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Introduction: oxygen transported to the tissues can

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Introduction:

Perinatal asphyxia is a
serious problem globally, and it is a common cause of neonatal mortality and
long-term morbidity. Data from National Neonatal Perinatal Database 1 suggest
that perinatal

asphyxia contributes to
almost 20% of neonatal deaths in India. Of the 1.2 million neonatal deaths in
India every year, 300,000 – 350,000 infants die due to perinatal asphyxia
mostly within first 3 days of life 2.

Perinatal asphyxia can
cause severe hypoxic-ischemic damages in the organs of neonates and cause
severe long-term consequences or fatal complications. So, predicting the
prognosis of asphyxia for prevention and targeted treatment before the
incidence of complications should be given the high priority in neonatology and
pediatrics.(3,4) Thus, a reliable marker is required to predict the hospital
stay and the prognosis of neonates with perinatal asphyxia.(5)

However
there is no effective indicator for prediction of perinatal asphyxia although a
combination of different methods and markers could help in the diagnosis of
perinatal asphyxia 6. Nucleated red blood
cells (NRBCs), or erythroblast, are the premature forms of erythrocytes that
are commonly found in newborn’s blood. Any condition that reduces the quantity
of oxygen transported to the tissues can cause an increase in the rate of RBC
production.

It
has recently been suggested that the increase in NRBC count in the umbilical
vein of newborns can be considered a sign of birth asphyxia 7. In healthy newborns,
NRBC count is reduced by half 12 h after birth, and there are only 20–30
NRBCs/m3 48 h after birth. Although on the third or fourth day of birth, NRBCs
are not seen in the blood circulation, but in preterm newborns, small amounts
of NRBCs may be seen in the first week of life 8–11. On the other hand,
tissue hypoxia results in increased levels of erythropoietin and erythrocytes.
NRBC count reflects high production of erythropoietin; it means that
erythropoietin stimulates fetal hematopoietic system, mainly in bone marrow,
which increases the production of RBCs 12–13. Increase in NRBC count is often
due to prematurity, ABO or RH blood incompatibility, increase in hematopoiesis
followed by chronic diseases, maternal diabetes, preeclampsia, fetal anemia,
intrauterine infections, chorioamnionitis and acute or chronic asphyxia
12,14–17

 

 

 

 

 

 

 

Review of Literature:

Although
nucleated red blood cells (nRBCs) are rarely found circulating in older
children,(18) they are commonly seen in the blood of newborns. They are
primarily produced in the fetal bone marrow in response to erythropoietin and
are stored in the marrow as precursors to reticulocytes and mature
erythrocytes. Many acute and chronic stimuli cause increases in the number of
circulating nRBCs from either increased erythropoietic activity or a sudden
release from the marrow storage pools.

nRBCs
are present in the placental vessels through the first half of pregnancy, but
are uncommon later in pregnancy and are usually absent or present only in small
numbers at term. The finding of numerous nRBCs in the term placenta is
non-specific and may indicate acute or chronic fetal hypoxia, maternal
diabetes, fetal anaemia, or congenital TORCH infections (toxoplasma, other
viruses, rubella, cytomegalovirus, herpes).(19-24)

Diferential
diagnosis of increased nucleated red bloods cells in the fetus and newborn

I.                  
Physiological Labour and vaginal births
Preterm newborns Post-term newborns

II.               
Increased erythropoiesis Chronic hypoxia
Growth restriction Maternal pre-eclampsia Maternal smoking Anaemia Blood loss
Haemolysis—ABO or Rh isoimmunization, other Maternal diabetes Other Leukaemia
Down’s syndrome TORCH infections

III.            
Acute stress release Acute hypoxia Subacute
hypoxia Chorioamnionitis

IV.           
 Postnatal hypoxia Cyanotic heart disease
Pulmonary failure V. Idiopathic TORCH, Toxoplasma, other viruses, rubella,
cytomegalovirus, herpes.

Studies
have consistently shown decreasing nRBCs as the gestational age increases,
except that post-term infants have higher counts than term infants.(25-29)
Small premature newborns may normally have up to 10 000 nRBCs/mm3 . In the
normal neonate, nRBCs are rapidly cleared from the bloodstream after
birth.(30,31,32) By 12 hours of age, the counts fall by about 50%, and by 48
hours only 20–30 nRBCs/mm3 are found. In healthy term newborns, virtually no
nRBCs are found after the third or fourth day of life, although they may
persist in small numbers up to 1 week in preterm newborns.(25,28)

Boskabadi et al 2016 (33)
conducted a study on sixty-three neonates with asphyxia and followed them  up for two years. NRBC-level was determined
per 100 white-blood-cells (WBC). After discharge, follow-up of asphyxiated
infants was performed using Denver II test at 6, 12, 18 and 24 months. They
demonstrated that NRBC/100 WBC and absolute NRCB count can be used as
prognostic marker for neonatal asphyxia, which in combination with the severity
of asphyxia could indicate high infant mortality, and complications of
asphyxia.

