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Polycythemia in the Newborn Juan I. Remon, Aarti Raghavan and Akhil Maheshwari NeoReviews 2011;12;e20-e28 DOI: 10.1542/neo.

12-1-e20

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://neoreviews.aappublications.org/cgi/content/full/neoreviews;12/1/e20

NeoReviews is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 2000. NeoReviews is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2011 by the American Academy of Pediatrics. All rights reserved. Online ISSN: 1526-9906.

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Article

hematology

Polycythemia in the Newborn


Juan I. Remon, MD,* Aarti Raghavan, MD,* Akhil Maheshwari, MD*

Abstract
Neonatal polycythemia, dened as a venous hematocrit 65% (0.65), is a common problem in newborns. Infants born postterm or small for gestational age, infants of diabetic mothers, recipient twins in twin-to-twin transfusion syndrome, and those who have chromosomal abnormalities are at higher risk. Although the cause of polycythemia is often multifactorial, most cases can be classied as having active (increased fetal erythropoiesis) or passive (erythrocyte transfusion) polycythemia. By increasing blood viscosity, polycythemia can impair microcirculatory ow in end organs and can present with neurologic, cardiopulmonary, gastrointestinal, and metabolic symptoms. In this article, we review the pathophysiology, clinical presentation, diagnosis, and management of polycythemia in the newborn.

Author Disclosure Drs Remon, Raghavan, and Maheshwari have disclosed no nancial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/ investigative use of a commercial product/device.

Objectives

After completing this article, readers should be able to:

1. List the causes of polycythemia and hyperviscosity in the neonate. 2. Review the signs, symptoms, and diagnostic criteria for polycythemia and hyperviscosity. 3. Discuss the treatment of polycythemia and hyperviscosity in the neonate.

Introduction
Polycythemia (or more accurately, erythrocythemia), an abnormal elevation of the circulating red blood cell (RBC) mass, is seen frequently in newborns. Although neonatal polycythemia usually represents a normal fetal adaptation to hypoxemia rather than a true hematopoietic defect, the abnormal increase in hematocrit increases the risk of hyperviscosity, microcirculatory hypoperfusion, and multisystem organ dysfunction. In this article, we review the denition, pathophysiology, clinical presentation, and management of polycythemia in the newborn.

Denition
In healthy term infants, the hematocrit and hemoglobin concentrations in venous blood obtained at birth are 50.26.9% (0.50.07) (mean standard deviation) and 15.91.86 g/dL (15918.6 g/L), respectively. (1) Polycythemia is dened in newborns as a venous hematocrit greater than 65% (0.65) or a hemoglobin value greater than 22 g/dL (220 g/L). (2)(3)(4) Based on this denition, the incidence of polycythemia in healthy newborns has been reported to be 0.4% to 5%. (5)(6)(7) Increased incidence is seen in certain high-risk groups such as postterm neonates, small-for-gestational age infants, infants of diabetic mothers, identical twins who share the same placenta and develop twin-to-twin transfusion, and infants who have chromosomal abnormalities. (7)(8)(9)

Pathophysiology
Although the cause of polycythemia is often multifactorial, most patients can be classied as having active (increased fetal erythropoiesis) or passive (erythrocyte transfusion) polycythemia (Table 1). (5)(7)

*Department of Pediatrics, University of Illinois at Chicago, Chicago, IL. e20 NeoReviews Vol.12 No.1 January 2011

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Conditions Associated With Neonatal Polycythemia


Table 1.

