Efficacy and Safety of Levetiracetam vs. Phenobarbital for Neonatal Seizures: A Systematic Review and Meta-Analysis.

Background: Neonatal seizures are a common neurological emergency in newborns. Phenobarbital (PB) is the first-line antiepileptic drug (AED). However, PB has some side effects, such as hypotension and respiratory depression, and it can accelerate neuronal apoptosis in the immature brain. Levetiracetam (LEV), a new antiepileptic drug, has been used as a second-line drug for the treatment of neonatal seizures. Compared with PB, LEV has many advantages, including a low incidence of side effects and better neurodevelopmental outcomes. However, there are only a few systematic reviews of LEV for the treatment of neonatal seizures. Objective: To evaluate the efficacy and safety of LEV for neonatal seizures and to compare the efficacy, side effects, and neurological outcomes between LEV and PB in the treatment of neonatal seizures. Methods: The keywords LEV, PB, and neonatal seizure were searched in the MEDLINE, Cochrane Library, Web of Science, EMBASE, clinicaltrials.gov, and China National Knowledge Internet (CNKI) databases with a last update in July 2021 to collect high-quality studies. We collected studies studying the efficacy or safety of LEV and PB in the treatment of neonatal seizures applying strict inclusion and exclusion criteria. The data were extracted and outcome measures, including efficacy, side effect rate, neurological score, and mortality rate, were analyzed with RevMan 5.3 software. Results: Ten articles were finally included in the meta-analysis. The meta-analysis showed that there was no difference in efficacy between LEV and PB in the treatment of neonatal seizures. Compared with PB, the incidence of side effects of LEV was lower. The incidence of hypotension and respiratory depression in the LEV group was significantly lower than that in the PB group. In terms of long-term neurodevelopmental outcomes, there was no significant difference in the Bayley Scales of Infant Development (BSID) scores between LEV and PB. Conclusion: PB is still the first-line AED recommended by the WHO for the treatment of neonatal seizures. The new AEDs LEV may not have better efficacy than PB. At the same time, LEV is associated with better neurodevelopment outcomes and a lower risk of adverse effects. In addition, continuous EEG monitoring should be used to diagnose neonatal seizures to evaluate the severity of the seizures, remission, and drug efficacy. Systematic Review Registration: PROSPERO, identifier: CRD42021279029.

Comparative efficacy of anti-epileptic drugs for neonatal seizures: A network meta-analysis.

BACKGROUND: Anti-epileptic drugs have different effects on neonatal seizures, and new agents have been widely used in recent years. Meanwhile, significant differences still exist in the treatment for neonatal seizures, whether in choice of drug or in duration of treatment. And with the increase in options for treatment, the best choice of second-line treatment has not been recommended. METHODS: The MEDLINE, the Cochrane Library, Web of Science, Embase and clinicaltrials.gov databases were searched (January 1, 1960 to October 20, 2020). Randomized controlled trials (RCTs) or observational investigations studying anti-epileptic drugs for neonatal seizures were selected. And then we conducted a network meta-analysis and examined comparative efficacy of the first-line and second-line anti-epileptic drugs for neonatal seizures. RESULTS: Data were extracted from 11 included studies by 2 independent investigators. Random effects models were used to estimate odds ratios (ORs). We performed direct meta-analyses with a random effects model and network meta-analyses for first-line and second-line drugs. Five published RCTs and 6 observational investigations with 1333 patients and 6 interventions contributed to the analysis. CONCLUSION: We recommend phenobarbital as the first-line drug for neonatal seizures. In addition, there is a tendency for levetiracetam to be an effective second-line treatment for neonatal seizures after failure of first-line drugs.

How to Early Identify and Prevent the SARS-CoV-2 Infection in Children for Families?

Importance: COVID-19 has become a worldwide pandemic. Many countries have reported cases of infection in children and newborns, and there is a trend of significantly increasing infections among these populations. Therefore, it is important to provide advice and guidance for the prevention and control of COVID-19 in children. Observations: Children are as susceptible to SARS-CoV-2 infection as adults. The manifestations in children are atypical, and children are much less likely to have critical cases. If children are infected, they may play an important role in the spread of SARS-CoV-2 because their symptoms are less obvious and less likely to be detected. To prevent COVID-19 from spreading among children, efforts to prevent, and control the infection should be increased by controlling the source of infection, blocking the route of transmission and protecting the susceptible population. Conclusions and Relevance: The early identification of the COVID-19 in children and the protection of families are important measures to prevent the continued spread of SARS-CoV-2.

Corrigendum: Risk Factors in Predicting Prognosis of Neonatal Bacterial Meningitis-A Systematic Review.

[This corrects the article DOI: 10.3389/fneur.2018.00929.].

Risk Factors in Predicting Prognosis of Neonatal Bacterial Meningitis-A Systematic Review.

Background: Neonatal bacterial meningitis is a severe infection with high mortality and morbidity. It is necessary to identify factors associated with a high risk of a poor prognosis so that we can prevent them with more appropriate treatments. This study was performed to summarize the prognostic factors known to predict adverse outcomes in neonatal bacterial meningitis. Methods: The Medline/PubMed, Cochrane Library and Embase databases were searched for studies of prognostic risk factors in neonates with bacterial meningitis. Studies published from the initiation of the database to April 30th, 2017 were included. The quality of cohort studies was assessed by the Newcastle-Ottawa Scale (NOS). The quality of cross-section studies was assessed by the Agency for Healthcare Research and Quality (AHRQ) scale. Each prognostic factor known to cause adverse outcomes is summarized. Results: Sixteen studies were identified, including 7 cohort studies and 9 cross section studies. Seizure and high protein levels in the cerebrospinal fluid (CSF) predict a poor prognosis in this disease. Coma, the need for ventilation support, and leukopenia also had some value for predicting poor prognoses. A bulging anterior fontanelle was valuable for predicting mortality. Low CSF glucose levels, thrombocytopenia, gestational age (GA) < 37 weeks and an altered sensorium were correlated with a poor prognosis. A birth weight < 2500 g, early onset meningitis and positive CSF cultures were correlated with mortality. Conclusions: This study provides a preliminary exploration of prognostic factors in neonatal bacterial meningitis and thereby fills some of the gaps in the study of prognoses in this disease. These prognostic factors can be used to predict and estimate outcomes in neonatal bacterial meningitis. Without a meta-analysis, the reliability of these factors cannot be assured. In addition, these results emphasize that there is an urgent need for a standardized protocol for follow-up and well-designed prognostic studies in neonatal bacterial meningitis.