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Chapter 24 - Reference Intervals in Neonatal Hematology

from Section IX - Miscellaneous

Published online by Cambridge University Press:  30 January 2021

By
Robert D. Christensen
Edited by
Pedro A. de Alarcón ,
Eric J. Werner ,
Robert D. Christensen  and
Martha C. Sola-Visner
Pedro A. de Alarcón
Affiliation:
University of Illinois College of Medicine
Eric J. Werner
Affiliation:
Children's Hospital of the King's Daughters
Robert D. Christensen
Affiliation:
University of Utah
Martha C. Sola-Visner
Affiliation:
Harvard University, Massachusetts
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Summary

“Normal ranges” for hematologic values of neonates are not available. This is because blood is not drawn on healthy normal neonates to establish such ranges, as is done with the consent of healthy adult volunteers. Instead, neonatal hematology utilizes “reference intervals.” These consist of 5th to 95th percentile values compiled from laboratory tests that were performed on neonates thought to have minimal pathology relevant to the specific laboratory test under consideration, or with pathology unlikely to significantly affect that test result. The premise on which the reference interval concept is based is that these values approximate normal ranges, although they were admittedly obtained for a clinical reason and not from healthy volunteers. Basically, reference intervals are the best tools we have to interpret a neonate’s complete blood count (CBC), and they likely will continue to be the best we will have for several years to come [1].

Type
Chapter
Information
Neonatal Hematology
Pathogenesis, Diagnosis, and Management of Hematologic Problems
 , pp. 440 - 469
Publisher: Cambridge University Press
Print publication year: 2021

