Part II – Prenatal exposure to wildfire smoke and perinatal outcomes

Pregnancy as a vulnerable period to air pollution

Fetal Growth and Development

Gestation is a period of rapid fetal growth and development, and the placenta serves multiple critical functions and acts as the primary metabolic barrier to environmental chemicals. Air pollutants, including PM2.5, a well-studied and primary pollutant in wildfire smoke, have the potential to cross the placental barrier (Malley et al., 2017). Altered or impaired placental function is significantly linked with common pregnancy complications, lower birth weight, developmental delay, and diseases that manifest later in life such as hypertension, coronary heart disease and type 2 diabetes (Maltepe and Fisher, 2015). Recent evidence suggests black carbon, a component of PM2.5 formed from incomplete combustion, accumulates on the fetal side of the placenta (Bove et al., 2019).
Two of the most studied perinatal outcomes – fetal growth and preterm birth – are key indicators of public health. Fetal growth, as measured by birth weight for gestational age, has important influences on human health. Low birth weight (birth weight below 2500 grams) is associated with increased rates of cardiovascular and cerebrovascular diseases in adulthood (Barker, 2004) and more immediate adverse outcomes including neonatal mortality and childhood morbidity (Saigal and Doyle, 2008, Zhang et al., 2014). Preterm birth is an important contributor of perinatal morbidity and mortality, with potential lifelong health implications for being preterm (Diamanti-Kandarakis et al., 2009, President’s Cancer Panel, 2010, Welshons et al., 2006, American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women et al., 2013) including pulmonary and neurodevelopmental outcomes (Behrman and Butler, 2007). In 2010, 2.7-3.4 million preterm births globally were estimated to be associated with PM2.5 exposure (Malley et al., 2017). In California between 2007-2012, an estimated 6,974 preterm births were attributable to wildfire smoke (Heft-Neal et al., 2022). Annual percentages of preterm births attributable to wildfire smoke ranged from 1.8% in 2011 to 6.3% in 2008, a high wildfire year (Heft-Neal et al., 2022).
While research specific to wildfire smoke exposures are limited, numerous studies across different years and countries have found consistent associations between3 ambient air pollution including PM2.5, a primary wildfire smoke pollutant, and measures of fetal growth (i.e. , birth weight, low birth weight, and small for gestational age) (Bekkar et al., 2020, Klepac et al., 2018, Shah et al., 2011, Yuan et al., 2020, Stieb et al., 2012). Similarly, higher ambient air pollution levels have been consistently associated with a ~10% increase in risk of preterm birth (Li et al., 2017, Klepac et al., 2018). Furthermore, epidemiological studies demonstrate that exposures to high levels of PM2.5second trimester and the end of pregnancy are most critical with regard to risk of preterm birth (Padula et al., 2014, Chang et al., 2015) and associations are stronger for earlier (i.e. , shorter gestation) preterm births (Padula et al., 2014).
Ambient air pollution exposures during pregnancy are associated with perinatal mortality (Li et al., 2021a) and sudden infant death syndrome (Chen et al., 2021). Higher levels of air pollution are associated with increased risk several structural birth defects including neural tube defects (Padula et al., 2013a), heart defects (Padula et al., 2013b, Yang et al., 2021), and other defects (Padula et al., 2013c). Additionally, PM2.5 exposure to mothers is associated with shorter telomere length in their offspring (Martens et al., 2017).
Cigarette smoke contains many of the same toxic compounds as those found in wildfire smoke including polycyclic aromatic hydrocarbons, carbon monoxide and free radicals (Zeglinski et al., 2019). Cigarette smoking during pregnancy is associated with a range of offspring outcomes including IQ (Corrêa et al., 2021) and academic achievement in school (Kristjansson et al., 2018). Prenatal exposure to smoke from traditional cookstoves using solid fuel is linked to increased adverse birth outcomes (Amegah et al., 2014), decreased childhood pulmonary function, and increased childhood risk of pneumonia and hospitalization (Lee et al., 2019).
Socioeconomically disadvantaged populations often face heightened exposures to structural and individual-level stressors and bear a disproportionate burden of environmental exposures including air pollution. Research demonstrates stronger associations between air pollution and preterm birth in neighborhoods with lower socioeconomic status (Padula et al., 2014, Gray et al., 2014, Mekonnen et al., 2021). Low socioeconomic status may have greater exposure to air pollution in general and wildfire smoke in particular due to higher rates of outdoor work, occupancy in poor-quality housing, linguistic barriers to access information, limited ability to evacuate, and structural barriers to healthcare access (Kizer, 2020). This double jeopardy of exposure to pollutants and poverty may contribute to disparities in adverse pregnancy outcomes.

