Anti-sepsis prophylaxis with GM-CSF in extremely preterm, small-for-dates babies

Among extremely preterm newborns, reported rates of sepsis have varied from 25% to 65%. Neonatal sepsis may be fatal or cause brain injury. Immuno­logical immaturity, including a reduced capacity for neutrophil production, plays an important part. There is some, but inadequate, evidence that the prophylactic use of the haemopoietic growth factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), may reduce the risk of neonatal sepsis. Now a multicentre UK trial of prophylactic GM-CSF has produced disappointing results.

The trial included 280 neonates (birthweight <10th centile at up to 31 weeks’ gestation) rand­omized at 26 centres within 72 hours of birth to GM-CSF 10 µg/kg/day subcutaneously for 5 days or standard care. In the first 11 days after randomi­zation, neutrophil counts rose significantly more rapidly in the GM-CSF group (difference 0.34 x 10⁹ neutrophils/L/day). The rate of sepsis-free survival at 14 days was 93/139 (67%) in the GM-CSF group and 105/141 (74%) in the control group, a non­significant difference. A meta-analysis of this and previously reported trials confirmed no increased survival with prophylactic GM-CSF.

Prophylactic GM-CSF given to very preterm, small-for-gestational-age neonates was not beneficial.
 

Carr R, et al. Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomized controlled trial. Lancet 2009;373:226–233; Shann F. Sepsis in babies: should we stimulate the phagocytes? Ibid:188–190 (comment).