Air Pollution Exposure and Risk of Spontaneous Abortion in the Nurses' Health Study II

Audrey J. Gaskins; Jaime E. Hart; Jorge E. Chavarro; Stacey A. Missmer; Janet W. Rich-Edwards; Francine Laden; Shruthi Mahalingaiah


Hum Reprod. 2019;34(9):1809-1817. 

In This Article

Abstract and Introduction


Study Question: Is there an association between air pollution exposures and the risk of spontaneous abortion (SAB)?

Summary Answer: Higher exposure to particulate matter (PM) air pollution above and beyond a woman's average exposure may be associated with greater risk of SAB, particularly among women experiencing at least one SAB during follow-up.

What is Known Already: There is sufficient biologic plausibility to suggest that air pollution adversely affects early pregnancy outcomes, particularly pregnancy loss; however, the evidence is limited.

Study Design, Size, Duration: Our prospective cohort study included 19 309 women in the Nurses' Health Study II who contributed a total of 35 025 pregnancies between 1990 and 2008. We also conducted a case-crossover analysis among 3585 women (11 212 pregnancies) with at least one SAB and one live birth during follow-up.

Participants/Materials, Setting, Methods: Proximity to major roadways and exposure to PM <10 microns (PM10), 2.5–10 microns (PM2.5–10) and <2.5 microns (PM2.5) were determined for residential addresses between 1989 and 2007. Pregnancy outcomes were self-reported biannually throughout follow-up and comprehensively in 2009. Multivariable log-binomial regression models with generalized estimating equations were used to estimate the risk ratios and 95% CIs of SAB. Conditional logistic regression was used for the case-crossover analysis.

Main Results and the Role of Chance: During the 19 years of follow-up, 6599 SABs (18.8% of pregnancies) were reported. In the main analysis, living closer to a major roadway and average exposure to PM10, PM10–2.5 or PM2.5 in the 1 or 2 years prior to pregnancy were not associated with an increased risk of SAB. However, small positive associations between PM exposures and SAB were observed when restricting the analysis to women experiencing at least one SAB during follow-up. In the case-crossover analysis, an increase in PM10 (per 3.9 μg/m3), PM2.5–10 (per 2.3 μg/m3) and PM2.5 (per 2.0 μg/m3) in the year prior to pregnancy was associated with 1.12 (95% CI 1.06, 1.19), 1.09 (95% CI 1.03, 1.14) and 1.10 (95% CI 1.04, 1.17) higher odds of SAB, respectively.

Limitations, Reasons for Caution: We did not have information on the month or day of SAB, which precluded our ability to examine specific windows of susceptibility or acute exposures. We also used ambient air pollution exposures as a proxy for personal exposure, potentially leading to exposure misclassification.

Wider Implications of the Findings: In our case-crossover analysis (but not in the entire cohort) we observed positive associations between exposure to all size fractions of PM exposure and risk of SAB. This may suggest that changes in PM exposure confer greater risk of SAB or that women with a history of SAB are a particularly vulnerable subgroup.

Study Funding/Competing Interest(s): The authors are supported by the following NIH grants UM1CA176726, R00ES026648 and P30ES000002. The authors have no actual or potential competing financial interests to disclose.


Miscarriage, or spontaneous abortion (SAB), is defined as fetal loss before 20 weeks gestation and affects up to ~30% of pregnancies (Wilcox et al., 1988). Chromosomal aneuploidy accounts for ~50% of SABs (Cramer and Wise, 2000); however, the remaining 50% of the causes are not well understood. The most well-known risk factors for SAB include maternal age (Wyatt et al., 2005), previous history of SABs (Regan et al., 1989) and uterine and endocrine abnormalities (Regan and Rai, 2000), all nonmodifiable factors. Environmental exposures, such as air pollution, have been studied in relation to SAB, but the literature remains sparse. Particulate matter (PM) air pollution, in particular, is a potential exposure of prime concern given its known links to chronic disease incidence and mortality (Dai et al., 2014) as well as many adverse pregnancy outcomes (Li et al., 2017). PM is classified into three size fractions, including fine particles <2.5 μm in aerodynamic diameter (PM2.5), particles <10 μm (PM10) and particles between 2.5 and 10 μm (PM2.5–10). PM comes from various sources including motor vehicle emissions, tire fragments, road dust, industrial and agricultural combustion, wood burning, pollens and molds, forest fires, volcanic emissions and sea spray. The varying contribution of these sources is different worldwide as well as across each region of the USA.

To date, the majority of studies have documented an association between higher levels of air pollution and increased risk of SAB (Dastoorpoor et al., 2018; Di Ciaula and Bilancia, 2015; Enkhmaa et al., 2014; Green et al., 2009; Ha et al., 2018; Hou et al., 2014; Leiser et al., 2019; Moridi et al., 2014; Perin et al., 2010a; Perin et al., 2010b) yet results have been inconsistent across specific pollutants. Some of the limitations of previous studies have included small sample sizes, sole reliance on clinical reports of SAB, low-quality study designs and highly selected populations. In addition, most previous studies have focused on acute exposure to air pollution in relation to risk of SAB; however, there is sufficient biological plausibility to suspect that chronic exposure may be important to consider as well. For instance, long-term exposure to PM2.5 has been associated with endothelial dysfunction (Liu et al., 2015), impaired functioning of the uterus (Bolden et al., 2017, Lin et al., 2019), heightened oxidative stress and systemic inflammation (Hajat et al., 2015) and alterations in DNA methylation and microRNA expression (Baccarelli and Bollati, 2009, Hou et al., 2011). Taken together, all of these pathways could potentially influence oocyte quality, implantation and early embryo growth, as well as the development and function of the placenta, which has direct implications in the etiology of SAB.

Therefore, the objective of our study was to examine whether chronic exposure to PM is associated with risk of SAB in a large geographically diverse, prospective cohort of women.