PDF herunterladen
Am J Perinatol 2017; 34(05): 458-464
DOI: 10.1055/s-0036-1593349
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effectiveness of Granulocyte Colony-Stimulating Factor in Hospitalized Infants with Neutropenia

Jin A. Lee
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
2   Boramae Hospital, Seoul National University, Seoul, South Korea
3   College of Medicine, Seoul National University, Seoul, South Korea
,
Brooke Sauer
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
,
William Tuminski
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
,
Jiyu Cheong
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
,
John Fitz-Henley II
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
,
Megan Mayers
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
,
Chidera Ezuma-Igwe
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
,
Christopher Arnold
4   Division of Infectious Diseases and International Health, University of Virginia Health System, Charlottesville, Virginia
,
Christoph P. Hornik
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
5   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
,
Reese H. Clark
6   Pediatrix-Obstetrix Center for Research and Education, Sunrise, Florida
,
Daniel K. Benjamin Jr.
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
5   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
,
P. Brian Smith
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
5   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
,
Jessica E. Ericson
1   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
7   Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania
,
on behalf of the Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee › Institutsangaben
Weitere Informationen

Publikationsverlauf

06. Mai 2016

15. August 2016

Publikationsdatum:
20. September 2016 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Objective The objective of this study was to determine the time to hematologic recovery and the incidence of secondary sepsis and mortality among neutropenic infants treated or not treated with granulocyte colony-stimulating factor (G-CSF).

Study Design We identified all neutropenic infants discharged from 348 neonatal intensive care units from 1997 to 2012. Neutropenia was defined as an absolute neutrophil count ≤ 1,500/µL for ≥ 1 day during the first 120 days of life. Incidence of secondary sepsis and mortality and number of days required to reach an absolute neutrophil count > 1,500/µL for infants exposed to G-CSF were compared with those of unexposed infants.

Results We identified 30,705 neutropenic infants, including 2,142 infants (7%) treated with G-CSF. Treated infants had a shorter adjusted time to hematologic recovery (hazard ratio: 1.36, 95% confidence interval [CI]: 1.30–1.44) and higher adjusted odds of secondary sepsis (odds ratio [OR]: 1.50, 95% CI: 1.20–1.87), death (OR: 1.33, 95% CI: 1.05–1.68), and the combined outcome of sepsis or death (OR: 1.41, 95% CI: 1.19–1.67) at day 14 compared with untreated infants. These differences persisted at day 28.

Conclusion G-CSF treatment decreased the time to hematologic recovery but was associated with increased odds of secondary sepsis and mortality in neutropenic infants. G-CSF should not routinely be used for infants with neutropenia.

