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Neonatology pp 822-829 | Cite as

Therapy with Recombinant Leukocyte Growth Factors

  • Robert D. Christensen

Abstract

The complete blood count (CBC) is one of the most commonly obtained laboratory tests in Neonatology. When a neonatologist finds a low blood concentration of neutrophils, it can be expected as in a neonate with septic shock, or it can be unanticipated and puzzling. A neonatologist finding neutropenia might wonder: What conditions should I consider in the differential diagnosis? Will the neutropenia be a significant clinical problem or will it be trivial and transient? Should I order rG-CSF? This chapter will focus on the last of these questions, reviewing the studies and the reasoning involved in this decision, and will include an algorithm as a guide to answering this question.

Keywords

Glycogen Storage Disease Exocrine Pancreatic Insufficiency Autoimmune Neutropenia Chronic Idiopathic Neutropenia Severe Chronic Neutropenia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Schmutz N, Henry E, Jopling J, Christensen RD (2008) Expected ranges for blood neutrophil concentrations of neonates: the Manroe and Mouzinho charts revisited. J Perinatol 28: 275–281PubMedCrossRefGoogle Scholar
  2. 2.
    Christensen RD, Henry E, Wiedmeier SE et al (2006) Neutropenia among extremely low birth-weight neonates: data from a multihospital healthcare system. J Perinatol 26: 682–687PubMedCrossRefGoogle Scholar
  3. 3.
    Calhoun DA, Christensen RD, Edstrom CS et al (2000) Consistent approaches to procedures and practices in neonatal hematology. Clin Perinatol 27: 733–753PubMedCrossRefGoogle Scholar
  4. 4.
    Manroe BL, Weinberg AG, Rosenfeld CR, Browne R (1979) The neonatal blood count in health and disease. I. Reference values for neutrophilic cells. J Pediatr 95: 89–98Google Scholar
  5. 5.
    Mouzinho A, Rosenfeld CR, Sanchez PJ, Risser R (1992) Effect of maternal hypertension on neonatal neutropenia and risk of nosocomial infection. Pediatrics 90: 430–435PubMedGoogle Scholar
  6. 6.
    Hill HR (1987) Biochemical, structural, and functional abnormalities of polymorphonuclear leukocytes in the neonate. Pediatr Res 22: 375–382PubMedCrossRefGoogle Scholar
  7. 7.
    Cairo MS (1989) Neutrophil storage pool depletion in neonates with sepsis. J Pediatr 114: 1064–1065PubMedGoogle Scholar
  8. 8.
    Morstyn G, Foote M, Nelson S (1997) Clinical benefits of improving host defenses with rHuG-CSF. Ciba Found Symp 204: 78–85PubMedGoogle Scholar
  9. 9.
    Alter BP (2002) Bone marrow failure syndromes in children. Pediatr Clin North Am 49: 973–988PubMedCrossRefGoogle Scholar
  10. 10.
    Zeidler C, Schwinzer B, Welte K (2003) Congenital neutropenias. Rev Clin Exp Hematol 7: 72–83PubMedGoogle Scholar
  11. 11.
    Stein SM, Dale DC (2003) Molecular basis and therapy of disorders associated with chronic neutropenia. Curr Allergy Asthma Rep 3: 385–388PubMedCrossRefGoogle Scholar
  12. 12.
    Zeidler C, Boxer L, Dale DC et al (2000) Management of Kostmann syndrome in the G-CSF era. Br J Haematol 109: 490–495PubMedCrossRefGoogle Scholar
  13. 13.
    Calhoun DA, Christensen RD (1997) The occurrence of Kostmann syndrome in preterm neonates. Pediatrics 99: 259–261PubMedCrossRefGoogle Scholar
  14. 14.
    Fujiu T, Maruyama K, Koizumi T (2002) Early-onset group B streptococcal sepsis in a preterm infant with Kostmann syndrome. Acta Paediatr 91: 1397–1399PubMedCrossRefGoogle Scholar
  15. 15.
    Christensen RD, Calhoun DA (2004) Congenital neutropenia. Clin Perinatol 31: 29–38PubMedCrossRefGoogle Scholar
  16. 16.
    Engle WD, Rosenfeld CR (1984) Neutropenia in high risk neonates. J Pediatr 105: 982–986PubMedCrossRefGoogle Scholar
  17. 17.
