Introduction: oxygen transported to the tissues can

Introduction: Perinatal asphyxia is aserious problem globally, and it is a common cause of neonatal mortality andlong-term morbidity. Data from National Neonatal Perinatal Database 1 suggestthat perinatalasphyxia contributes toalmost 20% of neonatal deaths in India. Of the 1.2 million neonatal deaths inIndia every year, 300,000 – 350,000 infants die due to perinatal asphyxiamostly within first 3 days of life 2.Perinatal asphyxia cancause severe hypoxic-ischemic damages in the organs of neonates and causesevere long-term consequences or fatal complications. So, predicting theprognosis of asphyxia for prevention and targeted treatment before theincidence of complications should be given the high priority in neonatology andpediatrics.(3,4) Thus, a reliable marker is required to predict the hospitalstay and the prognosis of neonates with perinatal asphyxia.(5)Howeverthere is no effective indicator for prediction of perinatal asphyxia although acombination of different methods and markers could help in the diagnosis ofperinatal asphyxia 6.

Nucleated red bloodcells (NRBCs), or erythroblast, are the premature forms of erythrocytes thatare commonly found in newborn’s blood. Any condition that reduces the quantityof oxygen transported to the tissues can cause an increase in the rate of RBCproduction.Ithas recently been suggested that the increase in NRBC count in the umbilicalvein of newborns can be considered a sign of birth asphyxia 7.

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In healthy newborns,NRBC count is reduced by half 12 h after birth, and there are only 20–30NRBCs/m3 48 h after birth. Although on the third or fourth day of birth, NRBCsare not seen in the blood circulation, but in preterm newborns, small amountsof 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 thaterythropoietin stimulates fetal hematopoietic system, mainly in bone marrow,which increases the production of RBCs 12–13. Increase in NRBC count is oftendue to prematurity, ABO or RH blood incompatibility, increase in hematopoiesisfollowed by chronic diseases, maternal diabetes, preeclampsia, fetal anemia,intrauterine infections, chorioamnionitis and acute or chronic asphyxia12,14–17       Review of Literature:Althoughnucleated red blood cells (nRBCs) are rarely found circulating in olderchildren,(18) they are commonly seen in the blood of newborns. They areprimarily produced in the fetal bone marrow in response to erythropoietin andare stored in the marrow as precursors to reticulocytes and matureerythrocytes. Many acute and chronic stimuli cause increases in the number ofcirculating nRBCs from either increased erythropoietic activity or a suddenrelease from the marrow storage pools. nRBCsare present in the placental vessels through the first half of pregnancy, butare uncommon later in pregnancy and are usually absent or present only in smallnumbers at term. The finding of numerous nRBCs in the term placenta isnon-specific and may indicate acute or chronic fetal hypoxia, maternaldiabetes, fetal anaemia, or congenital TORCH infections (toxoplasma, otherviruses, rubella, cytomegalovirus, herpes).(19-24)Diferentialdiagnosis of increased nucleated red bloods cells in the fetus and newbornI.

                  Physiological Labour and vaginal birthsPreterm newborns Post-term newbornsII.               Increased erythropoiesis Chronic hypoxiaGrowth restriction Maternal pre-eclampsia Maternal smoking Anaemia Blood lossHaemolysis—ABO or Rh isoimmunization, other Maternal diabetes Other LeukaemiaDown’s syndrome TORCH infections III.            Acute stress release Acute hypoxia Subacutehypoxia ChorioamnionitisIV.            Postnatal hypoxia Cyanotic heart diseasePulmonary failure V. Idiopathic TORCH, Toxoplasma, other viruses, rubella,cytomegalovirus, herpes.

Studieshave 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 thenormal neonate, nRBCs are rapidly cleared from the bloodstream afterbirth.(30,31,32) By 12 hours of age, the counts fall by about 50%, and by 48hours only 20–30 nRBCs/mm3 are found. In healthy term newborns, virtually nonRBCs are found after the third or fourth day of life, although they maypersist 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 determinedper 100 white-blood-cells (WBC).

