Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Late-onset neutropenia: defining limits of neutrophil count in very low birth weight infants

Journal of Perinatology volume 34, pages 22–26 (2014)Cite this article

Subjects

Abstract

Objective:

To evaluate the incidence, onset, duration, characteristics and importance of late-onset neutropenia (defined as absolute neutrophil count<1500 μl−1 at 3 weeks of age or later) in a group of very low birth weight (VLBW) infants.

Study design:

Routine complete blood cell counts (CBCs) obtained from VLBW infants over a period of 7 years were gathered retrospectively, including those of newborns with weekly CBCs taken over a duration of at least 3 weeks. Data were obtained from between January 2003 and December 2009.

Result:

CBCs of 399 newborns were included. Values were obtained from birth to 36 weeks of postnatal age. Late-onset neutropenia was observed in 259 cases (65%). Neutropenic infants had a mean of 0.5 weeks lower gestational age. Late-onset neutropenia was more frequent in children with intraventricular hemorrhage but not in patients who received erythropoietin. The median age of neutropenia onset was 7 weeks in extremely low birth weight infants and 6 weeks in VLBW infants. The fifth percentile of neutrophils between weeks 3 and 4 was 1280 μl−1 and between weeks 13 and 15 was 500 μl−1. The average duration was 2 weeks with normalized values after 18 weeks.

Conclusion:

A neutrophil count <1500 μl−1 after the third week of life is frequently observed in VLBW infants and should not be used as a lower reference limit. The fifth percentile varies according to postnatal age from around 1300 μl−1 in week 4 of life, decreasing to a nadir of 500 μl−1 between 3 and 4 months of age. Values normalize in the first year of life.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Omar SA, Salhadar A, Wooliever DE, Alsgaard PK . Late-onset neutropenia in very low birth weight infants. Pediatrics 2000; 106: 55–72.

    Article  Google Scholar 

  2. Mouzhino A . Revised reference ranges for circulating neutrophils in very low birth weight neonates. Pediatrics 1994; 94: 76–82.

    Google Scholar 

  3. Coulombel L, Denhan M, Tchernia G . The number of polymorphonuclear leukocytes in relation to gestational age in the newborn. Acta Paediatr Scand 1979; 68: 709–711.

    Article  CAS  Google Scholar 

  4. Lloyd BW, Oto A . Normal values for mature and immature neutrophils in very preterm babies. Arch Dis Child 1982; 57: 233–235.

    Article  CAS  Google Scholar 

  5. Nash PL, Kwon IG . CBC and differential in VLBW infants. Neonatal Netw 1998; 17: 17–21.

    CAS  PubMed  Google Scholar 

  6. Christensen RD . Expected hematologic values for term and preterm neonates In: Christensen RD (eds). Hematologic Problems of the Neonate. WB Saunders Co: Philadelphia, PA, 2000 pp 117–136.

    Google Scholar 

  7. 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: 682–687.

    Article  CAS  Google Scholar 

  8. Obladen M, Diepold K, Maier R . Venous and arterial hematologic profiles of very low birth weight Infants. European Multicenter rhEPO Study Group. Pediatrics 2000; 106: 707–711.

    Article  CAS  Google Scholar 

  9. Christensen RD, Henry E, Jopling J, Wiedmeier SE . The CBC: reference ranges for neonates. Semin Perinatol 2009; 33: 3–11.

    Article  Google Scholar 

  10. Schibler K . Leukocyte development and disorders during the neonatal period In: Christensen RD (eds.) Hematologic Problems of the Neonate. WB Saunders Co: Philadelphia, PA, 2000 pp 311–342.

    Google Scholar 

  11. Gillan ER, Christensen R, 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: 1427–1433.

    CAS  PubMed  Google Scholar 

  12. Mouzhino A, Rosenfeld CR, Sanchez PJ, Risser R . Effect of maternal hypertension on neonatal neutropenia and risk of nosocomial infection. Pediatrics 1992; 90: 430–435.

    Google Scholar 

  13. Russel ARB, Davies EG, Ball SE, Gordon-Smith E . Granulocyte colony-stimulating factor treatment for neonatal neutropenia. Arch Dis Child 1995; 72: 53–54.

    Article  Google Scholar 

  14. Bilgin K, Yaramis A, Haspolat K, Tas A, Günbey S, Derman O . A randomized trial of granulocyte-macrophage colony-stimulating factor in neonates with sepsis and neutropenia. Pediatrics 2001; 107: 36–41.

    Article  CAS  Google Scholar 

  15. Funke A, Berner R, Traichel B, Schmeisse D, Jecabs U, Niemeyer CM et al. Frequency, natural course, and outcome of neonatal neutropenia. Pediatrics 2000; 106: 46–51.

