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Neonatology pp 1489-1514 | Cite as

Anemia in the Neonatal Period

  • Robert D. Christensen
  • Robin K. Ohls
Reference work entry

Abstract

Anemia is a pathological reduction in the hematocrit, blood hemoglobin concentration, and circulating erythrocyte count. Neonatal reference intervals for hematocrit and hemoglobin are characteristic of this age. Neonatal red cell survival is shorter than in children and adults and the lower end of the normal range for infants of this age is approximately 9 g/dl. This nadir is called physiologic anemia. Neonates have red cells with erythrocyte membranes and distinctive metabolic characteristics that differ slightly from those of adults and so does the antigen expression. Isoimmunization caused by maternal-fetal blood group incompatibility is the most common cause of newborn hemolytic jaundice. Alloimmunization can present with unique neonatal findings, with a low reticulocyte count along with a low hemoglobin and elevated bilirubin. Causes of hemorrhage resulting in fetal or neonatal anemia are divided into prenatal, perinatal, and postnatal varieties. The use of “early” and the use of “late” erythropoietin administration to prevent and treat the anemia of prematurity has decreased transfusion requirements in preterm infants and beneficial neurodevelopmental effects have been reported. This chapter reviews the various pathologies that give rise to anemia during the fetal and neonatal periods and provides practical approaches for dealing with these clinical issues.

References

  1. Aase JM, Smith DW (1969) Congenital anemia and triphalangeal thumbs: a new syndrome. J Pediatr 74:471–474PubMedCrossRefGoogle Scholar
  2. Abolmakarem H, Tharmaratnum S, Thilaganathan B (2001) Fetal anemia as a consequence of hemorrhage into an ovarian cyst. Ultrasound Obstet Gynecol 17:527–528PubMedCrossRefGoogle Scholar
  3. Aher SM, Ohlsson A (2014a) Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database Syst Rev 4:CD004863Google Scholar
  4. Aher SM, Ohlsson A (2014b) Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database Syst Rev 9:CD004868Google Scholar
  5. Aladangady N, McHugh S, Aitchison TC et al (2006) Infant’s blood volume in a controlled trial of placental transfusion at preterm delivery. Pediatrics 117:93–98PubMedCrossRefGoogle Scholar
  6. Baer VL, Lambert DK, Henry E, Snow GL, Butler A, Christensen RD (2011a) Among very-low-birth-weight neonates is red blood cell transfusion an independent risk factor for subsequently developing a severe intraventricular hemorrhage? Transfusion 51:1170–1178PubMedCrossRefGoogle Scholar
  7. Baer VL, Lambert DK, Henry E, Snow GL, Christensen RD (2011b) Red blood cell transfusion of preterm neonates with a Grade 1 intraventricular hemorrhage is associated with extension to a Grade 3 or 4 hemorrhage. Transfusion 51:1933–1939PubMedCrossRefGoogle Scholar
  8. Baer VL, Lambert DK, Carroll PD, Gerday E, Christensen RD (2013) Using umbilical cord blood for the initial blood tests of VLBW neonates results in higher hemoglobin and fewer RBC transfusions. J Perinatol 33:363–365PubMedCrossRefGoogle Scholar
  9. Bard H (2000) Fetal and neonatal hemoglobin structure and function. In: Christensen RD (ed) Hematologic problems of the neonate. WB Saunders, PhiladelphiaGoogle Scholar
  10. Bard H, Peri KG, Gagnon C (2001) Changes in the G gamma- and A gamma-globin mRNA components of fetal hemoglobin during human development. Biol Neonate 80:26–29PubMedCrossRefGoogle Scholar
  11. Barretto OC, Nonoyama K, Deutsch AD, Ramos J (1995) Physiological red cell, 2,3-diphosphoglycerate increase by the sixth hour after birth. J Perinat Med 23:365–369PubMedCrossRefGoogle Scholar
  12. Bautista ML, Altaf W, Lall R, Wapnir RA (2003) Cord blood red cell osmotic fragility: a comparison between preterm and full-term newborn infants. Early Hum Dev 72:37–46PubMedCrossRefGoogle Scholar
