U-shaped relationship between ozone exposure and preterm birth risk associated with preconception telomere length

There are conflicting findings regarding the association of ozone (O₃) exposure with preterm birth (PTB) occurrence. In the present study, two cohorts were combined to explore the relationship between maternal O₃ exposure during pregnancy and PTB risk, and analyze the underlying mechanisms of this relationship in terms of alterations in the preconception telomere length. Cohort 1 included mothers who participated in the National Free Preconception Health Examination Project in Henan Province from 2014 to 2018 along with their newborns (n = 1,066,696). Cohort 2 comprised mothers who conceived between 2016 and 2018 and their newborns (n = 1871) from six areas in Henan Province. The telomere length was assessed in the peripheral blood of mothers at the preconception stage. Data on air pollutant concentrations were collected from environmental monitoring stations and individual exposures were assessed using an inverse distance-weighted model. O₃ concentrations (100.60 ± 14.13 μg/m³) were lower in Cohort 1 than in Cohort 2 (114.09 ± 15.17 μg/m³). Linear analyses showed that PTB risk decreased with increasing O₃ exposure concentrations in Cohort 1 but increased with increasing O₃ exposure concentrations in Cohort 2. Nonlinear analyses revealed that PTB risk tended to decrease and then increase with increasing O₃ exposure concentrations in both cohorts. Besides, PTB risk was reduced by 88% for each-unit increase in telomere length in those exposed to moderate O₃ concentrations (92.4-123.7 μg/m³, P < 0.05). While no significant association was observed between telomere length and PTB at extreme O₃ concentration exposure during entire pregnancy (<92.4 or >123.7 μg/m³, P > 0.05) in Cohort 2. These findings reveal a nonlinear (U-shaped) relationship between O₃ exposure and PTB risk. Furthermore, telomere with elevated length was associated with decreased risk of PTB only when exposed to moderate concentrations of O₃, but not when exposed to extreme concentrations of O₃ during pregnancy.