Prenatal air pollution, fetal β-cell dysfunction and neurodevelopmental delay

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. We aim to identify sensitive windows of air pollution during pregnancy on neurodevelopmental delay, and examine whether cord blood C-peptide mediates the relationship. This study included 7438 mother-newborn pairs in Hefei, China, from 2015 to 2021. Weekly exposure to particulate matter of aerodynamic diameter <2.5 µm, 10 µm (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. 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 μg/m3), 1.40(1.28,1.53) in PM10 (per 10 μg/m3), 1.41(1.30,1.52) in CO (per 0.1 mg/m3), and 1.49(1.29,1.72) in NO2 (per 5 μg/m3)]. 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 β-cell function. Screening and treatment of abnormal glucose metabolism in infants could benefit the prevention of air pollution-associated neurodevelopment delay.