polycythemia neonate

1. Neonatal
PolycythemiaDr. vijay
Moderator : Dr. Sanjeev

2. OBJECTIVES
 Definition
 factors that potentially influence neonatal hematocrit
 Major causes of polycythemia
 Effects (signs and symptoms) and complications
 Clinical trials that studied the effects of partial
exchange transfusion (PET)
 Recommendations - diagnosis & management of NP

3. DEFINITION
 Neonatal polycythemia defined in most neonatology textbooks as a
venous HCT >65%
 This cutoff has been chosen based on the observation that blood
viscosity exponentially increases above a Hct of 65%
 or hemoglobin concentration higher than 22.0 g/dl
 a statistical definition of infants at risk
 neither based upon the risk for symptoms or for complications

5. MEASURE HEMATOCRIT OR BLOOD
VISCOSITY?
 How to define hyperviscosity ?
 Viscosity depends on Hematocrit, plasma proteins (especially
fibrinogen), deformability of erythrocytes, erythrocyte aggregation ,
interaction of cell components with vessel walls
 The gold standard - measurement of viscosity is a whole blood
viscometer that can accurately measure the viscosity of blood
(expressed in centipoise)
 whole blood viscometers are not universally available
 Because the erythrocyte number is the most important factor affecting
viscosity, measurement of the neonatal Hct has been suggested as the
best clinical screening test for identifying infants with presumed
hyperviscosity

6. factors influence normally HCT
 1. Gestational age
 HCT increases progressively with increasing gestational age, thus NP may occur at
much higher rates in post term than in preterm infants (Due to normal variation of
Hct)
 2. Degree of placental transfusion
 At term, the total fetoplacental blood volume is about 115 ml/kg fetal weight, and is
distributed in the "normal" full-term infant after birth as approximately 70 ml/kg
 in the infant, with 45 ml/kg remaining in the placenta. This distribution may vary
considerably, as more or less blood may remain in the placenta.
 The main factors influencing placental transfusion are time of cord clamping, position
of the delivered infant in relation to the placenta, onset of respiration, presence or not
of intrauterine hypoxia, and presence or not of cord compression

9. A. Time of cord clamping
Within 30 to 45 seconds following birth, the umbilical arteries are functionally
closed, while blood flow from placenta to fetus through the umbilical vein may
continue for a few additional minutes .
When the infant is delivered at or below the introitus level, if the cord is not
clamped, her/his blood volume will increase in a stepwise manner, reaching 55%
additional
volume after 3 minutes
B. Position of the delivered infant in relation to the placenta
In vaginally delivered infants who are kept 50 to 60 cm above the placenta,
placental transfusion does not occur (7). In contrast, if they are maintained 40 cm
below the placenta, placental transfusion is hastened
C. Onset of respiration
onset of respiration (through generating a negative intrathoracic pressure and
presumably increasing the placental-fetal transfusion process

10. Polycythemia
Study Level of Evidence Inclusion/Exclusion Intervention Outcomes Statistics/Notes
McDonald & Middleton, 2008 Cochrane Review; Cord
clamping effects in mothers
and term infants. 11 trials.
Term infants >= 37 weeks
gestation. Excluded breech
presentation & multiple
pregnancies.
Variable timing of cord
clamping in the various trials;
1-5 minutes, cessation of
pulsation, after placental
descent, etc.
Polycythemia, Hgb/Hct (@
birth, 24-48hrs, 2-4 months, 4
months, & 6 months).
No statistically significant
differences found for
polycythemia.
Hutton and Hassan, 2007 Meta-analysis (15 controlled
trials (8 randomized,7 not
randomized) of Late vs Early
clamping in full tern neonates
15 controlled trials (1912
newborns). 37 or greater
wks.
ICC vs. late (at least 2
minutes, as defined by this
meta-analysis).
Noted increased risk of
asymptomatic polycythemia >
65%
No treatment was needed for
noted asymptomatic
polycythemia.
Kugelman et al, 2007 RCT. 35 neonates. 24-34 6/7 wks.
Exluded: vaginal bleeding
(abruption, previa, placental
tear), major anomaly, severe
IUGR < 3%, MGDM w/
insulin, twin-twin or
discordant (>20% wt),
maternal drug abuse.
Hold baby as low as possible
without creating tension on
cord (20-30cmbelow vaginal
introitus, or below incision if
C/S). ICC (5-10”) vs. DCC
(30-45”)
Primary: Initial Hct, MAP
during 1st
24 hours.
No significant increase in
polycythemia.
Ultee et al, 2006 RCT 41 infants, 34 wks to 36 6/7
wks; Caucasian mothers.
Excluded DM, GDM, PIH,
twins, congenital abnls.
Infants placed on mother’s
abd at neutral position.
ICC < 30 seconds vs. DCC at
3 minutes.
Primary: Hct at 1 hour & 10
weeks of life; polycythemia
(defined as Hct > 0.7)
Hct higher w/ DCC compared
to ICC @ 1 hr & 10 wks (P <
0.05)
No significant differences
found between the two groups
in regards to polycythemia.
Chaparro et al, 2006 RCT 476 normal birthweight infants
between 36-42 weeks
gestation. Exclude: multiple
gestation, PreE or Eclamp,
hemorrhage,placental abnl,
Trisomy, congenital abnl, any
type of diabetes, HTN,
Early (10 seconds; mean <
20”)) vs. DCC (2 minutes;
mean > 90”). Timed from
delivery of shoulders.
Maintained @ level of uterus.
Secondary: Percentage of
infants w/ capillary Hct > 70%
Did not see significantly
increased risk of polycythemia
Delayed Cord Clamping

