Longitudinal Associations between Ambient Air Pollution and Angiogenic Biomarkers among Pregnant Women in the LIFECODES Study, 2006-2008

Background: Exposures to ambient air pollution during pregnancy have been linked to adverse pregnancy outcomes such as preeclampsia and fetal growth restriction. Although evidence has shown that women with preeclampsia have higher ratio of soluble fms-like tyrosine kinase 1 to placental growth factor (sFlt-1/PlGF ratio), the potential impact of air pollution on markers of placental growth and function has not been well studied.

Objectives: We aimed to examine longitudinal associations between ambient air pollution exposure and angiogenic factors among pregnant women in LIFECODES, a prospective birth cohort and biorepository in Massachusetts in the United States.

Methods: PlGF and sFlt-1 were measured among pregnant women using plasma samples collected around 10, 18, 26, and 35 wk' gestation. Women's exposures to ozone ($O_3$), fine particulate matter with aerodynamic diameter $\le 2.5\mu m$ (${\mathrm{PM}}_{2.5}$), and nitrogen dioxide (${\mathrm{NO}}_2$) within 1, 2, 4, and 8 wk prior to each plasma sample collection were estimated based on geocoded residential addresses, and mixed effect linear regression models were fitted to assess their associations with sFlt-1/PlGF ratio, sFlt-1 (ng/mL), and PlGF (pg/mL). Percent changes in outcomes associated with each interquartile range increase in exposures were reported, along with their 95% confidence intervals.

Results: A total of 1,066 pregnant women were included. In the multipollutant models, significant associations were observed for increased sFlt-1/PlGF ratio (${\mathrm{PM}}_{2.5}$ 3-8 wk' gestation, ${\mathrm{NO}}_2$: 35-39 wk' gestation), elevated sFlt-1 ($O_3$: 26-34 wk' gestation, ${\mathrm{PM}}_{2.5}$: 3-8 wk' gestation), decreased sFlt-1 (${\mathrm{NO}}_2$: 4-8 wk' gestation), and decreased PlGF (${\mathrm{NO}}_2$: 34-39 wk' gestation) after adjusting for sociodemographic status, smoking, drinking, body mass index, parity, history of chronic hypertension, and conception time.

Discussion: Exposures to ${\mathrm{PM}}_{2.5}$ during early pregnancy and exposures to $O_3$ and ${\mathrm{NO}}_2$ during late pregnancy were associated with increased sFlt-1/PlGF ratio, elevated sFlt-1 and with decreased PlGF, which may be a potential mechanism underlying ambient air pollution's impacts on adverse pregnancy and birth outcomes. https://doi.org/10.1289/EHP11909.