Combined effects of nitrogen dioxide and ozone air pollution on maternal liver function during pregnancy: a birth...

Nitrogen dioxide (NO₂) and ozone (O₃) exposure is associated with alterations in liver function, but epidemiological evidence in pregnant women remains limited, especially regarding the combined effects. This study aimed to investigate the associations of exposure to NO₂ and O₃ with maternal liver function and their roles in the combined effect of air pollutant mixture.

A birth cohort study with 11,909 pregnant women was conducted in Shenzhen, China. Exposure concentration of air pollutants during the first trimester were assessed based on the residential addresses of the pregnant women. Generalized additive model was used to analyze the association of NO₂ and O₃ exposure with maternal liver function. Furthermore, quantile G-computation model was used to investigate the combined effects of air pollutant mixture and the contribution of each pollutant.

Each 10 µg/m³ increase in first-trimester NO₂ exposure was associated with elevated alanine aminotransferase (ALT) and total bilirubin (TBIL) in both the second trimester (ALT: 15.45%, 95% CI: 10.12%, 21.04%; TBIL: 6.69%, 95% CI: 3.75%, 9.72%) and third trimester (ALT: 3.89%, 95% CI: 0.32%, 7.59%; TBIL: 9.27%, 95% CI: 6.52%, 12.10%). For O₃, first-trimester exposure showed a positive association with second-trimester TBIL (2.03%, 95% CI: 1.25%, 2.81%), but was inversely associated with third-trimester ALT (-2.73%, 95% CI: -3.86%, -1.58%) and TBIL (-0.81%, 95% CI: -1.45%, -0.17%). These associations remained significant in the two-pollutant model. The Qgcomp analysis revealed that a one-quartile increase in the air pollutant mixture was associated with a 2.05% (95% CI: 0.56%, 3.56%) increase in third-trimester TBIL, with NO₂ accounting for 55.6% of the positive weight in the model.

First-trimester NO₂ exposure was associated with elevated maternal liver function biomarkers in both the second and third trimesters, while O₃ showed trimester-dependent associations. Exposure to air pollutant mixture was associated with increased third-trimester TBIL, and NO₂ may be the predominant relative contributor. These findings highlight the need for further studies and public health attention to air pollution exposure during pregnancy to protect maternal and fetal health.