Cochrane · systematic review · CD014967
Anti‐seizure medications for neonates with seizures
Abiramalatha, T, Thanigainathan, S, Ramaswamy, VV, et al. · Cochrane Database of Systematic Reviews · 2023 · Cochrane Library
NeonatalAMSTAR 2: not assessed
SoF tableOnly the outcomes this review put in its Summary of Findings table are listed (the Cochrane Handbook caps them at about seven per comparison). Its other analyses are not shown here.
Questions
55
current version
GRADE rated
39
No studies
15
Included studies
NR
No studies 15 · 27.3%Ungraded 1 · 1.8%Very low 27 · 49.1%Low 10 · 18.2%Moderate 2 · 3.6%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Questions and results
Summary of findings table ‐ Phenobarbital versus levetiracetam as first‐line ASM for EEG‐confirmed neonatal seizures
Population: neonates with EEG‐confirmed seizures
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Proportion of infants who achieve seizure control after the first loading dose of ASM Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 2.32 [1.63, 3.3] | 1 study · 106 participants | Moderate Downgraded: imprecision |
Proportion of infants who achieve seizure control after the maximal loading dose of ASM Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 2.83 [1.78, 4.5] | 1 study · 83 participants | Moderate Downgraded: imprecision |
Mortality or neurodevelopment disability at 18 to 24 months' corrected age ‐ not reported Summary of findings table ‐ Phenobarbital vs levetiracetam | no estimate extracted | NR | No studies |
Mortality before hospital discharge Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 0.3 [0.04, 2.52] | 1 study · 106 participants | Very low Downgraded: imprecision, indirectness |
Requirement of mechanical ventilation Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 1.21 [0.76, 1.91] | 1 study · 106 participants | Very low Downgraded: imprecision, indirectness |
Proportion of infants who develop sedation or drowsiness Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 1.74 [0.68, 4.44] | 1 study · 106 participants | Very low Downgraded: imprecision, indirectness |
Proportion of infants who develop epilepsy post‐discharge Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 0.92 [0.48, 1.76] | 1 study · 45 participants | Very low Downgraded: imprecision, indirectness |
Summary of findings table ‐ Phenobarbital versus levetiracetam as first‐line ASM for clinically diagnosed neonatal seizures
Population: clinically diagnosed neonatal seizures
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Proportion of infants who achieve seizure control after first loading dose of ASM Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 0.69 [0.55, 0.86] | 3 studies · 286 participants | Very low Downgraded: risk of bias, imprecision |
Proportion of infants who achieve seizure control after maximal loading dose of ASM Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 0.58 [0.47, 0.72] | 3 studies · 260 participants | Very low Downgraded: risk of bias, imprecision |
Mortality or neurodevelopment disability at 18 to 24 months' corrected age ‐ not reported Summary of findings table ‐ Phenobarbital vs levetiracetam | no estimate extracted | NR | No studies |
Mortality before hospital discharge Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 1.41 [0.82, 2.43] | 6 studies · 452 participants | Low Downgraded: imprecision, indirectness |
Requirement of mechanical ventilation Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 2.2 [0.5, 9.68] | 5 studies · 394 participants | Very low Downgraded: imprecision, indirectness |
Proportion of infants who develop sedation or drowsiness Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 1.88 [0.66, 5.37] | 2 studies · 180 participants | Very low Downgraded: risk of bias, imprecision, inconsistency, indirectness |
Proportion of infants who develop epilepsy post discharge Summary of findings table ‐ Phenobarbital vs levetiracetam | RR 0.5 [0.05, 4.94] | 1 study · 30 participants | Very low Downgraded: risk of bias, imprecision |
Summary of findings table ‐ Phenobarbital versus phenytoin as first‐line ASM for EEG‐confirmed neonatal seizures
Population: neonates with EEG‐confirmed seizures
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Proportion of infants who achieve seizure control after the first loading dose of ASM ‐ not reported Summary of findings table ‐ Phenobarbital vs phenytoin | no estimate extracted | NR | No studies |
Proportion of infants who achieve seizure control after the maximal loading dose of ASM Summary of findings table ‐ Phenobarbital vs phenytoin | RR 0.97 [0.54, 1.72] | 1 study · 59 participants | Very low Downgraded: risk of bias, imprecision |
Mortality or neurodevelopmental disability at 18 to 24 months' corrected age ‐ not reported Summary of findings table ‐ Phenobarbital vs phenytoin | no estimate extracted | NR | No studies |