Increased Fetal Erythropoiesis

Placental insufciency due to preeclampsia, maternal chronic hypertension, chronic or recurrent placental abruption, maternal cyanotic congenital heart disease, postdate pregnancy, maternal smoking and heavy alcohol intake Endocrine abnormalities such as congenital thyrotoxicosis or maternal diabetes with poor glycemic control Genetic disorders such as trisomy 13, trisomy 18, trisomy 21, and Beckwith-Wiedemann syndrome Placental-fetal transfusion with delayed cord clamping, relative positioning of the delivered infant in relation to the maternal introitus before cord clamping, perinatal asphyxia, oxytocin administration Twin-to-twin transfusion syndrome

correlate with the severity of polycythemia, and current data do not support a causative role of leptin in this process. (18) Genetic disorders, such as trisomy 13, trisomy 18, trisomy 21, and Beckwith-Wiedemann syndrome. The incidence of polycythemia in infants who have Down syndrome is 15% to 33%. (19)(20)(21) Although the cause of polycythemia in Down syndrome is not known, high cord blood erythropoietin concentrations in affected infants has led to the speculation that intrauterine hypoxemia may play a role. (9) Among neonates who have trisomy 13 and trisomy 18, the prevalence of polycythemia has been estimated as 8% and 17%, respectively. (22)

Erythrocyte Transfusion

Increased fetal erythropoiesis is frequently seen in conditions associated with hypoxia:

Placental insufciency due to preeclampsia, primary renovascular disease, chronic or recurrent placental abruption, maternal cyanotic congenital heart disease, postdate pregnancy, maternal smoking, and maternal heavy alcohol intake. (10)(11)(12) The severity of hematopoietic dysfunction in these conditions appears to be proportional to the degree of placental insufciency and fetal growth restriction. (8) Whereas mild placental dysfunction and consequent tissue hypoxia are associated with increased erythropoietin concentrations and polycythemia, more severe placental vasculopathy may cause erythropoietin resistance and anemia. (13)(14) Endocrine abnormalities associated with increased fetal oxygen consumption, such as congenital thyrotoxicosis or maternal diabetes with poor glycemic control. (13)(14) Thyrotoxicosis is presumed to increase erythropoiesis through a direct effect on marrow progenitor cells, increased erythropoietin expression, and the indirect effects of intrauterine growth restriction. (15)(16) In diabetic mothers who have poor glycemic control, maternal hyperglycemia is proposed to increase fetal erythropoiesis through fetal hyperinsulinemia, tissue hypoxia, and increased erythropoietin concentrations. (17)(18) Although plasma leptin concentrations are frequently elevated in infants of diabetic mothers, the actual concentrations do not

Erythrocyte transfusion polycythemia can result from placental-fetal transfusion. Delayed cord clamping allows for delivery of an increased blood volume to the infant. When cord clamping is delayed more than 3 minutes after birth, blood volume may increase by as much as 30%. (23) Hutton and Hassan (24) analyzed data from seven randomized studies and showed that neonates in the late-clamping group had a higher incidence of asymptomatic polycythemia with a benign course (relative risk (RR), 3.82; 95% condence interval (CI), 1.11 to 13.21). However, a more recent meta-analysis showed that delayed cord clamping did not cause a clinically signicant change in hematocrit at 1 and 4 hours of age. (25) Placental-fetal transfusion is likely inuenced by gravity and the relative position of the delivered infant in relation to the maternal introitus before cord clamping; raising or lowering the baby by 15 to 20 cm or more with the cord intact appears to inuence placental transfusion. (26) No randomized studies have examined this issue to date. Placental transfusion is augmented in infants who have perinatal asphyxia, which causes an active shift of the blood volume from the placenta to the fetus. (27) Oxytocin administration to the mother can also increase the volume of placental transfusion to the newborn. (28) Twin-to-twin transfusion syndrome due to a vascular communication occurs in approximately 10% of monozygotic twin pregnancies. (29)

