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Updated: May 22, 2026
A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: outcomes at 2 years
Neil Marlow1, Timothy Morris, Peter Brocklehurst
1Institute for Womens Health, 74 Huntley Street, University College London, WC1E 6AU, UK. n.marlow@ucl.ac.uk
Insights
Granulocyte-macrophage colony-stimulating factor (GM-CSF) did not improve outcomes for very preterm small-for-gestational age (SGA) infants. The study found no significant differences in health, development, or costs at two years of age.
Area of Science:
- Neonatal Medicine
- Pediatric Critical Care
- Developmental Pediatrics
Background:
- Very preterm infants born small-for-gestational age (SGA) are at increased risk for adverse neonatal outcomes.
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been investigated for its potential to improve neutrophil counts and immune function in vulnerable infants.
Purpose of the Study:
- To evaluate the efficacy and safety of GM-CSF prophylaxis in very preterm SGA infants.
- To assess the impact of GM-CSF on neonatal sepsis-free survival and long-term neurodevelopmental and general health outcomes up to two years of age.
Main Methods:
- A randomized trial (PROGRAMS trial) involving 280 very preterm (<31 weeks gestation) SGA infants.
- Outcomes including neurodevelopmental status, general health, and economic costs were assessed at two years of age.
Main Results:
- GM-CSF administration did not significantly improve sepsis-free survival or overall health outcomes at two years.
- No significant differences in health and social care costs were observed between the GM-CSF and control groups.
- While neurological abnormality rates were similar, some children receiving GM-CSF showed a marginal increase in cough and signs of chronic respiratory disease.
Conclusions:
- GM-CSF prophylaxis in very preterm SGA infants is not associated with improved or more adverse outcomes at two years.
- The observed developmental impairments in the cohort may be linked to intrauterine growth restriction rather than GM-CSF treatment.
- Further research is needed to understand the long-term effects and potential benefits of immunomodulatory therapies in this population.
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.
