Chronic air pollution exposure during pregnancy and maternal and fetal C-reactive protein levels: the Generation R Study

Abstract

Background: Exposure to air pollution has been associated with higher C-reactive protein (CRP) levels, suggesting an inflammatory response. Not much is known about this association in pregnancy.

Objectives: We investigated the associations of air pollution exposure during pregnancy with maternal and fetal CRP levels in a population-based cohort study in the Netherlands.

Methods: Particulate matter (PM) with an aerodynamic diameter ≤ 10 μm (PM10) and nitrogen dioxide (NO2) levels were estimated at the home address using dispersion modeling for different averaging periods preceding the blood sampling (1 week, 2 weeks, 4 weeks, and total pregnancy). High-sensitivity CRP levels were measured in maternal blood samples in early pregnancy (n = 5,067) and in fetal cord blood samples at birth (n = 4,450).

Results: Compared with the lowest quartile, higher PM10 exposure levels for the prior 1 and 2 weeks were associated with elevated maternal CRP levels (> 8 mg/L) in the first trimester [fourth PM10 quartile for the prior week: odds ratio (OR), 1.32; 95% confidence interval (CI): 1.08, 1.61; third PM10 quartile for the prior 2 weeks: OR, 1.28; 95% CI: 1.06, 1.56]; however, no clear dose-response relationships were observed. PM10 and NO2 exposure levels for 1, 2, and 4 weeks preceding delivery were not consistently associated with fetal CRP levels at delivery. Higher long-term PM10 and NO2 exposure levels (total pregnancy) were associated with elevated fetal CRP levels (> 1 mg/L) at delivery (fourth quartile PM10: OR, 2.18; 95% CI: 1.08, 4.38; fourth quartile NO2: OR, 3.42; 95% CI: 1.36, 8.58; p-values for trend < 0.05).

Conclusions: Our results suggest that exposure to air pollution during pregnancy may lead to maternal and fetal inflammatory responses.

Figure 1

Associations of maternal air pollution exposure with the risks of elevated maternal CRP levels in early pregnancy (n = 5,067). Values [ORs (95% CI)] reflect the risk for elevated maternal CRP levels (> 8 mg/L) for each quartile (Q) of PM₁₀ exposure (A) and NO₂ exposure (B) in different periods preceding the first-trimester measurement compared with the reference group (lowest quartile). Cutoff values for categorization of PM₁₀ exposure were < 24.6, 24.6–28.8, 28.8–33.9, and > 33.9 μg/m³ for the prior week, < 25.4, 25.4–28.8, 28.8–33.7, and > 33.7 μg/m³ for the prior 2 weeks, and < 26.3, 26.3–29.4, 29.4–33.8, and > 33.8 μg/m³ for the prior 4 weeks. Cutoff values for NO₂ exposure were < 33.9, 33.9–39.9, 39.9–46.0, and > 46.0 μg/m³ for the prior week, < 35.2, 35.2–40.5, 40.5–45.3, and > 45.3 μg/m³ for the prior 2 weeks, and < 35.8, 35.8–40.8, 40.8–44.5, and > 44.5 μg/m³ for the prior 4 weeks. Tests for trend were performed by including PM₁₀ and NO₂ exposure as a continuous term (per 10‑μg/m³ increase) in the model. Number of subjects classified as having elevated CRP levels is indicated in Supplemental Material, Table S3 (http://dx.doi.org/10.1289/ehp.1104345). Models are adjusted for gestational age at measurement, maternal age, body mass index, parity, ethnicity, education, smoking, alcohol consumption, noise exposure, and season of conception. *p < 0.05; **p < 0.10.

Figure 2

Associations of maternal air pollution exposure with the risks of elevated fetal CRP levels at delivery (n = 4,450). Values [ORs (95% CI)] reflect the risk for elevated fetal CRP levels (> 1 mg/L) for each quartile (Q) of PM₁₀ exposure (A) and NO₂ exposure (B) in different periods preceding delivery compared with the reference group (lowest quartile). Cutoff values for categorization of PM₁₀ exposure were < 23.9, 23.9–27.7, 27.7–32.8, and > 32.8 μg/m³ for the prior week, < 24.7, 24.7–28.0, 28.0–32.1, and > 32.1 μg/m³ for the prior 2 weeks, < 25.6, 25.6–28.5, 28.5–32.8, and > 32.8 μg/m³ for the prior 4 weeks, and < 27.8, 27,8–30.0, 30.0–32.9, and > 32.9 μg/m³ for total pregnancy. Cutoff values for NO₂ exposure were < 33.2, 33.2–39.3, 39.3–45.6, and > 45.6 μg/m³ for the prior week, < 34.1, 34.1–39.8, 39.8–44.7, > and 44.7 μg/m³ for the prior 2 weeks, < 34.7, 34.7–40.2, 40.2–44.1, and > 44.1 μg/m³ for the prior 4 weeks, and < 37.2, 37.2–39.6, 39.6–42.3, and > 42.3 μg/m³ for total pregnancy. Number of subjects classified as having elevated CRP levels is indicated in Supplemental Material, Table S4 (http://dx.doi.org/10.1289/ehp.1104345). Models are adjusted for gestational age at birth, season of birth, maternal age, body mass index, parity, ethnicity, education, smoking, alcohol consumption, and noise exposure. Tests for trend were performed by including PM₁₀ and NO₂ exposure as a continuous term (per 10-μg/m³ increase) in the model. *p < 0.05; **p < 0.10.