Archives of Pediatric Infectious Diseases

Published by: Kowsar

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

Reza Saeidi 1 , Hossein Akhavan 1 , Jalil Tavakkolafshari 2 and Abbas Shapouri-Moghaddam 3 , *
Authors Information
1 Neonatal Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2 Immunology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3 Department of Immunology, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Article information
  • Archives of Pediatric Infectious Diseases: January 31, 2019, 7 (1); e67807
  • Published Online: January 27, 2019
  • Article Type: Research Article
  • Received: February 22, 2018
  • Revised: August 14, 2018
  • Accepted: October 26, 2018
  • DOI: 10.5812/pedinfect.67807

To Cite: Saeidi R, Akhavan H, Tavakkolafshari J , Shapouri-Moghaddam A. Clinical and Biochemical Effects of Recombinant Human Granulocyte Colony-Stimulating Factor on the Prognosis of Preterm Infants with Early Onset Neonatal Sepsis, Arch Pediatr Infect Dis. 2019 ; 7(1):e67807. doi: 10.5812/pedinfect.67807.

Copyright © 2019, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Methods
3. Results
4. Discussion
  • 1. Ng PC. Diagnostic markers of infection in neonates. Arch Dis Child Fetal Neonatal Ed. 2004;89(3):F229-35. doi: 10.1136/adc.2002.023838. [PubMed: 15102726]. [PubMed Central: PMC1721679].
  • 2. Bryce J, Boschi-Pinto C, Shibuya K, Black RE; W H O Child Health Epidemiology Reference Group. WHO estimates of the causes of death in children. Lancet. 2005;365(9465):1147-52. doi: 10.1016/S0140-6736(05)71877-8. [PubMed: 15794969].
  • 3. Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, et al. Global, regional, and national causes of child mortality: An updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012;379(9832):2151-61. doi: 10.1016/S0140-6736(12)60560-1. [PubMed: 22579125].
  • 4. Gebremedhin D, Berhe H, Gebrekirstos K. Risk factors for neonatal sepsis in public hospitals of Mekelle city, north Ethiopia, 2015: Unmatched case control study. PLoS One. 2016;11(5). e0154798. doi: 10.1371/journal.pone.0154798. [PubMed: 27163290]. [PubMed Central: PMC4862626].
  • 5. Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases. Prevention of perinatal group B streptococcal disease: Revised guidelines from CDC, 2010. Recommendations and reports. 2010. Report No.: RR10. 31 p.
  • 6. Jefferies AL. Management of term infants at increased risk for early-onset bacterial sepsis. Paediatr Child Health. 2017;22(4):223-8. doi: 10.1093/pch/pxx023. [PubMed: 29480905]. [PubMed Central: PMC5804707].
  • 7. Hornik CP, Fort P, Clark RH, Watt K, Benjamin DK, Smith PB, 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:S69-74. doi: 10.1016/s0378-3782(12)70019-1. [PubMed: 22633519]. [PubMed Central: PMC3513766].
  • 8. Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014;27(1):21-47. doi: 10.1128/CMR.00031-13. [PubMed: 24396135]. [PubMed Central: PMC3910904].
  • 9. Amponsah SK, Adjei GO, Sulley AM, Woode J, Lindholm JA, Enweronu-Laryea C. Diagnostic utility of procalcitonin versus C-reactive protein as markers for early-onset neonatal sepsis at Korle-Bu Teaching Hospital. Pan Africa Med J. 2017;27. doi: 10.11604/pamj.2017.27.142.12209.