  13. Beirer R, Peceny MC, Hartenberger CH, Ohls RK (2006) Erythropoietin concentrations and neurodevelopmental outcome in preterm infants. Pediatrics 118:635–640CrossRefGoogle Scholar
  14. Bell EF, Strauss RG, Widness JA et al (2005) Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants. Pediatrics 115:1685–1691PubMedPubMedCentralCrossRefGoogle Scholar
  15. Benirschke K (1994) Obstetrically important lesions of the umbilical cord. J Reprod Med 39:262–272PubMedGoogle Scholar
  16. Berkowitz K, Baxi L, Fox HE (1990) False-negative syphilis screening: the prozone phenomenon, nonimmune hydrops, and diagnosis of syphilis during pregnancy. Am J Obstet Gynecol 163:975–977PubMedCrossRefGoogle Scholar
  17. Bhutani VK, Donn SM, Johnson LH (2005) Risk management of severe neonatal hyperbilirubinemia to prevent kernicterus. Clin Perinatol 32:125–139PubMedCrossRefGoogle Scholar
  18. Bierer R, Peceny MC, Hartenberger CH, Ohls RK (2006) Erythropoietin concentrations and neurodevelopmental outcome in preterm infants. Pediatrics 118:e635–e640PubMedCrossRefGoogle Scholar
  19. Brace RA, Langendorfer C, Song TB, Mock DM (2000) Red blood cell life span in the ovine fetus. Am J Physiol Regul Integr Comp Physiol 279:R1196–R1204PubMedCrossRefGoogle Scholar
  20. Brace RA, Cheung CY, Davis LE, Gagnon R, Harding R, Widness JA (2006) Sources of amniotic fluid erythropoietin during normoxia and hypoxia in fetal sheep. Am J Obstet Gynecol 195:246–254PubMedCrossRefGoogle Scholar
  21. Brown MS, Garcia JF, Phibbs RH et al (1984) Decreased response of plasma immunoreactive erythropoietin to “available oxygen” in anemia of prematurity. J Pediatr 105:793–798PubMedCrossRefGoogle Scholar
  22. Buonocore G, Perrone S, Gioia D et al (1999) Nucleated red blood cell count at birth as an index of perinatal brain damage. Am J Obstet Gynecol 181:1500–1505CrossRefPubMedGoogle Scholar
  23. Chadwick LM, Pemberton PJ, Kurinczuk JJ (1996) Neonatal subgaleal haematoma: associated risk factors, complications and outcome. J Paediatr Child Health 32:228–232PubMedCrossRefGoogle Scholar
  24. Charles JM, Key LL (1998) Developmental spectrum of children with congenital osteopetrosis. J Pediatr 132:371–374PubMedCrossRefGoogle Scholar
  25. Chelmow D, Andrew DE, Baker ER (1996) Maternal cigarette smoking and placenta previa. Obstet Gynecol 87(5 Pt 1):703–706PubMedCrossRefGoogle Scholar
  26. Chen KH, Konchak P (1998) Use of transvaginal color Doppler ultrasound to diagnose vasa previa. J Am Osteopath Assoc 98:116–117PubMedGoogle Scholar
  27. Christensen RD (2013) Reference ranges in neonatal hematology. In: deAlarcon PA, Werner EJ, Christensen RD (eds) Neonatal hematology, 2nd edn. Cambridge, UK: Cambridge University Press, pp 404–406Google Scholar
  28. Christensen RD, Henry E (2010) Hereditary spherocytosis in neonates with hyperbilirubinemia. Pediatrics 125:120–125PubMedCrossRefGoogle Scholar
  29. Christensen RD, Henry E, Jopling J, Wiedmeier SE (2009) The CBC: reference ranges for neonates. Semin Perinatol 33:3–11PubMedPubMedCentralCrossRefGoogle Scholar
  30. Christensen RD, Henry E, Andres RL, Bennett ST (2011) Reference ranges for blood concentrations of nucleated red blood cells in neonates. Neonatology 99:289–294CrossRefPubMedGoogle Scholar
  31. Christensen RD, Lambert DK, Baer VL, Richards DS, Bennett ST, Ilstrup SJ, Henry E (2012) Severe neonatal anemia from fetomaternal hemorrhage: report from a multihospital health-care system. J Perinatol 33:429–434PubMedCrossRefGoogle Scholar
  32. Christensen RD, Yaish HM, Lemons RS (2014a) Neonatal hemolytic jaundice: morphologic features of erythrocytes that will help you diagnose the underlying condition. Neonatology 105:243–924PubMedCrossRefGoogle Scholar
  33. Christensen RD, Baer VL, Lambert DK, Ilstrup SJ, Eggert LD, Henry E (2014b) Association, among very-low-birthweight neonates, between red blood cell transfusions in the week after birth and severe intraventricular hemorrhage. Transfusion 54:104–108PubMedCrossRefGoogle Scholar
