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.