fetal time period is a critical window of immune system development and resulting heightened susceptibility to the adverse effects of environmental exposures. Epidemiologists and toxicologists have hypothesized that phthalates, bisphenol A (BPA) and perfluoroalkyl substance have immunotoxic properties. Immunotoxic effects of chemicals may manifest in an altered immune system profile at birth. Immunoglobulin E, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) are integral in the etiology of childhood allergy and detectable at birth. The objective of this study was to determine the association between maternal levels of phthalates, bisphenol A (BPA), and perfluoroalkyl substances and elevated umbilical cord blood levels of IgE, TSLP, and IL-33. This study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Of these women, 1258 had a singleton, term birth and cord blood sample. A Bayesian hierarchical model was employed to determine associations between log-transformed continuous variables and immune system biomarkers while adjusting for potential confounding from correlated environmental contaminants. Inverse, nonlinear associations were observed between maternal urinary MCPP levels and elevated levels of both IL-33/TSLP and IgE and between maternal urinary BPA levels and elevated levels of IL-33/TSLP. In this primarily urban Canadian population of pregnant women and their newborns, maternal urinary and plasma concentrations of phthalate metabolites, BPA, and perfluoroalkyl substances were not associated with immunotoxic effects that manifest as increased odds of elevated levels of IgE, TSLP or IL-33.

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

“…Recent studies found that maternal PFOA concentrations were inversely associated with current wheezing among Ukrainian but not in Greenlandic children aged 5–9 years (Smit et al 2015) and other types of maternal PFAS were inversely associated with allergic diseases among 4-year-old children (Goudarzi et al 2016). Several other analyses, however, showed no associations between pre-natal exposure to PFAS and cord blood IgE (Ashley-Martin et al 2015) or asthma and allergy in childhood (Wang et al 2011; Okada et al 2012; Granum et al 2013), which is in accordance with the current findings.…”

Assessment of recent developmental immunotoxicity studies with bisphenol A in the context of the 2015 EFSA t-TDI

“…These recent publications include both epidemiological studies and experimental studies using animal models. Although the epidemiological studies published after 2012 (5–8) provide additional evidence of a potential association between BPA and immune effects, the available human studies corroborated EFSA’s conclusions as described above, indicating that a causal link cannot be identified from human studies due to limitations. For example, spot urinary BPA levels do not provide a reliable measure for exposure over time.…”

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

“…Contrary to this study, decreased IgE levels were reported with higher maternal PFOA concentrations in 18-month-old Japanese children, and no associations were observed between PFASs and food allergy, eczema or wheezing [61]. The Canadian MIREC birth cohort also found no association between 1st trimester pregnancy PFASs concentrations and cord-blood IgE levels [45]. Similarly, no associations were found between maternal prenatal PFASs concentrations and eczema/itchiness, wheeze, atopic eczema or asthma in a small sample (n = 99) of Norwegian children ages 1 to 3 years [58].…”

“…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].…”

“…Another investigation in the Taiwanese GBCA reported positive associations between concurrent serum PFAS concentrations and levels of T helper 2 cytokines [interleukin-4 (IL-4) and IL-5] and negative associations with T helper 1 cytokines (interferon- γ and IL-2) [67]. Finally, umbilical cord blood thymic stromal lymphopoietin and interleukin-33 levels were not associated with 1st trimester pregnancy PFASs concentrations [45] in the Canadian MIREC study, whereas transcriptomics profiling of neonatal cord blood identified a set of differentially expressed genes as being associated with both maternal PFASs concentrations and common cold episodes or rubella titers [59] in a Norwegian study.…”