Summary of findings table ‐ Phenobarbital versus phenytoin as first‐line ASM for clinically diagnosed neonatal seizures
Population: neonates with clinically diagnosed seizures
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Proportion of infants who achieve seizure control after first loading dose of ASM Summary of findings table ‐ Phenobarbital vs phenytoin | RR 1.92 [1.4, 2.64] | 2 studies · 179 participants | Low Downgraded: risk of bias, inconsistency |
Proportion of infants who achieve seizure control after maximal loading dose ‐ not reported Summary of findings table ‐ Phenobarbital vs phenytoin | no estimate extracted | NR | No studies |
Mortality or neurodevelopmental disability at 18 to 24 months' corrected age ‐ not reported Summary of findings table ‐ Phenobarbital vs phenytoin | no estimate extracted | NR | No studies |
Mortality before hospital discharge Summary of findings table ‐ Phenobarbital vs phenytoin | RR 1.33 [0.79, 2.26] | 2 studies · 179 participants | Very low Downgraded: imprecision, inconsistency, indirectness |
Requirement of mechanical ventilation Summary of findings table ‐ Phenobarbital vs phenytoin | RR 7.13 [0.38, 134.78] | 1 study · 109 participants | Very low Downgraded: imprecision, indirectness |
Proportion of infants who develop sedation or drowsiness Summary of findings table ‐ Phenobarbital vs phenytoin | RR 23 [1.41, 375.77] | 1 study · 70 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Summary of findings table ‐ Phenobarbital versus Lorazepam as first‐line ASM for clinically diagnosed neonatal seizures
Population: Neonates with clinically diagnosed seizures
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Proportion of infants who achieve seizure control after the first loading dose of ASM Summary of findings table ‐ Phenobarbital vs Lorazepam | RR 0.71 [0.53, 0.94] | 1 study · 71 participants | Very low Downgraded: risk of bias, imprecision |
Proportion of infants who achieve seizure control after the maximal loading dose of ASM ‐ not reported Summary of findings table ‐ Phenobarbital vs Lorazepam | no estimate extracted | NR | No studies |
Mortality or neurodevelopmental disability at 18 to 24 months' corrected age ‐ not reported Summary of findings table ‐ Phenobarbital vs Lorazepam | no estimate extracted | NR | No studies |
Mortality before hospital discharge Summary of findings table ‐ Phenobarbital vs Lorazepam | RR 1.76 [0.79, 3.95] | 1 study · 71 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Proportion of infants who develop sedation or drowsiness Summary of findings table ‐ Phenobarbital vs Lorazepam | RR 5.66 [1.35, 23.71] | 1 study · 71 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Summary of findings table ‐ Phenytoin versus lorazepam as first‐line ASM for clinically diagnosed neonatal seizures
Population: neonates with clinically diagnosed seizures
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Proportion of infants who achieve seizure control after the first loading dose of ASM Summary of findings table ‐ Phenytoin vs lorazepam | RR 0.77 [0.6, 0.99] | 1 study · 71 participants | Very low Downgraded: risk of bias, imprecision |
Proportion of infants who achieve seizure control after the maximal loading dose of ASM ‐ not reported Summary of findings table ‐ Phenytoin vs lorazepam | no estimate extracted | NR | No studies |
Mortality or neurodevelopmental disability at 18 to 24 months' corrected age ‐ not reported Summary of findings table ‐ Phenytoin vs lorazepam | no estimate extracted | NR | No studies |
Mortality before hospital discharge Summary of findings table ‐ Phenytoin vs lorazepam | RR 0.44 [0.12, 1.57] | 1 study · 71 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Proportion of infants who develop sedation or drowsiness Summary of findings table ‐ Phenytoin vs lorazepam | RR 0.21 [0.01, 4.13] | 1 study · 71 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Summary of findings table ‐ Phenobarbital + bumetanide versus phenobarbital alone for EEG‐confirmed neonatal seizures
Population: neonates with EEG‐confirmed seizures
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Proportion of infants who achieve seizure control after the first loading dose of ASM Summary of findings table ‐ Phenobarbital + bumetanide vs phenobarbital alone | RR 0.95 [0.37, 2.4] | 1 study · 43 participants | Low Downgraded: imprecision |
Proportion of infants who achieve seizure control after the maximal loading dose of the ASM ‐ not reported Summary of findings table ‐ Phenobarbital + bumetanide vs phenobarbital alone | no estimate extracted | NR | No studies |
Mortality or neurodevelopmental disability at 18 to 24 months' corrected age ‐ not reported Summary of findings table ‐ Phenobarbital + bumetanide vs phenobarbital alone | no estimate extracted | NR | No studies |