Keywords

hematologic recovery - sepsis - prophylaxis
 

  • References

  • 1 Mouzinho A, Rosenfeld CR, Sanchez PJ, Risser R. Effect of maternal hypertension on neonatal neutropenia and risk of nosocomial infection. Pediatrics 1992; 90 (3) 430-435
    PubMedSuche in Google Scholar
  • 2 Funke A, Berner R, Traichel B, Schmeisser D, Leititis JU, Niemeyer CM. Frequency, natural course, and outcome of neonatal neutropenia. Pediatrics 2000; 106 (1 Pt 1): 45-51
    CrossrefPubMedSuche in Google Scholar
  • 3 Koenig JM, Christensen RD. Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med 1989; 321 (9) 557-562
    CrossrefPubMedSuche in Google Scholar
  • 4 Lieschke GJ, Burgess AW. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor (1). N Engl J Med 1992; 327 (1) 28-35
    CrossrefPubMedSuche in Google Scholar
  • 5 Schibler KR, Liechty KW, White WL, Christensen RD. Production of granulocyte colony-stimulating factor in vitro by monocytes from preterm and term neonates. Blood 1993; 82 (8) 2478-2484
    CrossrefPubMedSuche in Google Scholar
  • 6 La Gamma EF, Alpan O, Kocherlakota P. Effect of granulocyte colony-stimulating factor on preeclampsia-associated neonatal neutropenia. J Pediatr 1995; 126 (3) 457-459
    CrossrefPubMedSuche in Google Scholar
  • 7 Kuhn P, Messer J, Paupe A , et al. A multicenter, randomized, placebo-controlled trial of prophylactic recombinant granulocyte-colony stimulating factor in preterm neonates with neutropenia. J Pediatr 2009; 155 (3) 324-330.e1
    CrossrefPubMedSuche in Google Scholar
  • 8 Carr R, Modi N, Doré CJ, El-Rifai R, Lindo D. A randomized, controlled trial of prophylactic granulocyte-macrophage colony-stimulating factor in human newborns less than 32 weeks gestation. Pediatrics 1999; 103 (4 Pt 1): 796-802
    CrossrefPubMedSuche in Google Scholar
  • 9 Bedford Russell AR, Emmerson AJ, Wilkinson N , et al. 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 (3) F172-F176
    CrossrefPubMedSuche in Google Scholar
  • 10 Gillan ER, Christensen RD, Suen Y, Ellis R, van de Ven C, Cairo MS. A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia. Blood 1994; 84 (5) 1427-1433
    CrossrefPubMedSuche in Google Scholar
  • 11 Clark RH, Gordon P, Walker WM, Laughon M, Smith PB, Spitzer AR. Characteristics of patients who die of necrotizing enterocolitis. J Perinatol 2012; 32 (3) 199-204
    CrossrefPubMedSuche in Google Scholar
  • 12 Mouzinho A, Rosenfeld CR, Sánchez PJ, Risser R. Revised reference ranges for circulating neutrophils in very-low-birth-weight neonates. Pediatrics 1994; 94 (1) 76-82
    PubMedSuche in Google Scholar
  • 13 Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics 2010; 125 (2) e214-e224
    CrossrefPubMedSuche in Google Scholar
  • 14 Boghossian NS, Page GP, Bell EF , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births. J Pediatr 2013; 162 (6) 1120-1124 , 1124.e1
    Suche in Google Scholar
  • 15 Hornik CP, Fort P, Clark RH , et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev 2012; 88 (Suppl. 02) S69-S74
    CrossrefPubMedSuche in Google Scholar
  • 16 Brazy JE, Grimm JK, Little VA. Neonatal manifestations of severe maternal hypertension occurring before the thirty-sixth week of pregnancy. J Pediatr 1982; 100 (2) 265-271
    CrossrefPubMedSuche in Google Scholar
  • 17 Engle WD, Rosenfeld CR. Neutropenia in high-risk neonates. J Pediatr 1984; 105 (6) 982-986
    CrossrefPubMedSuche in Google Scholar
  • 18 Zuppa AA, Girlando P, Florio MG, Cota F, Romagnoli C, Tortorolo G. Influence of maternal preeclampsia on recombinant human granulocyte colony-stimulating factor effect in neutropenic neonates with suspected sepsis. Eur J Obstet Gynecol Reprod Biol 2002; 102 (2) 131-136
    CrossrefPubMedSuche in Google Scholar
  • 19 Juul SE, Haynes JW, McPherson RJ. Evaluation of neutropenia and neutrophilia in hospitalized preterm infants. J Perinatol 2004; 24 (3) 150-157
    Suche in Google Scholar
  • 20 Christensen RD, Henry E, Wiedmeier SE, Stoddard RA, Lambert DK. Low blood neutrophil concentrations among extremely low birth weight neonates: data from a multihospital health-care system. J Perinatol 2006; 26 (11) 682-687
    Suche in Google Scholar
  • 21 Kocherlakota P, La Gamma EF. Human granulocyte colony-stimulating factor may improve outcome attributable to neonatal sepsis complicated by neutropenia. Pediatrics 1997; 100 (1) E6
    PubMedSuche in Google Scholar
  • 22 Christensen RD, Yoder BA, Baer VL, Snow GL, Butler A. Early-onset neutropenia in small-for-gestational-age infants. Pediatrics 2015; 136 (5) e1259-e1267
    Suche in Google Scholar
  • 23 Doron MW, Makhlouf RA, Katz VL, Lawson EE, Stiles AD. Increased incidence of sepsis at birth in neutropenic infants of mothers with preeclampsia. J Pediatr 1994; 125 (3) 452-458
    Suche in Google Scholar
  • 24 Kocherlakota P, La Gamma EF. Preliminary report: rhG-CSF may reduce the incidence of neonatal sepsis in prolonged preeclampsia-associated neutropenia. Pediatrics 1998; 102 (5) 1107-1111
    CrossrefPubMedSuche in Google Scholar
  • 25 Lejeune M, Cantinieaux B, Harag S, Ferster A, Devalck C, Sariban E. Defective functional activity and accelerated apoptosis in neutrophils from children with cancer are differentially corrected by granulocyte and granulocyte-macrophage colony stimulating factors in vitro. Br J Haematol 1999; 106 (3) 756-761
    CrossrefPubMedSuche in Google Scholar
  • 26 Kücüködük S, Sezer T, Yildiran A, Albayrak D. 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. Scand J Infect Dis 2002; 34 (12) 893-897
    CrossrefPubMedSuche in Google Scholar
  • 27 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; 21 (11) 1061-1065
    CrossrefPubMedSuche in Google Scholar
  • 28 Miura E, Procianoy RS, Bittar C , et al. A randomized, double-masked, placebo-controlled trial of recombinant granulocyte colony-stimulating factor administration to preterm infants with the clinical diagnosis of early-onset sepsis. Pediatrics 2001; 107 (1) 30-35
    CrossrefPubMedSuche in Google Scholar
  • 29 Carr R, Brocklehurst P, Doré CJ, Modi N. 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, randomised controlled trial. Lancet 2009; 373 (9659): 226-233
    CrossrefPubMedSuche in Google Scholar
  • 30 Christensen RD, Rothstein G, Anstall HB, Bybee B. Granulocyte transfusions in neonates with bacterial infection, neutropenia, and depletion of mature marrow neutrophils. Pediatrics 1982; 70 (1) 1-6
    PubMedSuche in Google Scholar
  • 31 Barak Y, Leibovitz E, Mogilner B , et al. The in vivo effect of recombinant human granulocyte-colony stimulating factor in neutropenic neonates with sepsis. Eur J Pediatr 1997; 156 (8) 643-646
    CrossrefPubMedSuche in Google Scholar
  • 32 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 1998; 102 (1 Pt 1): 6-13
    CrossrefPubMedSuche in Google Scholar
  • 33 Aktaş D, Demirel B, Gürsoy T, Ovalı F. A randomized case-controlled study of recombinant human granulocyte colony stimulating factor for the treatment of sepsis in preterm neutropenic infants. Pediatr Neonatol 2015; 56 (3) 171-175
    CrossrefPubMedSuche in Google Scholar