BackgroundEpidemiological studies suggest that exposure to greenness during childhood may protect children from developing attention-deficit hyperactivity disorder (ADHD). ObjectiveWe analyzed the effect of both prenatal (pregnancy) and early childhood (4-5-year follow-up) residential greenness exposure and green space availability on ADHD symptoms during childhood (up to the age of 12 years) and further explored the potential mediating role of PM2.5 and physical activity in the association. MethodsThe study population included participants from the INfancia y Medio Ambiente (INMA) prospective birth cohort (Gipuzkoa, Sabadell, and Valencia). Average Normalized Difference Vegetation Index (NDVI) in buffers of 100-, 300- and 500-m around the residential addresses was used as an indicator of greenness, while green space availability was determined based on the presence of a major green space within 150-m from the residence. Childhood ADHD symptoms were assessed at the 6-8- and 10-12-year follow-ups using Conners Parents Rating Scale-Revised: Short Form. ResultsAlthough no association was found for the prenatal exposure period, increased early childhood NDVI inversely associated with the OR of clinically significant ADHD symptoms during the 6-8-year follow-up at the 100-m (OR 0.03, 95% CI: 0.003 to 0.44), 300-m (OR 0.04, 95% CI: 0.003 to 0.42) and 500-m (OR 0.08, 95% CI: 0.01 to 0.76) buffers, but exclusively in the context of direct effects. Additionally, the 10-12-year follow-up analysis found moderate to weak evidence of potential total and direct effects of NDVI at both 100- and 300-m buffers on inattention scores, as well as for NDVI at the 300-m buffer on ADHD index scores. The analysis did not reveal evidence of mediation through PM2.5 or physical activity. ConclusionsThe evidence suggests that early childhood greenness exposure may reduce the risk of developing ADHD symptoms later in childhood, and that this association is not mediated through PM2.5 and physical activity.