PM2.5 exposure exaggerates the risk of adverse birth outcomes in pregnant women with pre-existing hyperlipidemia: Modulation role of adipokines and lipidome

Highlights: • Maternal PM_2.5 exposure increased the risk of PTB, especially among women with pre-existing hyperlipidemia. • The susceptible exposure windows might be the second trimester of pregnancy. • The synergistic effects of PM_2.5 exposure and hyperlipidemia on lipid metabolism might be related to PTB. • Inflammation, IGF/IGFBP axis, and lipolysis might involved in the regulation of PM_2.5-induced lipid metabolism. The in-utero environmental exposure to fine particulate matter (PM_2.5) might lead to adverse birth outcomes, such as low birth weight (LBW) and preterm birth (PTB), thereby increasing susceptibility to diseases in later life. However, no studies have examined the underlying mechanism through cross-omics of lipidome and adipokines profiling, as well as the possible effect modification by maternal hyperlipidemia. In total, 203 mother-newborn pairs were recruited in the birth cohort study ongoing since February 2017 in Beijing, China. Individual-level of PM_2.5 exposure was estimated using a satellite data based random forest model. Cord blood lipidome and adipokines were assessed through the lipidomic approaches and antibody-based array. Multivariable logistic/linear regression models and moderation analysis were employed in this study. We observed a significantly increased risk of PTB associated with PM_2.5 exposure during the second trimester, especially in pregnant women with pre-existing hyperlipidemia. 9 lipid classes and 21 adipokines were associated with PM_2.5 exposure independently or significantly influenced by the interaction of maternal PM_2.5 exposure and hyperlipidemia. In addition, 4 adipokines (ANGPTL4, IGFBP-2, IL-12p40, and TNF-RII) and 3 lipid classes [phosphatidylcholines (PCs), phosphatidylinositols (PIs), and triglycerides (TGs)] were related to the increased risk of PTB, indicating that inflammation, IGF/IGFBP axis, and lipolysis induced lipid homeostasis disorder of PCs, TGs, and PIs might be the possible mediators for the PM_2.5-induced adverse birth outcomes. Our results substantiated the need for reducing exposure in susceptible populations.