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References

Henry, E, Christensen, RD. Reference Intervals in neonatal hematology. Clin Perinatol 2015;42:483–97.Google Scholar
International Committee for Standardization in Haematology. Recommendations for reference method for haemoglobinometry in human blood. J Clin Pathol 1978;31:139–43.Google Scholar
Jopling, J, Henry, E, Wiedmeier, SE, Christensen, RD. Reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period: data from a multihospital healthcare system. Pediatrics 2009;123;e333–77.Google Scholar
Wintrobe, MM. A simple and accurate hematocrit. J Lab Clin Med 1929;15:287–94.Google Scholar
Waugh, TF, Merchant, FT, Maugham, GB. Blood studies on newborn: Determination of hemoglobin, volume of packed red cells, reticulocytes and fragility of erythrocytes over 9 day period. Am J Med Sci 1939;198:646–9.Google Scholar
Perkins, SL. Principles of hematologic examination. In Greer, JP, Foerster, J, Rodgers, GM, et al. eds. Wintrobe’s Clinical Hematology. (Philadelphia, PA: Lippincott, Williams & Wilkins, 2009), p. 3.Google Scholar
Gairdner, D, Marks, J, Bosco, JD. Blood formation in infancy: The normal bone marrow. Arch Dis Child 1952;27:124–32.Google Scholar
Christensen, RD, Jopling, J, Henry, E, et al. The erythrocyte indices of neonates, defined using data from over 12,000 patients in a multihospital healthcare system. J Perinatol 2008;28:24–8.Google Scholar
Scott-Emuakpor, AB, Okolo, M, Omene, JA, Ukpe, SI. Normal hematological values of the African neonate. Blut 1985;51:11–18.Google Scholar
Michaels, LA, Cohen, AR, Zhao, H, et al. Screening for hereditary spherocytosis by use of automated erythrocyte indexes. J Pediatr 1997;130:57–61.Google Scholar
Christensen, RD, Yaish, HM, Henry, E, Bennett, ST. Red blood cell distribution width: reference intervals for neonates. J Matern Fetal Neonatal Med. 2015;28:883–8.Google Scholar
Dessypris, EN, Sawyer, ST. Erythropoiesis. In Greer, JP, Foerster, J, Rodgers, GM, et al. eds. Wintrobe’s Clinical Hematology. (Philadelphia, PA: Lippincott, Williams & Wilkins, 2009), pp. 108,109.Google Scholar
Killman, SA. On the size of normal human reticulocytes. Acta Med Scand 1964;176:529–31.Google Scholar
Warwood, TL, Ohls, RK, Lambert, DK, et al. Urinary excretion of darbepoetin after intravenous vs. subcutaneous administration to preterm neonates. J Perinatol 2006;26:636–9.Google Scholar
Wegelius, R. On changes in peripheral blood picture of newborn infant immediately after birth. Acta Paediatr 1948;35:1–6.Google Scholar
Humbert, JR, Abelson, H, Hathaway, WE, et al. Polycythemia in small for gestational age infants. J Pediatr 1969;75:812–18.Google Scholar
Christensen, RD, Henry, E, Bennett, ST, Yaish, HM. Reference intervals for reticulocyte parameters of infants during their first 90 days after birth. J Perinatol 2016;36:61–66.Google Scholar
Al-Ghananim, RT, Nalbant, D, Schmidt, RL, et al. Reticulocyte hemoglobin content during the first month of life in critically ill very low birth weight neonates differs from term infants, children, and adults. J Clin Lab Anal 2016;30:326–34.Google Scholar
Christensen, RD, Henry, E, Andres, RL, Bennett, ST. Neonatal reference ranges for blood concentrations of nucleated red blood cells. Neonatology 2010;99:289–94.Google Scholar
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 Ed 2005;90:F174–5.Google Scholar
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.Google Scholar
Green, DW, Hendon, B, Mimouni, FB. Nucleated erythrocytes and intraventricular hemorrhage in preterm neonates. Pediatrics 1995;96:475–8.Google Scholar
Judkins, AJ, MacQueen, BC, Christensen, RD, et al. Automated quantification of fragmented red blood cells: neonatal reference intervals and clinical disorders of neonatal intensive care unit patients with high values. Neonatology 2018;115:5–12.Google Scholar
Zipursky, A. Erythrocyte morphology in newborn infants: A new look. Pediatr Res 1977;11:843–8.Google Scholar
Pearson, EA, McIntosh, S, Rooks, Y, et al. Interference phase microscopic enumeration of pitted RBC and splenic hypofunction in sickle cell anemia. Pediatr Res 1978;12:471–5.Google Scholar
Oettinger, L Jr, ., Mills, WE. Simultaneous capillary and venous hemoglobin determinations in the newborn infant. J Pediatr 1949;35:362–70.Google Scholar