  34. Christensen RD, Nussenzveig RH, Yaish HM, Henry E, Eggert LD, Agarwal AM (2014c) Causes of hemolysis in neonates with extreme hyperbilirubinemia. J Perinatol 34:616–619PubMedCrossRefGoogle Scholar
  35. Christensen RD, Carroll PD, Josephson CD (2014d) Evidence-based advances in transfusion practice in neonatal intensive care units. Neonatology 106:245–253PubMedCrossRefGoogle Scholar
  36. Christensen RD, Baer VL, Gerday E, Sheffield MJ, Richards DS, Shepherd JG, Snow GL, Bennett ST, Frank EL, Oh W (2014e) Whole-blood viscosity in the neonate: effects of gestational age, hematocrit, mean corpuscular volume and umbilical cord milking. J Perinatol 34:16–21PubMedCrossRefGoogle Scholar
  37. Christensen RD, Lambert DK, Henry E, Yaish HM, Prchal JT (2015a) End-tidal carbon monoxide as an indicator of the hemolytic rate. Blood Cells Mol Dis 54:292–296PubMedCrossRefGoogle Scholar
  38. Christensen RD, Yaish HM, Gallagher PG (2015b) A pediatrician’s practical guide to diagnosing and treating hereditary spherocytosis in neonates. Pediatrics 135:1107–1114PubMedPubMedCentralCrossRefGoogle Scholar
  39. Christensen RD, Agarwal AM, Nussenzveig RH, Heikal N, Liew MA, Yaish HM (2015c) Evaluating eosin-5-maleimide binding as a diagnostic test for hereditary spherocytosis in newborn infants. J Perinatol 35:357–361PubMedCrossRefGoogle Scholar
  40. Dame C, Juul SE, Christensen RD (2001) The biology of erythropoietin in the central nervous system and its neurotrophic and neuroprotective potential. Biol Neonate 79:228–235PubMedCrossRefGoogle Scholar
  41. Davies MR (1997) Iatrogenic hepatic rupture in the newborn and its management by pack tamponade. J Pediatr Surg 32:1414–1419PubMedCrossRefGoogle Scholar
  42. de Jong EP, de Haan TR, Kroes AC (2006) Parvovirus B19 infection in pregnancy. J Clin Virol 36:1–7PubMedCrossRefGoogle Scholar
  43. De Lia JE, Kuhlmann RS, Harstad TW et al (1995) Fetoscopic laser ablation of placental vessels in severe previable twin-twin transfusion syndrome. Am J Obstet Gynecol 172(4 Pt 1):1202–1208PubMedCrossRefGoogle Scholar
  44. Deans A, Jauniaux E (1998) Prenatal diagnosis and outcome of subamniotic hematomas. Ultrasound Obstet Gynecol 11:319–323PubMedCrossRefGoogle Scholar
  45. Dennis LG, Winkler CL (1997) Twin-to-twin transfusion syndrome: aggressive therapeutic amniocentesis. Am J Obstet Gynecol 177:342–347PubMedCrossRefGoogle Scholar
  46. Dommergues M, Mandelbrot L, Delezoide AL et al (1995) Twin-to-twin transfusion syndrome: selective feticide by embolization of the hydropic fetus. Fetal Diagn Ther 10:26–31PubMedCrossRefGoogle Scholar
  47. Donato H (2005) Erythropoietin: an update on the therapeutic use in newborn infants and children. Expert Opin Pharmacother 6:723–734PubMedCrossRefGoogle Scholar
  48. Eddleman KA, Lockwood CJ, Berkowitz GS et al (1992) Clinical significance and sonographic diagnosis of velamentous umbilical cord insertion. Am J Perinatol 9:123–126PubMedCrossRefGoogle Scholar
  49. El-Ganzoury MM, Awad HA, El-Farrash RA, El-Gammasy TM, Ismail EA, Mohamed HE, Suliman SM (2014) Enteral granulocyte-colony stimulating factor and erythropoietin early in life improves feeding tolerance in preterm infants: a randomized controlled trial. J Pediatr 165:1140–1145PubMedCrossRefGoogle Scholar
  50. Emma F, Smith J, Moerman PH (1992) Subcapsular hemorrhage of the liver and hemoperitoneum in premature infants: report of 4 cases. Eur J Obstet Gynecol Reprod Biol 44:161–164PubMedCrossRefGoogle Scholar
  51. Fasth A (2009) Osteopetrosis – more than only a disease of the bone. Am J Hematol 84:469–470PubMedCrossRefGoogle Scholar
  52. Fauchère JC, Dame C, Vonthein R et al (2008) An approach to using recombinant erythropoietin for neuroprotection in very preterm infants. Pediatrics 122:375–382PubMedCrossRefGoogle Scholar
