Early Life Ambient Air Pollution, Sex Steroids and Neurodevelopment: Target Trial Emulation in a Prospective Cohort

Ambient air pollution may impair childhood neurodevelopment, but sensitive windows, mediating pathways, and the neurodevelopmental benefits of air-quality interventions remain unclear. In this prospective birth cohort of 3575 mother–child pairs in Wuhan, China (2014–2019), neurodevelopment at age two was assessed using the Bayley Scales, and cord serum sex steroids were measured in 897 pairs. Associations of air pollution exposure from preconception through the second postnatal year with neurodevelopment at age two and potential sex-steroid mediation were evaluated. Target trial emulation (TTE) was used to estimate neurodevelopmental differences associated with China’s 2013–2017 air-quality intervention. Most air pollutants were inversely associated with neurodevelopment across multiple exposure windows, with associations generally strongest during the first postnatal year. Mediation analyses suggested that androstenedione mediated 5–12% of associations between specific preconception/prenatal air pollutant exposures and Psychomotor Development Index, although inverse-probability-weighted indirect effects were no longer statistically significant. TTE suggested significant neurodevelopmental benefits following the air-quality intervention, with Mental Development Index and Psychomotor Development Index improving by 7.27 and 6.41 points in the later policy-period group, respectively. These findings support more stringent long-term air pollution standards and sustained air-quality interventions to protect child neurodevelopment.