Maternal Health

Pregnancy is also a period of physiological changes in the mother (Varshavsky et al., 2020) that result in vulnerability to air pollution including wildfire smoke. For example, during pregnancy respiratory rate and cardiac output are increased on average by 40% and 50%, respectively (Hegewald and Crapo, 2011, Bobrowski, 2010, Tan and Tan, 2013, Koman et al., 2018). Additionally, changes in the immune system are also subject to disruption by air pollution (Buxton et al., 2019). Smaller particles such as PM2.5 can travel and penetrate deeper into the lung and enter the bloodstream more easily than larger sized particulate matter, and higher concentrations of these small particles due to wildfire smoke result in more inhaled particles (Makkonen et al., 2010, Nance JD, 1993, U.S.EPA, 2009). This problem may be more dangerous as fires are occurring more often at the wildland-urban interface leading to structure burning, and in turn more toxic exposures. The toxicity of these wildland-urban interface fires are of increasing concern with respect to the chemical composition and subsequent health effects.
Prenatal exposures to ambient air pollution including PM2.5 are associated with maternal outcomes including hypertensive disorders in pregnancy (i.e. , gestational hypertension, pre-eclampsia and eclampsia) and gestational diabetes (Pedersen et al., 2014, Weber et al., 2019, Padula et al., 2018, Padula et al., 2020). These conditions may be on the causal pathway between air pollution and adverse perinatal outcomes. Maternal conditions are not only critical to the fetus’s health, but they also heighten maternal susceptibility to future metabolic and cardiovascular disease (Kampmann et al., 2015, Holdsworth-Carson et al., 2010). Exposure to wildfire PM2.5 may increase risk of pregnancy complications and adverse perinatal outcomes, particularly for vulnerable populations, which in turn could amplify existing reproductive and perinatal health disparities.
Potential biological pathways mediating the link between air pollution and adverse perinatal outcomes include oxidative stress (Moller et al., 2014), systemic inflammation (Panasevich et al., 2009), endothelial dysfunction (Wauters et al., 2013), and DNA damage (Risom et al., 2005, Gaskins et al., 2019), but less is known about the biological effects specifically of wildfire smoke. Maternal inflammatory responses are modified during pregnancy to establish and maintain a viable fetus and elevated inflammatory signals are linked with parturition (Palm et al., 2013). While the mechanisms remain unresolved, imbalances in anti- and pro-inflammatory mediators are associated with common pregnancy complications such as preterm birth and fetal growth restriction. Additionally, PM10 has been associated with the pro-inflammatory cytokines in pregnancy (Buxton et al., 2019).

Methodological considerations of wildfire smoke exposure in pregnancy

Quantification of adverse perinatal health effects attributable to wildfire smoke presents additional methodologic challenges including identification of critical windows of exposure. Studies must quantify drastic increases in air pollution from a wildfire event which can range in duration from days to weeks at varying levels during pregnancy. Critical periods of exposure depend on the outcome of interest and may not be consistent for maternal morbidity, fetal loss, birth defects, fetal growth, gestational length, and infant mortality.
Wildfires occur seasonally, though the length of the season has grown in some regions of the world (e.g. , Western United States and South Eastern Australia). Seasonal patterns of birth outcomes also occur, which could be a result of seasonal fluctuations in air pollution, or other factors such as demographics in the population and seasonal birth patterns (Currie and Schwandt, 2013). Wildfire events compound existing air pollution exposures from usual sources such as traffic. Owing to sources, meteorology and topography, ambient air pollution varies by season as well. Accounting for these existing sources of air pollution while evaluating the impact of additional wildfire impact is important to qualify the effects of wildfire smoke specifically.
Wildfires are natural experiments with combined environmental and psychosocial stressors. Families living near wildfires may face threatened or actual evacuation, which may increase psychosocial stress, previously linked to gestational hypertension and adverse birth outcomes (Muglia and Katz, 2010). The combined and heightened exposure to psychosocial stressors and environmental contaminants faced by pregnant women can affect their fetuses, with potentially irreversible adverse impacts on health and development. One limitation of wildfire research is a difficulty differentiating between the air pollution exposure and the psychosocial stressors to tease apart their individual contributions to adverse outcomes (Padula et al., 2020).

