Presence of Nucleated Red Blood Cells

  • Marta C. CohenEmail author
  • Theonia K. Boyd


Nucleated red blood cells (nRBCs) originate in blood islands of the yolk sac at 16–20 days of gestation. Within the extraembryonic (placental) compartment, nRBCs begin to populate villous capillaries of the developing embryo at ∼6 weeks postconception and remain prevalent until the end of the first trimester. Thereafter, their presence decreases so that at term, under normal circumstances of delivery, nRBCs are inapparent upon cursory examination in the placental fetal vasculature. Readily identifiable nRBCs are present on placental examination at term in a number of clinical circumstances and in conjunction with a variety of placental processes. Highlights are considered below.


Nucleated red blood cells Normoblasts Erythroblasts Normoblastemia Erythroblastosis 


  1. 1.
    Tavian M, Peault B. Embryonic development of the human hematopoietic system. Int J Dev Biol. 2005;49:243–50.CrossRefGoogle Scholar
  2. 2.
    McGrath KE, Koniski AD, Malik J, et al. Circulation is established in a stepwise pattern in the mammalian embryo. Blood. 2003;101:1669–76.CrossRefGoogle Scholar
  3. 3.
    Choi K, Kennedy M, Kazarov A, et al. A common precursor for hematopoietic and endothelial cells. Development. 1998;125:725–32.PubMedGoogle Scholar
  4. 4.
    Dzierzak E, Philipsen S. Erythropoiesis: Development and Differentiation. Cold Spring Harb Perspect Med. 2013;3:a011601.CrossRefGoogle Scholar
  5. 5.
    Hermansen MC. Nucleated red blood cells in the fetus and Newborn. Arch Dis Child Fetal Neonatal Ed. 2001;84:F211–5.CrossRefGoogle Scholar
  6. 6.
    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.CrossRefGoogle Scholar
  7. 7.
    Rolfo A, Maconi M, Cardaropoli S, et al. Nucleated red blood cells in term fetuses: reference values using an automated analyzer. Neonatology. 2007;92:205–8.CrossRefGoogle Scholar
  8. 8.
    Hanlon-Lundberg KM, Kirby RS, Gandhi S, et al. Nucleated red blood cells in cord blood of singleton term neonates. Am J Obstet Gynecol. 1997;176:1149–54.CrossRefGoogle Scholar
  9. 9.
    McCarthy JM, Capullari T, Thompson Z, et al. Umbilical cord nucleated red blood cell counts: normal values and the effect of labor. J Perinatol. 2006;26:89–92.CrossRefGoogle Scholar
  10. 10.
    Perrone S, Vezzosi P, Longini M, et al. Nucleated red blood cell count in term and preterm newborns: reference values at birth. Arch Dis Child Fetal Neonatal. 2005;90:F174–5.CrossRefGoogle Scholar
  11. 11.
    Lewis AB, Sadeghi M. Acidemia potentiates the plasma catecholamine response to hypoxemia in fetal sheep. Biol Neonate. 1987;52:285–91.CrossRefGoogle Scholar
  12. 12.
    Ferber A, Minior VK, Bornstein E, et al. Fetal “non-reassuring status” is associated with elevation of nucleated red blood cell counts and interleukin-6. Am J Obstet Gynecol. 2005;192:1427–9.CrossRefGoogle Scholar
  13. 13.
    von Lindern M, Zauner W, Mellitzer G, et al. The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro. Blood. 1999;94:550–9.Google Scholar
  14. 14.
    Falchi M, Varricchio L, Martelli F, et al. Dexamethasone targeted directly to macrophages induces macrophage niches that promote erythroid expansion. Haematologica. 2015;100:178–87.CrossRefGoogle Scholar
  15. 15.
    Stachon A, Bolulu O, Holland-Letz T, et al. Association between nucleated red blood cells in blood and the levels of erythropoietin, interleukin 3, interleukin 6, and interleukin 12p70. Shock. 2005;24:34–9.CrossRefGoogle Scholar
  16. 16.
    Widness JA, Teramo KA, Clemons GK, et al. Temporal response of immunoreactive erythropoietin to acute hypoxemia in fetal sheep. Pediatr Res. 1986;20:15–9.CrossRefGoogle Scholar
  17. 17.
    Yeruchimovich M, Mimouni FB, Green DW, et al. Nucleated red blood cells in healthy infants of women with gestational diabetes. Obstet Gynecol. 2000;95:84–6.PubMedGoogle Scholar
