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Comparative Analysis of Short-Chain Fatty Acid Levels as Predictors of Intestinal Mucosal Resilience in Pediatric Epilepsy Patients According to Duration of Valproic Acid Therapy

Manoppo, J. I. C.; Salendu, P. M.; Yulanda, H.

2025-08-01 pediatrics
10.1101/2025.07.31.25332438 medRxiv
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BackgroundEpilepsy is the most common neurological disorder in children and often requires long-term treatment with valproic acid, which may affect intestinal mucosal resilience. Short-chain fatty acid (SCFA) levels can serve as predictors of gut mucosal integrity in pediatric epilepsy patients undergoing valproic acid therapy. MethodsThis cross-sectional study was conducted at the Pediatric Outpatient Clinic, Department of Child Health, Prof. Dr. R.D. Kandou General Hospital, and Prodia Clinical Laboratory in Manado, from December 2023 to April 2024. Subjects were children with epilepsy aged 6 months to 18 years who met the inclusion criteria. SCFA levels--including total SCFA, acetic acid, propionic acid, and butyric acid--were measured using gas chromatography. ResultsOf the 56 participants, 28 children had received valproic acid therapy for less than one year, and 28 for more than one year. The <1-year therapy group showed significantly higher levels of total SCFA (MD = 4.67 [3.22-6.13]; p < 0.001), acetic acid (MD = 15.53 [12.65-18.41]; p < 0.001), propionic acid (MD = 6.25 [4.16-8.33]; p < 0.001), and butyric acid (MD = 9.53 [7.04-12.02]; p < 0.001) compared to the >1-year therapy group. A statistically significant difference in SCFA levels was observed between the two groups (p < 0.05). ConclusionDuration of valproic acid therapy significantly affects SCFA levels in children with epilepsy.

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