Epidemiological evidence of perinatal health effects of wildfire smoke

Numerous studies investigate the impact of ambient air pollution during pregnancy on adverse perinatal outcomes; however, fewer have examine the contribution of wildfire-specific air pollution exposure, especially beyond single wildfire events. Much remains unknown about potential risk of extremely high (and potentially more toxic) levels of exposure, critical windows of vulnerability, and longer-term effects of acute and prolonged exposure to wildfire smoke.
We summarize the studies that examine the effects of wildfire smoke exposure during pregnancy in relation to adverse birth outcomes including low birth weight, preterm birth, birth defects, and infant mortality as well as mental health outcomes (O’Donnell and Behie, 2015, Prass et al., 2012, O’Donnell and Behie, 2013, Jayachandran, 2009, Heft-Neal et al., 2022, Park et al., 2021, Requia et al., 2021a, Requia et al., 2021b). These studies have been conducted all over the world from wildfires in the western United States (Holstius et al., 2012, Abdo et al., 2019, Heft-Neal et al., 2022), Canada (Verstraeten et al., 2020), and Indonesia (Jayachandran, 2009), forest fires in South America (Prass et al., 2012, Requia et al., 2021a, Requia et al., 2021b), and bushfires in Australia (O’Donnell and Behie, 2015, O’Donnell and Behie, 2013). Additional evidence of the perinatal effects from landscape fires comes from low- and middle- income countries (Li et al., 2021b). These studies employ a variety of epidemiological study designs including retrospective cohorts (Abdo et al., 2019, O’Donnell and Behie, 2015, O’Donnell and Behie, 2013, Heft-Neal et al., 2022), case-control (Li et al., 2021b), case-crossover (Requia et al., 2021b), time series (Holstius et al., 2012), and ecological study designs (Prass et al., 2012, Jayachandran, 2009, Requia et al., 2021a).

Low birth weight and preterm birth

One of the first studies to examine wildfire smoke in relation to birth weight during the 2003 Southern California fires which included 886,034 mothers and compared those pregnant during the fires to those pregnant either before or after the fires (Holstius et al., 2012). They found that births whose mother was exposed to the wildfire had on average 9.7 grams lower birth weights when exposed during the second trimester. Models adjusted for characteristics from the birth certificate including maternal age, race/ethnicity, education, parity, infant sex, and gestational age. Sensitivity analyses accounted for season, additional PM10, measurements, and length of peak period. Small decreases were observed in the first and third trimesters (3.3 grams and 7.0 grams, respectively) (Holstius et al., 2012).
An additional study examined prenatal exposure to wildfires in Colorado between 2007-2015 and risk of preterm birth and effects on birth weight in 535,895 pregnancies (Abdo et al., 2019). They examined PM2.5 concentrations from the wildfire smoke at the ZIP code level during each trimester and found exposure in the second trimester was associated with 13% increased risk of preterm birth and exposure in the first trimester was associated with a decrease in birth weight of 5.7 grams (Abdo et al., 2019). They adjusted for maternal factors (age, income, education, race/ethnicity, smoking, drinking, asthma, prenatal care) as well as temperature deviation, month, year and other air pollution exposures including non-wildfire PM2.5, PM10 and ozone.
The largest study to date examined ~3 million births in California between 2006-2012 to estimate risk of preterm birth in relation to ZIP code level estimates of exposure based on satellite-based wildfire smoke plume boundaries and gridded estimates of surface PM2. 5 concentrations (Heft-Neal et al., 2022). This study found that for each day of exposure to any wildfire smoke was associated with an 0.49% increase in risk of preterm birth. Estimates by trimester suggest stronger associations with exposure later in pregnancy and estimates by smoke intensity indicate that observed associations were driven by higher intensity smoke-days.
Several studies conducted in the Brazilian Amazon examined prenatal exposure to deliberate but uncontrolled forest fires and other biomass burning. One study included a retrospective cohort study of 6147 full term, singleton births between 2004-2005 during periods of burning assessed with Brazilian Biomass Burning Emission Model based on hotspots identified by remote sensing (Candido da Silva et al., 2014). They found risk of term low birth weight (<2500 grams with gestational age ≥37 weeks) was 50% higher when women were exposed to the highest quartile of either PM2.5 in the second or third trimester, or CO in the second trimester. They adjusted for newborn’s sex, mother’s age and education and prenatal care (Candido da Silva et al., 2014). An ecologic study examined used heat spots from satellite images as they varied by month and year between 2001-2005 in relation to birth weight among boys and girls (Prass et al., 2012). This study did not find conclusive evidence and was limited by the inability to adjust for confounding and imprecise exposure measurement. More recently, a study examined associations between wildfire-related PM2.5 during trimesters of pregnancy and preterm birth using a case-crossover design (Requia et al., 2021b). They found increased odds of preterm birth in the Southeast regions when wildfire occurred during the first trimester (odds ratio, OR=1.41) and increased odds of preterm birth in the North region when wildfire exposure occurred during the second trimesters (OR=1.05) (Requia et al., 2021b).
A few studies come from Australia, an area of regular wildfire occurrence. During the 2003 Canberra bushfires, one study found that male infants born in the most severely fire-affected area had significantly higher average birth weights than their less exposed peers and were also heavier than males born in the same areas in non-fire years (O’Donnell and Behie, 2015). Higher average weights were attributable to an increase in the number of macrosomic infants (i.e > 4000 grams) (and potentially attributable to the stress of the wildfires in addition to the air pollution). There was no significant effect on the weight of female infants or on gestational age for either sex (O’Donnell and Behie, 2015). An additional study examined the bushfires in Victoria, Australia in 2009 and found small but significant increases in preterm birth and decreases in birth weight for those exposed to the fires in their second or third trimester. They assigned exposure based on maternal residence in a fire affected area, as defined by small administrative areas (Local Government Area), compared to women who resided in unaffected areas (O’Donnell and Behie, 2013).
One study examined fire-sourced PM2.5 in relation to birth weight in 54 low- and middle-income countries using Demographic and Health Survey data. They used a sibling-matched case control study of 227,948 newborns between 2000 to 2014 (Li et al., 2021b), and mothers with two births during the study period were included. A 1 μg/m3 increase in the concentration of fire sourced PM2.5 was associated with a 2.17 grams reduction in birth weight, a 2.80% increase in low birth weight risk, and an 11.68% increase in very low birth weight risk (Li et al., 2021b).

