A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: childhood outcomes at 5 years.
OBJECTIVE
We 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). GM-CSF was associated with improved neonatal neutrophil counts, but no change in other neonatal or 2-year outcomes. As subtle benefits in outcome may not be ascertainable until school age we performed an outcome study at 5 years.


METHODS
280 babies born at 31 weeks of gestation or less and SGA were entered into the trial. Outcomes were assessed at 5 years to determine neurodevelopmental and general health status and educational attainment.


RESULTS
We found no significant differences in cognitive, general health or educational outcomes between 83 of 106 (78%) surviving children in the GM-CSF arm compared with 81 of 110 (74%) in the control arm. Mean mental processing composite (equivalent to IQ) at 5 years were 94 (SD 16) compared with 95 (SD 15), respectively (difference in means -1 (95%CI -6 to 4), and similar proportions were in receipt of special educational needs support (41% vs 35%; risk ratio 1.2 (95% CI 0.8 to 1.9)). Performance on Kaufmann-ABC subscales and components of NEPSY were similar. The suggestion of worse respiratory outcomes in the GM-CSF group at 2 years was replicated at 5 years.


CONCLUSIONS
The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse neurodevelopmental, general health or educational outcomes at 5 years.


BACKGROUND
ISRCTN42553489.
UCL Institute for Women's Health, University College London, London, UK.
Neil
N
Marlow
MRC Clinical Trials Unit, University College London, London, UK.
Timothy
T
Morris
UCL Institute for Women's Health, University College London, London, UK.
Peter
P
Brocklehurst
Department of Haematology, Guy's and St Thomas' Hospital, King's College London, London, UK.
Robert
R
Carr
Section of Neonatal Medicine, Department of Medicine, Chelsea & Westminster campus, Imperial College London, London, UK.
Frances
F
Cowan
Department of Applied Health Research, University College London, London, UK.
Nishma
N
Patel
Warwick Medical School, University of Warwick, Coventry, UK.
Stavros
S
Petrou
National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK.
Margaret
M
Redshaw
Section of Neonatal Medicine, Department of Medicine, Chelsea & Westminster campus, Imperial College London, London, UK.
Neena
N
Modi
MRC Clinical Trials Unit, University College London, London, UK.
Caroline J
CJ
Doré
D002657:Child Development / Q000187:drug effects*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006401:Hematologic Agents / Q000008:administration & dosage; D006801:Humans; D062071:Infant, Extremely Premature / Q000097:blood / Q000254:growth & development; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000097:blood / Q000254:growth & development; D007958:Leukocyte Count; D008297:Male; D009483:Neuropsychological Tests; D009504:Neutrophils; D017063:Outcome Assessment, Health Care; D018805:Sepsis / Q000517:prevention & control*; D013995:Time
D006401:Hematologic Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
Child Psychology; Haematology; Neonatology; Neurodevelopment