Polycythemia and Hyperviscosity


Polycythemia remains an area of interest due to its potential effects on the viscosity of blood and its ow properties in the microcirculation. (5)(7)(8) Viscosity is a measure of the resistance of a uid that is being deformed by either shear stress or tensile stress. (30) More simply, viscosity refers to the thickness of a uid and is a measure of the uids internal resistance to ow.
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Hyperviscosity is arbitrarily dened as a viscosity measurement of greater than 14.6 centipoise detected in a viscometer at a shear rate of 11.5/sec. (5)(7)(30) Viscosity rises linearly with increasing hematocrit until the hematocrit reaches 60% (0.6) but increases exponentially when hematocrit equals or exceeds 70% (0.7). (5)(31)(32) Although the terms polycythemia and hyperviscosity are often used interchangeably, they are not equivalent and show only modest concordance in clinical cohorts. (5)(30) Furthermore, blood viscosity can also rise with an increase in plasma proteins, platelets, leukocytes, and endothelial factors. (30)(32) Hyperviscosity occurs in polycythemia due to the presence of an abnormally large number of circulating erythrocytes; the plasma viscosity in the newborn is almost always normal. (5)(7) According to Poiseuilles law, ow velocities in the circulation are determined by the resistance to ow, which varies with the viscosity of the blood and inversely with the fourth power of the radius of the blood vessel. This relationship can be expressed by the equation R8hL/r4, where R represents the resistance to blood ow, h is the viscosity, L is the length of the vessel, and r is the radius of the vessel. (33)(34) Because resistance is affected by viscosity as well as the caliber of the blood vessel, the effects of polycythemia on blood ow patterns are usually most pronounced in the microcirculation. (34) In these small vessels, non-newtonian mechanisms such as rouleaux formation and increased erythrocyte-endothelial interaction are also active and further contribute to the altered ow. (32) Polycythemia and hyperviscosity are associated with decreased blood ow to the brain, heart, lung, intestines, and carcass. (5)(7)(35)(36) Although renal blood ow is not affected, renal plasma ow and glomerular ltration rate are often diminished. (35) Hyperviscosity can also reduce pulmonary blood ow that, in turn, can cause systemic hypoxia. (36) In contrast to the effects of polycythemia on the kidney and lungs, reduced cerebral blood ow in polycythemia likely represents a vascular response to the increased arterial oxygen content (related to increased hemoglobin concentrations) rather than hyperviscosity. (7)(37) Changes in blood ow may also alter the delivery of substrates (such as glucose) to organs that are dependent on plasma ow. (7)(38)(39)

Clinical Findings
The symptom complex associated with polycythemia is frequently described by the term hyperviscosity syndrome, although it is important to remember that only 47% of infants who have polycythemia exhibit hypervise22 NeoReviews Vol.12 No.1 January 2011

cosity, and only 24% of infants who have hyperviscosity have a diagnosis of polycythemia. (6)(7)(40) Whereas most patients who have polycythemia remain asymptomatic, characteristic clinical features may be recognized as early as 1 to 2 hours after birth as the hematocrit peaks with normal postnatal uid shifts. (3) In some infants who have high borderline hematocrits, symptoms may be delayed until the second to third postnatal day, when excessive depletion of the extracellular uid may lead to hemoconcentration and hyperviscosity. Infants who have no symptoms by 48 to 72 hours of age are likely to remain asymptomatic. (3)(41) Clinical features associated with neonatal polycythemia are generally nonspecic and include ruddy complexion, irritability, jitteriness, tremors, feeding difculties, lethargy, apnea, cyanosis, respiratory distress, and seizures. (7) Neurologic symptoms occur in approximately 60% of affected patients. (5)(7)(42) The cause of these symptoms is uncertain, but reduced cerebral blood ow and altered tissue metabolism likely play important roles. Neurologic signs may also be related to metabolic changes such as hypoglycemia and hypocalcemia. Hypoglycemia is the most common metabolic derangement and is observed in 12% to 40% of infants who have polycythemia. Hypocalcemia is found in 1% to 11% of neonates who have polycythemia, possibly related to elevated concentrations of calcitonin gene-related peptide (CGRP) in affected infants. (43) The pathophysiology of increased CGRP concentrations is not clear; CGRP may play a role in the normal postnatal circulatory adaptation to extrauterine life, and this process is presumed to be accentuated in infants who have polycythemia. (44) Polycythemia and hyperviscosity have been implicated as pathogenic factors in necrotizing enterocolitis (NEC), particularly in term or near-term neonates. (45)(46)(47) (48)(49) Historically, polycythemia has been identied in up to half of all term infants who have NEC. (46)(47)(48) Although altered splanchnic perfusion is widely considered to cause gut mucosal injury in affected infants, recent data indicate that attempts to reduce the hematocrit with partial exchange transfusions (PET) also could contribute to the risk of NEC. (36)(42)(49) Renal manifestations of polycythemia include decreased glomerular ltration rates, oliguria, hematuria, proteinuria, and renal vein thrombosis. (5)(7) Thromboses can also be seen in other sites. Thrombocytopenia can be seen in up to one third of all cases, presumably due to platelet consumption in the microvasculature. (50)(51) In neonates who have polycythemia due to increased erythropoiesis, thrombocytopenia may also be related to

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progenitor steal, the diversion of hematopoietic progenitors toward erythropoiesis at the expense of other lineages. (8)(18) Overt disseminated intravascular coagulation is rare. (51)

Treatment
The management of polycythemia is controversial because of the lack of evidence showing that aggressive treatment improves long-term outcomes. Asymptomatic infants whose central hematocrits are between 60% (0.60) and 70% (0.70) can be monitored closely and aggressively hydrated with adequate enteral intake or administration of intravenous uids. The hematocrit should be reassessed in 12 to 24 hours, and plasma glucose and bilirubin and cardiorespiratory status should be monitored. If the hematocrit decreases or remains stable and the patient remains asymptomatic, monitoring can be continued for a further 24 to 48 hours. In asymptomatic infants whose hematocrits are greater than 70% (0.70), the treatment options are controversial. Although traditional treatment has been PET, studies show a lack of difference in outcomes with continued hydration and expectant management versus aggressive management with PET. (36)(42) In the absence of a consensus, the decision to perform PET is usually taken on a case-by-case basis, with a careful analysis of risks and potential benets. To perform PET, a precalculated volume of blood (calculated to reduce the central hematocrit to 50% [0.50] to 55% [0.55]) is replaced by an equivalent volume of normal saline, 5% albumin, commercially available solutions of human plasma protein fraction, or fresh frozen plasma. Colloid solutions do not offer any therapeutic advantages over normal saline and, at least in some studies, have been associated with a higher incidence of NEC. (53) Because of its lower cost, ready availability, and absence of risk of transfusion-associated infection, normal saline is generally accepted as the replacement uid of choice for PET in infants who have polycythemia. (54)(55) The total blood volume to be exchanged is determined as follows: [Total blood volume (patients hematocrit desired hematocrit)]/(patients hematocrit) where total blood volumethe patients weight in kilograms multiplied by a presumed blood volume of 90 mL/kg. PET can be performed through a single umbilical venous catheter using a pull-push technique (withdrawal of blood alternated with replacement of uid through a single catheter) or by withdrawing blood from an umbilical or peripheral arterial catheter and administering replacement uid simultaneously through an umbilical or peripheral venous catheter. Regardless of the sites used, small aliquots of 5 mL/kg or less should
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Diagnosis
The diagnosis of polycythemia requires detection of a venous hematocrit of at least 65% (0.65). (2)(3)(4) This cut-off nds its origins in studies on blood viscosity that show an exponential increase in viscosity above this value. (3)(7) However, clinical evidence for this threshold remains scant; studies have shown only modest concordance between a hematocrit greater than 65% (0.65) and actual demonstration of hyperviscosity. (7) Although blood viscosity could be a useful guide for deciding appropriate management strategies in affected patients, hematocrits continue to be widely used surrogate markers of hyperviscosity due to limited availability of tools for direct measurement of blood viscosity. Detection of high hematocrits (55% [0.55]) in cord blood could help predict the risk of polycythemia at 2 hours postnatal age, but such screening has not gained acceptance because of the lack of data showing that treatment of asymptomatic newborns who have elevated hematocrits alters outcomes. (3) The possibility of polycythemia should be considered in any infant exhibiting signs of hyperviscosity. Detection of a high hematocrit in the rst few hours after birth should trigger a follow-up measurement in a few hours to identify any further rise with normal postnatal uid shifts. (3) Close attention must be paid to the technique of sample collection while interpreting the test results. Capillary blood samples often show hematocrits that are 5% to 15% higher than venous samples, and, therefore, high hematocrit measurements in samples obtained by heelsticks should be conrmed in a free-owing venous sample. (3)(52) The technique of sample analyses should also be taken into account during serial evaluation of results because microcentrifuge hematocrit may be slightly higher (due to trapped plasma of about 2%) than that calculated from RBC volume and RBC count determined by hematology analyzer. (1) Neonates who have polycythemia should be evaluated for underlying causes such as intrauterine growth restriction, maternal diabetes, or birth asphyxia. Because clinical manifestations of hyperviscosity can overlap with other conditions, alternative causes for the symptoms should always be carefully excluded. Infants also should be monitored for systemic complications of polycythemia such as thromboses, NEC, hypoglycemia, hypocalcemia, hyperbilirubinemia, and thrombocytopenia.

