A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: Outcomes at 2 years
Marlow N., Morris T., Brocklehurst P., Carr R., Cowan FM., Patel N., Petrou S., Redshaw ME., Modi N., Dore C.
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. Patients and 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.