Randomized, Double-blinded, Placebo-controlled Trial of Early Administration of Recombinant Human Granulocyte Colony-stimulating Factor to Non-neutropenic Preterm Newborns Between 33 and 36 Weeks with Presumed Sepsis

Abstract

A randomized, double-blinded, placebo-controlled trial was conducted of early administration of recombinant granulocyte colony-stimulating factor (rGCSF) to 40 non-neutropenic, preterm infants between 33 and 36 weeks of gestational age with the diagnosis of presumed sepsis. The treatment group (n = 20) received 5 microg/kg per day of intravenous rGCSF once daily for 3 d and the control group (n = 20) received the same volume of physiological serum. Immediately before the first dose and on the 4th day, plasma levels of GCSF and tumour necrosis factor-alpha (TNF-alpha), absolute neutrophil counts (ANC), immature neutrophil count (INC), immature/total neutrophil (I/T) ratios and platelet counts were determined. At study entry, the plasma GCSF and TNF-alpha levels were similar. On day 4, there was no significant change in GCSF levels in either groups, whereas there was a significant decrease in TNF-alpha levels in the treatment group. ANC and INC of the treatment group also increased significantly. The I/T ratio continued at the same level in the treatment group, but decreased significantly on days 4 and 7 day in the control group. The length of time on the neonatal intensive care unit (NICU) was significantly shorter in the treatment group. In conclusion, early administration of 3 daily doses of rGCSF (5 microg/kg per day) to non-neutropenic, preterm infants who had presumed sepsis increased circulating ANC and INC, decreased plasma TNF-alpha levels and shortened the length of time on the NICU.

Clinical and Biochemical Effects of Recombinant Human Granulocyte Colony-Stimulating Factor on the Prognosis of Preterm Infants with Early Onset Neonatal Sepsis

“…In consistent with our findings, Kucukoduk et al used 5 µg/kg/day of intravenous rG-CSF for 3 days, and indicated a significant increase in ANC meanwhile no change was observed in immature/total neutrophil ratios. They recorded the shortened length of time on the NICU in the treated infants (27). Moreover, Miura et al corroborated the increased level of neutrophil counts in premature neonates with EONS who were exposed to 10 µg/kg/day of intravenous rG-CSF for 3 days.…”

“…G-CSF is a prominent cytokine improving the function and growth of neutrophils. Despite the early evidence indicating the positive contribution of G-CSF to the treatment of EONS (26)(27)(28), there are controversies still exist on its application in infants, so further studies are required in either clinical or non-clinical (in vitro and in vivo) settings (29)(30)(31)(32). Considering the high incidence of sepsis in preterm infants and its subsequent morbidity and mortality (33,34), the objective of the present study was to evaluate the efficacy of the recombinant human G-CSF (rhG-CSF) administration on blood parameters (WBC, ANC, hs-CRP level and the ratio of immature to total neutrophils), and clinical parameters (mortality rate, adverse effects and duration of hospital stay) in preterm infants with EONS hospitalized at the NICU of Qaem Hospital in Mashhad, Iran.…”