Mediating role of the maternal placental growth factor levels on association between ozone exposure and adverse pregnancy outcomes.

BACKGROUND

Maternal placental growth factor (PlGF) is closely associated with adverse pregnancy outcomes (APOs), and ozone (O3) exposure is considered a risk factor for APOs. However, whether PlGF mediates the relationship between O3 and APOs remains unclear. This study investigated the mediating role of PlGF in the association between O3 exposure and APOs.

METHODS

This study conducted a retrospective cohort analysis of 11,677 pregnant women in Tianjin, China (2017-2023). The association between O3 exposure and APOs was analyzed using Cox proportional hazards models, while multiple linear regression assessed O3-PlGF relationships. The mediating effect of PlGF was estimated through causal mediation analysis.

RESULTS

O3 exposure throughout pregnancy was significantly associated with elevated risks of APOs, including preterm birth (PTB; HR = 2.528, 95 %CI: 2.146, 2.979), low birth weight (LBW; HR = 2.503, 95 %CI: 2.061, 3.040), small for gestational age (SGA; HR = 1.543, 95 %CI: 1.284, 1.856), premature rupture of membranes (PROM; HR = 1.487, 95 %CI: 1.334, 1.657), and fetal growth restriction (FGR; HR = 2.235, 95 %CI: 1.539, 3.247). Per 10 μg/m3 increment in O3 concentration, these corresponded to elevated risks of 152.8 %, 150.3 %, 54.3 %, 48.7 %, and 123.5 %, respectively. Regression analysis demonstrated an inverse relationship between O3 exposure and PlGF levels, with each 10 μg/m3 increment in O3 associated with a 10.84 % reduction in PlGF (95 %CI: -18.11 %, -2.92 %). Mediation analysis identified decreased PlGF levels as a significant mediator in the associations between O3 exposure and the risk of PTB (mediation proportion:14.4 %), LBW (25.1 %), SGA (25.3 %), and FGR (18.8 %).

CONCLUSION

Our findings demonstrate that gestational O3 exposure increases the risk of APOs, which was mediated through reductions in maternal PlGF levels.