The Associations of Prenatal Exposure to Fine Particulate Matter and Its Chemical Components with Allergic Rhinitis in Children and the Modification Effect of Polyunsaturated Fatty Acids: A Birth Cohort Study

Background: Polyunsaturated fatty acids (PUFAs) have been shown to protect against fine particulate matter <2.5μm in aerodynamic diameter (PM2.5)-induced hazards. However, limited evidence is available for respiratory health, particularly in pregnant women and their offspring. Objectives: We aimed to investigate the association of prenatal exposure to PM2.5 and its chemical components with allergic rhinitis (AR) in children and explore effect modification by maternal erythrocyte PUFAs. Methods: This prospective birth cohort study involved 657 mother–child pairs from Guangzhou, China. Prenatal exposure to residential PM2.5 mass and its components [black carbon (BC), organic matter (OM), sulfate (SO42−), nitrate (NO3−), and ammonium (NH4+)] were estimated by an established spatiotemporal model. Maternal erythrocyte PUFAs during pregnancy were measured using gas chromatography. The diagnosis of AR and report of AR symptoms in children were assessed up to 2 years of age. We used Cox regression with the quantile-based g-computation approach to assess the individual and joint effects of PM2.5 components and examine the modification effects of maternal PUFA levels. Results: Approximately 5.33% and 8.07% of children had AR and related symptoms, respectively. The average concentration of prenatal PM2.5 was 35.50±5.31 μg/m3. PM2.5 was positively associated with the risk of developing AR [hazard ratio (HR)=1.85; 95% confidence interval (CI): 1.16, 2.96 per 5 μg/m3] and its symptoms (HR=1.79; 95% CI: 1.22, 2.62 per 5 μg/m3) after adjustment for confounders. Similar associations were observed between individual PM2.5 components and AR outcomes. Each quintile change in a mixture of components was associated with an adjusted HR of 3.73 (95% CI: 1.80, 7.73) and 2.69 (95% CI: 1.55, 4.67) for AR and AR symptoms, with BC accounting for the largest contribution. Higher levels of n-3 docosapentaenoic acid and lower levels of n-6 linoleic acid showed alleviating effects on AR symptoms risk associated with exposure to PM2.5 and its components. Conclusion: Prenatal exposure to PM2.5 and its chemical components, particularly BC, was associated with AR/symptoms in early childhood. We highlight that PUFA biomarkers could modify the adverse effects of PM2.5 on respiratory allergy. https://doi.org/10.1289/EHP13524