After discharge, follow-up of asphyxiatedinfants was performed using Denver II test at 6, 12, 18 and 24 months. Theydemonstrated that NRBC/100 WBC and absolute NRCB count can be used asprognostic marker for neonatal asphyxia, which in combination with the severityof asphyxia could indicate high infant mortality, and complications ofasphyxia.Ghoshet al 2003(6)  conducted a study todetermine normal level of nucleated red blood cells (NRBC) per 100 white bloodcells (WBC) in cord blood of term non-asphyxiated newborns and to investigatevariations in NRBC counts in perinatal asphyxia.

The study showed high NRBCcount in umbilical blood correlated with poor early neonatal outcome.The levelof NRBC per 100 WBC correlates both with acute as well as chronic antepartumasphyxia. It  further concluded that NRBCcan be used as a reliable index of early neonatal outcome.Goel et al  2013 (34) conducted a case control study on50 asphyxiated and 50 normal newborns  toinvestigate variations in nucleated red blood cell (NRBC) in blood associatedwith perinatal asphyxia and its relationship to both the severity and shortterm prognosis of asphyxia.the study showed there was a significant (P <0.01) correlation of the number of NRBC100 WBC with Apgar scoring, HIE stagingand mortality.

It concludedthat NRBCs/100 WBCs can be used as a simple marker for the assessment ofseverity and early outcome of perinatal asphyxia.Mohanty et al 2014(35)conducted a study for  the correlation ofcord blood nucleated red blood cell (NRBC)/100 white blood cell (WBC) countwith perinatal asphyxia in terms of severity and short-term outcome.  A statistically significant correlationexisted between severity of asphyxia (stage of hypoxic-ischemic encephalopathyHIE), poor outcome and higher number of NRBC/100 WBC count (p < 0.001).

Itfurther concluded  that it  is an inexpensive and easily availableprocedure to evaluate perinatal asphyxia, specially in a resource poor countrylike ours, where blood gas analysis facilities are not available in majority ofplaces. Also, it is a good predictor of short-term outcome of asphyxiatedbabies.Rai et al 2015 (5) studiedimmediate and short term outcomes of term newborns with perinatal asphyxia inrelation to the nucleated red blood cell count. The NRBC count and NRBC/100WBCswere significantly higher in newborns who had a convulsion within 12 h ofbirth, those who developed hypoxic ischemic encephalopathy (HIE) stage III,those who required a second loading with phenobarbitone, and those requiring asecond anticonvulsant. In this study, NRBC count at birth was significantlyhigher among newborns with sequelae and those who expired.They concludedconclude that nucleated RBC count can be used as an early marker of severity ofbirth asphyxia during hospital stay, and may be useful to predict theneurological 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 termnewborns.

It concluded a simple, cheap, rapid and non-invasive test of NRBCcount from umbilical cord blood correlates well with APGAR score and cord bloodpH to predict the severity of birth asphyxia and immediate outcome.  Hemalatha et al 2016(37)conducted a  prospective case-controlstudy on asphyxiated and non-asphyxiated term neonates from the neonatalintensive care unit and post-natal wards to investigate the association betweennucleated red blood cells count (RBCs) per 100 white blood cells (WBCs) andperinatal 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) of7.89 in the study group. The control group showed a mean value of 1.55 and SDof 0.78. The P = 0.

001 was statistically significant and, therefore, a goodpredictor for birth asphyxia. Conclusion: Early NRBC count in cord blood is aneffective, simple, cost effective baseline diagnostic tool for detectingneonatal asphyxia.Chand et al 2016(38)  conducted a prospectivecomparative study  in which  newborns of term gestation were selectedafter satisfying inclusion criteria and were divided in 2 groups. The controlgroup consisted 60 normal newborns and case group had 60 asphyxiated newborns.The cord blood was collected soon after birth, investigated for pH and makingsmears that were stained with Leishman’s stain. NRBCs were counted against 100WBCs.

The NRBC count was significantly higher in low pH, neonates with lowApgar scores of < 3 at 1 minutes, newborns with HIE stage III & in neonateswho were neurological abnormal at discharge (P=0.0001).      


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