title: A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: outcomes at 2 years.
abstract: OBJECTIVE
  The authors performed a randomised trial in very preterm small-for-gestational age (SGA) babies to determine if prophylaxis with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). Despite increased neutrophil counts following GM-CSF, the authors reported no significant difference in neonatal sepsis-free survival.
  
  
  METHODS
  280 babies born <31 weeks of gestation and SGA were entered into the trial. Outcome was determined at 2 years to determine neurodevelopmental and general health outcomes, including economic costs.
  
  
  RESULTS
  The authors found no significant differences in health outcomes or health and social care costs between the trial groups. In the GM-CSF arm, 87 of 134 (65%) babies survived to 2 years without severe disability compared with 87 of 131 (66%) controls (RR: 1·0, 95% CI 0·8 to 1·2). Marginally, more children receiving GM-CSF were reported to have cough (RR 1·7, 95% CI 1·1 to 2·6) and had signs of chronic respiratory disease (Harrison's sulcus; RR 2·0, 95% CI 1·0 to 3·9) though this was not reflected in bronchodilator use or need for hospitalisation for respiratory disease. Overall, the rate of neurologic abnormality (7%-9%) was similar but mean overall developmental scores were lower than expected for gestational age.
  
  
  CONCLUSIONS
  The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse outcomes at 2 years of age. The apparent excess of developmental impairment in the entire PROGRAMS cohort, without corresponding increase in neurological abnormality, may represent diffuse brain injury attributable to intrauterine growth restriction.
authors.affiliation: Institute for Womens Health, 74 Huntley Street, University College London, WC1E 6AU, UK. n.marlow@ucl.ac.uk
authors.forename: Neil
authors.initials: N
authors.lastname: Marlow
authors.forename: Timothy
authors.initials: T
authors.lastname: Morris
authors.forename: Peter
authors.initials: P
authors.lastname: Brocklehurst
authors.forename: Robert
authors.initials: R
authors.lastname: Carr
authors.forename: Frances M
authors.initials: FM
authors.lastname: Cowan
authors.forename: Nishma
authors.initials: N
authors.lastname: Patel
authors.forename: Stavros
authors.initials: S
authors.lastname: Petrou
authors.forename: Maggie E
authors.initials: ME
authors.lastname: Redshaw
authors.forename: Neena
authors.initials: N
authors.lastname: Modi
authors.forename: Caroline
authors.initials: C
authors.lastname: Dore
mesh_terms: D002658:Developmental Disabilities / Q000453:epidemiology; D019988:Children with Disabilities / Q000706:statistics & numerical data; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000401:mortality / Q000517:prevention & control*; D007236:Infant, Small for Gestational Age; D008297:Male; D018805:Sepsis / Q000401:mortality / Q000517:prevention & control*
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor