title: A randomized, placebo-controlled trial of granulocyte colony-stimulating factor administration to newborn infants with neutropenia and clinical signs of early-onset sepsis.
abstract: OBJECTIVE
  To determine whether recombinant human granulocyte colony-stimulating factor (G-CSF) administration: 1) accelerates production of neutrophils; 2) increases bone marrow stored and precursor neutrophils; and 3) is safe in newborn infants with neutropenia and clinical signs of early-onset sepsis.
  
  
  METHODS
  We randomized 20 infants with neutropenia and clinical signs of early-onset sepsis in the first 3 days of life to receive G-CSF (10 microg/kg/d) or placebo for 3 days. Entry criteria included neutropenia as defined by Manroe criteria, an elevated immature to total neutrophil ratio [(I/T) >/=0.25], and a requirement for ventilatory support. Cultures were obtained and antibiotics initiated on all study infants. Circulating absolute neutrophil count (ANC), I/T ratio, bone marrow neutrophil storage pool (NSP) and neutrophil proliferative pool (NPP), and plasma G-CSF concentrations were evaluated. Also, severity of illness as determined using the Score for Neonatal Acute Physiology (SNAP), morbidity, and mortality were recorded.
  
  
  RESULTS
  Circulating ANC increased in both G-CSF and placebo recipients by day 1. Also, the I/T neutrophil ratio decreased in both G-CSF and placebo recipients. There were no significant differences in the ANC or I/T ratio between the two groups during the study period. Similarly, bone marrow NSP and NPP did not differ between G-CSF and placebo recipients at study entry or day 2. No differences were observed in the secondary outcome measures including severity of illness, morbidity, and mortality.
  
  
  CONCLUSIONS
  Administration of recombinant G-CSF to infants with neutropenia and clinical signs of early-onset sepsis did not increase circulating ANC, or bone marrow NSP and NPP compared with placebo. No differences were observed between G-CSF and placebo recipients in severity of illness, morbidity, or mortality. No adverse effects of G-CSF administrations were noted.
authors.affiliation: Department of Pediatrics, Division of Neonatology, and the Clinical Research Center, University of Utah School of Medicine, Salt Lake City, Utah 34132, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Schibler
authors.forename: K A
authors.initials: KA
authors.lastname: Osborne
authors.forename: L Y
authors.initials: LY
authors.lastname: Leung
authors.forename: T V
authors.initials: TV
authors.lastname: Le
authors.forename: S I
authors.initials: SI
authors.lastname: Baker
authors.forename: D D
authors.initials: DD
authors.lastname: Thompson
mesh_terms: D016470:Bacteremia / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D004311:Double-Blind Method; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D007958:Leukocyte Count / Q000187:drug effects; D009503:Neutropenia / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins; D015996:Survival Rate
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor