The association between inflammatory markers in routine blood counts at 1 year and attention-deficit/hyperactivity disorder (ADHD): A case–control study

Background: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder marked by persistent patterns of inattention, disorganization, hyperactivity, and impulsivity. Increasing evidence implicates immune-inflammatory processes in its etiology, with observed associations between ADHD and infectious diseases, allergic conditions, and recent findings involving SARS-CoV-2. This study investigated whether early-life inflammatory markers, as measured by routine complete blood counts (CBCs) in clinically healthy 1-year-old children, were associated with subsequent diagnoses of ADHD. Methods: A retrospective case–control study was conducted using electronic medical records from Leumit Health Services, encompassing children under 18 years between January 1, 2006, and June 30, 2021. The sample included children who underwent routine CBC testing at age one during a well-child visit, without signs of acute illness. ADHD cases were identified based on ICD-9/10 criteria. Controls, free of any ADHD diagnosis, were randomly selected at a 1:2 ratio and matched for age, sex, socioeconomic status, and cultural sector. Analyses included white blood cell (WBC) subtypes and platelet counts, with the calculation of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR). Results: Children who were subsequently diagnosed with ADHD demonstrated statistically significant elevated total WBC counts at age one, including higher neutrophil, eosinophil, and lymphocyte levels, and lower basophil counts compared to matched controls (all p <.05). No significant differences were observed in PLR between groups. Conclusions: Elevated inflammatory markers were detectable in clinically healthy 1-year-old children who were later diagnosed with ADHD. These findings suggest a potential preclinical inflammatory phenotype linked to ADHD risk, highlighting the need for further investigation into early immune dysregulation as a contributing factor in ADHD pathophysiology. Early identification of such biomarkers may inform preventive strategies and targeted interventions in high-risk pediatric populations.