Figure S2.
Directed acyclic graph for the hypothesized causal relationship between prenatal PM2.5 and allergic rhinitis and its symptoms in children by age two.
Table S2.General characteristics of study population recruited in 2017 and 2018 stratified by allergic rhinitis symptoms among Chinese children by age two years (n=657).
Table S3.Summary distribution of PM2.5 and its chemical composition in the first two years of life among Chinese children from 2018 to 2020 (n=657, unit: μg/m 3 ).Table S4.Prediction data for concentration-response curves (smoothing by restricted cubic spline in Figure S3 and Figure S4) between prenatal exposure PM2.5 and its chemical composition in 2017 and 2018 and allergic rhinitis (AR) or AR symptoms in Chinese children by age two (n=657).Table S5.Maternal erythrocyte PUFA levels during pregnancy among Chinese women in 2017 and 2018 (n=657).
Table S6.S6 Association between prenatal exposure to PM2.5 and its chemical composition in 2017 and 2018 and allergic rhinitis (AR) or AR symptoms in Chinese children by age two in the model additionally adjusted for other risk factors of outcomes (n=657).
Table S7.Association between prenatal exposure to a mixture of five PM2.5 components in 2017 and 2018 and allergic rhinitis (AR) or AR symptoms among Chinese children by age two from quantile-based g-computation models additionally adjusted for other risk factors of outcomes (n=657).
Table S8.Subsample analyses of association between prenatal exposure to PM2.5 and its chemical composition in 2017 and 2018 and allergic rhinitis (AR) or AR symptoms among Chinese children excluding those with preterm birth and low birth weight (n=621).
Table S9.Association between prenatal exposure to PM2.5 and its chemical composition in 2017 and 2018 and allergic rhinitis (AR) or AR symptoms in Chinese children adjusted for the postnatal exposure in the first two years of life (n=657).
Table S10.Association of prenatal exposure to PM2.5 and its chemical composition in 2017 and 2018 with allergic rhinitis (AR) or AR symptoms in Chinese children by age two with multiple imputation covariates dataset (n=657).
Table S11.Estimated HR and 95%CI for allergic rhinitis (AR) or AR symptoms in Chinese children in association with prenatal exposure to PM2.5 (per 5 μg/m 3 ) at 10-km spatial resolution in 2017 and 2018 (n=657).
Table S12.Association of postnatal exposure to PM2.5 and its chemical composition from 2018 to 2020 with allergic rhinitis (AR) or AR symptoms in Chinese children by age two (n=657).
Table S13.Quantile-based g-computation models for the association of postnatal exposure to a mixture of five PM2.5 components from 2018 to 2020 with allergic rhinitis (AR) or AR symptoms in Chinese children by age two (n=657).
Table S14.The modification of maternal erythrocyte DPA on the association of first-year exposure to PM2.5 and its constituents in 2018 and 2019 with allergic rhinitis (AR) or AR symptoms of Chinese children by age two (n=657).a Maternal employment had missing data for 5.6% (n=37), maternal smoking and/or passive smoking for 3.0% (n=20), and exclusive breastfeeding for 1.7% (n=11).

Supplementary Materials
Data were presented as mean ± SD or n (%).
P value from chis-square test or analysis of variance.The numeric data for the concentration-response curves are shown in Table S4.
Abbreviations: HR, hazard ratio; CI, confidential interval; AR, allergic rhinitis; PM 2.5 , particulate matter with an aerodynamic diameter ≤2.5 μm; SO 4 2-, sulfate; NO 3 -, nitrate; NH 4 + , ammonium; OM, organic matter; BC, black carbon.The solid line and shaded area represent HR and its 95% CI for allergic rhinitis, respectively.The dotted line represents HR=1.The histograms represent the distributions of PM 2.5 components (expressed in percentages) among the study population.
The model was adjusted for maternal age, maternal employment, maternal education, monthly household income, parity, child's sex, temperature, residential greenness, and 2 ; Maternal employment had missing for 5.6% (n=37).
.     There were 36 children excluded for preterm birth and low birth weight.a PM 2.5 was estimated at 1-km spatial resolution, and the HRs were associated with 5-μg/m 3 increase in the exposure.b single component model, estimated effects associated with one-unit (μg/m 3 ) increase (an interquartile range increase of 0.30 μg/m 3 for BC).c quantile-based g-computation model, estimated effects associated with one quintile increase in exposures to five PM 2.5 constituents.
The Cox regression model was adjusted for maternal age, maternal employment, maternal education, monthly household income, parity, child's sex, temperature, residential greenness, and NO 2 ; Maternal employment had missing data for 5.6% (n=37).a PM 2.5 was estimated at 1-km spatial resolution, and the HRs were associated with 5-μg/m 3 increase in the exposure.b single component model, estimated effects associated with one-unit (μg/m 3 ) increase (an interquartile range increase of 0.30 μg/m 3 for BC).c quantile-based g-computation model, estimated effects associated with one quintile increase in exposures to five PM 2.5 constituents.
The Cox regression model was adjusted for maternal age, maternal employment, maternal education, monthly household income, parity, child's sex, temperature, residential greenness, NO 2, and PM 2.5 and its composition in postnatal two years, respectively; Maternal employment had missing data for 5.6% (n=37).Abbreviations: HR, hazard ratio; CI, confidential interval; AR, allergic rhinitis; PM 2.5 , particulate matter with an aerodynamic diameter ≤2.5 μm; SO 4 2-, sulfate; NO 3 -, nitrate; NH 4 + , ammonium; OM, organic matter; BC, black carbon.a PM 2.5 was estimated at 1-km spatial resolution, and the HRs were associated with 5-μg/m 3 increase in the exposure.b single component model, estimated effects associated with one-unit increase (an interquartile range increase for BC).c quantile-based g-computation model, estimated effects associated with one quintile increase in exposures to five PM 2.5 constituents.
The main model of Cox regression was adjusted for maternal age, maternal employment, maternal education, monthly household income, parity, child's sex, temperature, residential greenness, NO 2; Other risk factors: maternal smoking or passive smoking, child's secondhand smoking, household dampness, birth season, family history of allergies, and exclusive breastfeeding.
Maternal employment had missing data for 5.6% (n=37), maternal smoking or passive smoking for 3.0% (n=20), and exclusive breastfeeding for 1.7% (n=11).Missing observations for covariates were included in the models using multiple imputation (m=5).Maternal employment had missing data for 5.6% (n=37), maternal smoking or passive smoking for 3.0% (n=20), and exclusive breastfeeding for 1.7% (n=11).a DPA was stratified into higher and lower levels based on the median concentration.b PM 2.5 was estimated at 1-km spatial resolution, and the HRs were associated with 5-μg/m 3 increase in the exposure.c single pollutant model, estimated effects associated with one-unit (μg/m 3 ) increase (an interquartile range increase of 0.19 μg/m 3 for BC).d quantile-based g-computation model, estimated effects associated with one-quintile increase in exposures to five PM 2.5 constituents.
The Cox regression model was adjusted for maternal age, maternal employment, maternal education, monthly household income, parity, child's sex, temperature, residential greenness, and NO 2 ; Maternal employment had missing data for 5.6% (n=37).

