A Multicenter, Randomized, Placebo-Controlled Trial of Prophylactic Recombinant Granulocyte-Colony Stimulating Factor in Preterm Neonates with Neutropenia

Objective

To test the hypothesis that prophylactic treatment of neutropenic premature neonates with recombinant granulocyte-colony stimulating factor (rG-CSF) would reduce the incidence of nosocomial infections (NIs).

Study design

A total of 25 neonatal intensive care units participated in this multicenter, randomized, double-blind, placebo-controlled trial. Premature infants of gestational age (GA) ≤ 32 weeks were included if they had a peripheral blood count showing < 1500 neutrophils/mm³ for at least 24 hours during the first 3 weeks of life. A total of 200 infants received either rG-CSF (10 μg/kg/day) or placebo for 3 days. Primary outcome was survival free of infection for 4 weeks after treatment, assessed in an intention-to-treat analysis.

Results

A total of 102 infants received rG-CSF (mean GA, 29.2 weeks), and 98 received placebo (mean GA, 29.1 weeks). Survival free of confirmed infection for 4 weeks after treatment was 74/102 in the rG-CSF group and 66/98 in the placebo group (P = .42). However, during 2 weeks, there was a significant difference between groups (86/102 vs 70/98; P = .028).

Conclusions

In this population, prophylactic rG-CSF did not significantly increase survival free of infection at 4 weeks after treatment. The transient effect observed at 2 weeks in the most immature infants should be evaluated further.

AGA, Appropriate for gestational age, ANC, Absolute neutrophil count, BPD, Bronchopulmonary dysplasia, CI, Confidence interval, CLD, Chronic lung disease, CRP, C-reactive protein, GA, Gestational age, GM-CSF, Granulocyte macrophage colony-stimulating factor, NEC, Necrotizing enterocolitis, NI, Nosocomial infection, rG-CSF, Recombinant granulocyte colony-stimulating factor, ROP, Retinopathy of prematurity, SD, Standard deviation, SGA, Small for gestational age