Table 1_Circulating BDNF in pediatric neurodevelopmental disorders: a meta-analysis of case–control differences and cognitive severity.docx

Five comparisons (four studies, five case–control arms, 322 unique participants) reported extractable means and standard deviations and were pooled using Hedges’ g in a random-effects (DerSimonian-Laird) model; three additional studies, providing within-group severity-gradient data, were retained for narrative synthesis or sensitivity analysis because of missing healthy-control comparators, non-standard assay platforms, or data reported only in figures.</p>Results<p>The case–control comparison yielded a pooled effect size of 0.46 (95% CI: −0.44 to 1.35), which was not statistically significant (z = 1.00, p = 0.32).

Heterogeneity was very high (Q = 53.71, df = 4, p < 0.001; I² = 92.6%; τ² = 0.96). Subgrouping by diagnostic category did not reduce heterogeneity (I² = 96.0% within studies of intellectual disability alone). A sensitivity analysis incorporating an additional digitised Down syndrome dataset yielded a consistent conclusion (pooled g = 0.54, 95% CI: −0.25 to 1.33).</p>Conclusion<p>Current evidence does not support circulating BDNF as a reliable case–control or severity biomarker of cognitive impairment in children with CP, ID, or DS.

The direction of association is inconsistent even within the same diagnostic category, likely reflecting methodological heterogeneity (assay platform, age-matching of controls) rather than a genuine, replicable biological signal. Age-matched studies using standardised assay protocols are needed before BDNF can be considered for clinical or research use in this population.</p>