11. Clinical bottom line: Delayed cord clamping does not increase the risk of polycythemia,
especially in preterm neonates. Most studies found no clinically or statistically significant
increases in polycythemia for babies who received delayed cord clamping. Studies of term
infants were also included; any polycythemia seen in these children was asymptomatic/not
clinically significant and required no therapy.
cardiopathies, chronic renal dz,
+ tobacco use, not planning to
breastfeed for @ least 6
months.
Cernadas et al, 2006 RCT 2 obstetrical units in
Argentina. 276 neonates with
uneventful pregnancies >= 36
wks. Included those with
uneventful cephalic vaginal or
C/S delivery, singletons.
Excluded if > singleton,
complicated course, cliinca ldz
(DM, PreE, HTN, etc.),
evidence of congenital
malformations, IUGR (<
10th
%ile).
CC within first 15 seconds
(group 1; mean 12.7 sec),
within 1 minute (group 2;
mean 59.8 sec), or at 3
minutes (group 3; mean 169.5
sec).
For vaginal deliveries, babies
held in mother’s arms. C/S,
placed on mother’s lap.
Babies received ICC if no
spontaneous respiratory effort
in first 10 seconds, or if
discovered congenital
malformation, unexpectedly
low birthweight, tight nuchal
cord.
Primary: Hct at 6hrs of life.
Secondary: Hct @ 24 & 48
hrs, bili levels, neonatal
morbidity/mortality, maternal
hemorrhage/Hct, etc.
Prevalence of Hct < 45%
significantly less in grps 2&3
vs. 1.
Prevalence of Hct > 65%
significantly increased in grp
3 (14.1%) vs. grps 1 (4.4%)
&2 (5.9%).
No babies w/ Hct > 65 were
symptomatic.
Van Rheenen et al, 2007 RCT. 91 term babies. Exclusions:
Twins, history of post-partum
hemorrhage, GDM, PreE,
placental separation before
delivery, C/S, tight nuchal cord
necessitating early cutting,
need for resuscitation, major
congenital anomalies.
Vaginal births; held 10 cm
below introitus. ICC within
20 seconds (mean 15”) vs.
DCC done after cessation of
cord pulsation (mean 305
seconds, with SD of 136”).
Secondary: Included possible
side effects (neonatal
polycythemia/hyperviscosity,
maternal blood loss, etc.)
No statistically significant
differences were found.
RCT in malaria-endemic area.
Partially blinded RCT. Not
intention to treat.
Ibrahim et al, 2000 RCT 32 infants with bwt 501-1250
grams and gestational ages of
24 to less than 29 weeks.
Excluded major congenital
anomalies, twin to twin
transfusion, maternal diabetes,
placenta previa/abruption, or
maternal history of drug abuse.
DCC (20 seconds). Timing
started once baby completely
out of birth canal in VD. Held
supine at level of introitus.
Primary: Initial Hct/Hgb. No polycythemia seen.