    Gessler P, Luders R, Konig S et al (1995) Neonatal neutropenia in low birthweight premature infants. Am J Perinatol 12: 34–38PubMedCrossRefGoogle Scholar
  18. 18.
    Juul SE, Haynes JW, McPherson RJ (2004) Evaluation of neutropenia and neutrophilia in hospitalized preterm infants. J Perinatol 24: 150–157PubMedCrossRefGoogle Scholar
  19. 19.
    Christensen RD, Calhoun DA, Rimsza LM (2000) A practical approach to evaluating and treating neutropenia in the neonatal intensive care unit. Clin Perinatol 27: 577–601PubMedCrossRefGoogle Scholar
  20. 20.
    Funke A, Berner R, Traichel B et al (2000) Frequency, natural course, and outcome of neonatal neutropenia. Pediatrics106: 45–51Google Scholar
  21. 21.
    Kostmann R (1956) Infantile genetic agranulocytosis; agranulocytosis infantilis hereditaria. Acta Paediatr 45 (Suppl 105): 1–78Google Scholar
  22. 22.
    Carlsson G, Fasth A (2001) Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases from the original “Kostmann family” and a review. Acta Paediatr 90: 757–764PubMedCrossRefGoogle Scholar
  23. 23.
    Aprikyan AA, Carlsson G, Stein S et al (2004) Neutrophil elastase mutations in severe congenital neutropenia patients of the original Kostmann family. Blood 103: 389PubMedCrossRefGoogle Scholar
  24. 24.
    Zeidler C, Welte K (2002) Kostmann syndrome and severe congenital neutropenia. Semin Hematol 39: 82–88PubMedCrossRefGoogle Scholar
  25. 25.
    Ancliff PJ, Gale RE, Liesner R (2001) Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease. Blood 98: 2645–2650PubMedCrossRefGoogle Scholar
  26. 26.
    Bellanne-Chantelot C, Clauin S, Leblanc T et al (2004) Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. Blood 103: 4119–4125PubMedCrossRefGoogle Scholar
  27. 27.
    Kollner I, Sodeik B, Schreek S (2006) Mutations in neutrophil elastase causing congenital neutropenia lead to cytoplasmic protein accumulation and induction of the unfolded protein response. Blood 108: 493–500PubMedCrossRefGoogle Scholar
  28. 28.
    Zetterstrom R (2002) Kostmann disease-infantile genetic agranulocytosis: historical views and new aspects. Acta Paediatr 91: 1279–1281PubMedCrossRefGoogle Scholar
  29. 29.
    Carlsson G, Wahlin YB, Johansson A (2006) Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia. J Periodontol 77: 744–751PubMedCrossRefGoogle Scholar
  30. 30.
    Faber J, Lauener R, Wick F et al (1999) Shwachman-Diamond syndrome: early bone marrow transplantation in a high risk patient and new clues to pathogenesis. Eur J Pediatr 158: 995–1000PubMedCrossRefGoogle Scholar
  31. 31.
    Donadieu J, Michel G, Merlin E et al (2005) Hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: experience of the French neutropenia registry. Bone Marrow Transplant 36: 787–792PubMedCrossRefGoogle Scholar
  32. 32.
    Huhta JC, Pomerance HH, Barness EG (2005) Clinicopathologic conference: Barth Syndrome. Fetal Pediatr Pathol 24: 239–254Google Scholar
  33. 33.
    Barth PG, Van den Bogert C, Bolhuis PA et al (1996) X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): respiratory- chain abnormalities in cultured fibroblasts. J Inherit Metabl Dis 19: 157–160CrossRefGoogle Scholar
  34. 34.
    Barth PG, Valianpour F, Bowen VM et al (2004) X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): an update. Am J Med Genet 126A: 349–353CrossRefGoogle Scholar
  35. 35.
    Alter BP (1999) Bone marrow failure syndromes. Clin Lab Med 19: 113–133PubMedGoogle Scholar
  36. 36.
    Dale DC, Bolyard AA, Aprikyan A (2002) Cyclic neutropenia. Semin Hematol 39: 89–94PubMedCrossRefGoogle Scholar
  37. 37.
