Prenatal Air Pollution, Fetal Β-Cell Dysfunction and Neurodevelopmental Delay

Background: Emerging evidence has reported significant associations of prenatal air pollution exposure with neurodevelopmental delay in offspring. Sensitive exposure windows and the modifiable factor remain elusive.Objective: We aim to identify sensitive windows of air pollution during pregnancy on neurodevelopmental delay, and examine whether cord blood C-peptide mediates the relationship.Methods: This study included 7438 mother-newborn pairs in Hefei, China, from 2015 to 2021. Weekly exposure to particulate matter of aerodynamic diameter <2.5 m, 10 mu m (PM2.5, PM10), nitrogen dioxide (NO2) and carbon monoxide (CO) was estimated at regulatory air monitoring stations in Hefei. Denver Developmental Screening Test-II and the Gesell Developmental Schedules were applied to assess the neurodevelopmental delay in children 6-36 mon of age. Distributed lag nonlinear models examined sensitive time windows of prenatal air pollutants exposure. Mediation analysis estimated the mediating role of cord blood C-peptide.Results: The sensitive PM2.5, PM10, NO2, and CO exposure windows associated with neurodevelopmental delay were throughout pregnancy. Weekly air pollutants exposure was related to higher neurodevelopmental delay risks [cumulative odds ratio (OR): 1.40(1.29,1.53) in PM2.5 (per 10 mu g/m(3)), 1.40(1.28,1.53) in PM10 (per 10 mu g/m(3)), 1.41(1.30,1.52) in CO (per 0.1 mg/m(3)), and 1.49(1.29,1.72) in NO2 (per 5 mu g/m(3))]. Mediation analysis indicated 18.3 % contributions of cord C-peptide to the relationship [average mediation effect: 0.04(0.01.0.06); average direct effect: 0.15(0.07.0.25)]. Conclusions: Exposure to air pollution throughout pregnancy is linked to neurodevelopmental delay mediated by poorer fetal beta-cell function. Screening and treatment of abnormal glucose metabolism in infants could benefit the prevention of air pollution-associated neurodevelopment delay.