Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 144 No. 1314 (2014)

Prognostic value of nucleated red blood cells in critically ill children

  • Caroline Schaer
  • Markus Schmugge
  • Bernhard Frey
Cite this as:
Swiss Med Wkly. 2014;144:w13944


QUESTION: Is there an association between the presence of nucleated red blood cells (NRBCs) in the peripheral blood and outcomes in critically ill children?

METHODS: Prospective observational study conducted in 2008 (January to December) in a multidisciplinary paediatric intensive care unit (PICU) of a tertiary children’s hospital. We provide univariate analysis, stratified by age group (neonates and children >28 days of age), and multiple logistic regression, comparing clinically important outcomes (death, ventilation, renal replacement therapy, inotropic support) with haematological (NRBC, haemoglobin, platelets, leucocytes), illness severity (expected mortality [paediatric index of mortality, PIM2]), demographic (age, sex) and diagnostic parameters and length of stay. Haematological parameters correspond to the first 24 hours of PICU admission.

RESULTS: Out of 670 patients, 195 (29.1%) were NRBC positive and 475 (70.9%) were NRBC negative. In the neonatal age group (n = 232), patients who died, were ventilated or received inotropic support had significantly more NRBCs than patients without these conditions (p = 0.032, 0.038 and 0.029, respectively). In the child age group (n = 438), only renal replacement therapy was significantly associated with NRBC (p <0.001). High PIM score (p <0.001) and longer length of stay (p <0.001) were independently associated with bad outcomes (composite endpoint: mortality and/or ventilation and/or renal replacement therapy and/or inotropic support); NRBC positivity was not an independent predictor of bad outcome (odds ratio 1.44, 95% confidence interval 0.62‒3.41).

CONCLUSIONS: NRBCs are not an independent risk factor for bad outcomes in paediatric intensive care. However, NRBCs may have some prognostic value in the first month of life. In children >1 month of age, the association between NRBC and outcome is much less pronounced.

Trial registration number: StV-01/08


  1. Orkin SH, Nathan DG, Ginsburg D, Look AT, Fisher DE, Lux SE. Nathan and Oski’s Hematology of infancy and childhood. 7th ed. Philadelphia: 2009; p. 1838 and 1840.
  2. Christensen RD, Henry E, Andres RL, Bennett ST. Reference ranges for blood concentrations of nucleated red blood cells in neonates. Neonatology. 2011;99:289–94.
  3. Green DW, Mimouni F. Nucleated erythrocytes in healthy infants and in infants of diabetic mothers. J Pediatr. 1990;116:129–31.
  4. Phelan JP, Ahn MO, Korst LM, Marti GI. Nucleated red blood cells: a marker of fetal asphyxia? Am J Obstet Gynecol. 1995;173:1380–4.
  5. Soothill PW, Nicolaides KH, Campbell S. Prenatal asphyxia, hyperlacticaemia, hypoglycaemia and erythroblastosis in growth retarded fetuses. BMJ. 1987;294:1051–3.
  6. Stachon A, Segbers E, Holland-Letz T, Kempf R, Hering S, Krieg M. NRBC in the blood of medical intensive care patients indicate increased risk: a prospective cohort study. Critical Care. 2007;11:R62.
  7. Stachon A, Sondermann N, Imohl M, Krieg M. Nucleated red blood cells indicate high risk of in-hospital mortality. J Lab Clin Med. 2002;140:407–12.
  8. Frey B, Duke T, Horton SB. Nucleated red blood cells after cardiopulmonary bypass in infants and children: is there a relationship to the systemic inflammatory response syndrome? Perfusion. 1999;14:173–80.
  9. Stachon A, Böning A, Krismann M, Weisser H, Lacskovics A, Skipka G, Krieg M. Prognostic significance of the presence of erythroblasts in blood after cardiothoracic surgery. Clin Chem Lab Med. 2001;39:239–43.
  10. Frey B, Horisberger T. Release of nucleated red blood cells early after cardiorespiratory arrest. J Pediatr Hematol Oncol. 2003;25:180–1.
  11. Hermansen MC. Nucleated red blood cells in the fetus and newborn. Arch Dis Child. Feta. Neonata. Ed. 2001;84:F211–15.
  12. Slater A, Shann F, McEniery J. The ANZPIC registry diagnostic codes: a system for coding reasons for admitting children to intensive care. Intensive Care Med. 2003;29:271–7.
  13. Slater A, Shann F, Pearson G. PIM2: a revised version of the paediatric index of mortality. Intensive Care Med. 2003;29:278–85.
  14. Leisch F. Sweave: dynamic generation of statistical reports using literate data analysis. Compstat – Proceedings in Computational Statistics. Heidelberg: 2002;p:575–80.
  15. Krafte-Jacobs B, Bock GH. Circulating erythropoietin and interleukin-6 concentrations increase in critically ill children with sepsis and septic shock. Crit Care Med. 1996;24:1455–9.
  16. Ferber A, Fridel Z, Weissmann-Brenner A, Minior VK, Divon MY. Are elevated fetal nucleated red blood cell counts an indirect reflection of enhanced erythropoietin activity? Am J Obstet Gynecol. 2004;190:1473–5.
  17. Frey B. Transfusion in premature infants impairs production and/or release of red blood cells, white blood cells and platelets. J Paediatr Child Health. 2002;38:265–7.
  18. Fisher JW. Erythropoietin: pharmacology, biogenesis and control of production. Pharmacol Rev. 1972;24:459–508.
  19. Gross DM, Fisher JW. Effects of terbutaline, a synthetic beta adrenoceptor agonist, on in vivo erythropoietin production. Arch Int Pharmacodyn Ther. 1978;236:192–201.
  20. Shah R, Reddy S, Horst M, Stassinopoulos J, Jordan J, Rubinfeld I. Getting back to zero with nucleated red blood cells: following trends is not necessarily a bad thing. The American Journal of Surgery. 2012;203:343–46.