    Article  Google Scholar 

  16. 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: a single-blind, multicenter randomized controlled trial. Lancet 2009; 17: 188–190.

    Google Scholar 

  17. Chirico G, Motta M, Villani P, Couzza A . Late-onset neutropenia in very low birth weight infants. Acta Paediatr Suppl 2002; 91: 104–108.

    Article  CAS  Google Scholar 

  18. Halperin DS, Wacker P, Lacount G . Effects of recombinant human erythropoietin in infants with anemia of prematurity. J Pediatr 1990; 116: 779–786.

    Article  CAS  Google Scholar 

  19. Christensen RD . Hematopoiesis in the fetus and neonate. Pediatr Res 1989; 26: 531–535.

    Article  CAS  Google Scholar 

  20. Van Zant G, Goldwasser E . Simultaneous effects of erythropoietin and colony-stimulating factors on bone marrow cells. Science 1977; 198: 733–735.

    Article  CAS  Google Scholar 

  21. Christensen RD, Liechty KW, Koenig JM, Schibler KR, Ohls RK . Administration of erythropoietin to newborn rats results in diminished neutrophil production. Blood 1991; 78: 1241–1246.

    CAS  PubMed  Google Scholar 

  22. Aher SM, Ohlsson A . Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2006; 3: CD004865.

    Google Scholar 

  23. Christensen RD, Rothstein G . Erythropoietin affects the maturation pattern of fetal G-CSF-responsive progenitors. Am J Hematol 1992; 39: 108–112.

    Article  CAS  Google Scholar 

  24. Latini G, Rosati E . Transient neutropenia may be a risk of treating preterm neonates with high doses of recombinant erythropoietin. Eur J Pediatr 1998; 157: 443–444.

    Article  CAS  Google Scholar 

  25. Donato H, Bacciedoni V, Garcia C, Schvartzman G, Vain N . Recombinant erythropoietin as treatment for hyporegenerative anemia following hemolytic disease of the newborn. Arch Argent Pediatr 2009; 107: 119–125.

    PubMed  Google Scholar 

  26. Mizuno S, Sasaki J, Suzuki C, Kono H, Kojima S . Effect of recombinant human erythropoietin administration on peripheral blood neutrophil count of premature infants. J Pediatr 1994; 124: 467–470.

    Article  CAS  Google Scholar 

  27. Maier RF, Obladen M, Scigalla P et al. The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth weight infants. N Engl J Med 1994; 330: 1173–1178.

    Article  CAS  Google Scholar 

  28. Gessler P, Luders R, Konig S, Haas N, Lasch P, Kachel W . Neonatal neutropenia in low birth weight premature infants. Am J Perinatal 1995; 12: 34–38.

    Article  CAS  Google Scholar 

  29. Palta M, Sadek-Badawi M, Carlton DP . Association of BPD and IVH with early neutrophil and white counts in VLBW neonates with gestational age &lt;32 weeks. J Perinatol 2008; 28: 604–610.

    Article  CAS  Google Scholar 

  30. Manroe BL, Weinberg AG, Rosenfeld CR, Browne R . The neonatal blood count in health and disease. Reference values for neutrophilic cells. J Pediatr 1979; 95: 89–98.

    Article  CAS  Google Scholar 

  31. Schmutz N, Henry E, Jopling J, Christensen RD . Expected ranges for blood neutrophil concentrations in neonates: the Manroe and Mouzhino charts revisited. J Perinatol 2008; 28: 275–281.

    Article  CAS  Google Scholar 

  32. Sarkar S, Bhagat I, Hieber S, Donn SM . Can neutrophil response in very low birth weight infants predict the organism responsible for late-onset bacterial or fungal sepsis? J Perinatol 2006; 26: 501–505.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Gerard Laracy for his editorial assistance in the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, Hospital Universitari Son Espases, Palma de Mallorca, Spain

    S Vetter-Laracy & P-R Balliu

  2. Division of Hematology-Oncology, Department of Pediatrics, Hospital Universitari Son Espases, Palma de Mallorca,, Spain

    J A Salinas

  3. Department of Hematology, Hospital Universitari Son Espases, Palma de Mallorca, Spain

    M A Duran

Authors
  1. S Vetter-Laracy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P-R Balliu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J A Salinas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M A Duran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Vetter-Laracy.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vetter-Laracy, S., Balliu, PR., Salinas, J. et al. Late-onset neutropenia: defining limits of neutrophil count in very low birth weight infants. J Perinatol 34, 22–26 (2014). https://doi.org/10.1038/jp.2013.111

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2013.111

Keywords

This article is cited by

Search

Advanced search

Quick links