Cord Serum Neonicotinoid-Related Biomarkers and Neurodevelopment From Early to Middle Childhood

Importance Despite widespread neonicotinoid insecticide use, evidence on prenatal exposure and neurodevelopment beyond early childhood remains limited. Objective To examine whether cord serum concentrations of the neonicotinoid-related biomarkers dinotefuran and desmethyl-acetamiprid (dm-ACE) are associated with domain-specific neurodevelopment from infancy through middle childhood. Design, Setting, and Participants This prospective cohort study included individuals randomly selected from eligible Hamamatsu Birth Cohort for Mothers and Children Study participants born between December 2007 and March 2012 in Japan; assessments spanned ages 10 months to 9 years. Data were analyzed between October 2025 and September 2026. Exposures Cord serum dinotefuran and dm-ACE concentrations measured at birth and categorized into quartiles. Main Outcomes and Measures Outcomes were standardized scores for 5 Mullen Scales of Early Learning (MSEL) domains at ages 10 to 32 months and 4 Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) indices at age 9 years. Associations were examined using linear regression and expressed as mean MSEL or WISC-IV differences in SD units at quartile 3 (Q3) and Q4 concentrations (combined Q1-Q2 was the reference). Results Among 200 individuals, 102 (51.0%) were male and 13 (6.5%) were born preterm; 185 (92.5%) to 195 (97.5%) were included in age-specific MSEL analyses and 178 (89.0%) in WISC-IV analyses. Dinotefuran groups included 96 individuals (48.0%) in Q1 and Q2, 47 (23.5%) in Q3, and 57 (28.5%) in Q4. dm-ACE groups included 82 (41.0%) in Q1 and Q2, 63 (31.5%) in Q3, and 55 (27.5%) in Q4. Early childhood associations across neurodevelopmental scale scores varied by age and concentration group, and there were no associations after false discovery rate (FDR) correction. At age 9 years, Q3 dinotefuran concentration was associated with lower WISC-IV Processing Speed Index scores compared with Q1 to Q2 scores (mean difference, −0.50 [95% CI, −0.81 to −0.20] SDs; q = .01), and Q4 dm-ACE concentration was associated with lower Perceptual Reasoning Index scores (mean difference, −0.47 [95% CI, −0.81 to −0.14] SDs; q = .03). Conclusions and Relevance In this cohort study of infants and children in Japan, small differences in some neurodevelopmental scale scores in early childhood were observed in association with dinotefuran and dm-ACE cord serum concentrations, but there were no associations after FDR correction. At age 9 years, dinotefuran was associated with lower processing speed and dm-ACE with lower perceptual reasoning. Overall, these findings suggest domain- and age-specific associations rather than a uniform or sustained pattern across development; confirmation in larger cohorts is needed.