Evidence map›Paper›PMID 41668002›Full record

SynthesisBMC pediatrics2026

Levetiracetam versus phenobarbital as first-line therapy for neonatal seizures: a comprehensive systematic review and meta-analysis with meta-regression of 26 studies involving 9,854 neonates.

Mostafa Hossam El Din Moawad, Abdelrahman M Elettreby, Ibraheem M Alkhawaldeh, Hamza A Abdul-Hafez, Ali Mohammad Asar Mohammad Ali, Omar Mohamed Helal, Mohamed Karawya, Abdallah AlHusan, Malik Allahham, Youcef Chair and 3 more

Abstract readSystematic ReviewMeta-AnalysisComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMC pediatrics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Mostafa Hossam El Din MoawadAlexandria Main University Hospital, Alexandria, Egypt.
Abdelrahman M ElettrebyFaculty of Medicine, Mansoura University, Mansoura, Egypt.
Ibraheem M AlkhawaldehFaculty of Medicine, Mutah University, Al-Karak, Jordan.
Hamza A Abdul-HafezDepartment of Medicine, Faculty of Medicine and Health Sciences, An- Najah National University, Nablus, Palestine. hamzaakrm12@gmail.com.
Ali Mohammad Asar Mohammad AliBaraem Specialized Hospital, Suez, Egypt.
Omar Mohamed HelalFaculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Mohamed KarawyaAlexandria Main University Hospital, Alexandria, Egypt.
Abdallah AlHusanFaculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
Malik AllahhamDepartment of Neurology, Jordan University of Science and Technology, Irbid, Jordan.
Youcef ChairFaculty of Medicine, The University of Jordan, Amman, Jordan.
Hadeel Amin Al KabiDepartment of Optometry, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary.
Ibrahim SeragFaculty of Medicine, Mansoura University, Mansoura, Egypt.
Mohamed AbouzidDepartment of Physical Pharmacy and Pharmacokinetics, Faculty of Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3 St, Poznan, 60-806, Poland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPhenobarbital (PB) has long been considered the standard first-line therapy for neonatal seizures, despite suboptimal efficacy and concerns about neurotoxicity and adverse cardiopulmonary effects. Levetiracetam (LEV), a newer antiseizure medication with a more favorable safety profile, has emerged as a potential alternative. This systematic review and meta-analysis aimed to compare the efficacy and safety of LEV versus PB when used as first-line treatment for neonatal seizures.

methodsA systematic search of PubMed, Scopus, and Web of Science from inception to September 2025 identified eligible randomized controlled trials (RCTs) and observational studies comparing first-line LEV with PB in neonates. Data were pooled using random-effects models to calculate risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity, publication bias, and potential effect modifiers were explored through subgroup, and meta-regression analyses.

resultsTwenty-six studies (13 RCTs and 13 observational cohorts) including 9,854 neonates (LEV = 1,601; PB = 8,253) were analyzed. The overall rate of seizure control did not differ significantly between LEV and PB (RR = 0.92, 95% CI 0.82-1.03; p = 0.16). Subgroup analyses by study design yielded consistent findings. LEV was associated with significantly fewer adverse events (RR = 3.59, 95% CI 1.85-6.95; I² = 86%), particularly lower risks of hypotension (RR = 3.90, 95% CI 1.94-7.87) and respiratory depression (RR = 2.06, 95% CI 1.23-3.47) compared with PB. Mortality rates were similar between groups (RR = 1.27, 95% CI 0.84-1.91). Meta-regression revealed that higher gestational age and birth weight were associated with better seizure control, whereas older age at seizure onset predicted poorer response.

conclusionLEV and PB demonstrate comparable efficacy for first-line treatment of neonatal seizures; however, LEV provides a more favorable safety and tolerability profile, particularly with respect to cardiopulmonary stability. These findings support the consideration of LEV as an alternative first-line agent, especially in neonates at risk for hemodynamic or respiratory compromise. Further large, high-quality RCTs with standardized EEG confirmation and long-term neurodevelopmental follow-up are warranted.

Indexed as

AnticonvulsantsLevetiracetamPhenobarbitalSeizuresHumansInfant, NewbornTreatment OutcomeAnticonvulsantsLevetiracetamPhenobarbitalAntiseizure medicationsFirst-line therapyLevetiracetamMeta-analysisNeonatal seizuresPhenobarbitalSystematic review

Identifiers

PMID41668002
PMCPMC12990488

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Registered trials

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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.