Associations of Placental Oxidative Stress with Exposure to Gestational Air Pollution: Evidence from the UPSIDE Cohort

Increased placental oxidative stress is frequently documented in pregnant women with adverse maternal outcomes such as preeclampsia. However, environmental determinants of placental oxidative stress remain poorly understood.

To determine whether exposure to air pollution and polycyclic aromatic hydrocarbons (PAHs) are associated with placental levels of malondialdehyde (MDA), a biomarker of oxidative stress; to assess whether placental MDA reflects short-term (lag days 0-7) or longer-term (trimester-specific) exposure; and to evaluate whether these associations differ by fetal sex.

Participants were drawn from the UPSIDE ECHO BABIES cohort (n = 222). Placental MDA concentrations were quantified using an HPLC method. The ambient PM₂.₅ and NO₂ exposures were estimated using high-resolution random forest models. PAH exposure was assessed using trimester-specific maternal blood concentration of PAH-hemoglobin adducts. Associations between exposure and placental MDA were evaluated using multivariable linear regression and distributed lag non-linear models (DLNMs), adjusting for maternal and demographic covariates.

A 1-IQR increase in the second trimester, specifically month 5 p.m.₂.₅, was associated with a 24.8% (95% CI: 3.3-50.7), and 13.7% (95% CI: 0.1-29.16) increase in MDA concentration, respectively. Similarly, the second-trimester hemoglobin adduct of benzo [a]pyrene showed a positive, non-significant association with MDA. Although week-specific DLNM estimates were not statistically significant, the analysis showed that exposure to PM₂.₅ during gestational weeks 16-20 was positively associated with MDA concentration. When stratified by placenta sex, female placentas had increased MDA in the second trimester associated with PM₂.₅, and male placentas had increased MDA in the second trimester associated with PAH-hemoglobin adducts. No significant associations were observed for either pollutant when estimated one lag week before birth. No significant associations were observed for NO₂ exposure.

Second-trimester PM₂.₅ exposure was linked to elevated placental MDA concentration at delivery, indicating that placental MDA may reflect longer-term air pollution exposure. These findings emphasize the importance of investigating specific gestational windows through which air pollution induces oxidative injury to the placenta.