  53. Fauchère JC, Koller BM, Tschopp A, Dame C, Ruegger C, Bucher HU, Swiss Erythropoietin Neuroprotection Trial Group (2015) Safety of early high-dose recombinant erythropoietin for neuroprotection in very preterm infants. J Pediatr.  https://doi.org/10.1016/j.jpeds.2015.02.052CrossRefPubMedGoogle Scholar
  54. Felc Z (1995) Ultrasound in screening for neonatal adrenal hemorrhage. Am J Perinatol 12:363–366PubMedCrossRefGoogle Scholar
  55. Gazda HE, Sieff CA (2006) Recent insights into the pathogenesis of Diamond-Blackfan anaemia. Br J Haematol 135:149–157PubMedCrossRefGoogle Scholar
  56. Geifman-Holtzman O, Wojtowycz M, Kosmos E et al (1997) Female alloimmunization with antibodies known to cause hemolytic disease. Obstet Gynecol 89:272–275PubMedCrossRefGoogle Scholar
  57. Giacoia GP (1997) Severe fetomaternal hemorrhage: a review. Obstet Gynecol Surv 52:372–380PubMedCrossRefGoogle Scholar
  58. Gulbis B, Ferster A, Cotton F (2006) Neonatal haemoglobinopathy screening: review of a 10-year programme in Brussels. J Med Screen 13:76–78PubMedCrossRefGoogle Scholar
  59. Haiden N, Klebermass K, Cardona F (2006) A randomized, controlled trial of the effects of adding vitamin B12 and folate to erythropoietin for the treatment of anemia of prematurity. Pediatrics 118:180–188PubMedCrossRefGoogle Scholar
  60. Henry E, Christensen RD (2015) Reference intervals for CBC parameters of neonates. Clin Perinatol 42:3CrossRefGoogle Scholar
  61. Henry E, Christensen RD, Sheffield MJ, Eggert LD, Carroll PD, Minton SD, Lambert DK, Ilstrup SJ (2015) Why do four NICUs using identical RBC transfusion guidelines have different gestational age-adjusted RBC transfusion rates? J Perinatol 35:132–136PubMedCrossRefGoogle Scholar
  62. Huissoud C, Divry V, Dupont C et al (2009) Large fetomaternal hemorrhage: prenatal predictive factors for perinatal outcome. Am J Perinatol 26:227–233PubMedCrossRefGoogle Scholar
  63. Jopling J, Henry E, Wiedmeier SE, Christensen RD (2009) Reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period: data from a multihospital health care system. Pediatrics 123:e333–e337PubMedGoogle Scholar
  64. Juul SE (2000) Nonerythropoietic roles of erythropoietin in the fetus and neonate. Clin Perinatol 27:527–541PubMedCrossRefGoogle Scholar
  65. Juul SE (2004) Recombinant erythropoietin as a neuroprotective treatment: in vitro and in vivo models. Clin Perinatol 31:129–142PubMedCrossRefGoogle Scholar
  66. Juul SJ, Li Y, Christensen RD (1997) Erythropoietin is present in the cerebrospinal fluid of neonates. J Pediatr 130:428–433PubMedCrossRefGoogle Scholar
  67. Juul SJ, Li Y, Anderson DK, Christensen RD (1998a) Erythropoietin and erythropoietin receptor in the developing human central nervous system. Pediatr Res 43:40–47PubMedCrossRefGoogle Scholar
  68. Juul SE, Yachnis AT, Christensen RD (1998b) Tissue distribution of erythropoietin and erythropoietin receptor in the developing human fetus. Early Hum Dev 52:235–239PubMedCrossRefGoogle Scholar
  69. Juul SE, Stallings SA, Christensen RD (1999) Erythropoietin in the cerebrospinal fluid of neonates who sustained CNS injury. Pediatr Res 46:543–548PubMedCrossRefGoogle Scholar
  70. Juul SE, Zhao Y, Dame JB et al (2000) Origin and fate of erythropoietin in human milk. Pediatr Res 48:600–607CrossRefGoogle Scholar
  71. Juul SE, Ledbetter DJ, Joyce AE et al (2001) Erythropoietin acts as a trophic factor in neonatal rat intestine. Gut 49:182–189PubMedPubMedCentralCrossRefGoogle Scholar
  72. Juul SE, McPherson RJ, Farrell F et al (2004) Erythropoietin concentrations in cerebrospinal fluid of nonhuman primates and fetal sheep following high-dose recombinant erythropoietin. Biol Neonate 85:138–144PubMedCrossRefGoogle Scholar
  73. Kilani RA, Wetmore J (2006) Neonatal subgaleal hematoma: presentation and outcome – radiological findings and factors associated with mortality. Am J Perinatol 23:41–48PubMedCrossRefGoogle Scholar
