Background: Enterovirus (EV) is a common cause of infection in neonates. Neonates are at high risk of enterovirus infection with serious clinical manifestations and high lethality. This review systematically summarized the clinical characteristics of neonates with severe enteroviral infection to provide evidence for the identification and treatment of severe neonatal EV infection. Methods: PubMed, Embase, and Web of Science were searched for original studies on neonates with severe EV infections from January 1, 2000, to November 27, 2020. Two reviewers independently screened the literature, extracted the data, and performed a descriptive analysis. Results: In total, 66 articles with 237 cases of severe neonatal enterovirus infection were included. All neonates developed severe complications. Among them, 46.0% neonates had hepatitis or coagulopathy, 37.1% had myocarditis, 11.0% had meningoencephalitis, and 5.9% had other complications such as hemophagocytic lymphohistiocytosis and pulmonary hemorrhage. The lethality rate of neonates with severe infection was 30.4%. The highest lethality rate was 38.6%, which was observed in neonates with myocarditis. In 70.5% neonates, the age at the onset of symptoms was less than 7 days. Coxsackievirus B infection was seen in 52.3% neonates. The most common symptoms included temperature abnormalities (127, 53.6%), rash (88, 37.1%), poor feeding (58, 24.5%), and respiratory symptoms (52, 21.9%). The main treatment included transfusion of empirical antibiotics (127, 53.6%), blood components (100, 42.2%), intravenous immunoglobulin (IVIG; 97, 40.9%), mechanical ventilation (51, 21.5%), and extracorporeal membrane oxygenation (ECMO; 43, 18.1%). Additionally, antiviral medications pleconaril (14, 5.9%) and pocapavir (3, 1.3%) were administered. Conclusions: Lethality was high in neonates with severe enterovirus infection, especially in those complicated with myocarditis. The most common symptoms included temperature abnormalities, rash, and poor feeding. The chief supportive treatment consisted of transfusion of blood components, mechanical ventilation, and ECMO. Empirical antibiotics and IVIG were widely used. Antiviral medications included pocapavir and pleconaril; however, more clinical evidence regarding their efficacy is needed.

Objective Hyperbilirubinemia is one of the most common clinical symptoms in newborns. To improve patient outcomes, evidence-based and implementable guidelines are required. However, clinical guidelines may vary in quality, criteria and recommendations among regions and countries. In this study, we aimed to systematically assess the quality of guidelines using the Appraisal of Guidelines for Research & Evaluation (AGREE)-II instrument and summarise the specific recommendations for neonatal hyperbilirubinemia in order to provide suggestions for future guideline development. Design Systematic review. Interventions We searched the PubMed, Embase, Medline and guideline databases for relevant articles on 10 April 2020. The studies were screened by two independent reviewers according to our inclusion criteria. Two reviewers independently extracted the descriptive data. Four appraisers assessed the guidelines using the AGREE-II instrument. Results Our systematic review appraised 12 clinical practice guidelines for the diagnosis and management of neonatal hyperbilirubinemia. The 12 guidelines achieved an average score of 36%–89%. The guidelines received the highest scores for clarity of presentation and lowest scores for rigour of development. Most recommendations for diagnosis were relatively consistent, but recommendations regarding risk factors, the initiating threshold of treatment and pharmacotherapy varied. Conclusions Our study revealed that current guidelines vary in the quality of the developing process and are inconsistent with regards to recommendations. Future guidelines should afford more attention to the quality of methodologies in guideline development, and more qualified evidence is needed to standardise the initiating threshold of treatment for neonatal hyperbilirubinemia.

Respiratory support is crucial for the survival of preterm infants, and High-flow Nasal Cannula Oxygen Therapy (HFNC) and Continuous Positive Airway Pressure (CPAP) are commonly used for neonatal respiratory support. This meta-analysis aimed to compare the effects of HFNC and CPAP in primary respiratory support for preterm infants, to provide evidence-based support for clinical practice. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, VIP, WANFANG and SinoMed were searched for eligible studies. The primary outcomes included the incidence of treatment failure and the application of mechanical ventilation. A total of 27 eligible studies with 3,351 participants were included. There was no significant difference in the incidence of respiratory support failure [RR = 1.17, 95%CI (0.88–1.56)] and the application of mechanical ventilation [RR = 1.00, 95%CI (0.84–1.19)] between HFNC group and CPAP group. HFNC resulted in lower rate of air leaks [RR = 0.65, 95%CI (0.46–0.92)], nasal trauma [RR = 0.36, 95%CI (0.29–0.45)] and abdominal distension [RR = 0.39, 95%CI (0.27–0.58)], and later time of mechanical ventilation initiating [SMD = 0.60, 95%CI (0.21–0.99)], less duration of oxygen therapy [SMD = −0.35, 95%CI (−0.68 to −0.02)] and earlier enteral feeding [SMD = −0.54, 95%CI (−0.95 to −0.13)]. Alternative non-invasive respiratory support after initial treatment failure resulted in no difference in the application of mechanical ventilation between the two groups [RR = 0.99, 95%CI (0.52–1.88)]. HFNC might be more effective and safer in primary respiratory support for preterm infants. Using CPAP as a remedy for the treatment failure of HFNC could not avoid intubation. For premature infants with the gestational age <28 weeks, HFNC as primary respiratory support still needs to be further elucidated.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022313479, identifier: CRD42022313479.