Prenatal depression increases susceptibility to periconceptional ambient air pollution exposure in relation to risk of gestational hypertension

Background: Exposure to air pollutants has been associated with elevated blood pressure during pregnancy. However, the influences of preconception and prenatal exposures to ambient air pollution on gestational hypertension (GH) remain unclear. Even less is known about the potential effect modification by individual risk factors, including depression. Methods: In 559 pregnant participants enrolled the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, we estimated daily levels of ambient particulate matter (PM₁₀; PM₂.₅), nitrogen dioxide (NO₂), and ozone (O₃) using spatial interpolation. Gestational hypertension without proteinuria was ascertained from medical records by physician diagnosis or defined as two abnormally high blood pressure measurements after 20 gestational weeks (GW). We used distributed lag models with Poisson regression to identify sensitive exposure windows by estimating weekly associations of exposures from pre-conception week 12 to GW 24 with GH risk, adjusting for maternal and meteorological factors. Analyses were additionally stratified by the Center for Epidemiologic Studies Depression Scale score (CES-D, <16 vs. ≥16), median pre-pregnancy body mass index (BMI, <27.5 vs. ≥27.5 kg/m²), median age (<28 vs. ≥28 years), and newborn sex to explore differential susceptibilities. Results: Forty-two (7.5%) participants were diagnosed with GH. An IQR increase in PM₂.₅ exposure in the window from GW6 to GW17 and PM₁₀ from GW7 to GW14 was associated with 10.1% (95% CI: 9.5-10.8%) and 10.9% (9.7-12.2%) increased risk of GH, respectively. Among 163 participants with probable depression (CES-D≥16), per IQR increase in PM₂.₅ exposure from GW6 to GW24 was associated with 26.8% (25.7-27.9%) increased GH risk. Conclusions: Early-to-mid pregnancy exposures to ambient air pollution were associated with increased risk of GH. A wider sensitive window of PM₂.₅ exposure and stronger effects were seen in participants with probable depression compared to those without. Keywords: air pollution, gestational hypertension, sensitive window, susceptibility, prenatal depression, preconception