• 
• 

Three Part Question

Does [GM CSF] has any role in treating [septic newborns] with [neutropenia]

Clinical Scenario

In a tertiary care Neonatal department, we came across a 4 day old 28+1 week preterm baby with suspected sepsis and low neutropil count. I wonder whether giving GM-CSF or G-CSF improves final outcome

Search Strategy

Pubmed: The search term [({G CSF}{neutropenia} AND {septic newborn}] Limits: Humans, Clinical Trial, Randomized Controlled Trial, English, Newborn: birth-1 month

Search Outcome

Pubmed, Hit 6, relevant 3

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Ahmad A et al 2002 USA	Twenty-eight septic preterm neonate with clinical signs of sepsis with/without positive blood cultures & neutropenia (<1 x 10-9	Multi-centre Randomized Double-blind Placebo Controlled trial	Mortality	Although the neutrophil count in the G-CSF group increased significantly faster than that in the placebo or GM-CSF group but the mortality and morbidity were not statistically significantly different between the groups	Small number
			Neutropil counts (days 2, 5 & 7) from study entry
			3 infants died directly related to the septic episode
A R Bedford Russell et al, 2001, UK	Twenty eight neonates with birth weight b/w 500-1500gms, with clinical signs of sepsis & ANC 5 × 109/l; 13 received hG-CSF & 15 received placebo	Prospective Randomized Double blind Placebo Controlled, Multi-centre study	Adverse events (peripheral edema, anemia, thrombocytopenia, bradycardia, & hyponatraemia) and oxygenation index.	Significantly more rapid increase in ANC in the rhG-CSF treated babies	Small number Babies with ANC of < 5 x 109 were included in the study, which overestimated neutropenia
				Mortality during 42 days after enrollment & survival at 6 and 12 months postmenstrual age was significantly lower in the treatment group
Schibler KR et al, 1998, USA	20 neonates age <3 day with early onset sepsis and neutropenia. Neutropenia plus elevated Immature to Total neutrophil (I/T) ratio (>/= 0.25)	Multi-centre ,Randomized, Double-blind ,Placebo Controlled trial	Increase in serum Neutrophils	Administration of recombinant G-CSF to infants with neutropenia and clinical signs of early-onset sepsis did not increase circulating ANC, or bone marrow precursors of neutrophils.	Small Number Not stratified
			Increase in bone marrow stored and precursor neutrophils	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

Comment(s)

Granulocyte Colony stimulating factor is a glycoprotein produce by different cells of the body. It acts on bone marrow and stimulates the production of white cells. It also possibly up-regulates receptors on neutrophils that are involved in antibody-mediated cytotoxicity and killing of microorganisms. The recombinant form of G-CSF is used in cancer patients to accelerate recovery from neutropenia after chemotherapy. Various studies have shown that using G-CSF in septic newborn improves neutrophil count rapidly but it doesn't improve long term outcome or mortality.1 2 Miura et al showed using recombinant G-CSF in non neutropenic septic preterm did not improve mortality but was associated with acquiring fewer nosocomial infections over the subsequent 2 weeks. 3 An extensive systemic review by Carr R et al evaluated the use of G CSF in established systemic infection, especially when complicated by a low neutrophil count as well as use of CSF prophylactically, to prevent sepsis prospectively through stimulation of neutrophil production and bactericidal function. They concluded that although it is safe to use G-CSF in preterm neonates and no toxicity was reported in any of the study but there is currently insufficient data to support the routine use of G-CSF in routine neonatal practice.4

Clinical Bottom Line

Currently available data is insufficient to support the routine use of G-CSF in routine neonatal practice.

References

1. Ahmad A, Laborada G, Bussel J, Nesin M Comparison of recombinant granulocyte colony-stimulating factor, recombinant human granulocyte-macrophage colony-stimulating factor and placebo for treatment of septic preterm infants. Pediatr Infect Dis J. 2002 Nov;21(11):1061-5
2. A R Bedford Russella, A J B Emmersonb, N Wilkinsona, T Chantb, D G Sweetc, H L Hallidayc, B Hollandd, E G Daviesa A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia Arch Dis Child Fetal Neonatal Ed 2001;84:F172-F176 ( May )
3. Schibler KR, Osborne KA, Leung LY, Le TV, Baker SI, Thompson DD A randomized, placebo-controlled trial of granulocyte colony-stimulating factor administration to newborn infants with neutropenia and clinical signs of early-onset sepsis Pediatrics. 1999 Jun;103(6 Pt 1):1310-1.