Cord blood C-reactive protein and ADHD symptoms at age 5: Evidence from two French birth cohorts

Conditions associated with perinatal inflammation have been identified as risk factors for neurodevelopmental disorders, including Attention-Deficit/Hyperactivity Disorder (ADHD). However, data linking early inflammatory biomarkers with later ADHD symptoms remain scarce. The acute phase C-reactive protein (CRP) is a key marker of systemic inflammation. To date, no studies have examined the association between CRP levels in cord blood (reflecting neonatal inflammation) and subsequent childhood ADHD symptoms. Here, we aimed to investigate whether elevated cord blood CRP concentrations are associated with child's ADHD symptoms at age 5.

We analyzed data from 1,019 and 831 mother-child pairs enrolled in the ELFE and EDEN prospective birth cohorts, respectively. CRP levels in cord blood were measured using an immunoassay. ADHD symptoms were assessed at age 5 using the hyperactivity-inattention subscale of the Strengths and Difficulties Questionnaire (SDQ). Outcomes included both continuous scores and categorical thresholds: borderline (≥6) and abnormal (≥7) hyperactivity-inattention symptoms. Multivariate linear and logistic regression models were conducted within each cohort to assess associations between elevated CRP levels (≥75th percentile) and ADHD symptoms. Results were then pooled using random-effects meta-analytic methods. All analyses were conducted using R version 4.5.0.

Borderline hyperactivity-inattention scores were observed in 21% of children in the ELFE cohort and 14% in EDEN. After adjusting for maternal sociodemographic, lifestyle, and pregnancy-related factors, as well as child characteristics at birth, elevated cord blood CRP was significantly associated with higher odds of ADHD symptoms: borderline scores (adjusted odds ratio [aOR] = 1.42; 95% CI: 1.08-1.86), abnormal scores (aOR = 1.48; 95% CI: 1.06-2.08), and increased continuous symptom scores (β = 0.29; 95% CI: 0.04-0.54).

Higher CRP concentrations in cord blood are associated with greater ADHD symptom severity at age 5. These findings support the hypothesis that early-life inflammation may contribute to the developmental origins of ADHD and suggest that CRP could serve as a potential early biomarker of neurodevelopmental vulnerability.