  74. Kirpalani H, Whyte RK, Andersen C et al (2006) The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr 149:301–307PubMedPubMedCentralCrossRefGoogle Scholar
  75. Kling PJ (2002) Roles of erythropoietin in human milk. Acta Paediatr Suppl 91:31–35PubMedCrossRefGoogle Scholar
  76. Kling PJ (2013) Anemia of prematurity and erythropoietin therapy. In: de Alarcon PA, Werner EJ, Christensen RD (eds) Neonatal hematology, 2nd edn. Cambridge, UK: Cambridge University Press, pp 37–46Google Scholar
  77. Kling PJ, Schmidt RL, Roberts RA et al (1996) Serum erythropoietin levels during infancy: associations with erythropoiesis. J Pediatr 128:791–796PubMedCrossRefGoogle Scholar
  78. Kosasa TS, Ebesugawa I, Nakayama RT et al (1993) Massive fetomaternal hemorrhage preceded by decreased fetal movement and a nonreactive fetal heart rate pattern. Obstet Gynecol 82:711–714PubMedGoogle Scholar
  79. Kozlowski CL, Lee D, Shwe KH et al (1995) Quantification of anti-c in haemolytic disease of the newborn. Transfus Med 5:37–42PubMedCrossRefGoogle Scholar
  80. Kramer MS, Usher RH, Pollack R et al (1997) Etiologic determinants of abruptio placentae. Obstet Gynecol 89:221–226PubMedCrossRefGoogle Scholar
  81. Landmann E, Bluetters-Sawatzki R, Schindler D, Gortner L (2004) Fanconi anemia in a neonate with pancytopenia. J Pediatr 145:125–127PubMedCrossRefGoogle Scholar
  82. Li Y, Juul SE, Morris-Winman JA et al (1996) Erythropoietin receptors are expressed in the central nervous system of mid-trimester human fetuses. Pediatr Res 40:376–381PubMedCrossRefGoogle Scholar
  83. Li Y, Xiao Z, Yan J, Li X, Wang Q, Zhu H, Pan J, Zhu X, Wang J, Feng X (2013) Urine erythropoietin level is associated with kidney and brain injury in critically ill neonates. Neonatology 104:87–94PubMedCrossRefGoogle Scholar
  84. Linderkamp O (1977) Capillary-venous hematocrit differences in newborn infants. Eur J Pediatr 127:9–15PubMedCrossRefGoogle Scholar
  85. Linderkamp O (1978) The effect of intra-partum and intra-uterine asphyxia on placental transfusions in premature and full-term infants. Eur J Pediatr 127:91–99PubMedCrossRefGoogle Scholar
  86. Linderkamp O (1986) Deformability and intrinsic material properties of neonatal red blood cells. Blood 67:1244PubMedGoogle Scholar
  87. Linderkamp O, Nelle M, Kraus M, Zilow EP (1992) The effect of early and late cord-clamping on blood viscosity and other hemorheological parameters in full-term neonates. Acta Paediatr 81:745–750PubMedCrossRefGoogle Scholar
  88. Lipitz S, Many A, Mitrani-Rosenbaum S et al (1998) Obstetric outcome after RhD and Kell testing. Hum Reprod 13:1472–1475PubMedCrossRefGoogle Scholar
  89. Lipton JM, Ellis SR (2009) Diamond-Blackfan anemia: diagnosis, treatment, and molecular pathogenesis. Hematol Oncol Clin North Am 23:261–282PubMedPubMedCentralCrossRefGoogle Scholar
  90. Lopriore E, Vandenbussche FP, Tiersma ES et al (1995) Twin-to-twin transfusion syndrome: new perspectives. J Pediatr 127:675–680PubMedCrossRefGoogle Scholar
  91. Lundby C, Olsen NV (2011) Effects of recombinant human erythropoietin in normal humans. J Physiol 589:1265–1271PubMedCrossRefGoogle Scholar
  92. Maisels MJ, Kring E (2006) The contribution of hemolysis to early jaundice in normal newborns. Pediatrics 118:276–279PubMedCrossRefGoogle Scholar
  93. Manea EM, Leverger G, Bellmann F (2009) Pearson syndrome in the neonatal period: two case reports and review of the literature. Pediatr Hematol Oncol 31:947CrossRefGoogle Scholar
  94. Matovcik LM (1986) Myosin in adult and neonatal human erythrocyte membranes. Blood 67:1668PubMedGoogle Scholar
  95. Matsuda H, Sakaguchi K, Shibasaki T et al (2005) Intrauterine therapy for parvovirus B19 infected symptomatic fetus using B19 IgG-rich high titer gammaglobulin. J Perinat Med 33:561–563PubMedGoogle Scholar