12. D. Presence or not of intrauterine hypoxia
Acute intrapartum and intrauterine asphyxia can be accompanied by an
increase in hematocrit (presumably through increased transcapillary escape of
plasma)
E. Presence or not of cord compression
Because the umbilical vein is more compressible than the
umbilical arteries, infants born with a tight nuchal cord may actually have low
blood volume at birth
F. Dehydration
Relative loss of water from body
3. Site of blood sampling
Capillary HCT is generally higher than venous HCT which in turn is higher
than "central" HCT (from umbilical vein) . Capillary HCT from warmed heels
correlates well with venous HCT

13. 4. Time of blood sampling
Hematocrit rises from values obtained at birth (from cord venous or arterial
sampling) to reach a peak at 2 hours of age, staying at a plateau for 2 additional hours,
then decreases to go back to values close to cord blood values by 12 to 18 hours of age.

14. CAUSES OF POLYCYTHEMIA
Classified as
 Normovolemic
 hypervolemic
 Hypovolemic

15. 1. Normovolemic Polycythemia
condition where normal intravascular volume is present despite an increase in
red cell mass. It results from increased RBC production due to placental
insufficiency and/or chronic intrauterine hypoxia
Intrauterine Growth Restriction
Maternal Pregnancy Induced Hypertension
Discordant Twins
Maternal Diabetes Mellitus
Prolonged Intrauterine Tobacco Exposure
Postmaturity

16. 2. Hypervolemic polycythemia
occurs when higher than average blood volume is accompanied by an increased
red cell mass
acute transfusion to the fetus such as maternal-fetal transfusion
twin-to-twin transfusion
3. Hypovolemic polycythemia
occurs secondary to a relative increase in number of erythrocytes to plasma
volume
intravascular dehydration

17. EFFECTS AND
COMPLICATIONS OF
POLYCYTHEMIA

18. A. Hyperviscosity
leads to a reduction in cerebral blood flow
decreased blood flow to the brain→ decrease supply to the brain of other substances
carried by plasma, such as glucose, amino acids
B. Decreased cerebral blood flow
glucose delivery and utilization in the brain decreases
C. Increased cellular breakdown of the increased red cell mass
Increased breakdown of red cells in NP may be a significant contributing factor of
neonatal hyperbilirubinemia
D. Hemodynamic effects of hypervolemia or of hypovolemia
hypervolemia may lead to congestive heart failure, pulmonary edema, and
cardiorespiratory failure
hypovolemia can lead to hypoxic-ischemic injury to vital organs.

19. A. Central nervous system (CNS).
Poor feeding,
lethargy,
hypotonia,
apnea,
tremors,
jitteriness,
seizures,
cerebral venous thrombosis.
B. Cardiorespiratory.
Cyanosis,
tachypnea,
heart murmur,
congestive heart failure,
cardiomegaly,
devated pulmonary vascular resistance,
prominent vascular markings on chest x-ray.

20. C. Renal.
Decreased glomerular filtration,
decreased sodium excretion,
renal vein thrombosis,
hematuria,
proteinuria.
D. Other.
thrombocytopenia,
poor feeding,
increased jaundice,
persistent hypoglycemia,
hypocalcemia,
testicular infarcts,
necrotizing enterocolitis (NEC),
priapism,
disseminated intravascular coagulation.

21. The long-term neurodevelopmental outcome controversial.
 higher risk for development delays
 Speech and fine motor abnormalities
 lower spelling and arithmetic achievement test results and gross motor
skills

22. Indications for polycythemia screening
 Do not routinely screen well term newborns for this syndrome,
because there are few data showing that treatment of asymptomatic
patients with partial exchange transfusion is beneficial in the long
term
 Small for gestational age (SGA) neonates
 Large for gestational age (LGA) neonates
 Infants of diabetic mothers (IDM)
 Newborns with morphological features of growth restriction
 Monochorionic twins especially the recipient twin

23. How to screen
Hematocrit at 2nd- 4th HOL
Hematocrit > 65%
Hematocrit < 65%.
No symptoms
No further evaluation
With symptoms Without
symptoms
PET
repeat -12 & 24
HOL

24. MANAGEMENT

25. A. Once other causes of illness have been considered and excluded (e.g., sepsis,
pneumonia, hypoglycemia), any child with symptoms that could be due to
hyperviscosity should be considered for partial exchange transfusion if the
peripheral venous hematocrit is >65%.
B. Asymptomatic infants with a peripheral venous hematocrit between 60% and
70% can usually be managed by increasing fluid intake and repeating the
hematocrit in 4 to 6 hours.

