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

About This Grant

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.