Associations of air pollutants and related metabolites with preterm birth during pregnancy.

OBJECTIVE

This study aimed to investigate the influence of exposure to ambient fine particulate matter (PM) and its components during pregnancy on the prevalence of preterm birth (PTB). Additionally, we sought to identify the susceptible exposure window. Furthermore, we explored the potential mediating role of blood analysis and a comprehensive metabolic panel in the association between pollutant exposure and PTB incidence.

METHODS

This birth cohort study recruited 139 participants with PTB outcomes and 1713 controls from Fujian Maternal and Child Health Hospital between January 2021 and June 2023. Sociodemographic characteristics and clinical treatment data during participants' first pregnancies were collected. The exposure levels to pollutants during pregnancy were estimated via a combined geographic-statistical model utilising satellite remote sensing data. The distributional lag nonlinear modelling was employed to assess associations between pollutant exposure during pregnancy and the prevalence of PTB. Weighted quantile regression was used to identify key components associated with PM and PTB during pregnancy. Additionally, a mediating effect analysis was conducted to evaluate the role of blood analysis. The metabolic profile was used to screen for differentially abundant metabolites associated with PTB and explore their relative expression in relation to air pollutants and PTB incidence.

RESULTS

Following the adjustment for potential confounding variables, the mean weekly susceptibility windows for PM were identified as 7-10, 16-19, and 22-28 weeks; 8-10, and 15-19 weeks for inorganic sulfate; 6-10, and 15-28 weeks for nitrate; 6-12, and 15-28 weeks for ammonium (NH); and 7-9, 18-20, and 22-36 weeks for organic matter. During mixed exposure to PM components, the key component is NH. In the mixed exposure to PM components, NH emerged as a key contributor. The results of the mediation analysis revealed that haemoglobin played a mediating role, accounting for 21.53 % of the association between exposure to environmental pollutants and the prevalence of PTB. It is noteworthy that, no mediating effects were observed for the other variables. Furthermore, non-targeted metabolomics identified 17 metabolites associated with PTB. Among these factors, hydrogen phosphate may impact metabolic pathways such as oxidative phosphorylation, influencing the risk of PTB. The interplay between environmental pollutants and metabolites, particularly through oxidative phosphorylation pathways, may contribute to PTB incidence.

CONCLUSIONS

The evidence indicates that exposure to PM and its components during pregnancy were a significant risk factor for PTB. Notably, specific weekly exposure windows were identified for pollutants during pregnancy. Among the PM components, NH exhibited the most substantial weight in the association analysis between exposure to the mixture of components and PTB. Furthermore, our mediation analysis revealed that haemoglobin serves as a partial mediator in the relationship between exposure to pollutants during pregnancy and the prevalence of PTB. Additionally, maternal serum metabolic profiles differed between the preterm and control groups. Notably, a combined effect involving hydrogen phosphate and mixed exposure to PM fractions further contributed to the development of PTB. Oxidative phosphorylation pathways may play pivotal roles in this intricate association.