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be used for removal or delivery, with each step carried out over 2 to 3 minutes. Several randomized studies have evaluated the efcacy of PET in patients who have polycythemia (Table 2). Malan and de V Heese (n49), (56) Goldberg and colleagues (n20), (57) Black and coworkers (n94), (58) and Ratrisawadi and associates (n42) (59) randomly assigned infants to receive either PET using plasma or supportive care. Bada and colleagues (n28) (60) compared PET using a commercially available human plasma protein solution with supportive care. Kumar and Ramji (61) randomized 45 infants to peripheral PET using normal saline or to routine medical management. None of these six studies documented a benecial effect of PET on neurodevelopmental outcome. Dempsey and Barrington (42) systematically reviewed ve of these studies to investigate whether PET was associated with improved short- and long-term outcomes in neonates who had polycythemia. They documented no improvement in long-term neurologic outcome (mental developmental index, incidence of developmental delay, and incidence of neurologic diagnoses) after PET in symptomatic or asymptomatic infants. There was also no evidence of improvement in early neurobehavioral assessment scores (Brazelton neonatal behavioral assessment scale). PET could have been associated with an earlier improvement in symptoms, but the data were insufcient to calculate the size of the effect. Ozek and coworkers (36) reviewed six randomized trials to determine the effect of PET on primary outcomes of mortality and neurodevelopmental outcomes at 2 years and at school age. Secondary outcomes included seizures, cerebral infarction, NEC (Bell stage 2 or greater), hypoglycemia, hyperbilirubinemia, and thrombocytopenia. Only one study reported data on mortality, and no signicant increase was noted with PET (RR, 5.23; 95% CI, 0.66, 41.26). Four studies reported neurodevelopmental outcomes at 18 months or older, and no signicant delay was reported in the PET group (typical RR, 1.45; 95% CI, 0.83 to 2.54 including all studies and typical RR, 1.35; 95% CI, 0.68 to 2.69 when only randomized, controlled trials were included). However, these results were based on data limited by poor follow-up and did not account for patients who were lost to follow-up. The authors performed a worst case/best case scenario post hoc analysis, which showed a signicant skewing toward or away from the association of PET with poor neurodevelopmental outcomes and was considered to reect the wide distribution of data points rather than actual outcomes. The authors concluded that
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there is no signicant benet of PET in asymptomatic patients or those who have mild symptoms. Patients who have polycythemia and show signs or symptoms that may be related to hyperviscosity are frequently treated with PET, even though the practice is not supported by high-quality evidence. The arguments in favor of PET are based on the pathophysiology of hyperviscosity syndrome because most of the symptoms are presumed to be related to altered microcirculatory perfusion and tissue hypoxia. (5)(7) By replacing some of the circulating RBC mass with a crystalloid solution, PET is believed to reduce blood viscosity and improve end-organ perfusion. However, no randomized clinical studies demonstrate a clear benet of PET in the treatment of symptomatic polycythemia. The groups led by Bada, (60) Ratrisawadi, (59) and Kumar (61) randomized only asymptomatic polycythemic infants, while those led by Black, (58) Goldberg, (57) and Malan (56) made no distinction between symptomatic and asymptomatic newborns. In nonrandomized clinical reports, PET has been shown to lower pulmonary vascular resistance, improve cerebral blood ow velocity, (63)(64) and possibly normalize cerebral hemodynamics and improve the clinical status of infants who have polycythemia. (65) However, the long-term benets of PET remain unclear. Concerns remain about potential adverse events following PET. PET was associated with an increased risk of NEC in the systematic reviews performed by both Dempsey (42) (RR, 8.68; 95% CI, 1.06 to 71.1) and Ozek (36) (two studies: typical RR, 11.18; 95% CI, 1.49, 83.64 and typical risk difference, 0.14; 95% CI, 0.05, 0.22). Malan and de V Heese (56) reported that 1 of their 24 patients in the exchanged group developed NEC within the rst 24 hours after PET compared with none of the control patients. Black and associates (58) recorded NEC in 8 of their 43 infants in the PET group compared with none of the 50 control infants. PET also did not alter the frequency of hypoglycemia (two studies) or thrombocytopenia (one study). (36) Given the risks of PET for polycythemia in the newborn and the lack of evidence indicating clear benet, we are generally reluctant to use PET in asymptomatic infants. We do offer PET for treatment of infants who have symptoms that could be ascribed to hyperviscosity, but this decision is taken cautiously, with a careful review of all risk factors. Routine use of PET in neonatal polycythemia is not supported by current evidence, and further study is needed to identify patients who would be more likely to benet from aggressive correction of polycythemia.

