Neonatal Hyperviscosity

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PEDIATRICS Vol. 72 No. 4 October 1983 567

COMMENTARIES

Neonatal

Hyperviscosity

Increased viscosity of the blood in newborn

in-fants has been known to be associated with

signifi-cant morbidity for more than a decade.4 A recent

review of neonatal polycythemia and hyperviscosity

by Black and Lubchenco5 summarizes the available

literature and emphasizes the diagnostic and

man-agement problems that pediatricians currently face.

This commentary will attempt to highlight some of

these problems. During this discussion, measure-ments of hematocrit refer to venous microhemato-crits and viscosity refers to measurements by the

Wells-Brookfield microviscometer on heparinized

whole blood samples, unless otherwise specified.

The syndrome of neonatal hyperviscosity may be

defined as alterations in flow properties of blood

associated with symptoms and signs of organ dys-function. The major determinates of blood flow

properties or viscosity are erythrocyte number,

erythrocyte deformability, and plasma proteins.

Neonatal polycythemia, defined as a venous

hem-atocrit greater than 65%, is the primary cause of

hyperviscosity in the newborn infant. At a

hema-tocrit level of 63% to 65% and above, the viscosity

of whole blood is beyond two or even three6

stand-ard deviations from the mean in newborns. As the

hematocrit increases, changes in RBC

deformabil-ity have a great effect on viscosity. If RBCs were

nondeformable, blood would cease to flow at

hem-atocrit levels greater than 60%. Although studies of

fetal RBC deformability have been controversial,7’8

abnormal RBCs (antibody damage, inherited RBC

membrane defects, RBC fragmentation) might be

expected to decrease deformability and increase the

whole blood viscosity as well as alter

microcircula-tory rheology. More specific information on

neo-natal erythrocytic deformability and its relation to

the hyperviscosity syndrome is needed. In the past

it has been assumed that the effect of plasma pro-teins on neonatal viscosity is minor. Fibrinogen is

the major protein that affects the interaction

be-tween RBCs and thus whole blood viscosity. In

normal infants, the relatively lower fibrinogen level

would have little effect on increasing the blood

viscosity; however, in pathologic or stress states, a

high fibrinogen level may be associated with

in-creased viscosity.9

Clinical manifestations that have been associated

with neonatal polycythemia and hyperviscosity in

both animals and man include the following. (1)

Cardiopulmonary signs may mimic congenital heart

disease and include cyanosis, tachypnea, evidence

for persistent fetal circulation, and cardiomegaly. (2) Central nervous system manifestations are poor

feeding, lethargy, jitteriness, apnea, and seizures.

Brazelton behavior assessment abnormalities in-dude hypotonia, poor state control, weak suck, and

vasomotor instability followed later (24 to 48 hours)

by hypertonia, startles, and irritability. These

in-fants often require intravenous fluid

supplementa-tion. Severe structural abnormalities of the brain

(infarction, hemorrhage) rarely occur. Cerebral

blood flow is reduced in polycythemic adults and

infants.’0 (3) The gastrointestinal tract

manifesta-tions of hyperviscosity include necrotizing

entero-colitis.” In addition, preliminary studies have noted

more necrotizing enterocolitis in hyperviscous

in-fants who underwent exchange transfusion.’2 (4)

Renal manifestations associated with polycythemia have included decreased renal plasma flow and

decreased glomerular filtration in both animals and

man. Transient renal failure in the newborn may

be related to hyperviscosity.13 (5) Hematologic

changes include thrombocytopenia, RBC

fragmen-tation, and, occasionally, activation of coagulation.

Most infants with hyperviscosity show coagulation

tests and factor levels compatible with their age.” Thrombotic complications have been seen in

asso-ciation with polycythemia but the relationship of

neonatal hyperviscosity to neonatal

hypercoagula-bility has not been well studied. (6) Metabolic

de-rangements such as hypoglycemia and

hypocalce-mia are relatively frequently associated with

hyper-viscosity, especially in small-for-gestational age

in-fants. In summary, the clinical manifestations of

the hyperviscosity syndrome are well documented and, indeed, do appear to be related to the altered rheology of the infant’s blood.

Neonatal hyperviscosity is a common disorder. The incidence has been reported as 5% at 1,612

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568 PEDIATRICS

Vol. 72 No. 4 October

1983

meters’5 and 2.9% at sea level.’6 In addition to the

possible effect of altitude, several other factors are

etiologically related to the syndrome. Twin-to-twin

transfusions, delayed cord clamping at delivery,

chronic intrauterine hypoxia (small-for-gestational age and postmature infants), infants of diabetic mothers and large-for-gestational age infants, chro-mosomal abnormalities, and neonatal

thyrotoxi-cosis have all been associated with polycythemia

and hyperviscosity. The syndrome is rarely seen in

preterm infants. The relationship of these factors

to erythropoietin levels, RBC deformability, and plasma protein levels is largely unknown.

