title: Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis.
abstract: To systematically review and meta-analyse the relationship between antibiotic exposure in neonates and the following early adverse outcomes: necrotizing enterocolitis (NEC), invasive fungal infections (IFIs) and/or death.
  
  
  
  Data sources were PubMed, Embase, Medline and the Cochrane Database (to December 2016), supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic exposures (yes versus no, long versus short duration, and/or broad- versus narrow-spectrum regimens) and the risk of developing NEC, IFI and/or death in the neonatal period. Two reviewers extracted data and evaluated the risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, meta-analyses were conducted using the random-effect model.
  
  
  
  We identified 9 RCTs and 38 observational studies. The quality of the majority of studies was poor to moderate. There was a significant association between prolonged antibiotic exposure and an increased risk of NEC in five observational studies (5003 participants) and/or risk of death in five observational studies (13 534 participants). Eleven of 15 studies with data on broad- versus narrow-spectrum regimens reported an increased risk of IFI after broad-spectrum antibiotic exposure, in particular with third-generation cephalosporins and carbapenems. Meta-analysis was limited by few and old RCTs, insufficient sample sizes and diversity of antibiotic exposure and outcomes reported.
  
  
  
  Prolonged antibiotic exposure in uninfected preterm infants is associated with an increased risk of NEC and/or death, and broad-spectrum antibiotic exposure is associated with an increased risk of IFI.
authors.affiliation: Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway.|Paediatric Research Group, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
authors.forename: Eirin
authors.initials: E
authors.lastname: Esaiassen
authors.affiliation: Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway.|Paediatric Research Group, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
authors.forename: Jon Widding
authors.initials: JW
authors.lastname: Fjalstad
authors.affiliation: Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway.|University College of Southeast Norway, Notodden, Norway.
authors.forename: Lene Kristine
authors.initials: LK
authors.lastname: Juvet
authors.affiliation: Division of Paediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Basel, Switzerland.|Division of Clinical Pharmacology, Children's National Health System, Washington, DC, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: van den Anker
authors.affiliation: Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway.|Paediatric Research Group, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
authors.forename: Claus
authors.initials: C
authors.lastname: Klingenberg
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000453:epidemiology* / Q000401:mortality; D000072742:Invasive Fungal Infections / Q000453:epidemiology* / Q000401:mortality; D064887:Observational Studies as Topic; D012307:Risk Factors; D018805:Sepsis / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents