Air pollution’s chemical punch alters immune markers in pregnant women, study finds

New research reveals that it’s not just the amount, but the oxidative power of air pollution that shifts key immune signals in expectant mothers, potentially impacting both maternal defenses and fetal development.

Study: Personal exposure to air pollutants and immune system biomarkers in pregnant women. Image Credit: chayanuphol / Shutterstock

In a recent study published in the journal Scientific Reports, a group of researchers assessed how personal exposure to nitrogen dioxide (NO₂), fine particulate matter (PM2.5), and the oxidative potential (OP) of PM2.5 influences immune system biomarkers in pregnant women at rest and after immune cell activation. The study notes that the participant group had a high level of postgraduate education and a low rate of smoking, which may limit the generalizability of findings to all pregnant women.

Background

Each year, air pollution contributes to over seven million premature deaths worldwide. Pregnant women are particularly sensitive due to immune system adaptations that support fetal development. NO₂ and PM2.5 have been linked to systemic inflammation. However, recent attention has shifted to the OP of PM2.5—its ability to generate reactive oxygen species—as a more biologically relevant indicator than mass concentration alone. Few studies have investigated these mechanisms during pregnancy, especially under immune stimulation. Further research is needed to clarify pollutant-specific immunological changes in this vulnerable population.

About the study

This study analyzed data from 270 pregnant women in the French SEPAGES cohort. Participants wore portable air samplers for 7 to 8 consecutive days during their second or third trimester to measure personal exposure to PM2.5 (MicroPEM™, RTI International) and NO₂ (Passam AG passive sampler). Filters were analyzed for PM2.5 OP using two assays: the dithiothreitol assay (OPDTT) and the ascorbic acid assay (OPAA). Each was expressed per microgram of PM2.5 (OPmDTT, OPmAA) or per air volume (OPvDTT, OPvAA).

Blood samples were collected within 48 hours of the exposure assessment. Whole blood was incubated with phytohemagglutinin (PHA) to stimulate T cells and with resiquimod (R848) to stimulate dendritic cells. Twenty-nine cytokines and chemokines were measured using cytometric bead arrays. Only cytokines with ≥70% detectable values were analyzed. Concentrations were log₁₀-transformed and standardized to correct for technical variation. Multivariable linear regression models estimated associations between each pollutant and cytokine, adjusted for maternal age, pre-pregnancy body mass index, active/passive smoking, leukocyte count, gestational age, education level, and season. Missing covariate data were imputed using chained equations. Sensitivity analyses were examined under various exclusions and model variations.

Study results

Participants had a median age of 32.1 years and a median pre-pregnancy body mass index of 21.6 kg/m². Most had postgraduate education (58%), and 10% reported smoking during or before pregnancy. Sixteen percent reported asthma symptoms, and 40% reported rhinitis. Median exposure levels were 20.2 µg/m³ for NO₂ and 13.8 µg/m³ for PM2.5. The median OP values were 0.11 nmol/min/µg (OPmDTT), 1.48 nmol/min/m³ (OPvDTT), 0.12 nmol/min/µg (OPmAA), and 1.65 nmol/min/m³ (OPvAA).

Baseline cytokine concentrations varied widely. Interleukin-8 (IL-8) ranged from 17.8 to 283.1 pg/mL. After PHA stimulation, interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) showed elevated levels, with medians of 2,664.7 pg/mL and 760.2 pg/mL, respectively. After R848 stimulation, IL-6 and IL-8 were the most expressed.

Multivariable analyses revealed several significant pollutant-cytokine associations. A 10 µg/m³ increase in NO₂ was linked to increased PHA-activated IL-10 (β = 0.18, 95% CI: 0.03 to 0.32) and decreased TNF-α (β = -0.18, 95% CI: -0.32 to -0.02). PM2.5 mass concentration was not significantly associated with cytokine levels.

Pairwise Pearson’s correlations between air pollutants (a). Pairwise Pearson’s correlations between cytokines (imputed, corrected and log-10 transformed) and number of leukocytes (b). The Pearson correlation coefficients are indicated using a scale of size and color only when the p-values were less than 0.05. Abbreviations: PM2.5 particulate matter with diameter ≤ 2.5 μm; NO2 nitrogen dioxide; OP: oxidative potential; DTT: dithiothreitol; AA: ascorbic acid; IL interleukin; IFN interferon; TNF tumor necrosis factor; RANTES regulated on activation, normal T cell expressed and secreted; MCP monocyte chemoattractant protein; PHA phytohemagglutinin; R848 resiquimod

In contrast, PM2.5 oxidative potential showed specific immune effects. An interquartile range (IQR) increase in OPvAA (1.65 nmol/min/m³) was associated with lower R848-activated IL-8 (β = -0.17, 95% CI: -0.33 to 0.00). A similar, though not statistically significant, trend was observed for baseline IL-8 (β = -0.18, p = 0.14). Likewise, OPmAA was associated with reduced IL-8 secretion upon R848 activation (β = -0.12, p = 0.05).

An IQR increase in OPmDTT was significantly associated with elevated IL-17A after PHA stimulation (β = 0.11, 95% CI: 0.00 to 0.22). Weaker positive associations for IL-17A were also seen with OPvDTT and OPmAA. These results suggest that OP-related stimulation of T-helper 17 (Th17) cell responses is known to mediate autoimmune inflammation.

Sensitivity analyses showed consistent results. The NO₂–IL-10 association lost statistical significance when extreme or influential values were excluded and in models adjusted for other pollutants. However, the NO₂–TNF-α and OP–IL-17A findings remained robust. The lack of significant associations with PM2.5 mass but clear links with OPDTT and OPAA support the hypothesis that chemical reactivity, rather than particle mass, drives immune responses during pregnancy.

Conclusions

To summarize, this study demonstrates that personal exposure to NO₂ and the OP of PM2.5, but not its mass concentration, influences immune biomarker levels in pregnant women. Exposure to NO₂ was associated with increased anti-inflammatory IL-10 and reduced TNF-α following T-cell activation. Higher OPAA and OPDTT levels were linked to lower IL-8 and higher IL-17A, reflecting shifts in inflammatory and regulatory immune pathways. These immune modulations may influence maternal resistance to infections and fetal immune development. However, as the study population may not be fully representative of all pregnant women, these findings should be interpreted with some caution. Reducing the OP of PM2.5 in urban air could offer a targeted approach to protect pregnant women and their developing children.