Figure S1 .
Figure S1.Flowchart of the study design and population.

Figure S3 .
Figure S3.Concentration-response curves (smoothing by restricted cubic spline) between prenatal exposure to PM2.5 and its chemical components in 2017 and 2018 and allergic rhinitis (AR) in Chinese children by age two (n=657).

Figure S4 .
Figure S4.Concentration-response curves (smoothing by restricted cubic spline) between prenatal exposure to PM2.5 and its chemical composition in 2017 and 2018 and allergic rhinitis (AR) symptoms in Chinese children (n=657).

Figure
Figure S1 Flowchart of the study design and population.

Figure
Figure S2 Directed acyclic graph for the hypothesized causal relationship between prenatal PM2.5 and allergic rhinitis and its symptoms in children by age two.

Figure
Figure S3 Concentration-response curves (smoothing by restricted cubic spline) between prenatal exposure to PM2.5 and its chemical components in 2017 and 2018 and allergic rhinitis (AR) in Chinese children by age two (n=657)

Figure S4
Figure S4 Concentration-response curves (smoothing by restricted cubic spline) between prenatal exposure to PM2.5 and its chemical composition in 2017 and 2018 and allergic rhinitis (AR) symptoms in Chinese children (n=657)

Table S4
Prediction data for concentration-response curves (smoothing by restricted cubic spline in FigureS3and FigureS4) between prenatal exposure PM2.5 and its chemical composition in 2017 and 2018 and allergic rhinitis (AR) or AR symptoms in Chinese children by age two (n=657) The model was adjusted for maternal age, maternal employment, maternal education, monthly household income, parity, child's sex, temperature, residential greenness, and NO 2; Maternal employment had missing for 5.6% (n=37).

Table S5
Maternal erythrocyte PUFA levels during pregnancy among Chinese women in2017 and 2018 (n=657) a %: percentage of total fatty acids.

