# Levetiracetam as First-Line Anti-seizure Medicine in Electrographically Confirmed Neonatal Seizures: A Literature Review

**Authors:** Khalid M Saifullah

PMC · DOI: 10.7759/cureus.101814 · Cureus · 2026-01-18

## TL;DR

This review evaluates levetiracetam as a potential first-line treatment for neonatal seizures, finding it possibly as effective and safer than phenobarbitone, but with insufficient evidence to recommend it widely.

## Contribution

The paper provides a critical review of levetiracetam's role in neonatal seizures, highlighting its potential and limitations compared to phenobarbitone.

## Key findings

- Levetiracetam may be equally effective and safer than phenobarbitone for neonatal seizures.
- Levetiracetam is effective in neonates with low seizure burden when used alone.
- The evidence quality is poor, preventing levetiracetam from being recommended as a first-line treatment.

## Abstract

Phenobarbitone (PHB), the recommended first-line anti-seizure medicine (ASM) in neonatal seizure (NS), has many side effects needing monitoring and management; therefore, it may not be a good choice in low-to-middle-income countries (LMICs) with poor facilities. Levetiracetam (LEV), an emerging ASM in NS with a good short-term safety record, is evaluated with or without a comparator ASM as a first-line ASM. Using strict inclusion and exclusion criteria, a comprehensive literature search was undertaken using PubMed, Medline, Cochrane, CINAHL, Embase, Clinical.Trials, Scopus, Trip database, and NHS Evidence. The quality of the papers was assessed using Critical Appraisal Tool Program (CASP), and the risk of bias (ROB) was assessed using the Newcastle-Ottawa Scale (NOS). Data was extracted in a predefined proforma. In total, five retrospective observational studies were included in the review. All included studies suffered from moderate to high ROB. The evidence suggests that when compared to PHB, LEV is possibly equally effective and safer, and, when used without comparison, is effective in neonates with low seizure burden. However, it cannot be recommended as a first-line ASM in NS due to poor quality of evidence. Well-designed randomized controlled trials are urgently needed, preferably from LMICs.

## Linked entities

- **Chemicals:** Levetiracetam (PubChem CID 5284583), Phenobarbitone (PubChem CID 4763)

## Full-text entities

- **Genes:** SV2A (synaptic vesicle glycoprotein 2A) [NCBI Gene 9900] {aka DEE113, SLC22B1, SV2}, PHB1 (prohibitin 1) [NCBI Gene 5245] {aka BAP32, HEL-215, HEL-S-54e, PHB}
- **Diseases:** HIE (MESH:D020925), hypotension (MESH:D007022), NS (MESH:C535466), NOS (MESH:D009521), ASM (MESH:D012640), bradycardia (MESH:D001919), hypoxia (MESH:D000860), status epilepticus (MESH:D013226), and cognitive functions (MESH:D003072), IVH (MESH:D000074042), neurological emergency (MESH:D004630), cardio-respiratory depression (MESH:D012131), stroke (MESH:D020521), irritability (MESH:D001523), agitation (MESH:D011595), infection (MESH:D007239), perinatal asphyxia (MESH:D001237), CHD (MESH:D006330), CP (MESH:D002547), Epilepsy (MESH:D004827), somnolence (MESH:D006970), ICH (MESH:D013345), apnea (MESH:D001049), NDO (MESH:D011248), death (MESH:D003643)
- **Chemicals:** LEV (MESH:D000077287), PHB (MESH:D010634), PHE (MESH:D010672), pyrrolidine (MESH:C032519), ASM (-), BZD (MESH:D001569)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC12914151/full.md

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Source: https://tomesphere.com/paper/PMC12914151