Efficacy and Safety of Hopantenic Acid in Pediatric Neurological and Developmental Disorders: A Systematic Review and...

Neurodevelopmental disorders (NDDs) are pediatric conditions characterized by impairments in cognition, behavior, language, motor coordination, and social functioning. Hopantenic acid (N-pantoyl-γ-aminobutyric acid {GABA}), a selective partial GABA-B receptor agonist with neuroprotective and nootropic properties, has been utilized in various pediatric neurological disorders; however, consolidated evidence regarding its efficacy and safety remains limited. This systematic review and meta-analysis aimed to evaluate the therapeutic efficacy and safety of hopantenic acid in pediatric NDDs and to assess its impact across major neurodevelopmental domains represented by the language, cognition, motor coordination, and social communication (LCMS) framework. The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Electronic databases, including PubMed/MEDLINE, SpringerLink, ScienceDirect, and regional neurological journals, were systematically searched for controlled clinical trials involving children and adolescents treated with hopantenic acid. Quantitative synthesis was performed using a random-effects Mantel-Haenszel model to calculate pooled risk ratios (RR) with 95% confidence intervals (CI), while outcomes unsuitable for pooling were synthesized narratively. Six controlled studies involving 439 pediatric participants were included, of which four studies (n=272) were eligible for meta-analysis. Pooled analysis demonstrated greater clinical improvement with hopantenic acid compared with control therapy (RR=2.13, 95% CI: 1.11-4.08; I²=81%; p=0.02). More pronounced effects were observed in epilepsy and anxiety-related conditions, while moderate benefits were reported in hypoxic-ischemic encephalopathy. Narrative synthesis further indicated improvements across LCMS-related domains, including speech and hearing development, attention, memory, psychomotor performance, behavioral regulation, visual-motor coordination, social functioning, emotional stability, learning ability, and overall quality of life, without increasing seizure frequency. Safety outcomes were favorable, with adverse events comparable to placebo and no treatment-related serious adverse events reported. Overall, current evidence suggests that hopantenic acid may provide potential clinical and neurodevelopmental improvement across multiple pediatric NDDs, with benefits extending beyond symptomatic relief to broader developmental functioning. Its multimodal neuroprotective and GABA-B modulatory mechanisms provide a plausible biological basis for these findings. Nevertheless, inter-study heterogeneity and limited geographic representation highlight the need for larger, well-designed randomized controlled trials with standardized neurodevelopmental endpoints.