    Sera Y, Kawaguchi H, Nakamura K et al (2005) A comparison of the defective granulopoiesis in childhood cyclic neutropenia and in severe congenital neutropenia. Haematologica 90: 1032–1041PubMedGoogle Scholar
  38. 38.
    Dale DC, Cottle TE, Fier CJ et al (2003) Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. Am J Hematol 72: 82–93PubMedCrossRefGoogle Scholar
  39. 39.
    Chow JY (2001) The molecular basis of type I glycogen storage diseases. Curr Mol Med 1: 25–44CrossRefGoogle Scholar
  40. 40.
    Lalezari P, Khorshidi M, Petrosova M (1986) Autoimmune neutropenia of infancy. J Pediatr 109: 764–769PubMedCrossRefGoogle Scholar
  41. 41.
    Boxer LA (1996) Leukocyte disorders: quantitative and qualitative disorders of the neutrophil, Part 1. Pediatr Rev 17: 19–28PubMedCrossRefGoogle Scholar
  42. 42.
    Boxer LA (1981) Immune neutropenias. Clinical and biological implications. Am J Pediatr Hematol Oncol 3: 89–96PubMedGoogle Scholar
  43. 43.
    Maheshwari A, Christensen RD, Calhoun DA (2002) Immune-mediated neutropenia in the neonate. Acta Paediatr Suppl 91: 98–103PubMedCrossRefGoogle Scholar
  44. 44.
    Makeshwari A, Christensen RD, Calhoun DA (2002) Immune neutropenia in the neonate. Adv Pediatr 49: 317–339Google Scholar
  45. 45.
    Curtis BR, Reon C, Aster RH (2005) Neonatal alloimmune neutropenia attributed to maternal immunoglobulin G antibodies against the neutrophil alloantigen HNA1c(SH): a report of five cases. Transfusion 45: 1308–1313PubMedCrossRefGoogle Scholar
  46. 46.
    Davoren A, Saving K, McFarland JG et al (2004) Neonatal neutropenia and bacterial sepsis associated with placental transfer of maternal neutrophil-specific autoantibodies. Transfusion 44: 1041–1046PubMedCrossRefGoogle Scholar
  47. 47.
    Calhoun DA, Rimsza LM, Burchfield DJ et al (2001) Congenital autoimmune neutropenia in two premature neonates. Pediatrics 108: 181–184PubMedCrossRefGoogle Scholar
  48. 48.
    Bux J, Behrens G, Jaeger G, Welte K (1998) Diagnosis and clinical course of autoimmune neutropenia in infancy; analysis of 240 cases. Blood 91: 181–186PubMedGoogle Scholar
  49. 49.
    Lekjowski M, Maheshwari A, Calhoun DA et al (2003) Persistent perianal abcess in early infancy as a presentation of autoimmune neutropenia. J Perinatol 23: 428–430CrossRefGoogle Scholar
  50. 50.
    Conway LT, Clay ME, Kline WE et al (1987) Natural history of primary autoimmune neutropenia in infancy. Pediatrics 79: 728–733PubMedGoogle Scholar
  51. 51.
    Koenig JM, Christensen RD (1989) Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med 321: 557–562PubMedCrossRefGoogle Scholar
  52. 52.
    Koenig JM, Christensen RD (1991) The mechanism responsible for diminished neutrophil production in neonates delivered of women with pregnancy-induced hypertension. Am J Obstet Gynecol 165: 467–473PubMedGoogle Scholar
  53. 53.
    Tsao PN, Teng RJ, Tang JR, Yau KI (1999) Granulocyte colony stimulating factor in the cord blood of premature neonates born to mothers with pregnancy induced hypertension. J Pediatr 135: 56–59PubMedCrossRefGoogle Scholar
  54. 54.
    Zuppa AA, Girlando P, Florio MG (2002) Influence of maternal preeclampsia on recombinant human granulocyte colony-stimulating factor effect in neutropenic neonates with suspected sepsis. Eur J Obstet Gynecol Reprod Biol 102: 131–136PubMedCrossRefGoogle Scholar
  55. 55.
    Doron MW, Makhlouf RA, Katz VL et al (1994) Increased incidence of sepsis at birth in neutropenic infants of mothers with preeclampsia. J Pediatr 125: 452–458PubMedCrossRefGoogle Scholar
  56. 56.