The recognition and diagnosis of neonatal

hyper-viscosity is usually based on two clinical

ap-proaches: (1) the routine screening of all infants for

an elevated capillary hematocrit level; and/or (2)

the testing of infants who develop signs and

symp-toms that may be attributable to neonatal

hyper-viscosity. Most investigators have shown good

cor-relation between capillary and venous hematocrit levels obtained after four hours of age, although the capillary hematocrit level is usually higher. At the present time, the evidence would indicate that a

capillary hematocrit level obtained from a warm

heel at about four to six hours of age that is greater than 70% will detect most hyperviscous infants. Hyperviscous infants who have venous hematocrit

levels less than 63% to 65% may be missed by

capillary screening. The detection of these infants

who have hyperviscosity without significant

poly-cythemia (incidence unknown) or who develop

po-lycythemia in the first few days of life (incidence unknown) must rely on a high index of suspicion based on clinical signs and symptoms. Because of the difficulty in objective assessment of the subtle

signs of the hyperviscosity syndrome (lethargy,

jit-teriness, alteration in awareness state and muscular tone, poor feeding, etc), reliance upon these signs to indicate which infants should have blood viscos-ity measurements may be too insensitive. The

com-mon sense approach would indicate that both

rou-tine capillary hematocrit measurements and clini-cal assessment of pertinent signs are indicated to detect infants who should have further testing.

Ramamurthy and Brans6 have recently

demon-strated that the umbilical vein hematocrit level was significantly lower (mean = 63%) than in peripheral

vein (mean = 71%) in infants who capillary

hema-tocrit levels were 70% or greater. Whole blood

viscosity was directly related to the hematocrit

levels. These authors suggest that reliance on the

peripheral venous hematocrit would lead to

unnec-essary exchange transfusions. However, many of

the infants who would have been excluded from treatment by use of umbilical vein measurements

did have significant symptoms. Previous studies have shown good correlation of symptoms with

abnormal peripheral venous viscosity

measure-ments. Therefore, further information on the site of sampling for whole blood viscosity, patient symp-toms, and ultimate outcome are needed to resolve

this controversy. Certainly, abnormal high capillary

hematocrit levels should be confirmed by peripheral venous hematocrit and viscosity measurements in borderline instances before therapeutic endeavors.

Once the diagnosis of neonatal hyperviscosity has

been made, the decision to treat by lowering the

viscosity is mainly related to two factors: (1) clinical

illness at the moment; and (2) long-term neurologic

or other morbidity. Hyperviscous infants who show

significant neurologic or cardiorespiratory signs as

well as those with evidence of gastrointestinal or

renal function impairment should be treated. Other factors that are possibly contributory to abnormal neurologic outcome (maternal preeclampsia, fetal

distress, hypoglycemia) should be considered in the

clinical evaluation.’7

The decision to treat the asymptomatic

hypervis-cous infant must, at present, be based on relatively

little data. In a study of 49 hyperviscous infants (24

had partial plasma exchange transfusion), all were developmentally and neurologically normal at 8 months of age.’8 In contrast, in a similar study, Goldberg and others’9 found that neurologic abnor-malities were more common in nonexchanged

in-fants (four of six) than exchanged infants (five of

ten). In a randomized study of 94 polycythemic

hyperviscous infants, Black and others’2 showed

that neurologic abnormalities were more common among the nonexchanged group at 2 years of age

and were independent of nursery symptoms. Of 55

infants who were asymptomatic in the newborn

period, 22 (40%) had mild to moderate neurologic sequelae at the 2-year follow-up. Thus, treatment of the asymptomatic and definitely hyperviscous infant would appear to be indicated to this observer

from data discussed above.

Several methods have been suggested to

accom-plish the decrease in blood viscosity; these include

partial exchange transfusion through the umbilical vein, removal of blood from the umbilical artery and replacement through peripheral veins, or ye-nous/arterial phlebotomy alone plus intravenous fluid replacement. All methods have used various replacement fluids including 5% albumin solution, fresh frozen plasma, or Plasmanate. No data exist

as to which of these methods is most efficient and

with the least complications. The author’s preferred method is partial exchange through an umbilical vein catheter (check position by lateral abdominal roentgenogram) in the ductus venosus (not portal

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COMMENTARIES 569

system) or vena cava using fresh frozen plasma or

Plasmanate in a volume calculated as follows:

(oh-served venous hematocrit - desired venous

hema-tocrit (55%)/observed venous hematocrit x weight

(kilograms) x blood volume. The blood volume may

vary in polycythemic infants20 and may be

esti-mated as 100 mL/kg in smaller babies and 85 mL/ kg in larger infants. Adjunctive measures to prevent

aggravation or occurrence of necrotizing

enterocol-itis need evaluation (heparin, blood filters, dextran,

etc).

