ArticleAnnals of neurology2012
Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development.
Article in Annals of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 6 of them syntheses that pooled it.
What it found
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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.
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Who cites it
93 citing papers in PubMed, 6 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- Pooled it
- Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants.The Cochrane database of systematic reviews · 2023Pooled it
- Efficacy of the anti-seizure medications in acute symptomatic neonatal seizures caused by stroke. A systematic review.Acta bio-medica : Atenei Parmensis · 2022Pooled it
- Treating the symptom or treating the disease in neonatal seizures: a systematic review of the literature.Italian journal of pediatrics · 2021Pooled it
- Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants.The Cochrane database of systematic reviews · 2013Pooled it
- Pharmacological treatment of neonatal seizures: a systematic review.Journal of child neurology · 2013Pooled it
- Effect of Treatment of Clinical Seizures vs Electrographic Seizures in Full-Term and Near-Term Neonates: A Randomized Clinical Trial.JAMA network open · 2021Trial
- Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial.Pediatrics · 2020Trial
- Short-Term Neurodevelopmental Outcome in Term Neonates Treated with Phenobarbital versus Levetiracetam: A Single-Center Experience.Behavioural neurology · 2019Trial
- Distinct electrophysiology and dopaminergic modulation of medium spiny neurons across divisions of the tail striatum and the dorsolateral striatum.Experimental physiology · 2026Article
- Breastfeeding and Neurodevelopmental Outcomes in Children of Women Taking Antiseizure Medications.JAMA network open · 2026Observational
- Prenatal Azithromycin Exposure and Risk of Neurodevelopmental Disorders in Children.JAMA network open · 2026Article
- Prominent astrocytic GLAST pathology occurs in newborn human and piglet hypoxic-ischemic encephalopathy: modeling relationships among laminar neuropathology, seizures, and therapeutic hypothermia.Frontiers in cellular neuroscience · 2026Article
- Review
- Efficacy of phenobarbital is maintained after exposure to mild-to-moderate seizures in neonates.Epilepsia open · 2025Article
- Early neurodevelopmental follow-up results from the NEOLEV2 cohort.Annals of the Child Neurology Society · 2025Article
- Padsevonil suppresses seizures without inducing cell death in neonatal rats.Pharmacological reports : PR · 2024Article
- Cenobamate suppresses seizures without inducing cell death in neonatal rats.Epilepsy & behavior : E&B · 2024Article
- Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.Pediatric research · 2024Article
- Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveDrug exposure during critical periods of brain development may adversely affect nervous system function, posing a challenge for treating infants. This is of particular concern for treating neonatal seizures, as early life exposure to drugs such as phenobarbital is associated with adverse neurological outcomes in patients and induction of neuronal apoptosis in animal models. The functional significance of the preclinical neurotoxicity has been questioned due to the absence of evidence for functional impairment associated with drug-induced developmental apoptosis.
methodsWe used patch-clamp recordings to examine functional synaptic maturation in striatal medium spiny neurons from neonatal rats exposed to antiepileptic drugs with proapoptotic action (phenobarbital, phenytoin, lamotrigine) and without proapoptotic action (levetiracetam). Phenobarbital-exposed rats were also assessed for reversal learning at weaning.
resultsRecordings from control animals revealed increased inhibitory and excitatory synaptic connectivity between postnatal day (P)10 and P18. This maturation was absent in rats exposed at P7 to a single dose of phenobarbital, phenytoin, or lamotrigine. Additionally, phenobarbital exposure impaired striatal-mediated behavior on P25. Neuroprotective pretreatment with melatonin, which prevents drug-induced neurodevelopmental apoptosis, prevented the drug-induced disruption in maturation. Levetiracetam was found not to disrupt synaptic development.
interpretationOur results provide the first evidence that exposure to antiepileptic drugs during a sensitive postnatal period impairs physiological maturation of synapses in neurons that survive the initial drug insult. These findings suggest a mechanism by which early life exposure to antiepileptic drugs can impact cognitive and behavioral outcomes, underscoring the need to identify therapies that control seizures without compromising synaptic maturation.
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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.