    Greco P, Manzionna M, Vimercati A et al (1997) Neutropenia in neonates delivered of women with pre-eclampsia. Acta Biomed Ateneo Parmense 68 (Suppl 1): 91–94PubMedGoogle Scholar
  57. 57.
    Paul DA, Kepler J, Leef KH et al (1998) Effect of preeclampsia on mortality, intraventricular hemorrhage, and need for mechanical ventilation in very low-birth-weight infants. Am J Perinatol 15: 381–386PubMedCrossRefGoogle Scholar
  58. 58.
    Kocherlakota P, La Gamma EF (1998) Preliminary report: rhGCSF may reduce the incidence of neonatal sepsis in prolonged preeclampsia-associated neutropenia. Pediatrics 102: 1107–1111PubMedCrossRefGoogle Scholar
  59. 59.
    Christensen RD, Henry E, Wiedmeier SE et al (2006) Neutropenia among extremely low birth-weight neonates: data from a multihospital healthcare system. J Perinatol 26: 682–687PubMedCrossRefGoogle Scholar
  60. 60.
    Koenig JM, Hunter DD, Christensen RD (1991) Neutropenia in donor (anemic) twins involved in the twin-twin transfusion syndrome. J Perinatol 11: 355–358PubMedGoogle Scholar
  61. 61.
    Koenig JM, Christensen RD (1989) Neutropenia and thrombocytopenia in infants with Rh hemolytic disease. J Pediatr 114: 625–631PubMedCrossRefGoogle Scholar
  62. 62.
    Carr R, Modi N, Dore C (2003) G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Syst Rev 3:CD003066Google Scholar
  63. 63.
    Ahmad A, Laborada G, Bussel J, Nesin M (2002) Comparison of recombinant G-CSF, recombinant human GM-CSF and placebo for treatment of septic preterm infants. Pediatr Infect Dis J 21: 1061–1065PubMedCrossRefGoogle Scholar
  64. 64.
    Bedford-Russell AR, Emmerson AJB, Wilkinson N et al (2001) 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 84: F172–F176PubMedCrossRefGoogle Scholar
  65. 65.
    Bilgin K, Yaramis A, Haspolat K et al (2001) A randomized trial of granulocyte-macrophage colony-stimulating factor in neonates with sepsis and neutropenia. Pediatrics 107: 36–41PubMedCrossRefGoogle Scholar
  66. 66.
    Drossou-Agakidou V, Kanakoudi-Tsakalidou F, Taparkou A et al (1998) Administration of recombinant human granulocyte-colony stimulating factor to septic neonates induces neutrophilia and enhances the neutrophil respiratory burst and beta2 integrin expression Results of a randomized controlled trial. Eur J Pediatr 157: 583–588PubMedCrossRefGoogle Scholar
  67. 67.
    Miura E, Procianoy RS, Bittar C et al (2001) 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 107: 30–35PubMedCrossRefGoogle Scholar
  68. 68.
    Schibler KR, Osborne KA, Leung LY et al (1998) A randomized placebo-controlled trial of granulocyte colony-stimulating factor administration to newborn infants with neutropenia and clinical signs of early-onset sepsis. Pediatrics 102: 6–13PubMedCrossRefGoogle Scholar
  69. 69.
    Gillan ER, Christensen RD, Suen Y et al (1994) 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 84: 1427–1433PubMedGoogle Scholar
  70. 70.
    Cairo MS, Christensen RD, Sender LS et al (1995) Results of a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor in very low birthweight neonates: significant induction of circulatory neutrophils, monocytes, platelets, and bone marrow neutrophils. Blood 86: 2509–2515PubMedGoogle Scholar
  71. 71.
    Cairo MS, Agosti J, Ellis R et al (1999) A randomised double-blind placebo-controlled trial of prophylactic recombinant human GMCSF to reduce nosocomial infection in very low birthweight neonates. J Pediatrics 134: 64–70CrossRefGoogle Scholar
  72. 72.
    Carr R, Modi N, Doré CJ et al (1999) A randomised controlled trial of prophylactic GM-CSF in human newborns less than 32 weeks gestation. Pediatrics 103: 796–802PubMedCrossRefGoogle Scholar
  73. 73.
    Rosenthal J, Healey T, Ellis R et al (1996) A two year follow-up of neonates with presumed sepsis treated with recombinant human GCSF during the first week of life. J Pediatr 128: 135–137PubMedCrossRefGoogle Scholar
  74. 74.
