Association of first-month beta-hydroxybutyrate levels with subsequent ketogenic diet response in children with drug-resistant epilepsy: a prospective cohort study.

Background: Ketogenic diet therapy (KDT) is an established treatment for children with drug-resistant epilepsy (DRE), but the prognostic value of early blood beta-hydroxybutyrate (BHB) during diet stabilization remains uncertain. Methods: This single-center prospective cohort study enrolled children with DRE who initiated classical KDT at Peking University First Hospital between June 2023 and January 2025. First-month BHB was defined as the mean of two fasting pre-breakfast BHB measurements obtained during the final week of the first month after KDT initiation. Continuous first-month BHB was analyzed in relation to 3-month seizure reduction. An exploratory group-based analysis used a 3.0 mmol/L cutoff. The primary outcome was 3-month treatment response, defined as ≥50% seizure reduction from baseline. Later response and retention were summarized descriptively. Results: Of 40 screened children, 38 were analyzed (19 per group). Seizure type differed between groups ( Conclusion: Continuous first-month BHB showed no clear monotonic association with 3-month seizure reduction; an exploratory 3.0 mmol/L cutoff analysis similarly did not distinguish subsequent responders from non-responders. These findings describe the prognostic value of first-month BHB measured after individualized KDT titration and should not be interpreted as evidence regarding the benefit of deliberately targeting higher BHB levels.