Biological signatures of prenatal wildfire smoke exposure and fetal and infant growth

Wildfires are occurring across the US and globally with potentially harmful impacts on
maternal and child health. Although research into health effects specific to wildfire smoke
exposure in pregnancy is nascent, a recent meta-analysis on more than 1.7 million births
showed that maternal exposure during late pregnancy was linked to reduced birth weight
and preterm birth. However, the short and long-term effects of repeated wildfire smoke
exposure during pregnancy on maternal and fetal health outcomes have not been
investigated in depth, nor are any molecular mechanisms responsible for such effects well
understood. Therefore, there is an urgent need to understand the how wildfire smoke
exposure affects health and wellbeing. One hypothesized mechanism to facilitate
biological communication from pollutants inhaled in the lung to distal organs and tissues
is through extracellular vesicles (EVs). EVs contain a variety of biologically active
molecules including microRNAs (miRNAs) which are small ~22 nucleotide-long noncoding
RNA molecules. EV-miRNA might be the ideal candidates to mediate effects of wildfire
smoke exposures on pregnancy because they can be produced by the respiratory system
where the initial exposure occurs and then enter the circulation to affect distant tissues
and organs. We hypothesize that prenatal exposure to wildfire smoke triggers a biological
response that can be measured in EV-miRNA, and that these wildfire smoke-related
biological signatures are negatively associated with fetal and infant growth. We will
additionally investigate the interplay between smoke exposure and miRNA signatures with
neighborhood characteristics, including housing, infrastructure, and other factors that may
modify effects on fetal and infant growth. We will examine this hypothesis in 466
participants in MADRES—a cohort representative of the population living in Los Angeles,
CA – in the following aims: Aim 1) Identify unique EV-miRNA transcriptomic signatures of
wildfire smoke across pregnancy and the biological pathways associated with their
predicted gene targets in a population of 466 pregnant participants with 666 maternal
biospecimens. Aim 2) Evaluate the influence of wildfire-associated EV-miRNA signatures
on ultrasound-measured fetal growth, infant birthweight, body composition and child
growth through age 7. We will additionally evaluate effect modification by sex of child and
neighborhood characteristics. Aim 3) In exploratory analyses in a subset of 96
mother/child pairs, we will test whether wildfire smoke exposures affect newborn miRNA
levels in cord blood and further investigate the correlation of EV-miRNA expression
profiles between mother and infant. Findings from this study may inform future screening,
diagnostic, or treatment, interventions by helping us understand the biological effects of
wildfire smoke.

Grant Number: 7R21ES036649-02
NIH Institute/Center: NIH
Principal Investigator: Carrie Breton