    Bernstein HM, Pollock BH, Calhoun DA, Christensen RD (2001) Administration of recombinant G-CSF to neonates with septicemia: a meta-analysis. Pediatrics 138: 917–920CrossRefGoogle Scholar
  75. 75.
    Carr R, Modi N (1997) Haemopoietic colony stimulating factors for preterm neonates. Arch Dis Child 76: F128–133Google Scholar
  76. 76.
    Carr R (2000) Neutrophil production and function in newborn infants. Br J Haematol 110: 18–28PubMedCrossRefGoogle Scholar
  77. 77.
    Carr R, Huizinga TWJ (2000) Low sFcRIII demonstrates reduced neutrophil reserves in preterm neonates. Arch Dis Child Fetal Neonatal Ed 83: F160PubMedCrossRefGoogle Scholar
  78. 78.
    Carr R, Modi N (2004) Haemopoietic growth factors for neonates: assessing risks and benefits. Acta Paediatr Suppl 93: 15–19PubMedCrossRefGoogle Scholar
  79. 79.
    Bracho F, Goldman S, Cairo MS (1998) Potential use of granulocyte colony stimulating factor and granulocyte macrophage colony stimulating factor in neonates. Curr Opin Hematol 5: 215–220PubMedCrossRefGoogle Scholar
  80. 80.
    Parravicini E, van de Ven C, Anderson L, Cairo MS (2002) Myeloid hematopoietic growth factors and their role in prevention and/or treatment of neonatal sepsis. Transfus Med Rev 16: 11–24PubMedGoogle Scholar
  81. 81.
    Modi N, Carr R (2000) Promising stratagems for reducing the burden of neonatal sepsis. Arch Dis Child Fetal Neonat Ed 83: F150–F153CrossRefGoogle Scholar
  82. 82.
    Roberts RL, Szelc CM, Scates SM et al (1991) Neutropenia in an extremely premature infant treated with recombinant human granulocyte colony-stimulating factor. Am J Dis Child 145: 808–812PubMedGoogle Scholar
  83. 83.
    Lejeune M, Cantineiux B, Harag S et al (1999) Defective functional activity and accelerated apoptosis in neutrophils from children with cancer are differentially corrected by granulocyte and granulocytemacrophage colony stimulating factors in vitro. Br J Haematol 106: 756–761PubMedCrossRefGoogle Scholar
  84. 84.
    Hutter JJ Jr, Hathaway WE, Wayne ER (1976) Hematologic abnormalities in severe neonatal necrotizing enterocolitis. J Pediatr 88: 1026–1031PubMedCrossRefGoogle Scholar
  85. 85.
    Kling PJ, Hutter JJ (2003) Hematologic abnormalities in severe neonatal necrotizing enterocolitis: 25 years later. J Perinatol 23: 523–530PubMedCrossRefGoogle Scholar
  86. 86.
    Juul SE, Calhoun DA, Christensen RD (1998) “Idiopathic neutropenia” in very low birthweight infants. Acta Paediatr 87:963–968Google Scholar
  87. 87.
    Juul SE, Christensen RD (2003) Effect of recombinant granulocyte colony-stimulating factor on blood neutrophil concentrations among patients with “idiopathic neonatal neutropenia”: a randomized, placebo-controlled trial. J Perinatol 23: 493–497PubMedCrossRefGoogle Scholar
  88. 88.
    Chirico G, Motta M, Villani P et al (2002) Late-onset neutropenia in very low birthweight infants. Acta Paediatr Suppl 91: 104–108PubMedCrossRefGoogle Scholar
  89. 89.
    Omar SA, Salhadar A, Wooliever DE, Alsgaard PK (2000) Lateonset neutropenia in very low birth weight infants. Pediatrics 106: e55Google Scholar
  90. 90.
    Golde DW, Gasson JC (1988) Hormones that stimulate the growth of blood cells. Sci Am 259: 62–71PubMedCrossRefGoogle Scholar
  91. 91.
    Davis I, Morstyn G (1992) Clinical uses of growth factors. Baillieres Clin Haematol 5: 753–786PubMedCrossRefGoogle Scholar
  92. 92.