  96. May-Wewers J, Kaiser JR, Moore EK et al (2006) Severe neonatal hemolysis due to a maternal antibody to the low-frequency Rh antigen C(w). Am J Perinatol 23:213–217PubMedCrossRefGoogle Scholar
  97. McCoy TE, Conrad AL, Richman LC, Lindgren SD, Nopoulos PC, Bell EF (2011) Neurocognitive profiles of preterm infants randomly assigned to lower or higher hematocrit thresholds for transfusion. Child Neuropsychol 17:347–367PubMedPubMedCentralCrossRefGoogle Scholar
  98. McMahon MJ, Li R, Schenck AP et al (1997) Previous cesarean birth. A risk factor for placenta previa? J Reprod Med 42:409–412PubMedGoogle Scholar
  99. McPherson RJ, Juul SE (2008) Recent trends in erythropoietin-mediated neuroprotection. Int J Dev Neurosci 26:103–111PubMedCrossRefGoogle Scholar
  100. Mercer JS, Vohr BR, McGrath MM et al (2006) Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics 117:1235–1242PubMedPubMedCentralCrossRefGoogle Scholar
  101. Miele V, Galluzzo M, Patti G et al (1997) Scrotal hematoma due to neonatal adrenal hemorrhage: the value of ultrasonography in avoiding unnecessary surgery. Pediatr Radiol 27:672–674PubMedCrossRefGoogle Scholar
  102. Mock DM, Bell EF, Lankford GL, Widness JA (2001) Hematocrit correlates well with circulating red blood cell volume in very low birth weight infants. Pediatr Res 50:525–531PubMedCrossRefGoogle Scholar
  103. Nagaya M, Kato J, Niimi N et al (1998) Isolated cavernous hemangioma of the stomach in a neonate. J Pediatr Surg 33:653–654PubMedCrossRefGoogle Scholar
  104. Nguyen AQ, Cherry BH, Scott GF, Ryou MG, Mallet RT (2014) Erythropoietin: powerful protection of ischemic and post-ischemic brain. Exp Biol Med (Maywood) 239:1461–1475CrossRefGoogle Scholar
  105. Nopoulos PC, Conrad AL, Bell EF, Strauss RG, Widness JA, Magnotta VA, Zimmerman MB, Georgieff MK, Lindgren SD, Richman LC (2011) Long-term outcome of brain structure in premature infants: effects of liberal vs restricted red blood cell transfusions. Arch Pediatr Adolesc Med 165:443–450PubMedPubMedCentralCrossRefGoogle Scholar
  106. Oettinger L, Mills WB (1949) Simultaneous capillary and venous hemoglobin determinations in newborn infant. J Pediatr 35:362–369PubMedCrossRefGoogle Scholar
  107. Ohls RK (2002a) Erythropoietin and hypoxia inducible factor-1 expression in the mid-trimester human fetus. Acta Pediatr 91(Suppl A 38):27–32CrossRefGoogle Scholar
  108. Ohls RK (2002b) Erythropoietin treatment in extremely low birth weight infants: blood in versus blood out. J Pediatr 140:3–6CrossRefGoogle Scholar
  109. Ohls RK (2009) Why, when and how should we provide red cell transfusions to neonates? In: Ohls RK, Yoder MC (eds) Hematology, immunology and infections disease. Saunders Elsevier, Philadelphia, pp 44–57Google Scholar
  110. Ohls RK (2013) Why study erythropoietin in preterm infants? Acta Paediatr 102:567–568PubMedCrossRefGoogle Scholar
  111. Ohls RK, Liechty KW, Turner MC et al (1990) Erythroid “burst promoting activity” in the serum of patients with the anemia of prematurity. J Pediatr 116:786–789PubMedCrossRefGoogle Scholar
  112. Ohls RK, Ehrenkranz RA, Das A (2004) Neurodevelopmental outcome and growth at 18 to 22 months’ corrected age in extremely low birth weight infants treated with early erythropoietin and iron. Pediatrics 114:1287–1291PubMedCrossRefGoogle Scholar
  113. Ohls RK, Christensen RD, Kamath-Rayne BD, Rosenberg A, Wiedmeier SE, Roohi M, Lacy CB, Lambert DK, Burnett JJ, Pruckler B, Schrader R, Lowe JR (2014a) A randomized, masked, placebo-controlled study of darbepoetin alfa in preterm infants. Pediatrics 132:e119–e127CrossRefGoogle Scholar
  114. Ohls RK, Kamath-Rayne BD, Christensen RD, Wiedmeier SE, Rosenberg A, Fuller J, Lacy CB, Roohi M, Lambert DK, Burnett JJ, Pruckler B, Peceny H, Cannon DC, Lowe JR (2014b) Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo. Pediatrics 133:1023–1030PubMedPubMedCentralCrossRefGoogle Scholar