  • 10. Maternal-Infant Care Research Center. The Canadian neonatal network. Toronto, Ontario; 2013.
  • 11. Weston EJ, Pondo T, Lewis MM, Martell-Cleary P, Morin C, Jewell B, et al. The burden of invasive early-onset neonatal sepsis in the United States, 2005-2008. Pediatr Infect Dis J. 2011;30(11):937-41. doi: 10.1097/INF.0b013e318223bad2. [PubMed: 21654548]. [PubMed Central: PMC3193564].
  • 12. Stoll BJ. Early-onset neonatal sepsis: A continuing problem in need of novel prevention strategies. Pediatrics. 2016;138(6). doi: 10.1542/peds.2016-3038. [PubMed: 27940736].
  • 13. Money D, Allen VM, Yudin MH, Allen VM, Bouchard C, Boucher M, et al. The prevention of early-onset neonatal group B streptococcal disease. J Obstetrics Gyn Can. 2013;35(10):939-48. doi: 10.1016/s1701-2163(15)30818-5.
  • 14. Lim WH, Lien R, Huang YC, Chiang MC, Fu RH, Chu SM, et al. Prevalence and pathogen distribution of neonatal sepsis among very-low-birth-weight infants. Pediatr Neonatol. 2012;53(4):228-34. doi: 10.1016/j.pedneo.2012.06.003. [PubMed: 22964280].
  • 15. Hengst JM. The role of C-reactive protein in the evaluation and management of infants with suspected sepsis. Adv Neonatal Care. 2003;3(1):3-13. [PubMed: 12882177].
  • 16. Ali AM, Moaz MA, Ghoniem E, Abd El Motaleb T, Sheri N. Reliability of serum procalcitonin concentrations for the diagnosis of sepsis in neonates. Egypt J Immunol. 2008;15(1):75-84. [PubMed: 20306671].
  • 17. Nuntnarumit P, Pinkaew O, Kitiwanwanich S. Predictive values of serial C-reactive protein in neonatal sepsis. J Med Assoc Thai. 2002;85 Suppl 4:S1151-8. [PubMed: 12549789].
  • 18. Benitz WE, Han MY, Madan A, Ramachandra P. Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics. 1998;102(4). E41. doi: 10.1542/peds.102.4.e41. [PubMed: 9755278].
  • 19. Jankovic B, Pasic S, Markovic M, Veljkovic D, Milicic M. [C-reactive protein concentrations during initial (empiric) treatment of neonatal sepsis]. Srp Arh Celok Lek. 2001;129 Suppl 1:17-22. Serbian. [PubMed: 15637985].
  • 20. Pulliam PN, Attia MW, Cronan KM. C-reactive protein in febrile children 1 to 36 months of age with clinically undetectable serious bacterial infection. Pediatrics. 2001;108(6):1275-9. doi: 10.1542/peds.108.6.1275. [PubMed: 11731648].
  • 21. Ng PC, Cheng SH, Chui KM, Fok TF, Wong MY, Wong W, et al. Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 1997;77(3):F221-7. doi: 10.1136/fn.77.3.F221. [PubMed: 9462194]. [PubMed Central: PMC1720722].
  • 22. Mishra UK, Jacobs SE, Doyle LW, Garland SM. Newer approaches to the diagnosis of early onset neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2006;91(3):F208-12. doi: 10.1136/adc.2004.064188. [PubMed: 16632649]. [PubMed Central: PMC2672708].
  • 23. Ng PC, Lam HS. Diagnostic markers for neonatal sepsis. Curr Opin Pediatr. 2006;18(2):125-31. doi: 10.1097/01.mop.0000193293.87022.4c. [PubMed: 16601490].
  • 24. Horisberger T, Harbarth S, Nadal D, Baenziger O, Fischer JE. G-CSF and IL-8 for early diagnosis of sepsis in neonates and critically ill children - safety and cost effectiveness of a new laboratory prediction model: Study protocol of a randomized controlled trial [ISRCTN91123847]. Crit Care. 2004;8(6):R443-50. doi: 10.1186/cc2971. [PubMed: 15566590]. [PubMed Central: PMC1065067].