  18. 18.
    Şaracoglu F, Sahin I, Eser E, et al. Nucleated red blood cells as a marker in acute and chronic fetal asphyxia. Int J Gynaecol Obstet. 2000;71:113–8.CrossRefGoogle Scholar
  19. 19.
    Hanlon-Lundberg KM, Kirby RS. Nucleated red blood cells as a marker of acidemia in term neonates. Am J Obstet Gynecol. 1999;181:196–201.CrossRefGoogle Scholar
  20. 20.
    Ferber A, Grassi A, Akyol D, et al. The association of fetal heart rate patterns with nucleated red blood cell counts at birth. Am J Obstet Gynecol. 2003;188:1228–30.CrossRefGoogle Scholar
  21. 21.
    Goel M, Dwivedi R, Gohiya P, Hedge D. Nucleated red blood cell in cord blood as a marker of perinatal asphyxia. J Clin Neonatol. 2013;2:179–82.CrossRefGoogle Scholar
  22. 22.
    Boskabadi H, Zakerihamidi M, Sadeghian MH, et al. Nucleated red blood cells count as a prognostic biomarker in predicting the complications of asphyxia in neonates. J Matern Fetal Neonatal Med. 2016;24:1–6.Google Scholar
  23. 23.
    Walsh BH, Boylan GB, Dempsey EM, et al. Association of nucleated red blood cells and severity of encephalopathy in normothermic and hypothermic infants. Acta Paediatr. 2013;102:e64–7.CrossRefGoogle Scholar
  24. 24.
    Ghosh B, Mittal S, Kumar S, Dadhwal V. Prediction of perinatal asphyxia with nucleated red blood cells in cord blood of newborns. Int J Gynaecol Obstet. 2003;81:267–71.CrossRefGoogle Scholar
  25. 25.
    Li J, Kobata K, Kamei Y, et al. Nucleated red blood cell counts: an early predictor of brain injury and 2-year outcome in neonates with hypoxicischemic encephalopathy in the era of cooling-based treatment. Brain Dev. 2014;36:472–8.CrossRefGoogle Scholar
  26. 26.
    Buonocore G, Perrone S, Gioia D, et al. Nucleated red blood cell count at birth as an index of perinatal brain damage. Am J Obstet Gynecol. 1999;181:1500–5.CrossRefGoogle Scholar
  27. 27.
    Korst LM, Phelan JP, Ahn MO, Martin GI. Nucleated red blood cells: an update on the marker for fetal asphyxia. Am J Obstet Gynecol. 1996;175(4 Pt 1):843–6.CrossRefGoogle Scholar
  28. 28.
    Redline RW. Elevated circulating fetal nucleated red blood cells and placental pathology in term infants who develop cerebral palsy. Hum Pathol. 2008;39:1378–84.CrossRefGoogle Scholar
  29. 29.
    Bryant C, Beall M, McPhaul L, Forston W, Ross M. Do placental sections accurately reflect umbilical cord nucleated red blood cell differential counts? J Mat Fetal Neonatal Med. 2006;19:105–8.CrossRefGoogle Scholar
  30. 30.
    Spencer MK, Khong TY, Matthews BL, MacLennan AH. Haematopoietic indicators of fetal metabolic acidosis. Aust N Z J Obstet Gynaecol. 2000;40:286–9.CrossRefGoogle Scholar
  31. 31.
    Boskabadi H, Zakerihamidi M, Sadeghian MH, et al. Nucleated red blood cells count as a prognostic biomarker in predicting the complications of asphyxia in neonates. J Matern Fetal Neonatal Med. 2017;30:2551–6.CrossRefGoogle Scholar
  32. 32.
    Cohen MC, Peres LC, Al-Adnani M, et al. Increased number of fetal nucleated red blood cells in the placentas of term or near-term stillborn and neonates correlates with the presence of diffuse intradural hemorrhage in the perinatal period. Pediatr Dev Pathol. 2014;17:1–9.CrossRefGoogle Scholar
  33. 33.
    Walsh BH, Boylan GB, Murray DM. Nucleated red blood cells and early EEG: predicting Sarnat stage and two year outcome. Early Hum Dev. 2011;87:335–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Sheffield Children’s HospitalSheffieldUK
  2. 2.University of SheffieldSheffieldUK
  3. 3.Division of Anatomic Pathology, Department of PathologyBoston Children’s HospitalBostonUSA
  4. 4.Division of Women’s and Perinatal PathologyBrigham and Women’s HospitalBostonUSA
  5. 5.Department of PathologyHarvard Medical SchoolBostonUSA

Personalised recommendations