ReviewPloS one2014
Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase.
Review in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Safety of lamotrigine in paediatrics: a systematic review.BMJ open · 2015Pooled it
- Drug hypersensitivity reactions in children in clinical practice: A WAO Statement.The World Allergy Organization journal · 2025Review
- Pediatric Pharmacy Association 2025 KIDs List of Key Potentially Inappropriate Drugs in Pediatrics.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Drug-Induced Liver Injury-Pharmacological Spectrum Among Children.International journal of molecular sciences · 2025Review
- The safety of valproic acid treatment in children with epilepsy: a retrospective real-world research.Acta epileptologica · 2024Article
- Multidisciplinary approach on divergent outcomes in spinal muscular atrophies: comparing DYNC1H1 and SMN1 gene mutations.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Age-related differences in drug-induced liver injury: a retrospective single-center study from a large liver disease specialty hospital in China, 2002-2022.Hepatology international · 2024Article
- Challenges of pediatric pharmacotherapy: A narrative review of pharmacokinetics, pharmacodynamics, and pharmacogenetics.European journal of clinical pharmacology · 2024Review
- The role of SIRT1-FXR signaling pathway in valproic acid induced liver injury: a quantitative targeted metabolomic evaluation in epileptic children.Frontiers in pharmacology · 2024Article
- Monitoring of the trough concentration of valproic acid in pediatric epilepsy patients: a machine learning-based ensemble model.Frontiers in pharmacology · 2024Article
- Analysis of Adverse Drug Reactions in Pediatric Patients with Epilepsy: An Intensive Pharmacovigilance Study.Children (Basel, Switzerland) · 2023Article
- [Advances in clinical diagnosis and treatment of drug-induced liver injury in children].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Review
- Article
- Management of Status Epilepticus by Different Pediatric Departments: Neurology, Intensive Care, and Emergency Medicine.European neurology · 2023Article
- Valproic acid for children below 2 years of age with epilepsy.Neurosciences (Riyadh, Saudi Arabia) · 2021Article
- Preliminary Results Regarding Sleep in a Zebrafish Model of Autism Spectrum Disorder.Brain sciences · 2021Article
- Valproic Acid-Induced Liver Injury: A Case-Control Study from a Prospective Pharmacovigilance Program in a Tertiary Hospital.Journal of clinical medicine · 2021Article
- Valproate Interaction With Carbapenems: Review and Recommendations.Hospital pharmacy · 2020Article
- Paradoxical Effects of a Cytokine and an Anticonvulsant Strengthen the Epigenetic/Enzymatic Avenue for Autism Research.Frontiers in cellular neuroscience · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionValproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine.
objectiveFirstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporting over time of hepatotoxicity with fatal outcome.
methodsIndividual case safety reports (ICSRs) for children ≤ 17 years with valproic acid and fatal outcome were retrieved from the WHO Global ICSR database, VigiBase, in June 2013. Reports were classified into hepatotoxic reactions or other reactions. Shrinkage observed-to-expected ratios were used to explore the relative reporting trend over time and for patient age. The frequency of polytherapy, i.e. reports with more than one antiepileptic medicine, was investigated.
resultsThere have been 268 ICSRs with valproic acid and fatal outcome in children, reported from 25 countries since 1977. A total of 156 fatalities were reported with hepatotoxicity, which has been continuously and disproportionally reported over time. There were 31 fatalities with pancreatitis. Other frequently reported events were coma/encephalopathy, seizures, respiratory disorders and coagulopathy. Hepatotoxicity was disproportionally and most commonly reported in children aged 6 years and under (104/156 reports) but affected children of all ages. Polytherapy was significantly more frequently reported for valproic acid with fatal outcome (58%) compared with non-fatal outcome (34%).
conclusionHepatotoxicity remains a considerable problem. The risk appears to be greatest in young children (6 years and below) but can occur at any age. Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions with valproic acid.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.