Congenital Anomalies

A study in Brazil examined wildfire smoke exposure in relation to congenital anomalies between 2001-2018 (Requia et al., 2021a). The number of wildfires within the boundaries of a mother’s home municipality during each trimester was compared in relation to 12 categories of birth defects in a population of 16,825,497 births (7,595 cases). They found associations between exposure and cleft lip/cleft palate (OR: 1.007) during the second trimester of exposure, congenital anomalies of the respiratory system (OR: 1.013) in the second trimester of exposure, and congenital anomalies of the nervous system (OR: 1.002) during the first trimester of exposure for the regions South, North, and Midwest, respectively (Requia et al., 2021a).
In California, wildfire smoke during the first trimester was associated with gastroschisis, an abdominal wall defect, when compared to no wildfire smoke (7.8 compared to 5.7 per 10,000 births (relative risk, RR: 1.28) (Park et al., 2021). Although the exposure assessment and case ascertainment in these studies are likely to be subject to misclassification, these results prompt a need for further studies to confirm (Padula and Benmarhnia, 2022).

Infant Mortality and Pregnancy Loss

One study examined pollution from land clearing fires that got out of control in 1997 in Indonesia and population-level infant mortality (Jayachandran, 2009). They estimated smoke exposure during prenatal and postnatal periods by month and district and gauged impact on fetal, infant and childhood mortality based on the 2000 census count. The study found that fire-related increases in air pollution were associated with a 1.2% decrease in cohort size. The under-three mortality during this period was 6%, approximately 20% higher than during other times. They found in utero exposure to have the largest impact on survival, particularly exposure in the third trimester, which was associated with the smaller cohort size (Jayachandran, 2009).
A case-control study of rhesus macaques during the Northern Californian Camp Fire in November 2018, which affected the peak breeding season at the California National Primate Research Center provides evidence of pregnancy loss (Willson et al., 2021). All females in the study were maintained in outdoor fields and exposed to high levels of PM2.5 during the wildfires. Archival records of approximately 5,000 conceptions from the previous nine years served as a comparison group. They observed increased pregnancy loss during the breeding season especially for those whose exposure occurred during the first 60 days of gestation (Willson et al., 2021). Although early pregnancy loss is difficult to capture in epidemiologic studies, this study in macaques provides evidence of early gestational exposure and the potential for increased risk of pregnancy loss in humans.

Mental Health Outcomes

As mentioned above, the consequences of wildfires are beyond the smoke exposure, but also include the psychological impact of the fire threat and trauma. One Canadian study of 200 women who experienced the Fort McMurray Wood Buffalo wildfire during or shortly before pregnancy examined distress (Verstraeten et al., 2020). Greater peritraumatic distress and dissociative experiences correlated with more severe Post Traumatic Stress Syndrome-like symptoms. Greater social support satisfaction was associated with less severe post-traumatic stress symptoms but only when peritraumatic distress was below average; at more severe levels of Peritraumatic Distress Inventory, this psychosocial variable was not protective (Verstraeten et al., 2020).

Summary of pregnancy studies

The most conclusive findings from the studies summarized above were between wildfire smoke during pregnancy and both lower birth weight and increased risk of preterm birth. Additional infant outcomes such as birth defects and infant mortality were explored but are less definitive and subject to more extensive methodologic issues including exposure misclassification, exposure measurement error, critical periods of exposure, unmeasured confounding and outcome ascertainment. The effect of stress due to the wildfire event has been associated with maternal mental health and may be an additional pathway by which wildfires may affect adverse outcomes, particularly preterm birth, as stress can result in the premature onset of labor. As more research is underway to help inform policy to protect those pregnant during wildfire events, precautions should be taken to reduce exposure during this vulnerable period for both the mother and child.