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Table 2.

Clinical Trials of Partial Exchange Transfusion in Neonatal Polycythemia


Study Malan and de V Heese (56) Not clearly stated; n49 Hct >65% (0.65) UVC FFP Randomization/ Sample Size Outcome Measurements Brazelton neonatal scale Prechtl neurologic assessment at 10 days Neurodevelopmental assessment at 8 months Hematocrit (Hct) at Enrollment Mode of Exchange/ Replacement uid

Goldberg et al (57)

Not clearly stated; n20

Hct >64% (0.64) and hyperviscosity

UVC FFP

Studies included in the meta-analysis by Ozek et al (36)

Black et al (58)

Randomized; n93

Antecubital venous Hct >65% (0.65) and hyperviscosity

UVC FFP

Bada et al (60)

Not clearly stated; n28 Randomized; n105

Radial artery Hct >65% (0.65) Central venous Hct >65% (0.65) Hyperviscosity (undened) Peripheral venous Hct >70% (0.70)

Route not stated; Plasma protein solution Route not stated Not clearly stated; FFP Peripheral; Normal saline

Studies included in the meta-analysis by Dempsey and Barrington (42)

Ratrisawadi et al (59) Hakanson et al (62)* Kumar and Ramji (61)

Brazelton neonatal scale at 8 hours, 24 hours, 72 hours, and 2 weeks BSID and neurologic assessment at 8 months Neonatal signs BSID and neurologic assessment at 1 and 2 years Cognitive testing at 7 years Cerebral artery Doppler measurement BSID or cognitive testing at 30 months Gasel Development at 1.5 to 2 years BSID at 8 months
hematology

Not clearly stated; n24 Randomized; n22

Neurologic decits at 3, 6, 9, 12, 18 months

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FFPfresh frozen plasma, BSIDBayley Scale of Infant Development, UVCumbilical venous line, * abstract only

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19. Weinberger MM, Oleinick A. Congenital marrow dysfunction

American Board of Pediatrics Neonatal-Perinatal Medicine Content Specications


Know the causes of neonatal polycythemia. Know the clinical manifestations, management, and outcomes of neonatal polycythemia.