  115. Ohls RK, Christensen RD, Widness JA, Juul SE (2015) Erythropoiesis stimulating agents demonstrate safety and show promise as neuroprotective agents in neonates. J Pediatr.  https://doi.org/10.1016/j.jpeds.2015.03.054CrossRefPubMedPubMedCentralGoogle Scholar
  116. Oski FA, Komazawa M (1975) Metabolism of the erythrocytes of the newborn infant. Semin Hematol 12:49Google Scholar
  117. Oski FA, Smith C (1968) Red cell metabolism in the premature infant. III. Apparent inappropriate glucose consumption for cell age. Pediatrics 41:473PubMedGoogle Scholar
  118. Patel S, Ohls RK (2015) Darbepoetin administration in term and preterm neonates. Clin Perinatol.  https://doi.org/10.1016/j.clp.2015.04.016CrossRefPubMedPubMedCentralGoogle Scholar
  119. Pearson HA (1967) Life-span of the fetal red blood cell. J Pediatr 70:166–171PubMedCrossRefGoogle Scholar
  120. Pearson HA, Vertrees KM (1961) Site of binding to chromium-51 by hemoglobin. Nature 189:1019–1021PubMedCrossRefGoogle Scholar
  121. Pearson HA, Lobel JS, Kocoshis SA et al (1979) A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction. J Pediatr 95:976–984PubMedCrossRefGoogle Scholar
  122. Perrone S, Vezzosi P, Longini M et al (2005) Nucleated red blood cell count in term and preterm newborns: reference values at birth. Arch Dis Child Fetal Neon Ed 90:F174–F175CrossRefGoogle Scholar
  123. Pinto E, Guignard JP (1995) Renal masses in the neonate. Biol Neonate 68:175–184PubMedCrossRefGoogle Scholar
  124. Rabe H, Reynolds G, Diaz-Rossello J (2004) Early versus delayed umbilical cord clamping in preterm infants. Cochrane Database Syst Rev CD003248Google Scholar
  125. Rabe H, Alvarez JR, Lawn C (2009) A management guideline to reduce the frequency of blood transfusion in very-low-birth-weight infants. Am J Perinatol 26:179–183PubMedCrossRefGoogle Scholar
  126. Rhondeau SM, Christensen RD, Ross MP et al (1988) Responsiveness to recombinant human erythropoietin of marrow erythroid progenitors from infants with the “anemia of prematurity”. J Pediatr 112:935–940PubMedCrossRefGoogle Scholar
  127. Ruef P, Linderkamp O (1999) Deformability and geometry of neonatal erythrocytes with irregular shapes. Pediatr Res 45(1):114–119PubMedCrossRefGoogle Scholar
  128. Runsewe-Abiodun IT, Ogunfowora OB, Fetuga BM (2006) Neonatal malaria in Nigeria – a 2 year review. BMC Pediatr 6:19PubMedPubMedCentralCrossRefGoogle Scholar
  129. Ruth V, Widness JA, Clemons G, Raivio JO (1990) Postnatal changes in serum immunoreactive erythropoietin in relation to hypoxia before and after birth. J Pediatr 116:950–954PubMedCrossRefGoogle Scholar
  130. Shah M, Li Y, Christensen RD (1996) Effects of perinatal zidovudine on hematopoiesis: a comparison of effects on progenitors from human fetuses versus mothers. AIDS 10:1239–1247PubMedCrossRefGoogle Scholar
  131. Shannon KM, Naylor GS, Torkildson JC et al (1987) Circulating erythroid progenitors in the anemia of prematurity. N Engl J Med 31:728–733CrossRefGoogle Scholar
  132. Soubasi V, Kremenopoulos G, Tsantali C et al (2000) Use of erythropoietin and its effects on blood lactate and 2, 3-diphosphoglycerate in premature neonates. Biol Neonate 78:281–287PubMedCrossRefGoogle Scholar
  133. Stevenson DK, Wong RJ, DeSandre GH, Vreman HJ (2004) A primer on neonatal jaundice. Adv Pediatr 51:263–288PubMedGoogle Scholar
  134. Strauss RG, Mock DM, Johnson K et al (2003) Circulating RBC volume, measured with biotinylated RBCs, is superior to the Hct to document the hematologic effects of delayed versus immediate umbilical cord clamping in preterm neonates. Transfusion 43:1168–1172PubMedCrossRefGoogle Scholar
  135. Strauss RG, Mock DM, Johnson KJ et al (2008) A randomized clinical trial comparing immediate versus delayed clamping of the umbilical cord in preterm infants: short-term clinical and laboratory endpoints. Transfusion 48:658–665PubMedPubMedCentralCrossRefGoogle Scholar