    Sullivan GW, Carper HT, Mandell GL (1993) The effects of three human recombinant hematopoietic growth factors (granulocytemacrophage colony-stimulating factor, granulocyte colony-stimulating factor, and interleukin-3) on phagocyte oxidative activity. Blood 81: 1863–1870PubMedGoogle Scholar
  93. 93.
    Dale DC, Bonilla MA, Davis MW et al (1993) A randomized, controlled phase ill trial of recombinant human granulocyte colonystimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood 81: 2496–2502PubMedGoogle Scholar
  94. 94.
    Bonilla MA, Gillio AP, Ruggeiro M et al (1989) Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis. N Engl J Med 320: 1574–1580PubMedCrossRefGoogle Scholar
  95. 95.
    Cairo M, Suen Y, Knoppel E et al (1992) Decreased G-CSF and IL-3 production and gene expression from mononuclear cells of newborn infants. Pediatr Res 31: 574–578PubMedCrossRefGoogle Scholar
  96. 96.
    Schibler K, Leichty K, White W, Christensen RD (1993) Production of granulocyte colony-stimulating factor in vitro by monocytes from-preterm and term neonates. Blood 82: 2479–2484Google Scholar
  97. 97.
    Gessler P, Kirchmann N, Kientsch-Engel R et al (1993) Serum concentrations of granulocyte colony-stimulating factor in healthy term and preterm neonates and in those with various diseases including bacterial infections. Blood 82: 3177–3182PubMedGoogle Scholar
  98. 98.
    Lieschke G, Grail D, Hodgson G et al (1994) Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor deficiency, and impaired neutrophil mobilization. Blood 84: 1737–1746PubMedGoogle Scholar
  99. 99.
    Leichty K, Schibler K, Ohls R et al (1993) The failure of newborn mice infected with Escherichia coli to accelerate neutrophil production correlates with their failure to increase transcripts for granulocyte colony-stimulating factor and interleukin-6. BioI Neonate 64: 331–340CrossRefGoogle Scholar
  100. 100.
    Cairo M, Plunkett J, Mauss D, van de Ven C (1990) Seven-day administration of recombinant granulocyte colony-stimulating factor to newborn rats: modulation of neonatal neutrophilia, myelopoiesis, and group B streptococcal sepsis. Blood 76: 1788–1794Google Scholar
  101. 101.
    Cairo MS, van de Ven C, Mauss D et al (1991) Modulation of neonatal rat myeloid kinetics resulting in peripheral neutrophilia by single pulse administration of Rh granulocyte-macrophage colony-stimulating factor and Rh granulocyte colony-stimulating factor. Biol Neonate 59: 13–21PubMedCrossRefGoogle Scholar
  102. 102.
    Lieschke GJ, Stanley E, Grail D et al (1994) Mice lacking both macrophage and granulocyte-macrophage colony-stimulating factor have macrophages and coexistent osteopetrosis and severe lung disease. Blood 84: 27–35PubMedGoogle Scholar
  103. 103.
    Calhoun DA, Lunoe M, Du Y et al (2000) Granulocyte colonystimulating factor serum and urine concentrations in neutropenic neonates before and after intravenous administration of recombinant granulocyte colony-stimulating factor. Pediatrics 105: 392–397PubMedCrossRefGoogle Scholar
  104. 104.
    Cadnapaphornchai M, Faix RG (1992) Increased nosocomial infection in neutropenic low birth weight (2000 grams or less) infants of hypertensive mothers. J Pediatr 121: 956–961PubMedCrossRefGoogle Scholar
  105. 105.
    La Gamma EF, Alpan O, Kocherlakota P (1995) Effects of granulocyte colony-stimulating factor on preeclampsia-associated neonatal neutropenia. J Pediatr 126: 457–459PubMedCrossRefGoogle Scholar
  106. 106.
    Makhlouf RA, Doron MW, Bose CL et al (1995) Administration of granulocyte colony-stimulating factor to neutropenic low birth weight infants of mothers with preeclampsia. J Pediatr 126: 454–456PubMedCrossRefGoogle Scholar
  107. 107.
    Carr R, Brocklehurst P, Dore CJ, Modi N (2009) Granulocytemacrophage 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 373: 226–233PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Robert D. Christensen
    • 1
  1. 1.Women and Newborns ProgramIntermountain HealthcareOgdenUSA

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