Are we ready to establish a causal relationship between air pollution and pregnancy loss?
Authors: Sandie Ha, Pauline Mendola
Journal: The Lancet Planetary Health (2019)

The incidence of pregnancy loss is about 28% in preconception cohorts,1Buck Louis GM Schisterman EF Sweeney AM et al.Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development--the LIFE Study.Paediatr Perinat Epidemiol. 2011; 25: 413-424Crossref PubMed Scopus (134) Google Scholar and self-reported prevalence of pregnancy loss is increasing in the USA.2Rossen LM Ahrens KA Branum AM Trends in risk of pregnancy loss among US women, 1990–2011.Paediatr Perinat Epidemiol. 2018; 32: 19-29Crossref PubMed Scopus (83) Google Scholar The causes of most pregnancy losses are unclear, posing a major challenge for intervention efforts. Mounting evidence suggests that air pollution might affect embryonic and fetal development in both in vitro and population-based studies.3Legro RS Sauer MV Mottla GL et al.Effect of air quality on assisted human reproduction.Hum Reprod. 2010; 25: 1317-1324Crossref PubMed Scopus (87) Google Scholar, 4Munch EM Sparks AE Duran HE Van Voorhis BJ Lack of carbon air filtration impacts early embryo development.J Assist Reprod Genet. 2015; 32: 1009-1017Crossref PubMed Scopus (14) Google Scholar, 5Mendola P Ha S Pollack AZ et al.Chronic and acute ozone exposure in the week prior to delivery is associated with the risk of stillbirth.Int J Environ Res Public Health. 2017; 14: E731Crossref PubMed Scopus (24) Google Scholar, 6Ha S Liu D Zhu Y et al.Ambient temperature and stillbirth: a multi-center retrospective cohort study.Environ Health Perspect. 2017; 125: 067011Crossref PubMed Scopus (45) Google Scholar However, few studies have explored whether air pollution affects the risk of pregnancy loss, particularly in low-income areas of the world where the incidence is high. The scarcity of studies investigating the effects of air pollution on the risk of pregnancy loss is partly driven by the scarcity of available data coupled with the challenges associated with prospectively monitoring pregnancy loss and personal air monitoring. Existing studies often use retrospective data on known pregnancy or live births because of accessibility. This presents a crucial limitation because a considerable proportion of pregnancy losses occur early, even before entry into the health-care system. Thus, retrospective data cannot adequately capture early losses, leading to a missed opportunity to explore more upstream effects of air pollution. The second challenge involves assessment of air pollution. Personal exposures are commonly estimated using local stationary air monitors or mathematical models. Although feasible, these methods do not effectively capture small spatiotemporal variations in air pollution, especially because most women are mobile. These sources of measurement error are generally thought to be non-differential, adding random error that will bias study results towards the null. To better understand the causal relationship between air pollution and pregnancy loss, it is crucial to prospectively enroll participants before conception, use personal air monitors to measure air pollution, and implement detailed protocols with fertility and pregnancy testing. However, such studies would unquestionably be expensive and require high compliance from couples attempting to conceive, who might be difficult to identify and recruit. Alternatively, self-match case-control study designs have received attention because of their efficiency and ability to effectively control for time-invariant confounding. The study by Tao Xue and colleagues7Xue T Zhu T Geng G Zhang Q Association between pregnancy loss and ambient PM2·5 using survey data in Africa: a longitudinal case-control study, 1998–2016.Lancet Planetary Health. 2019; 3: e219-e225Summary Full Text Full Text PDF PubMed Scopus (31) Google Scholar is the first large study to examine the association between fine particles and pregnancy loss across 33 African countries. The authors took advantage of a large multicountry sample of 42 952 women with self-reported pregnancy losses (1998–2016), who also had a successful pregnancy before or after the index loss. Monthly area-level exposures to PM2·5 and its five major constituents were estimated using satellite remote sensing technology and the chemical transport models accounting for meteorological factors. For each pregnancy loss, the monthly average concentration of PM2·5 and its constituents during various windows of pregnancy was compared with the corresponding window of a successful pregnancy within the same mother. A 10 μg/m3 increment in PM2·5 over the full gestational length was associated with an increased risk in overall pregnancy loss (adjusted OR of 1·122; 95% CI 1·107–1·137), with similar results for miscarriage (1·125; 1·109–1·142) and stillbirth (1·094; 1·051–1·138). In pollutant-specific analyses, dust particles had the strongest effects on pregnancy loss risk. A major strength of this study is that its self-match nature adjusts for factors that do not change between the pregnancies (eg, genetics).8Maclure M The case-crossover design: a method for studying transient effects on the risk of acute events.Am J Epidemiol. 1991; 133: 144-153Crossref PubMed Scopus (1701) Google Scholar However, it is important to also note that factors that can change between pregnancies, which could be years apart, could have confounded the observed association (eg, lifestyle choices, stress, comorbidities, and seasonality) in addition to changes in maternal characteristics that might vary with age such as blood pressure, body-mass index, and chronic disease risk. Xue and colleagues7Xue T Zhu T Geng G Zhang Q Association between pregnancy loss and ambient PM2·5 using survey data in Africa: a longitudinal case-control study, 1998–2016.Lancet Planetary Health. 2019; 3: e219-e225Summary Full Text Full Text PDF PubMed Scopus (31) Google Scholar estimated exposure to air pollution using satellite remote sensing technology and the chemical transport model, which produces monthly outputs at a spatial resolution of 0·1° × 0·1° across Africa. This method is subject to misclassification because it cannot account for patterns in daily activities, residential mobility, or spatiotemporal variation less than 1 month and 0·1° × 0·1°. Nevertheless, given the scope of the study and the challenges related to personal monitoring, it provides a cost-effective opportunity to explore the effects of air pollution on fetal outcomes. Since pregnancy loss was self-reported, early losses were probably missed, especially those that occur early when women might not know they are pregnant. Furthermore, the exact date of loss was not known, leading to potential misclassification of the case and control periods. The authors have done several sensitivity analyses using different methods to select the control live-birth pregnancies and tested for potential effect modifiers. The overall findings were robust and at the same exposure level, women with increased maternal age or low socioeconomic status had higher risk. Given the growing complexity of environmental threats, future studies need to investigate susceptible subgroups and pollutant interactions. In summary, although large detailed preconception cohorts are still needed to establish a causal relationship between air pollution and pregnancy loss, the work by Xue and colleagues is an interesting and pragmatic approach to investigate the effects of air pollution on pregnancy loss in low-income and middle-income countries. We declare no competing interests. Association between pregnancy loss and ambient PM2·5 using survey data in Africa: a longitudinal case-control study, 1998–2016Our findings from African DHS data showing that PM2·5 exposure is significantly associated with increased risk of pregnancy loss add to the existing epidemiological evidence from middle-income and high-income countries on the health impacts of poor air quality. Our results support public health interventions for reducing ambient particulate matter to improve maternal health in Africa. Full-Text PDF Open Access