ReviewInternational journal of molecular sciences2023
Valproic Acid in Pregnancy Revisited: Neurobehavioral, Biochemical and Molecular Changes Affecting the Embryo and Fetus in Humans and in Animals: A Narrative Review.
Review in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
31 citing papers in PubMed, 3 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Autism Spectrum Disorders and Purinergic Signaling: A Systematic Review of Emerging Insights from Preclinical Studies.Journal of molecular neuroscience : MN · 2026Pooled it
- Valproate Exposure as anCNS & neurological disorders drug targets · 2025Pooled it
- Exposure to anti-seizure medication during pregnancy and the risk of autism and ADHD in offspring: a systematic review and meta-analysis.Frontiers in neurology · 2024Pooled it
- Craniofacial development: genetics, signaling pathways, teratogenic mechanisms, and clinal significance.Molecular biomedicine · 2026Review
- Global trends in epilepsy and the Chinese experience: Epidemiological transitions, underlying mechanisms, and integrated strategies (1990-2021).Neuroprotection (Chichester, England) · 2026Review
- Advances in the etiology of congenital scoliosis: from morphology to spatiotemporal molecular mechanisms (2015-2025).EFORT open reviews · 2026Article
- Evaluation of colostrum-coated ZnO nanoparticles (C-ZnONPs) in attenuating valproic acid-induced prenatal toxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Assessing molecular gene by treatment interactions using a population of neural progenitors exposed to valproic acid and lithium.Molecular psychiatry · 2026Article
- Article
- Vocal and social impairments in songbirds embryonically exposed to an autism risk factor.iScience · 2026Article
- Protective role of methylcobalamin (Vit B12) and pyridoxine (Vit B6) combination against teratogenic effects induced by lead in chick embryo.Toxicology reports · 2026Article
- Differential Neurodevelopmental Disruption by Bisphenol A (BPA) and Valproic Acid (VPA) in Human Forebrain Organoids.bioRxiv : the preprint server for biology · 2026Article
- Risk assessment of drug-associated miscarriage using XGBoost and SHAP explainability: a real-world pharmacovigilance analysis based on the FAERS database.Frontiers in pharmacology · 2026Article
- Brivaracetam monotherapy in juvenile myoclonic epilepsy: a safety and efficacy evaluation.Therapeutic advances in neurological disorders · 2026Article
- Effect of high altitude on the pharmacokinetics and pharmacodynamics of valproate in epileptic rats.Frontiers in pharmacology · 2026Article
- Comparative Analysis of Cannabidiol and Risperidone on Behavioral and Neurochemical Outcomes, and Neurodevelopment Markers in a Zebrafish Model of Embryonic Exposure to Sodium Valproate.Autism research : official journal of the International Society for Autism Research · 2025Article
- Intralitter Variability Influences the Developmental Impact of Valproic Acid Exposure in CD-1 Mice.Journal of applied toxicology : JAT · 2025Article
- The anticonvulsant and mood-stabilizing drug valproic acid attractsbioRxiv : the preprint server for biology · 2025Article
- Beyond epilepsy: The expanding role of valproic acid in Alzheimer disease therapy - a review.The Journal of pharmacology and experimental therapeutics · 2025Review
- Prenatal Valproic Acid Exposure Affects Song Learning in Zebra Finches: A Potential Model for Vocal Development in Autism.Life (Basel, Switzerland) · 2025Article
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Valproic acid (VPA) is a very effective anticonvulsant and mood stabilizer with relatively few side effects. Being an epigenetic modulator, it undergoes clinical trials for the treatment of advanced prostatic and breast cancer. However, in pregnancy, it seems to be the most teratogenic antiepileptic drug. Among the proven effects are congenital malformations in about 10%. The more common congenital malformations are neural tube defects, cardiac anomalies, urogenital malformations including hypospadias, skeletal malformations and orofacial clefts. These effects are dose related; daily doses below 600 mg have a limited teratogenic potential. VPA, when added to other anti-seizure medications, increases the malformations rate. It induces malformations even when taken for indications other than epilepsy, adding to the data that epilepsy is not responsible for the teratogenic effects. VPA increases the rate of neurodevelopmental problems causing reduced cognitive abilities and language impairment. It also increases the prevalence of specific neurodevelopmental syndromes like autism (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). High doses of folic acid administered prior to and during pregnancy might alleviate some of the teratogenic effect of VPA and other AEDs. Several teratogenic mechanisms are proposed for VPA, but the most important mechanisms seem to be its effects on the metabolism of folate, SAMe and histones, thus affecting DNA methylation. VPA crosses the human placenta and was found at higher concentrations in fetal blood. Its concentrations in milk are low, therefore nursing is permitted. Animal studies generally recapitulate human data.
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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.