There is a need for a reliable marker to predict the
course of hospital stay and short term prognosis in term newborns with
perinatal asphyxia. Chronic or acute hypoxia is one of the most
important causes of increased nucleated RBC count (NRBC count) in a
neonate [1]. We studied the role of NRBC count in prediction of
neurological outcome in perinatal asphyxia. Term newborns with perinatal
asphyxia (Apgar Score <7 at 1 min) were enrolled within 6 hours of
birth. The study was approved by the Institutional Ethical Committee.
Absolute NRBC count and NRBC count per 100 white
blood cells (WBC) were done at admission using a venous sample. The
smear was stained using Leishman stain. The NRBCs and leucocytes were
counted manually till 500 white blood cells (WBCs) and then reported as
NRBC/100 WBCs. All the counts were done by a 3rd year post graduate
student of pathology and cross checked by the consultant. The consultant
who finally reported remained same for all the samples. Neonates with
convulsions were managed as per standard protocols. The immediate
outcome was categorized into: neurologically normal (those who had
normal tone and posture, were free from seizures, had good cry and
activity and normal neonatal reflexes) and neurologically abnormal
(those with an abnormal tone and posture or poor cry and activity or any
abnormal neonatal reflexes at discharge or death). Children were
followed up till 6 months for any sequelae such as hypertonia, epilepsy,
spasticity and delayed milestones.
A total of 177 neonates were enrolled but 12 of the
discharged neonates did not report for follow-up at six months; final
analysis of 165 was done. Out of these, 97 were born vaginally and 68
were born by lower segment caesarean section (LSCS). Fifteen neonates
died during hospital stay. At discharge, 127 neonates were
neurologically normal and 23 neonates were neurologically abnormal. At
six months follow-up, 68.7% neonates were neurologically normal and
31.3% developed sequelae. The NRBC/100WBC was significantly higher in
sequelae group than normal (P <0.001) (Table I). By
drawing receiver operating characteristics (ROC) curves, NRBC > 450/mm
3
and NRBC/100WBC >3.25 prediction had a sensitivity of 90% and
specificity of 74.3% for predicting development of neurological sequelae
at 6 months of age. Many studies have estimated the NRBC count in the
cord blood [2-5].
TABLE I Nucleated RBC Counts Related to Birth Asphyxia
Characteristics |
NRBC/100WBC |
P value |
|
mean (SD) |
|
Hypoxemic Ischaemic Encephalopathy |
|
|
Stage II |
4.4 (4.5) |
0.005
|
Stage III |
8.1 (5.2) |
|
Need for 2nd loading with phenobarbitone |
|
|
Yes |
7.2 (4.8) |
0.048 |
No |
4.6 (5.2) |
|
Need for 2nd anticonvulsant |
|
|
Yes
|
7.1 (4.8) |
0.387 |
No |
5.4 (5.1)
|
|
Age at first convulsion |
|
|
<12h |
7.7 (5.6) |
0.007 |
≥12 h
|
4.3 (4.2) |
|
Age at start of feeds |
|
|
<48h
|
5.1 (7.1) |
0.987 |
≥48h |
5.1 (6.7) |
|
Outcome |
|
|
Discharged
|
5.0 (6.7) |
0.322
|
Expired
|
7.0 (5.2) |
|
Neurological status at discharge |
|
|
Normal |
4.4 (6.6) |
0.007 |
Abnormal
|
7.9 (6.0) |
|
Neurological status at 6 mo |
|
|
Sequelae present |
9.8 (8.9) |
0.001 |
No sequelae |
2.9 (4.3) |
|
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 our study, NRBC count at birth was
significantly higher among newborns with sequelae and those who expired,
which was also observed in other studies [6-8]. The limitations of the
study are short duration of follow-up and absence of other
parameters like magnetic resonance imaging, cord blood pH and
electro-encephalography.
We 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.
Contributors: RR: conceptualization and
conduct of the study, data collection and analysis; GT: conduct of the
the study, data analysis and writing the manuscript; DKS: critical
evaluation and reviewing the manuscript.
Funding: None; Competing interests:
None stated.
References
1. Hermansen MC. Nucleated red blood cells in the
fetus and newborn. Arch Dis Child Fetal Neonatal Ed. 2001;84:211-5.
2. Oski FA, Naiman JL. Normal Blood Values in the
Newborn Period. In: Hematologic Problems in The Newborn. 3rd ed.
Philadelphia: WB Saunders, 1982: 1-30.
3. Boskabadi H, Maamouri G, Sadeghian MH, Ghayour-Mobarhan
M, Heidarzade M, Shakeri MT, et al. Early diagnosis of perinatal asphyxia by
nucleated red blood cell count: a case-control study. Arch Iran
Med. 2010;13:275-81.
4. Hanlon-Lundberg KM, Kirby RS. Nucleated red blood
cells as a marker of acidemia in term neonates. Am J Obstet Gynecol.
1999;181:196-201.
5. Ghosh B, Mittal S, Kumar S, Dadhwal V. Prediction
of perinatal asphyxia with nucleated red blood cells in cord blood of
newborns. Int J Obstet Gynecol. 2003;81:267-71.
6. Fotopoulos S, Pavlou K, Skouteli H, Papassotiriou
I, Lipsou N, Xanthou M. Early markers of brain damage in premature
low-birth-weight neonates who suffered from perinatal asphyxia and/or
infection. Biol Neonate. 2001;79:213-8.
7. Naeye RL, Localio AR. Determining the time before
birth when ischemia and hypoxemia initiated cerebral palsy.
Obstet Gynecol. 1995;86:713-9.
8. Ferns SJ, Bhat BV, Basu D. Value of nucleated red
blood cells in predicting severity and outcome of perinatal asphyxia.
Indian J Pathol Microbiol. 2004;47:503-5.