  • 25. Hopkins SJ, McMahon CJ, Singh N, Galea J, Hoadley M, Scarth S, et al. Cerebrospinal fluid and plasma cytokines after subarachnoid haemorrhage: CSF interleukin-6 may be an early marker of infection. J Neuroinflammation. 2012;9:255. doi: 10.1186/1742-2094-9-255. [PubMed: 23176037]. [PubMed Central: PMC3526412].
  • 26. 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. doi: 10.1186/1742-2094-9-255. [PubMed: 9200380].
  • 27. Kucukoduk 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):893-7. doi: 10.1080/0036554021000026966. [PubMed: 12587621].
  • 28. Miura E, Procianoy RS, Bittar C, Miura CS, Miura MS, Mello 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):30-5. doi: 10.1542/peds.107.1.30. [PubMed: 11134430].
  • 29. 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):1061-5. doi: 10.1097/01.inf.0000036091.75362.b9. [PubMed: 12442030].
  • 30. Chaudhuri J, Mitra S, Mukhopadhyay D, Chakraborty S, Chatterjee S. Granulocyte colony-stimulating factor for preterms with sepsis and neutropenia: A randomized controlled trial. J Clin Neonatol. 2012;1(4):202-6. doi: 10.4103/2249-4847.105993. [PubMed: 24027727]. [PubMed Central: PMC3762052].
  • 31. Hollingshead LM, Goa KL. Recombinant granulocyte colony-stimulating factor (rG-CSF). A review of its pharmacological properties and prospective role in neutropenic conditions. Drugs. 1991;42(2):300-30. doi: 10.2165/00003495-199142020-00009. [PubMed: 1717226].
  • 32. Lee JA, Sauer B, Tuminski W, Cheong J, Fitz-Henley J2, Mayers M, et al. Effectiveness of granulocyte colony-stimulating factor in hospitalized infants with neutropenia. Am J Perinatol. 2017;34(5):458-64. doi: 10.1055/s-0036-1593349. [PubMed: 27649291]. [PubMed Central: PMC5359073].
  • 33. Schrag SJ, Farley MM, Petit S, Reingold A, Weston EJ, Pondo T, et al. Epidemiology of invasive early-onset neonatal sepsis, 2005 to 2014. Pediatrics. 2016;138(6). doi: 10.1542/peds.2016-2013. [PubMed: 27940705].
  • 34. Zea-Vera A, Ochoa TJ. Challenges in the diagnosis and management of neonatal sepsis. J Trop Pediatr. 2015;61(1):1-13. doi: 10.1093/tropej/fmu079. [PubMed: 25604489]. [PubMed Central: PMC4375388].
  • 35. Willfort A, Lorber C, Kapiotis S, Sertl S, Hainz R, Kirchweger P, et al. Treatment of drug-induced agranulocytosis with recombinant granulocyte colony-stimulating factor (rh G-CSF). Ann Hematol. 1993;66(5):241-4. doi: 10.1007/BF01738472. [PubMed: 7685193].
  • 36. Newgard CD, Fleischman R, Choo E, Ma OJ, Hedges JR, McConnell KJ. Validation of length of hospital stay as a surrogate measure for injury severity and resource use among injury survivors. Acad Emerg Med. 2010;17(2):142-50. doi: 10.1111/j.1553-2712.2009.00647.x. [PubMed: 20370743]. [PubMed Central: PMC4715859].
  • 37. WHO. Perinatal mortality: A listing of available information. Geneva: WHO, Family and Reproductive Health; 1996.
  • 38. Aktas D, Demirel B, Gursoy T, Ovali 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):171-5. doi: 10.1016/j.pedneo.2014.06.007. [PubMed: 25458637].
  • 39. Borjianyazdi L, Froomandi M, Noori Shadkam M, Hashemi A, Fallah R. The effect of granulocyte colony stimulating factor administration on preterm infant with neutropenia and clinical sepsis: A randomized clinical trial. Iran J Ped Hematol Oncol. 2013;3(2):64-8. [PubMed: 24575272]. [PubMed Central: PMC3915446].