Table S6
Association between prenatal exposure to PM2.5 and its chemical composition in 2017 and 2018 and allergic rhinitis (AR) or AR symptoms in Chinese children by age two in the model additionally adjusted for other risk factors of outcomes (n=657) a PM 2.5 was estimated at 1-km spatial resolution.bEstimatedeffectsassociated with per interquartile range increase (0.30 μg/m 3 ) in BCThe main model of Cox regression was adjusted for maternal age, maternal employment, maternal education, monthly household income, parity, child's sex, temperature, residential greenness, and NO 2 ;Other risk factors: maternal smoking and/or passive smoking, child's secondhand smoking, household dampness, birth season, family history of allergies, and exclusive breastfeeding; Maternal employment had missing data for 5.6% (n=37), maternal smoking and/or passive smoking for 3.0% (n=20), and exclusive breastfeeding for 1.7% (n=11).

Table S7
Association between prenatal exposure to a mixture of five PM2.5 components in 2017 and 2018 and allergic rhinitis (AR) or AR symptoms among Chinese children by age two from quantile-based g-computation models additionally adjusted for other risk factors of outcomes (n=657).
a Estimated effects associated with one quintile increase in exposures to five PM 2.5 constituents.The main model of Cox regression was adjusted for maternal age, maternal employment, maternal education, monthly household income, parity, child's sex, temperature, residential greenness, and NO 2 ;Other risk factors: maternal smoking and/or passive smoking, child's secondhand smoking, household dampness, birth season, family history of allergies, and exclusive breastfeeding; Maternal employment had missing data for 5.6% (n=37), maternal smoking and/or passive smoking for 3.0% (n=20), and exclusive breastfeeding for 1.7% (n=11).

Table S8
Subsample analyses of association between prenatal exposure to PM2.5 and its chemical composition in 2017 and 2018 and allergic rhinitis (AR) or AR symptoms among Chinese children excluding those with preterm birth and low birth weight (n=621).

Table S9
Association between prenatal exposure to PM2.5 and its chemical composition in 2017 and 2018 and allergic rhinitis (AR) or AR symptoms in Chinese children adjusted for the postnatal exposure in the first two years of life (n=657).

Table S10
Association of prenatal exposure to PM2.5 and its chemical composition in 2017 and 2018 with allergic rhinitis (AR) or AR symptoms in Chinese children by age two with multiple imputation covariates dataset (n=657).

Table S11 Estimated
HR and 95%CI for allergic rhinitis (AR) or AR symptoms in Chinese children in association with prenatal exposure to PM2.5 (per 5 μg/m 3 ) at 10-km spatial resolution in 2017 and 2018 (n=657).The main model of Cox regression was adjusted for maternal age, maternal employment, maternal education, monthly household income, parity, child's sex, temperature, residential greenness, and NO 2; Other risk factors: maternal smoking or passive smoking , child's secondhand smoking, household dampness, birth season, family history of allergies, and exclusive breastfeeding;

Table S12
Association of postnatal exposure to PM2.5 and its chemical composition from 2018 to 2020 with allergic rhinitis (AR) or AR symptoms in Chinese children by age two (n=657).
a PM 2.5 was estimated at 1-km spatial resolution.bEstimated effects associated with per interquartile range increase in BC.

Table S13
Quantile-based g-computation models for the association of postnatal exposure to a mixture of five PM2.5 components from 2018 to 2020 with allergic rhinitis (AR) or AR symptoms in Chinese children by age two (n=657).Estimated effects associated with one quintile increase in exposures to five PM 2.5 constituents.The Cox regression model was adjusted for maternal age, maternal employment, maternal education, monthly household income, parity, child's sex, temperature, residential greenness, and NO 2. Maternal employment had missing data for 5.6% (n=37).
aBold font face indicates a positive index weight.

Table S14
The modification of maternal erythrocyte DPA on the association of firstyear exposure to PM2.5 and its constituents in 2018 and 2019 with allergic rhinitis (AR) or AR symptoms of Chinese children by age two (n=657).HR, hazard ratio; CI, confidential interval; AR, allergic rhinitis; PM 2.5 , particulate matter with an aerodynamic diameter ≤2.5 μm; SO 4 2-, sulfate; NO 3 -, nitrate; NH 4 + , ammonium; OM, organic matter; BC, black carbon.