Oh, W, Lind, J. Venous and capillary hematocrit in newborn infants and placental transfusion. Acta Paediatr Scand 1966;55:38–42.Google Scholar
Moe, PJ. Umbilical cord blood and capillary blood in the evaluation of anemia in erythroblastosis fetalis. Acta Paediatr Scand 1967;56:391–400.Google Scholar
Linderkamp, O, Versmold, HT, Strohhacker, I, et al. Capillary–venous hematocrit differences in newborn infants.1. Relationship to blood volume, peripheral blood flow, and acid-base parameters. Eur J Pediatr 1977:127;9–14.Google Scholar
Turner, CW, Luzins, J, Hutcheson, C. A modified harvest technique for cord blood hematopoietic stem cells. Bone Marrow Transpl 1992;10:89–92.Google Scholar
Vahlquist, B. Das Serumeisen. Eine padiatrischklinische und experimentelle Studie. Acta Paediatr 1941;28:1–9.Google Scholar
Mollision, PL. Blood transfusion in clinical medicine, 3rd ed. (Oxford: Blackwell, 1951).Google Scholar
Rivera, LM, Rudolph, N. Postnatal persistence of capillary-venous differences in hematocrit and hemoglobin values in low-birth-weight and term infants. Pediatrics 1982;70:956.Google Scholar
Thurlbeck, SM, McIntosh, N. Preterm blood counts vary with sampling site. Arch Dis Child 1987;62:74–9.Google Scholar
Carroll, PD, Christensen, RD. New and underutilized uses of umbilical cord blood in neonatal care. Matern Health Neonatol Perinatol. 2015;16;1–16.Google Scholar
Vain, NE, Satragno, DS, Gorenstein, AN, et al. Effect of gravity on volume of placental transfusion: a multicentre, randomised, non-inferiority trial. Lancet 2014;384:235–40.Google Scholar
Katheria, A, Garey, D, Truong, G, et al. A randomized clinical trial of umbilical cord milking vs delayed cord clamping in preterm infants: neurodevelopmental outcomes at 22–26 months of corrected age. J Pediatr 2018;194:76–80.Google Scholar
Barnett, HL, Einhorn, AH, eds. and Holt, LE (author). Pediatrics 15th ed. (New York: Appleton Century-Crofts, 1972), p. 597.Google Scholar
Xanthou, M. Leukocyte blood picture in healthy full term and premature babies during the neonatal period. Arch Dis Child 1970;45:242–7.Google Scholar
Akenzua, GI, Hui, IT, Milner, R, et al. Neutrophil and band counts in the diagnosis of neonatal infection. Pediatrics 1974;54:38–43.Google Scholar
Manroe, BL, Weinberg, AG, Rosenfeld, CR, et al. The neonatal blood count in health and disease. 1. Reference values for neutrophilic cells. J Pediatr 1979;95:89–98.Google Scholar
Christensen, RD, Rothstein, G. Pitfalls in the interpretation of leukocyte counts of newborn infants. Am J Clin Path 1979;72:608–12.Google Scholar
Chervenick, PA, Boggs, DR, March, JC, et al. Quantitative studies of blood and bone marrow neutrophils in normal mice. Am J Physiol 1968;215:353–9.Google Scholar
Mouzinho, A, Rosenfeld, CR, Sanchez, PJ, Risser, R. Revised reference ranges for circulating neutrophils in very-low-birth-weight neonates. Pediatrics 1994;94:76–81.Google Scholar
Maynard, EC, Reed, C, Kircher, T. Neutrophil counts in newborn infants at high altitude. J Pediatr 1993;122:990–1.Google Scholar
Schmutz, N, Henry, E, Jopling, J, Christensen, RD. Expected ranges for blood neutrophil concentrations of neonates: The Manroe and Mouzinho charts revisited. J Perinatol 2008;28:275–81.Google Scholar
Carballo, C, Foucar, K, Swanson, P, et al. Effect of high altitude on neutrophil counts in newborn infants. J Pediatr 1991;119:464–6.Google Scholar
Coulombel, L, Dehan, M, Tehernia, G, et al. The number of polymorphonuclear leukocytes in relation to gestational age in the newborn. Acta Padeiatr Scand 1979;68:709–12.Google Scholar
Lloyd, BW, Oto, A. Normal values for mature and immature neutrophils in very preterm babies. Arch Dis Child 1982;57:233–6.Google Scholar
MacQueen, BC, Christensen, RD, Yoder, BA, et al. Comparing automated vs manual leukocyte differential counts for quantifying the “left shift” in the blood of neonates. J Perinatol. 2016;36:843–8.Google Scholar
Calhoun, DA, Sullivan, SE, Lunoe, M, et al. Granulocyte-macrophage colony stimulating factor and interleukin-5 concentrations in premature neonates with eosinophilia. J Perinatol 2000;26:166–71Google Scholar
