A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: childhood outcomes at 5 years

Arch Dis Child Fetal Neonatal Ed. 2015 Jul;100(4):F320-6. doi: 10.1136/archdischild-2014-307410. Epub 2015 Apr 28.

Abstract

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.

Patients and 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.

Trial registration number: ISRCTN42553489.

Keywords: Child Psychology; Haematology; Neonatology; Neurodevelopment.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child Development / drug effects*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • Hematologic Agents / administration & dosage
  • Humans
  • Infant, Extremely Premature* / blood
  • Infant, Extremely Premature* / growth & development
  • Infant, Newborn
  • Infant, Small for Gestational Age* / blood
  • Infant, Small for Gestational Age* / growth & development
  • Leukocyte Count
  • Male
  • Neuropsychological Tests
  • Neutrophils
  • Outcome Assessment, Health Care
  • Sepsis / prevention & control*
  • Time

Substances

  • Hematologic Agents
  • Granulocyte-Macrophage Colony-Stimulating Factor

Associated data

  • ISRCTN/ISRCTN42553489