REFERENCES

WILLIAM E. HATHAWAY, MD

University of Colorado Health

Sciences Center

Denver

1. Sommer A, Kontras SB: Studies of blood viscosity in the

normal newborn. Biol Neonate 1971;17:441

2. Gross GP, Hathaway WE, McGaughey HR: Hyperviscosity

in the neonate. J Pediatr 1973;82:1004

3. Mackintosh TF, Walker CHM: Blood viscosity in the

new-born. Arch Dis Child 1973;48:547

4. Bergqvist G: Viscosity of the blood in the newborn infant.

Acta Paediatr Scand 1974;63:858

5. Black VD, Lubchenco LO: Neonatal polycythemia and

hy-perviscosity. Pediatr Clin North Am 1982;29:1137

6. Ramamurthy RS, Brans YW: Neonatal polycythemia: I. Criteria for diagnosis and treatment. Pediatrics 1981;68:168

7. Gross GP, Hathaway WE: Fetal erythrocyte deformability.

Pediatr Res 1972;6:593

8. Linderkamp 0, Wu PYK, Meiselman HJ: Deformability of

density separated red blood cells in normal newborn infants

and adults. Pediatr Res 1982;16:964

9. Riopel L, Fouron JC, Bard H: Blood viscosity during the

neonatal period: The role of plasma and red blood cell type. J Pediatr 1982;100:449

10. Rosenkrantz TS, Oh W: Cerebral flow velocity in infants

with polycythemia and hyperviscosity: Effects of partial

exchange transfusion with plasmanate. J Pediatr 1982;

101:94

1 1. Hakanson DO, Oh W: Necrotizing enterocolitis and

hyper-viscosity in the newborn infant. J Pediatr 1977;90:458

12. Black V, Lubchenco LO, Koops BL, et al: Neonatal

hyper-viscosity: Randomized study of partial plasma exchange in altering long-term outcome. Pediatr Res 1982;16:279A

13. Herson VC, Raye JR, Rowe JC, et al: Acute renal failure

associated with polycythemia in a neonate. J Pediatr

1982;100:137

14. Katz J, Rodriguez E, Mandani G, et a!: Normal coagulation findings, thrombocytopenia, and peripheral

hemoconcentra-tion in neonatal polcythemia. J Pediatr 1982;101:99

15. Wirth FH, Goldberg KE, Lubchenco LO: Neonatal

hyper-viscosity: I. Incidence. Pediatrics 1979;63:833

16. Stevens K, Wirth FH: Incidence of neonatal hyperviscosity at sea level. ,J Pediatr 1980;97:118

17. Black VD, Lubchenco LO, Luckey DW, et al: Developmental

and neurologic sequelae of neonatal hyperviscosity

syn-drome. Pediatrics 1982;69:426

18. van der Elst CW, Molteno CD, Malan AF, et al: The

man-agement of polycythemia in the newborn infant. Early Hum

Dev 1980;4:393

19. Goldberg K, Wirth FH, Hathaway WE, et a!: Neonatal

hyperviscosity: II. Effect of partial plasma exchange

trans-fusion. Pediatrics 1982;69:419

20. Rawlings JS, Pettett G, Wiswell TE, et al: Estimated blood

volumes in polycythemic neonates as a function of birth

weight. .tPediatr 1982;101:594

Maternal-Infant

Bonding:

A Joint

Rebuttal

Inaccuracies in Lamb’s recent review’ of studies

of maternal-infant bonding have resulted in

consid-erable confusion and misunderstanding among those not well acquainted with the field. This

re-buttal, prepared by the investigators whose works

were sited, addresses these inaccuracies so that a fuller and more productive discussion of this area of study can occur in the future. Under the name of each investigator, Lamb’s criticisms are quoted, after which the original researcher responds with corrected information.

Lamb in his criticism of the work of Hales et al2 notes that, “Many ofthe researchers have employed

multiple measures and observed statistically

sig-nificant differences on a small proportion of these.

Generally, the number of significant group

differ-ences usually hovers around the number that would

be expected to occur by chance.” He further

com-ments, “It is not clear that any effects observed are

accounted for by early contact rather than

differ-ences in treatment by medical and nursing staff

who know that the study group subjects are spe-cial.”

Hales responds, “We studied 60 healthy

primi-parous mothers in Guatemala. The study was

de-signed to test the effect of the differences of timing

of nude mother-infant contact on maternal

behav-ior at 36 hours postpartum. The early-contact group

received their nude infants immediately post

par-turn; the delayed-contact group received their nude infants 12 hours after delivery; and the control

group received their dressed infants in a crib after

12 hours. The observer and nursing staff were

un-informed as to the experience of the mothers .. . in

fact, the nurses on the postpartum division did not

even know which mothers were enrolled in the study. (At Roosevelt Hospital there were 60 deliv-eries per day, and we enrolled our 60 subjects over six weeks. Given the fact that there were only two

or three nurses on the entire maternity ward, it is

extremely unlikely they could have given special

attention to the mothers in the study.) We made

observations of 32 maternal-infant behaviors on

the second day after birth. Only 13 of these

behav-iors were used to compare the mothers. Prior to the

data collection, we had separated these 13 behaviors

Reprint requests to (M.H.K.) Departments of Pediatrics and Human Development, Michigan State University, E Lansing, MI 48824-1317.

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1983;72;567

Pediatrics

WILLIAM E. HATHAWAY