RESUMO
Background: Although levetiracetam and phenytoin are widely used antiseizure medications (ASM) in neonates, their efficacy on seizure freedom is unclear. We evaluated electroencephalographic (EEG) seizure freedom following sequential levetiracetam and phenytoin in neonatal seizures unresponsive to phenobarbital. Methods: We recruited neonates born ≥35 weeks and aged <72 h who had continued electrographic seizures despite phenobarbital, from three Indian hospitals, between 20 June 2020 and 31 July 2022. The neonates were treated with intravenous levetiracetam (20 mg/kg x 2 doses, second line) followed by phenytoin (20 mg/kg x 2 doses, third line) if seizures persisted. The primary outcome was complete seizure freedom, defined as an absence of seizures on EEG for at least 60 min within 40 min from the start of infusion. Findings: Of the 206 neonates with continued seizures despite phenobarbital, 152 received levetiracetam with EEG. Of these one EEG was missing, 47 (31.1%) were in status epilepticus, and primary outcome data were available in 145. Seizure freedom occurred in 20 (13.8%; 95% CI 8.6%-20.5%) after levetiracetam; 16 (80.0%) responded to the first dose and 4 (20.0%) to the second dose. Of the 125 neonates with persisting seizures after levetiracetam, 114 received phenytoin under EEG monitoring. Of these, the primary outcome data were available in 104. Seizure freedom occurred in 59 (56.7%; 95% CI 46.7%-66.4%) neonates; 54 (91.5%) responded to the first dose and 5 (8.5%) to the second dose. Interpretation: With the conventional doses, levetiracetam was associated with immediate EEG seizure cessation in only 14% of phenobarbital unresponsive neonatal seizures. Additional treatment with phenytoin along with levetiracetam attained seizure freedom in further 57%. Safety and efficacy of higher doses of levetiracetam should be evaluated in well-designed randomised controlled trials. Funding: National Institute for Health and Care Research (NIHR) Research and Innovation for Global Health Transformation (NIHR200144).
RESUMO
OBJECTIVE: Currently available gestational age scoring systems are complex and inaccurate for wider use in low- and middle-income countries (LMIC), particularly in infants with neonatal encephalopathy. Here, we aimed to develop a scoring system based on physical characteristics for identifying late preterm infants from term infants. STUDY DESIGN: This was a prospective observational study conducted in 2 phases- the discovery phase and validation phase. In the first phase, we examined the accuracy of 10 objective physical characteristics in a prospective cohort of 1,006 infants recruited from three hospitals in South India. A weighted scoring system and a photo card were then developed based on the six best performing characteristics which were validated in another prospective cohort of 1,004 infants. RESULTS: The final score had a sensitivity of 66.0% (95% confidence intervals [CIs], 58.4-73.8%), specificity of 80.0% (95% CI, 77.2-82.7%), and a negative predictive value of 93.0% (95% CI, 90.5-94.5%). CONCLUSION: This scoring system may have wider applications in LMIC, particularly in community settings and in infants with neonatal encephalopathy. KEY POINTS: · This is an easily administered scoring system using physical characters to identify late preterm infants.. · The scoring is not affected by neurological injury and can be used in encephalopathic infants.. · Overall accuracy is better than previous scores encompassing the physical criteria alone..
