Early Childhood Blood Lead Levels, Cognitive Trajectories, and School Readiness in a Birth Cohort: Dose-Response Analysis Below the CDC Reference Value of 3.5 ug/dL

This study investigates dose-response relationship between early childhood blood lead levels below the CDC reference value (3.5 ug/dL) and cognitive trajectories (IQ, executive function) and kindergarten school readiness at age 5 within the context of environmental pediatric epidemiology, an area of growing scientific importance given its implications for revised CDC blood lead reference value policy, pre-K lead screening protocol redesign, and primary lead exposure prevention investment for housing and water infrastructure. Using prospective birth cohort with capillary blood lead at 12/24/36 months, Bayley-III at 24/36 months, Differential Ability Scales-II at 48/60 months, and DIAL-4 school readiness at 60 months, with restricted cubic spline dose-response modeling and SES-adjusted regression, we examine low-level lead exposure disrupting hippocampal synaptic plasticity and prefrontal dopamine signaling even below current reference values, impairing working memory, inhibitory control, and phonological processing critical for school readiness in 2,840 children enrolled from birth (Cincinnati area), 84.2% retention at 60 months, 68% with complete blood lead and cognitive data (n=1,903 in primary analysis) drawn from Hamilton County, OH birth cohort 2014-2018, oversampled for low-income and high lead-risk zip codes with home visits for blood draw and assessments. Results indicate that linear dose-response relationship below 3.5 ug/dL: each 1 ug/dL increase in peak BLL associated with −1.84 DAS-II points (95% CI −2.48 to −1.20) and −2.24 DIAL-4 points (p<0.001), with no apparent lower threshold; children with BLL >=2.0 ug/dL show 28.4% higher kindergarten readiness failure rate (p < 0.001), with -1.84 DAS-II per 1 ug/dL; 28.4% higher readiness failure at BLL >=2 ug/dL as the primary quantitative benchmark. Concordance between primary and confirmatory measurement approaches exceeded 93%, validating the analytical framework. These findings contribute empirically to environmental pediatric epidemiology and carry actionable implications for the design of programs and policies targeting revised CDC blood lead reference value policy, pre-K lead screening protocol redesign, and primary lead exposure prevention investment for housing and water infrastructure.