Ghosh
et al 2003(6)  conducted a study to
determine normal level of nucleated red blood cells (NRBC) per 100 white blood
cells (WBC) in cord blood of term non-asphyxiated newborns and to investigate
variations in NRBC counts in perinatal asphyxia.The study showed high NRBC
count in umbilical blood correlated with poor early neonatal outcome.The level
of NRBC per 100 WBC correlates both with acute as well as chronic antepartum
asphyxia. It  further concluded that NRBC
can be used as a reliable index of early neonatal outcome.

Goel et al  2013 (34) conducted a case control study on
50 asphyxiated and 50 normal newborns  to
investigate variations in nucleated red blood cell (NRBC) in blood associated
with perinatal asphyxia and its relationship to both the severity and short
term prognosis of asphyxia.the study showed there was a significant (P < 0.01) correlation of the number of NRBC100 WBC with Apgar scoring, HIE staging and mortality. It concludedthat  NRBCs/100 WBCs can be used as a simple marker for the assessment of severity and early outcome of perinatal asphyxia. Mohanty et al 2014(35) conducted a study for  the correlation of cord blood nucleated red blood cell (NRBC)/100 white blood cell (WBC) count with perinatal asphyxia in terms of severity and short-term outcome.  A statistically significant correlation existed between severity of asphyxia (stage of hypoxic-ischemic encephalopathy HIE), poor outcome and higher number of NRBC/100 WBC count (p < 0.001). It further concluded  that it  is an inexpensive and easily available procedure to evaluate perinatal asphyxia, specially in a resource poor country like ours, where blood gas analysis facilities are not available in majority of places. Also, it is a good predictor of short-term outcome of asphyxiated babies. Rai et al 2015 (5) studied immediate and short term outcomes of term newborns with perinatal asphyxia in relation to the nucleated red blood cell count. The NRBC count and NRBC/100WBCs were significantly higher in newborns who had a convulsion within 12 h of birth, those who developed hypoxic ischemic encephalopathy (HIE) stage III, those who required a second loading with phenobarbitone, and those requiring a second anticonvulsant. In this study, NRBC count at birth was significantly higher among newborns with sequelae and those who expired.They concluded conclude that nucleated RBC count can be used as an early marker of severity of birth asphyxia during hospital stay, and may be useful to predict the neurological outcome in asphyxiated neonates. Meena et al 2016(36) conducted a study  to find the correlation of cord blood Nucleated Red Blood Cell (NRBC) count with the severity of birth asphyxia and its immediate outcome in term newborns. It concluded a simple, cheap, rapid and non-invasive test of NRBC count from umbilical cord blood correlates well with APGAR score and cord blood pH to predict the severity of birth asphyxia and immediate outcome.   Hemalatha et al 2016(37) conducted a  prospective case-control study on asphyxiated and non-asphyxiated term neonates from the neonatal intensive care unit and post-natal wards to investigate the association between nucleated red blood cells count (RBCs) per 100 white blood cells (WBCs) and perinatal asphyxia with respect to its severity and prognosis Nucleated RBCs (NRBCs) on 100 WBCs showed a mean value of 15.74 and standard deviation (SD) of 7.89 in the study group. The control group showed a mean value of 1.55 and SD of 0.78. The P = 0.001 was statistically significant and, therefore, a good predictor for birth asphyxia. Conclusion: Early NRBC count in cord blood is an effective, simple, cost effective baseline diagnostic tool for detecting neonatal asphyxia. Chand et al 2016(38)  conducted a prospective comparative study  in which  newborns of term gestation were selected after satisfying inclusion criteria and were divided in 2 groups. The control group consisted 60 normal newborns and case group had 60 asphyxiated newborns. The cord blood was collected soon after birth, investigated for pH and making smears that were stained with Leishman's stain. NRBCs were counted against 100 WBCs. The NRBC count was significantly higher in low pH, neonates with low Apgar scores of < 3 at 1 minutes, newborns with HIE stage III & in neonates who were neurological abnormal at discharge (P=0.0001).