INTRODUCTION: Neonatal sepsis is a leading cause of infant mortality worldwide with non-specific and varied presentation. We aimed to catalogue the current definitions of neonatal sepsis in published randomised controlled trials (RCTs). METHOD: A systematic search of the Embase and Cochrane databases was performed for RCTs which explicitly stated a definition for neonatal sepsis. Definitions were sub-divided into five primary criteria for infection (culture, laboratory findings, clinical signs, radiological evidence and risk factors) and stratified by qualifiers (early/late-onset and likelihood of sepsis). RESULTS: Of 668 papers screened, 80 RCTs were included and 128 individual definitions identified. The single most common definition was neonatal sepsis defined by blood culture alone (n = 35), followed by culture and clinical signs (n = 29), and then laboratory tests/clinical signs (n = 25). Blood culture featured in 83 definitions, laboratory testing featured in 48 definitions while clinical signs and radiology featured in 80 and 8 definitions, respectively. DISCUSSION: A diverse range of definitions of neonatal sepsis are used and based on microbiological culture, laboratory tests and clinical signs in contrast to adult and paediatric sepsis which use organ dysfunction. An international consensus-based definition of neonatal sepsis could allow meta-analysis and translate results to improve outcomes.

Clinic of Neonatology Department Mother Woman Child Lausanne University Hospital and University of Lausanne Lausanne Switzerland

Department of Neonatology Pirogov Russian National Research Medical University Moscow Russia

Department of Paediatrics Amsterdam UMC University of Amsterdam Emma Children's Hospital Amsterdam The Netherlands

Department of Paediatrics Tergooi Hospital Blaricum The Netherlands

Department of Pathology Immunology and Laboratory Medicine University of Florida Gainesville FL USA

Department of Pediatrics Bern University Hospital University of Bern Bern Switzerland

Department of Pediatrics Division of Neonatology Erasmus MC Sophia Children's Hospital Rotterdam The Netherlands

Department of Pediatrics University of Florida Gainesville FL USA

Department of Pediatrics Women and Infants Hospital of Rhode Island Alpert Medical School of Brown University Providence USA

Discipline of Paediatrics Trinity College Dublin the University of Dublin and Children's Hospital Ireland at Tallaght Dublin Ireland

Division of Neonatal Perinatal Medicine Department of Pediatrics Columbia University Medical Center New York City NY USA

Division of Neonatology Saint Louis University Edward Doisy Research Center St Louis MO USA

Institute of Pathological Physiology 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Translational Medicine University of Liverpool Centre for Women's Health Research Liverpool Women's Hospital Liverpool UK

John Stearne Medical Library Trinity College Dublin St James' Hospital Dublin Ireland

Neonatal Directorate King Edward Memorial Hospital for Women Perth WA Australia

Neonatal Health and Development Telethon Kids Institute Perth WA Australia

Neonatal Medicine School of Public Health Faculty of Medicine Chelsea and Westminster campus Imperial College London London UK

Neonatal Unit Department of Obstetrics and Gynecology Motol University Hospital and 2nd Faculty of Medicine Prague Czech Republic

Neonatology CHI at Crumlin Dublin Ireland

Neonatology Clinic for Paediatric Cardiology Intensive Care and Neonatology University Medical Centre Göttingen Göttingen Germany

Paediatric Critical Care Research Group Child Health Research Centre University of Queensland Brisbane Australia

Paediatric Intensive Care Unit Queensland Children's Hospital Brisbane Australia

Paediatrics Coombe Women's and Infant's University Hospital Dublin Ireland

Radboud Institute for Health Sciences Department of Neonatology Radboud University Medical Center Amalia Children's Hospital Nijmegen The Netherlands

Trinity Research in Childhood Centre Trinity College Dublin Dublin Ireland

Trinity Translational Medicine Institute St James Hospital Dublin Ireland

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Less is more: Antibiotics at the beginning of life