Sullivan, SE, Calhoun, DA. Eosinophils in the neonatal intensive care unit. Clin Perinatol 2000;27:603–9.Google Scholar
Medoff, HS, Barbero, GJ. Total blood eosinophil counts in the newborn period. Pediatrics 1950;6:737–50.Google Scholar
Xanthou, M. Leukocyte blood picture in ill newborn babies. Arch Dis Child 1972;47:741–7.Google Scholar
Burell, JM. A comparative study of the circulating eosinophil levels in babies. Arch Dis Child 1952;27:337–40.Google Scholar
Bass, DA. Behavior of eosinophil leukocytes in acute inflammation. II. Eosinophil dynamics during acute inflammation. J Clin Invest 1975;56:870–6.Google Scholar
Gibson, JG Jr., Vaucher, Y, Corrigan, JJ. Eosinophils in premature infants: Relationship to weight gain. J Pediatr 1979;95:99–104.Google Scholar
Portuguez-Molavasi, A, Cote-Boileau, T, Aranda, JV. Eosinophilia in the newborn, possible role in adverse drug reactions. Pediatr Res 1980;14:537–41.Google Scholar
Craver, RD. The cytology of cerebrospinal fluid associated with neonatal intraventricular hemorrhage. Pediatr Pathol Lab Med 1996;16:713–18.Google Scholar
Christensen, RD, Jensen, J, Maheshwari, A, Henry, E. Reference ranges for blood concentrations of eosinophils and monocytes during the neonatal period defined from over 63,000 records in a multihospital health-care system. J Perinatol 2010;30:540–5.Google Scholar
Rogers, GM. In Greer, JP, Forester, J, Rodgers, GM, et al., eds. Wintrobe’s Clinical Hematology(Philadelphia: Lippincott, Williams & Wilkins, 2009), p. 1277.Google Scholar
Wiedmeier, SE, Henry, E, Sola-Visner, MC, Christensen, RD. Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol 2009;29:130–6.Google Scholar
Peterec, SM, Brennan, SA, Tinder, EM, et al. Reticulated platelet values in normal and thrombocytopenic neonates. J Pediatr 1996;12:269–73.Google Scholar
Joseph, MA, Adams, D, Maragos, J, Saving, KL. Flow cytometry of neonatal platelet RNA. J Pediatr Hematol Oncol 1966;17:277–81.Google Scholar
MacQueen, BC, Christensen, RD, Henry, E, et al. The immature platelet fraction: Creating neonatal reference intervals and using these to categorize neonatal thrombocytopenias. J Perinatol. 2017;37:834–8.Google Scholar
Cremer, M, Weimann, A, Szekessy, D, et al. Low immature platelet fraction suggests decreased megakaryopoiesis in neonates with sepsis or necrotizing enterocolitis. J Perinatol 2013;33:622–6.Google Scholar
Cremer, M, Paetzold, J, Schmalisch, G, et al. Immature platelet fraction as novel laboratory parameter predicting the course of neonatal thrombocytopenia. Br J Haematol 2009;144:619–621.Google Scholar
Andrew, M, Castle, , Mitchell, L, Paes, B. Modified bleeding time in the infant. Am J Hematol 1989;30:190–1.Google Scholar
DelVecchio, A, Latin, G, Henry, E, Christensen, RD. Template bleeding times of 240 neonates born at 24–41 weeks’ gestation. J Perinatol 2008;28;427–31.Google Scholar
Boudewins, M. Raes, M, Pteters, V, et al. Evaluation of platelet function on cord blood in 80 healthy term neonates using the Platelet Function Analyser (PFA-100); Shorter in vitro bleeding times in neonates than adults. Eur J Pediatr 2003;162:212–13.Google Scholar
Saxonhouse, MA, Garner, R, Mammel, L, et al. Closure times measured by the platelet function analyzer PFA-100 are longer in neonatal blood compared to cord blood samples. Neonatol 2010;97:242–9.Google Scholar
Sheffield, MS, Schmutz, N, Lambert, DK, Henry, E, Christensen, RD. Ibuprofen lysine administration to neonates with a patent ductus arteriosus: Effect on platelet plug formation assed by in vivo and in vitro measurements. J Perinatol 2009;29:39–43.Google Scholar
Sheffield, MJ, Lambert, DK, Henry, E, Christensen, RD. Effect of ampicillin on the bleeding time of neonatal intensive care unit patients. J Perinatol 2010;30:527–30.Google Scholar
Sola, MC, Rimsza, LM, Christensen, RD. A bone marrow biopsy technique suitable for use in neonates. Br J Haematol 1999;107:458–60.Google Scholar
Rosse, C, Kraemer, MJ, Dillon, TL, et al. Bone marrow cell populations of normal infants: the predominance of lymphocytes. J Lab Clin Med 1977;89:1228–32.Google Scholar
Shapiro, LM, Bassen, FA. Sternal marrow changes during first week of life. Am J Med Sci 1941:202;341–54.Google Scholar

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