26. C. exchange transfusion when the peripheral venous hematocrit is >70% in the
absence of symptoms, but this is a controversial
D. The following formula can be used to calculate the exchange with normal saline
that will bring the hematocrit to 50% to 60%. In infants with polycythemia, the blood
volume varies inversely with the birth weight

27. TECHNICAL ASPECTS OF PET
 Which Diluting Fluid Should Be Used?
Plasma, 5% Albumin, Ns, Or Ringer Solution
PET Is Efficient In Relieving Immediate Symptoms And
Reducing HCT.
It Did Not Find Clinically Differences
Thus NS Is The Optimal Fluid (Cheapest, With Less Potential
Side-effects)

28. How much to exchange?
 Aim for a target, post PET HCT of 55%

29. CONCLUSIONS
 1. PCT is a venous hematocrit of at least 65%. Such a number
is much more likely to be significant in an infant >6 hours than
it is at 2-4 hours of age.
 2. Symptoms/complications of polycythemia are unlikely to be
related to a hematocrit of < 65%.
 3. The need for PET and its efficacy have not been
demonstrated when PET was conducted after 6 hours of life in
asymptomatic infants (regardless of their hematocrit). There is
no evidence that PET alters the neurologic or developmental
outcomes of asymptomatic polycythemic neonates.

30. Outcome of PET
Polycythemia
Hyperviscosity
Chonic intrauterine
hypoxia
Chronic uterine
hypoxia +
polycythemia
PET
will
help
PET
will
not
help
PET
partially
helps

31. Malan et al
1980
 RCT, 49 neonates
 Venous HCT>65
 No or mild symps
o PET> 12 hrs
o Follow up at 8 mo
No Diff
Goldberg et al
1982
 RCT, 20 neonates
 Capillary HCT>68% + presence
of hyperviscosity on venous blood
 nil symp
o PET was performed
at > 12 hrs
o Follow up at 8 mo
No diff
Black's et al
1985
 RCT, 93 neonates
 heel stick screening HCT > 65%,
a repeat venous
HCT>65%, and a venous blood
viscosity increased,
 all neonates
o PET performed at 8-
12 hrs
o Follow up at 2 yrs
o addnl follow up at 7
yrs
No diff in
mental
delay rate,
motor
delay
improved
Bada et al
1992
 RCT, 28 neonates
 cord blood HCT>57+ arterial
blood HCT >62%+ presence of
hyperviscosity
o PET at >6hrs(av 10
hrs)
o Follow up at 2 yrs
No diff in
MDI and
IQ

32. The clinical trials conducted to date do not allow to reach a practical conclusion,
because of the following inherent flaws in design:
1) CNS "damage" may have already occurred before PET was conducted, because
PET was performed too late.
2) Confounding variables that may have affected the outcome
(such as number of IDM’s, infants of pre eclamptic mothers, smokers, intrauterine
growth restriction (IUGR), in whom CNS “damage” may have occurred in utero,
unrelated to the polycythemia), were not taken into account in any study
3) the small sample size of all studies
4) follow up of infants was very partial, and did not included all of them. Thus this
working group concludes that PET performed after 6 hours of life (after the
peak hematocrit/viscosity) is not likely to significantly alter the neurologic or
developmental outcomes of asymptomatic polycythemic neonates
5) the effect of PET in symptomatic infants has not been systematically studied

33. RECOMMENDATIONS
 1. Routine screening for polycythemia is not recommended.
 2. Routine performance of PET in asymptomatic infants is not
recommended.
 3. Screening for symptoms should be performed carefully and
documented in all infants with polycythemia.
 4. Normality of blood glucose should be documented in all
infants found to have polycythemia.
 5. PET causes a prompt relief of symptoms. the presence of
symptoms (or of hypoglycemia) should lead to perform PET

34.  6. PET should be performed as early as possible whenever
symptoms are present, in view of the potential for more severe
symptoms and complications to develop. Before proceeding
with PET, it appears that there is a need for thorough, timely,
clinical and physical assessment of the newborn.
 7. If performed, PET should be done with normal saline.