Nucleated red blood cells in neonates with hypoxic ischaemic encephalopathy treated with hypothermia: A worthwhile prognostic biomarker for clinicians in LMIC?
Main Article Content
Abstract
Background. Neonatal hypoxic ischaemic encephalopathy (HIE) is a leading cause of term neonatal death worldwide, with a higher
incidence in low- to middle-income settings.
Objective. To investigate whether nucleated red blood cell (nRBC) counts could predict severity of HIE and outcomes in term neonates
treated with therapeutic hypothermia (TH).
Methods. We conducted a retrospective sub-study at Tygerberg Hospital in Cape Town, South Africa. The review included all cooled
neonates’ clinical records and blood samples from a National Health Laboratory Services database. One experienced neurodevelopmental expert assessed patients over a period of 12 months.
Results. Twenty-five files out of a total of 100 were excluded owing to missing data. In accordance with the Thompson HIE score,
the cohort was classified as mild (56%), moderate (27%), and severe (17%). All included patients (n=75) had full blood counts within
6 hours of delivery. nRBC were detected in 52% of the samples. There was no correlation between nRBC category and HIE severity
(p=0.265). Raised nRBCs (≥30 cells/100 white blood cells (WBCs)) were more frequent in infants who died than in those who
survived (p=0.008). Infants with nRBC counts ≥30 cells/100 WBCs had an increased likelihood of having cerebral palsy or impaired
neurodevelopment (p=0.013).
Conclusion. The study demonstrated a significant association between an early increase in nRBC counts in HIE infants treated with TH,
and both short- and long-term outcomes. A larger multicentre study is required to better understand the relationship between nRBC
counts and HIE in the era of cooling in our local setting.
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References
Lawn JE, Cousens S, Zupan J. 4 million neonatal deaths: When ? Where? Why? Lancet 2005;365(9462):891-900. https://doi.org/10.1016/s0140-6736(05)71048-5 2. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev
;2013(1):CD003311. https://doi.org/10.1002/14651858.CD003311.pub3
Kali GTJ, Martinez-Biarge M, van Zyl J, Smith J, Rutherford M. Management of therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy in a tertiary centre in South Africa. Arch Dis Child Fetal Neonatal Ed
;100(6):F519-F523. https://doi.org/10.1136/archdischild-2015-308398
Ghosh B, Mittal S, Kumar S, Dadhwal V. Prediction of perinatal asphyxia with nucleated red blood cells in cord blood of newborns. Int J Gynecol Obstet
;81(3):267-271.
Christensen RD, Lambert DK, Richards DS. Estimating the nucleated red blood
cell ‘emergence time̕ in neonates. J Perinatol 2014;34(2):116-119. https://doi.
org/10.1016/s0020-7292(03)00124-3
Hermansen MC. Nucleated red blood cells in the fetus and newborn. Arch Dis Child Fetal Neonatal Ed 2001;84(3):F211-F215. https://doi.org/10.1136/ fn.84.3.f211
H. Boskabadi, G. Maamouri, MH. Sadeghian et al. Early diagnosis of perinatal asphyxia by nucleated red blood cell count: A case-control study. Arch Iran Med 2010;13(4):275-281.
Tungalag L, Gerelmaa Z. Nucleated red blood cell counts in asphyxiated newborns. Open Sci J Clin Med 2014;2(1):33-38.
Mccarthy J, Capullari T, Thompson Z, Zhu Y, Spellacy W. Umbilical cord nucleated red blood cell counts: Normal values and the effect of labor. J Perinatol 2006;26:89-92. https://doi.org/10.1038/sj.jp.7211437
Ferber A, Grassi A, Akyol D, O’Reilly-Green C, Divon MY. The association of fetal heart rate patterns with nucleated red blood cell counts at birth. Am J Obstet Gynecol 2003;188(5):1228-1230. https://doi.org/10.1067/mob.2003.352
Hanlon-Lundberg KM, Kirby RS. Nucleated red blood cells as a marker of acidemia in term neonates. Am J Obstet Gynecol 1999;181(1):196-201. https:// doi.org/10.1016/s0002-9378(99)70459-x
Korst LM, Phelan JP, Ahn MO, Martin GI. Nucleated red blood cell: An update on the marker for fetal asphyxia. AJOG 1996;175(4):843-846. https://doi. org/10.1016/s0002-9378(96)80010-x
Li J, Kobata K, Kamei Y, et al. Nucleated red blood cell counts: An early predictor of brain injury and 2-year outcome in neonates with hypoxic-ischemic encephalopathy in the era of cooling-based treatment. Brain Dev 2014;36(6):472- 478. https://doi.org/10.1016/j.braindev.2013.06.012
Thompson CM, Puterman AS, Linley LL, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr 1997;86(7):757-761. https://doi.org/10.1111/j.1651-2227.1997. tb08581.x
Gosselin J, Gahagan S, Amiel-Tison C. The Amiel-Tison Neurological Assessment at Term: Conceptual and methodological continuity in the course of follow-up. Ment Retard Dev Disabil Res Rev 2005;11(1):34-51. https://doi.org/10.1002/mrdd.20049
Blackwell SC, Refuerzo JS, Wolfe HM, et al. The relationship between nucleated red blood cell counts and early-onset neonatal seizures. Am J Obstet Gynecol 2000;182(6):1452-1457. https://doi.org/10.1067/mob.2000.106854