  • 40. Teng RJ, Wu TJ, Sharma R, Garrison RD, Hudak ML. Efficacy of recombinant human granulocyte colony stimulating factor in very-low-birth-weight infants with early neutropenia. J Formos Med Assoc. 2015;114(2):174-9. doi: 10.1016/j.jfma.2012.10.009. [PubMed: 25678180].
  • 41. Gathwala G, Walia M, Bala H, Singh S. Recombinant human granulocyte colony-stimulating factor in preterm neonates with sepsis and relative neutropenia: A randomized, single-blind, non-placebo-controlled trial. J Trop Pediatr. 2012;58(1):12-8. doi: 10.1093/tropej/fmr012. [PubMed: 21296862].
  • 42. Bedford Russell AR, Emmerson AJ, Wilkinson N, Chant T, Sweet DG, Halliday HL, 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):F172-6. doi: 10.1136/fn.84.3.F172. [PubMed: 11320043]. [PubMed Central: PMC1721238].
  • 43. 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. doi: 10.1542/peds.102.1.6. [PubMed: 9651406].
  • 44. Carr R, Modi N, Doré CJ. G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Sys Rev. 2003;(3).
  • 45. Mathias B, Szpila BE, Moore FA, Efron PA, Moldawer LL. A review of GM-CSF therapy in sepsis. Medicine (Baltimore). 2015;94(50). e2044. doi: 10.1097/MD.0000000000002044. [PubMed: 26683913]. [PubMed Central: PMC5058885].
  • 46. Gille C, Steffen F, Lauber K, Keppeler H, Leiber A, Spring B, et al. Clearance of apoptotic neutrophils is diminished in cord blood monocytes and does not lead to reduced IL-8 production. Pediatr Res. 2009;66(5):507-12. doi: 10.1203/PDR.0b013e3181b9b470. [PubMed: 19668110].
  • 47. Christensen RD, Rothstein G. Exhaustion of mature marrow neutrophils in neonates with sepsis. J Pediatr. 1980;96(2):316-8. doi: 10.1016/S0022-3476(80)80837-7. [PubMed: 6985958].
  • 48. Melvan JN, Bagby GJ, Welsh DA, Nelson S, Zhang P. Neonatal sepsis and neutrophil insufficiencies. Int Rev Immunol. 2010;29(3):315-48. doi: 10.3109/08830181003792803. [PubMed: 20521927]. [PubMed Central: PMC3103186].
  • 49. Bo L, Wang F, Zhu J, Li J, Deng X. Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) for sepsis: A meta-analysis. Crit Care. 2011;15(1):R58. doi: 10.1186/cc10031. [PubMed: 21310070]. [PubMed Central: PMC3221991].
  • 50. Castagnola E, Dufour C. Role of G-CSF GM-CSF in the management of infections in preterm newborns: An update. Early Hum Dev. 2014;90 Suppl 2:S15-7. doi: 10.1016/S0378-3782(14)50005-9. [PubMed: 25220119].
  • 51. Kale A, Bonde V. Neonatal sepsis: An update. Iran J Neonatology IJN. 2014;4(4):39-51.
  • 52. Schuller SS, Kramer BW, Villamor E, Spittler A, Berger A, Levy O. Immunomodulation to prevent or treat neonatal sepsis: Past, present, and future. Front Pediatr. 2018;6:199. doi: 10.3389/fped.2018.00199. [PubMed: 30073156]. [PubMed Central: PMC6060673].
  • 53. Molloy EJ, O'Neill AJ, Grantham JJ, Sheridan-Pereira M, Fitzpatrick JM, Webb DW, et al. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have differential effects on neonatal and adult neutrophil survival and function. Pediatr Res. 2005;57(6):806-12. doi: 10.1203/01.PDR.0000156500.13600.B5. [PubMed: 15718363].

Featured Image:

Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments