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J Pediatr Infect Dis 2017; 12(03): 184-192
DOI: 10.1055/s-0037-1603331
Original Article
Georg Thieme Verlag KG Stuttgart · New York

White Blood Cell Changes Following Treatment with a Combination of Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) and Intravenous Immunoglobulin (IVIG) in Necrotizing Enterocolitis (NEC)

Prabhakar Kocherlakota
1   Department of Pediatrics, Division of Newborn Medicine, The Regional Neonatal Intensive Care Unit, Maria Fareri Children's Hospital at Westchester Medical Center, New York Medical College, Valhalla, New York, NY, United States
,
Sri K. P. Narayana
1   Department of Pediatrics, Division of Newborn Medicine, The Regional Neonatal Intensive Care Unit, Maria Fareri Children's Hospital at Westchester Medical Center, New York Medical College, Valhalla, New York, NY, United States
,
Jonathan Blau
2   Department of Pediatrics, Staten Island University Hospital, Staten Island, New York, NY, United States
,
Edmund F. La Gamma
1   Department of Pediatrics, Division of Newborn Medicine, The Regional Neonatal Intensive Care Unit, Maria Fareri Children's Hospital at Westchester Medical Center, New York Medical College, Valhalla, New York, NY, United States
› Author Affiliations
Further Information

Publication History

08 December 2016

28 December 2016

Publication Date:
30 May 2017 (online)

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Abstract

Objective We sought to determine whether recombinant human granulocyte colony stimulating factor (rhG-CSF) and intravenous immunoglobulin (IVIG) combination can increase white blood cell (WBC) count and improve the survival of extremely low-birth-weight (ELBW) neonates having necrotizing enterocolitis (NEC) with Bell stage II or above.

Methods This retrospective chart review consisted of ELBW neonates with NEC provided with standard of care (standard group) or standard of care and a combination of rhG-CSF along with IVIG (treated group) at the discretion of the treating physician. Serial blood counts (days 0,1,2,3, and 7 to 10), survival, need for surgical intervention, time to reach full feeds, and time to discharge were compared between the two groups.

Results The treated (27 neonates) and the standard (35 neonates) groups had birth weights of 857 ± 52 g and 1,009 ± 50 g; gestational ages of 26 ± 0.5 and 28 ± 0.5 weeks; WBC counts of 7,950 ± 6,452 and 14,105 ± 9,578/mm3; absolute neutrophil count (ANC) of 3,930 ± 5,152 and 7,117 ± 7,545/mm3, respectively (p < 0.05). During the study, WBC count and ANC increased in the treated group till days 7 to 10, but decreased till day 3 in the standard group (p < 0.05). ANC (11-fold) and monocytes (4-fold) increased in the treated patients with neutropenia by days 7 to 10 (p < 0.05). There was no change in the survival, need for surgery, time to reach full feed, or time to discharge between the two groups.

Conclusion The combination of rhG-CSF and IVIG increased WBC, ANC, and monocytes in the treated group but did not affect the survival, need for surgery, time to reach full feed, or time to discharge.

Keywords

absolute neutrophil count - intravenous immunoglobulin - neutropenia - necrotizing enterocolitis - recombinant human granulocyte colony stimulating factor

Contributors' Statement

Prabhakar Kocherlakota contributed to the design, acquired data, performed the initial analysis, drafted the manuscript, and approved the final manuscript as submitted.


Sri K.P. Narayanan acquired the data, performed the initial analysis, reviewed the initial manuscript, and approved the final manuscript as submitted.


Jonathan Blau acquired the data, performed the initial analysis, reviewed initial manuscript, and approved the final manuscript as submitted.


Edmund La Gamma conceptualized and designed the study, designed the data collection instruments, drafted the initial manuscript, and approved the final manuscript as submitted.


 

  • References

  • 1 Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med 2011; 364 (03) 255-264
    CrossrefPubMedGoogle Scholar
  • 2 Gordon PV, Swanson JR. Necrotizing enterocolitis is one disease with many origins and potential means of prevention. Pathophysiology 2014; 21 (01) 13-19
    CrossrefPubMedGoogle Scholar
  • 3 Lee WH, Soraisham AS, Shah VS. , et al. Incidence and timing of presentation of necrotizing enterocolitis in preterm neonates. Pediatrics 2012; 129: e298-e304
    CrossrefPubMedGoogle Scholar
  • 4 Ahle M, Drott P, Andersson RE. Epidemiology and trends of necrotizing enterocolitis in Sweden: 1987-2009. Pediatrics 2013; 132 (02) e443-e451
    CrossrefPubMedGoogle Scholar
  • 5 Henry MC, Moss R. Necrotizing enterocolitis. In: Holcom III GW, Murphy J. , eds. Aschcraft's pediatric surgery. 5th edition. Philadelphia: Saunders; 2010: 439-455
    Google Scholar
  • 6 Patel RM, Kandefer S, Walsh MC. , et al. Causes and timing of death in extremely premature infants from 2000 through 2011. N Engl J Med 2015; 372 (04) 331-340
    CrossrefPubMedGoogle Scholar
  • 7 Blakely ML, Lally KP, McDonald S. , et al; NEC subcommittee of the NICHD Neonatal Research Network. Postoperative outcomes of extremely low birth-weight infants with necrotizing enterocolitis or isolated intestinal perforation: a prospective cohort study by the NICHD Neonatal Research Network. Ann Surg 2005; 241 (06) 984-989 , discussion 989–994
    CrossrefPubMedGoogle Scholar
  • 8 Sharma R, Hudak ML. A clinical perspective of necrotizing enterocolitis: past, present, and future. Clin Perinatol 2013; 40 (01) 27-51
    CrossrefPubMedGoogle Scholar
  • 9 Miner CA, Fullmer S, Eggett DL, Christensen RD. Factors affecting the severity of necrotizing enterocolitis. J Matern Fetal Neonatal Med 2013; 26 (17) 1715-1719
    CrossrefPubMedGoogle Scholar
  • 10 Maheshwari A. Immunologic and hematological abnormalities in necrotizing enterocolitis. Clin Perinatol 2015; 42 (03) 567-585
    CrossrefPubMedGoogle Scholar
  • 11 Dominguez KM, Moss RL. Necrotizing enterocolitis. Clin Perinatol 2012; 39 (02) 387-401
    CrossrefPubMedGoogle Scholar
  • 12 La Gamma EF, Alpan O, Kocherlakota P. Effect of granulocyte colony-stimulating factor on preeclampsia-associated neonatal neutropenia. J Pediatr 1995; 126 (03) 457-459
    CrossrefPubMedGoogle Scholar
  • 13 Kocherlakota P, La Gamma EF, Breen C. , et al. Effects of rhG-CSF on neutrophil Fcy and complement receptors in ventilated very low birth weight human neonates in neonatal hematology and immunology III. In: Bellanti JA, Bracci R, Prindull G, Xanthou M. , eds. Elsevier Science B.V; 1997: 39-48
    Google Scholar
  • 14 Kocherlakota P, Vakkalanka R, Crow MK. , et al. Effect of human granulocyte colony stimulating factor (rhG-CSF) on cytokines in VLBW neonates. Pediatr Res 1998; 44: A1044
    PubMedGoogle Scholar
  • 15 Ahmad M, Fleit HB, Golightly MG, La Gamma EF. In vivo effect of recombinant human granulocyte colony-stimulating factor on phagocytic function and oxidative burst activity in septic neutropenic neonates. Biol Neonate 2004; 86 (01) 48-54
    CrossrefPubMedGoogle Scholar
  • 16 Bell MJ, Ternberg JL, Feigin RD. , et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187 (01) 1-7
    CrossrefPubMedGoogle Scholar
  • 17 Mouzinho A, Rosenfeld CR, Sánchez PJ, Risser R. Revised reference ranges for circulating neutrophils in very-low-birth-weight neonates. Pediatrics 1994; 94 (01) 76-82
    PubMedGoogle Scholar
  • 18 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163 (07) 1723-1729
    CrossrefPubMedGoogle Scholar
  • 19 Hamrick SE, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics 2010; 125 (05) 1020-1030
    CrossrefPubMedGoogle Scholar
  • 20 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92 (04) 529-534
    CrossrefPubMedGoogle Scholar
  • 21 Fierson WM. ; American Academy of Pediatrics Section on Ophthalmology; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus; American Association of Certified Orthoptists. Screening examination of premature infants for retinopathy of prematurity. Pediatrics 2013; 131 (01) 189-195
    CrossrefPubMedGoogle Scholar
  • 22 Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics 2010; 125 (02) e214-e224
    Google Scholar
  • 23 Gibbs RS, Duff P. Progress in pathogenesis and management of clinical intraamniotic infection. Am J Obstet Gynecol 1991; 164 (5 Pt 1): 1317-1326
    CrossrefPubMedGoogle Scholar
  • 24 Boyer KM, Gadzala CA, Burd LI, Fisher DE, Paton JB, Gotoff SP. Selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease. I. Epidemiologic rationale. J Infect Dis 1983; 148 (05) 795-801
    CrossrefPubMedGoogle Scholar
  • 25 Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood 1991; 78 (11) 2791-2808
    CrossrefPubMedGoogle Scholar
  • 26 Kocherlakota P, La Gamma EF. Preliminary report: rhG-CSF may reduce the incidence of neonatal sepsis in prolonged preeclampsia-associated neutropenia. Pediatrics 1998; 102 (05) 1107-1111
    CrossrefPubMedGoogle Scholar
  • 27 Kocherlakota P, La Gamma EF. Human granulocyte colony-stimulating factor may improve outcome attributable to neonatal sepsis complicated by neutropenia. Pediatrics 1997; 100 (01) E6
    PubMedGoogle Scholar
  • 28 Carr R, Modi N, Doré C. G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Syst Rev 2003; 3 (03) CD003066
    PubMedGoogle Scholar
  • 29 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 (03) F172-F176
    CrossrefPubMedGoogle Scholar
  • 30 Nayeri F, Soheili H, Kaveh M, Oloomi Yazdi Z, Shariat M, Dalili H. Comparison of two regimens of RhG-CSF in neutropenic neonatal septicemia: a randomized clinical trial. Acta Med Iran 2011; 49 (09) 575-578
    PubMedGoogle Scholar
  • 31 Ohlsson A, Lacy J. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev 2010; 3 (03) CD001239
    PubMedGoogle Scholar
  • 32 Bialek R, Bartmann P. Is there an effect of immunoglobulins and G-CSF on neutrophil phagocytic activity in preterm infants?. Infection 1998; 26 (06) 375-378
    CrossrefPubMedGoogle Scholar
  • 33 Ragazzi S, Pierro A, Peters M, Fasoli L, Eaton S. Early full blood count and severity of disease in neonates with necrotizing enterocolitis. Pediatr Surg Int 2003; 19 (05) 376-379
    CrossrefPubMedGoogle Scholar
  • 34 Canpolat FE, Yurdakök M, Korkmaz A, Yiğit S, Tekinalp G. Enteral granulocyte colony-stimulating factor for the treatment of mild (stage I) necrotizing enterocolitis: a placebo-controlled pilot study. J Pediatr Surg 2006; 41 (06) 1134-1138
    CrossrefPubMedGoogle Scholar
  • 35 Calhoun DA, Maheshwari A, Christensen RD. Recombinant granulocyte colony-stimulating factor administered enterally to neonates is not absorbed. Pediatrics 2003; 112 (02) 421-423
    CrossrefPubMedGoogle Scholar
  • 36 Simmonds A, LaGamma EF. Toward improving mucosal barrier defenses: rhG-CSF plus IgG antibody. Indian J Pediatr 2006; 73 (11) 1019-1026
    CrossrefPubMedGoogle Scholar
  • 37 Clark RH, Gordon P, Walker WM, Laughon M, Smith PB, Spitzer AR. Characteristics of patients who die of necrotizing enterocolitis. J Perinatol 2012; 32 (03) 199-204
    CrossrefPubMedGoogle Scholar
  • 38 Stey A, Barnert ES, Tseng CH. , et al. Outcomes and costs of surgical treatments of necrotizing enterocolitis. Pediatrics 2015; 135 (05) e1190-e1197
    CrossrefPubMedGoogle Scholar
  • 39 Kelleher J, Mallick H, Soltau TD, Harmon CM, Dimmitt RA. Mortality and intestinal failure in surgical necrotizing enterocolitis. J Pediatr Surg 2013; 48 (03) 568-572
    CrossrefPubMedGoogle Scholar
  • 40 Ballow M, Cates KL, Rowe JC, Goetz C, Desbonnet C. Development of the immune system in very low birth weight (less than 1500 g) premature infants: concentrations of plasma immunoglobulins and patterns of infections. Pediatr Res 1986; 20 (09) 899-904
    CrossrefPubMedGoogle Scholar