  136. Supski DW, Gurushanthaiah K, Chasen S (2002) The effect of treatment of twin-twin transfusion syndrome on the diagnosis-to-delivery interval. Twin Res 5:1–4CrossRefGoogle Scholar
  137. Teng FY, Sayre JW (1997) Vacuum extraction: does duration predict scalp injury? Obstet Gynecol 89:281–285PubMedCrossRefGoogle Scholar
  138. Uchil D, Arulkumaran S (2003) Neonatal subgaleal hemorrhage and its relationship to delivery by vacuum extraction. Obstet Gynecol Surv 58:687–693PubMedCrossRefGoogle Scholar
  139. Vain NE, Satragno DS, Gorenstein AN, Gordillo JE, Berazategui JP, Alda MG, Prudent LM (2014) Effect of gravity on volume of placental transfusion: a multicentre, randomised, non-inferiority trial. Lancet 384(9939):235–240PubMedCrossRefGoogle Scholar
  140. van den Ouweland JM, de Klerk JB, van de Corput MP et al (2000) Characterization of a novel mitochondrial DNA deletion in a patient with a variant of the Pearson marrow-pancreas syndrome. Eur J Hum Genet 8:195–203PubMedCrossRefGoogle Scholar
  141. van Dijk BA, Dooren MC, Overbeeke MA (1995) Red cell antibodies in pregnancy: there is no “critical titre”. Transfus Med 5:199–202PubMedCrossRefGoogle Scholar
  142. van Heteren CF, Nijhuis JG, Semmekrot BA et al (1998) Risk for surviving twin after fetal death of co-twin in twin-twin transfusion syndrome. Obstet Gynecol 92:215–219PubMedGoogle Scholar
  143. van Zoeren-Grobben D, Lindeman JH, Houdkamp E et al (1997) Markers of oxidative stress and antioxidant activity in plasma and erythrocytes in neonatal respiratory distress syndrome. Acta Paediatr 86:1356–1362PubMedCrossRefGoogle Scholar
  144. Vaughan JI, Manning M, Warwick RM et al (1998) Inhibition of erythroid progenitor cells by anti-Kell antibodies in fetal alloimmune anemia. N Engl J Med 338:798–803PubMedCrossRefGoogle Scholar
  145. Ville Y, Hyett J, Hecher K et al (1995) Preliminary experience with endoscopic laser surgery for severe twin-twin transfusion syndrome. N Engl J Med 332:224–227PubMedCrossRefGoogle Scholar
  146. Warwood TL, Ohls RD, Wiedmeier SE et al (2005) Single-dose darbepoetin administration to anemic preterm neonates. J Perinatol 25:725–730PubMedCrossRefGoogle Scholar
  147. Warwood TL, Ohls RK, Lambert DK et al (2006a) Intravenous administration of darbepoetin to NICU patients. J Perinatol 26:296–300PubMedCrossRefGoogle Scholar
  148. Warwood TL, Ohls RK, Lambert DK et al (2006b) Urinary excretion of darbepoetin after intravenous vs. subcutaneous administration to preterm neonates. J Perinatol 26:636–639PubMedCrossRefGoogle Scholar
  149. Weiner CP, Widness JA (1996) Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia. Am J Obstet Gynecol 174:547–551PubMedCrossRefGoogle Scholar
  150. Whyte RK, Kirpalani H, Asztalos EV, Andersen C, Blajchman M, Heddle N, LaCorte M, Robertson CM, Clarke MC, Vincer MJ, Doyle LW, Roberts RS, PINTOS Study Group (2009) Neurodevelopmental outcome of extremely low birth weight infants randomly assigned to restrictive or liberal hemoglobin thresholds for blood transfusion. Pediatrics 123:207–213PubMedCrossRefGoogle Scholar
  151. Widness JA, Madan A, Grindeanu LA (2005) Reduction in red blood cell transfusions among preterm infants: results of a randomized trial with an in-line blood gas and chemistry monitor. Pediatrics 115:1299–1306PubMedPubMedCentralCrossRefGoogle Scholar
  152. Zhao W, Kitidis C, Fleming MD, Lodish HF, Ghaffari S (2006) Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase/AKT signaling pathway. Blood 107:907–915PubMedPubMedCentralCrossRefGoogle Scholar
  153. Zipursky A (1983) The erythrocyte differential count in newborn infants. Am J Pediatr Hematol Oncol 5:45–52PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Divisions of Neonatology and Hematology, Department of PediatricsUniversity of Utah School of Medicine, Intermountain HealthcareSalt Lake CityUSA
  2. 2.Department of Pediatrics, Division of NeonatologyUniversity of New MexicoAlbuquerqueUSA

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