Mortality before hospital discharge Summary of findings table ‐ Phenobarbital + bumetanide vs phenobarbital alone | RR 0.2 [0.02, 1.74] | 1 study · 43 participants | Very low Downgraded: imprecision, indirectness |
Cognitive impairment at 18‐24 months Summary of findings table ‐ Phenobarbital + bumetanide vs phenobarbital alone | RR 0.53 [0.13, 2.15] | 1 study · 29 participants | Very low Downgraded: imprecision, indirectness |
Requirement of mechanical ventilation Summary of findings table ‐ Phenobarbital + bumetanide vs phenobarbital alone | no estimate extracted | 1 study · 1 participants | Ungraded |
Proportion of infants who develop epilepsy post‐discharge Summary of findings table ‐ Phenobarbital + bumetanide vs phenobarbital alone | RR 1.13 [0.43, 2.97] | 1 study · 39 participants | Very low Downgraded: imprecision, indirectness |
Summary of findings table ‐ Lignocaine versus benzodiazepines as second‐line ASM for EEG‐confirmed neonatal seizures
Population: neonates with EEG‐confirmed seizures
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Proportion of infants who achieve seizure control after first loading dose of ASM ‐ not reported Summary of findings table ‐ Lignocaine vs benzodiazepines | no estimate extracted | NR | No studies |
Proportion of infants who achieve seizure control after maximal loading dose of ASM Summary of findings table ‐ Lignocaine vs benzodiazepines | RR 8.17 [0.52, 128.42] | 1 study · 11 participants | Very low Downgraded: risk of bias, imprecision |
Mortality or neurodevelopmental disability at 12 months Summary of findings table ‐ Lignocaine vs benzodiazepines | RR 1 [0.71, 1.41] | 1 study · 10 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Mortality before hospital discharge Summary of findings table ‐ Lignocaine vs benzodiazepines | RR 1.2 [0.25, 5.71] | 1 study · 11 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Neurodevelopmental disability at 12 months Summary of findings table ‐ Lignocaine vs benzodiazepines | RR 1 [0.36, 2.75] | 1 study · 10 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Summary of findings table ‐ Maintenance ASM versus no maintenance ASM after achieving seizure control in clinically diagnosed neonatal seizures
Population: neonates with clinically diagnosed seizures
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Proportion of infants with repeat seizure before hospital discharge Summary of findings table ‐ Maintenance ASM vs no maintenance ASM after achieving seizure control | RR 0.76 [0.56, 1.01] | 2 studies · 373 participants | Very low Downgraded: risk of bias, imprecision |
Mortality or neurodevelopmental disability at 18 to 24 months' corrected age ‐ not reported Summary of findings table ‐ Maintenance ASM vs no maintenance ASM after achieving seizure control | no estimate extracted | NR | No studies |
Mortality before hospital discharge Summary of findings table ‐ Maintenance ASM vs no maintenance ASM after achieving seizure control | RR 0.69 [0.39, 1.22] | 2 studies · 373 participants | Low Downgraded: imprecision |
Mortality at 18‐24 months Summary of findings table ‐ Maintenance ASM vs no maintenance ASM after achieving seizure control | RR 0.94 [0.34, 2.61] | 1 study · 111 participants | Low Downgraded: imprecision |
Neurodevelopmental disability at 18‐24 months Summary of findings table ‐ Maintenance ASM vs no maintenance ASM after achieving seizure control | RR 0.89 [0.13, 6.12] | 1 study · 108 participants | Low Downgraded: imprecision |
Proportion of infants who develop epilepsy post‐discharge Summary of findings table ‐ Maintenance ASM vs no maintenance ASM after achieving seizure control | RR 3.18 [0.69, 14.72] | 1 study · 126 participants | Low Downgraded: imprecision |
Summary of findings table ‐ Treatment of clinical and electrographic seizures versus treatment of clinical seizures alone in neonates
Population: neonates
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Seizure burden during hospitalisation Summary of findings table ‐ Treatment of clinical and electrographic seizures vs treatment of clinical seizures alone | no estimate extracted | 2 studies · 68 participants | Low Downgraded: imprecision |
Mortality or neurodevelopmental disability at 18 to 24 months' corrected age ‐ not reported Summary of findings table ‐ Treatment of clinical and electrographic seizures vs treatment of clinical seizures alone | no estimate extracted | NR | No studies |
Mortality before hospital discharge Summary of findings table ‐ Treatment of clinical and electrographic seizures vs treatment of clinical seizures alone | RR 0.59 [0.28, 1.27] | 2 studies · 68 participants | Low Downgraded: imprecision |
Proportion of infants who develop epilepsy post‐discharge Summary of findings table ‐ Treatment of clinical and electrographic seizures vs treatment of clinical seizures alone | RR 0.75 [0.12, 4.73] | 1 study · 35 participants | Low Downgraded: imprecision |