Proactive Neonatal Treatment at 22 Weeks of Gestation: A Systematic Review and Meta-Analysis

Abstract Objective The objective of the present study was to provide a systemic review and meta-analysis to quantify prognosis and identify factors associated with variations in reported mortality estimates among infants born at 22 weeks of gestation and provided proactive treatment (resuscitation and intensive care). Data Sources PubMed, Scopus, and Web of Science databases, with no language restrictions, were searched for articles published January 2000 through February 2020. Study Eligibility Criteria Reports on live-born infants at 22 weeks of gestation and provided proactive care were included. The primary outcome was survival to hospital discharge; secondary outcomes included survival without major morbidity and survival without neurodevelopmental impairment (NDI). Because we expected differences across studies in the definitions for various morbidities, multiple definitions for composite outcomes of major morbidities were prespecified. NDI was based on Bayley Scales of Infant Development II or III. Data extractions were performed independently, and outcomes agreed upon a-priori. Study Appraisal and Synthesis Methods Methodological quality was assessed using the Quality in Prognostic Studies (QUIPS) tool. An adapted version of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for prognostic studies was used to evaluate confidence in overall estimates. Outcomes were assessed as prevalence and 95% confidence intervals. Variabilities across studies attributable to heterogeneity were estimated with the I2 statistic; publication bias was assessed with LFK index. Data were pooled using in inverse variance heterogeneity model. Results Literature searches returned 21,952 articles, with 2,034 considered in full; 31 studies of 2,226 infants delivered at 22 weeks of gestation and provided proactive neonatal treatment were included. No articles were excluded for study design or risk of bias. The pooled prevalence of survival was 29.0% (95% CI: 17.2%-41.6%; 31 studies, 2,226 infants; I2 = 79.4%, LFK index = 0.04). Survival among infants born to mothers receiving antenatal corticosteroids was twice the survival of infants born to mothers not receiving antenatal corticosteroids (39.0% vs. 19.5%, P Conclusion Reported survival rates varied greatly between studies and were likely influenced by combining observational data from disparate sources, lack of individual patient–level data, and bias in the component studies from which the data were drawn. Therefore, pooled results should be interpreted with caution. To answer fundamental questions beyond the breadth of available data, multicenter, multidisciplinary collaborations, including alignment of important outcomes by stakeholders, are needed.