in Downs syndrome. J Pediatr. 1970;77:273279

20. Miller M, Cosgriff JM. Hematological abnormalities in newborn infants with Down syndrome. Am J Med Genet. 1983;16: 173177 21. Widness JA, Pueschel SM, Pezzullo JC, Clemons GK. Elevated erythropoietin levels in cord blood of newborns with Downs syndrome. Biol Neonate. 1994;66:50 55 22. Wiedmeier SE, Henry E, Christensen RD. Hematological abnormalities during the rst week of life among neonates with trisomy 18 and trisomy 13: data from a multi-hospital healthcare system. Am J Med Genet A. 2008;146:312320 23. Rabe H, Mercer JS. Early cord clamping protects at-risk neonates from polycythemia. Biol Neonate. 2004;86:108 24. Hutton EK, Hassan ES. Late vs early clamping of the umbilical cord in full-term neonates: systematic review and meta-analysis of controlled trials. JAMA. 2007;297:12411252 25. Rabe H, Reynolds G, Diaz-Rossello J. A systematic review and meta-analysis of a brief delay in clamping the umbilical cord of preterm infants. Neonatology. 2008;93:138 144 26. Airey RJ, Farrar D, Duley L. Alternative positions for the baby at birth before clamping the umbilical cord. Cochrane Database Syst Rev. 2010;10:CD007555 27. Linderkamp O, Versmold HT, Messow-Zahn K, Mu llerHolve W, Reigel KP, Betke K. The effect of intra-partum and intra-uterine asphyxia on placental transfusion in premature and full-term infants. Eur J Pediatr 1978;127:9199 28. Rabe H, Wacker A, Hu lskamp G, et al. A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants. Eur J Pediatr. 2000;159: 775777 29. Chalouhi GE, Stirnemann JJ, Salomon LJ, Essaoui M, Quibel T, Ville Y. Specic complications of monochorionic twin pregnancies: twin-twin transfusion syndrome and twin reversed arterial perfusion sequence. Semin Fetal Neonatal Med. 2010;15:349 356 30. Somer T, Meiselman HJ. Disorders of blood viscosity. Ann Med. 1993;25:3139 31. Linderkamp O. Blood rheology in the newborn infant. Baillieres Clin Haematol. 1987;1:801 825 32. Pearson TC. Hemorheology in the erythrocytoses. Mt Sinai J Med. 2001;68:182191 33. Pozrikidis C. Numerical simulation of blood and interstitial ow through a solid tumor. J Math Biol. 2010;60:7594 34. Sirs JA. The ow of human blood through capillary tubes. J Physiol. 1991;442:569 583 35. Herson VC, Raye JR, Rowe JC, Philipps AF. Acute renal failure associated with polycythemia in a neonate. J Pediatr. 1982; 100:137139 36. Ozek E, Soll R, Schimmel MS. Partial exchange transfusion to prevent neurodevelopmental disability in infants with polycythemia. Cochrane Database Syst Rev. 2010;1:CD005089 37. Rosenkrantz TS, Stonestreet BS, Hansen NB, Nowicki P, Oh W. Cerebral blood ow in the newborn lamb with polycythemia and hyperviscosity. J Pediatr. 1984;104:276 280 38. Rosenkrantz TS, Phillipps AF, Knox I, et al. Regulation of cerebral glucose metabolism in normal and polycythemic newborn lambs. J Cereb Blood Flow Metab. 1992;12:856 865 39. Rosenkrantz TS, Philipps AF, Skrzypczak PS, Raye JR. Cerebral metabolism in the newborn lamb with polycythemia. Pediatr Res. 1988;23:329 333 40. Drew JH, Guaran RL, Cichello M, Hobbs JB. Neonatal whole blood hyperviscosity: the important factor inuencing later neuro-

