Prenatal exposure to residential traffic-related air pollution and immune system at birthresults from the NELA cohort

Abstract

Background: Considered as the second environmental risk factor causing non-communicable diseases, air pollution has become a public health concern worldwide. Alterations in the immune system are proposed as mechanisms underlying these adverse effects, and gestation may represent a period of increased vulnerability. However, the impact of prenatal exposure to traffic-related air pollution (TRAP) on immune system development has been poorly studied. Aims: To study the impact of prenatal exposure to TRAP on immune system at birth. Specific objectives: 1. To summarize the evidence on the associations between the prenatal and perinatal environment and changes in immune system cells and cytokine profiles in umbilical cord blood. 2. To characterize the immune system at birth analysing immune cell subpopulations, unstimulated cytokine profiles and cytokine responses to a wide panel of environmental stimuli in umbilical cord blood. 3. To study the effects of prenatal exposure to TRAP on distributions of immune system cell subpopulations in umbilical cord blood. 4. To investigate the effects of prenatal exposure to TRAP on cytokine profiles of unstimulated and stimulated umbilical cord blood cells. 5. To identify gestational windows of higher susceptibility of the developing immune system to prenatal exposure to TRAP. Methods: For the first objective, a PUBMED search limited to human and English results was conducted to review the available evidence on the associations between the prenatal and perinatal environment and changes in immune system cells and cytokine profiles at birth. For objectives 2 to 5 we used data from mother-newborn pairs embedded in the NELA study, a prospective population-based birth cohort (2015–2018). Long-term (whole pregnancy and trimesters) and short-term (15 days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10), and ozone (O3) during gestation were estimated using a dispersion/chemical transport modelling based on source apportionment methodologies. In-depth immunophenotyping of cord blood leukocyte subsets including T helper type 1 (Th1), Th2, Th17 and regulatory T (Treg) lymphocyte subsets was performed by flow cytometry. A wide cytokine panel (IFN-α, IFN-γ, IL1β, IL-10, IL-13, IL-17F, IL-2, IL-23, IL-4, IL-5, IL-6 and TNF-α) was assessed by Luminex technology in umbilical cord blood. Associations between TRAP concentrations and immune cell counts were assessed using multivariate Poisson regression models; and the relationships between TRAP exposure and cytokine production by cord blood cells were assessed fitting multivariate linear and logistic regression as well as multi-pollutant models. Results: 1. Prenatal and perinatal periods seem to represent crucial developmental windows of higher susceptibility of the immune system to diverse environmental influences. 2. Cord blood NK, cytotoxic T and Treg cells decreased in relation to higher prenatal exposure to TRAP; whereas, higher prenatal exposure to traffic-related PM was associated with increased total Th and Th1 cells in cord blood. 3. Prenatal exposure to higher levels of TRAP was associated with increased detection of unstimulated concentrations of pro-inflammatory (IL-1β and IL-6), Th2-related (IL-13), and IL-10 cytokines in newborns. 4. Exposures to NO2 and PM during pregnancy were associated with higher proinflammatory (IL-6 and IFN-α) and Th1-related (IFN-γ) cytokine responses of umbilical cord blood cells to environmental stimuli. 5. The first and the third trimester of gestation were identified as windows of higher susceptibility of foetal immune system to adverse effects of TRAP. Conclusions: Prenatal and perinatal periods are crucial developmental windows of higher susceptibility of the immune system to diverse environmental influences. Furthermore, prenatal exposure to TRAP could impair foetal immune system development through disturbances in leukocyte subsets and increased production of proinflammatory cytokines in cord blood. These changes might influence immune system responses and contribute to increase risk of respiratory infections, allergy, and wheezing in early life.