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53. Dempsey EM, Barrington K. Crystalloid or colloid for partial


exchange transfusion in neonatal polycythemia: a systematic review and meta-analysis. Acta Paediatr. 2005;94:1650 1655 54. de Waal KA, Baerts W, Offringa M. Systematic review of the optimal uid for dilutional exchange transfusion in neonatal polycythaemia. Arch Dis Child Fetal Neonatal Ed. 2006;91:F7F10 55. Wong W, Fok TF, Lee CH, et al. Randomised controlled trial: comparison of colloid or crystalloid for partial exchange transfusion for treatment of neonatal polycythaemia. Arch Dis Child Fetal Neonatal Ed. 1997;77:F115F118 56. Malan AF, de V Heese H. The management of polycythaemia in the newborn infant. Early Hum Dev. 1980;4:393 403 57. Goldberg K, Wirth FH, Hathaway WE, et al. Neonatal hyperviscosity. II. Effect of partial plasma exchange transfusion. Pediatrics. 1982;69:419 425 58. Black VD, Lubchenco LO, Koops BL, Poland RL, Powell DP. Neonatal hyperviscosity: randomized study of effect of partial plasma exchange transfusion on long-term outcome. Pediatrics. 1985;75:1048 1053 59. Ratrisawadi V, Plubrukarn R, Trakulchang K, Puapondh Y. Developmental outcome of infants with neonatal polycythemia. J Med Assoc Thai. 1994;77:76 80 60. Bada HS, Korones SB, Kolni HW, et al. Partial plasma exchange transfusion improves cerebral hemodynamics in symptomatic neonatal polycythemia. Am J Med Sci. 1986;291:157163 61. Kumar A, Ramji S. Effect of partial exchange transfusion in asymptomatic polycythemic LBW babies. Indian Pediatr. 2004;41: 366 372 62. Hakanson DO. Neonatal hyperviscosity syndrome: long-term benet of partial plasma exchange transfusion. [Abstract]. Pediatr Res. 1981;15:449A 63. Murphy DJ Jr, Reller MD, Meyer RA, Kaplan S. Effects of neonatal polycythemia and partial exchange transfusion on cardiac function: an echocardiographic study. Pediatrics. 1985;76:909 913 64. Maertzdorf WJ, Tangelder GJ, Slaaf DW, Blanco CE. Effects of partial plasma exchange transfusion on cerebral blood ow velocity in polycythaemic preterm, term and small for date newborn infants. Eur J Pediatr. 1989;148:774 778 65. Bada HS, Korones SB, Pourcyrous M, et al. Asymptomatic syndrome of polycythemic hyperviscosity: effect of partial plasma exchange transfusion. J Pediatr. 1992;120:579 585

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NeoReviews Vol.12 No.1 January 2011 e27

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polycythemia

NeoReviews Quiz
6. Polycythemia represents an abnormal elevation of the circulating red blood cell mass, which increases the risk of hyperviscosity, microcirculatory hypoperfusion, and multisystem organ dysfunction. Of the following, the hematocrit threshold that best denes polycythemia is: A. B. C. D. E. 55% 60% 65% 70% 75% (0.50). (0.60). (0.65). (0.70). (0.75).

7. Polycythemia in neonates is often associated with metabolic complications. Of the following, the most common metabolic abnormality associated with polycythemia in neonates is: A. B. C. D. E. Hyperchloremia. Hyperkalemia. Hypernatremia. Hypocalcemia. Hypoglycemia.

8. The treatment of polycythemia includes partial exchange transfusion in which a precalculated volume of blood is replaced by an equivalent volume of uid. Of the following, the most accepted choice of uid for partial exchange transfusion is: A. B. C. D. E. Albumin solution. Fresh frozen plasma. Lactated Ringer solution. Normal saline. Plasma protein fraction.

e28 NeoReviews Vol.12 No.1 January 2011

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Polycythemia in the Newborn Juan I. Remon, Aarti Raghavan and Akhil Maheshwari NeoReviews 2011;12;e20-e28 DOI: 10.1542/neo.12-1-e20

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