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Nucleated Red Blood Cell Counts Differentiate Cardiac from Respiratory Causes of Cyanosis at Birth

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Abstract

Tissue hypoxia increases erythropoietin production and release of immature erythrocytes that can be measured using nucleated red blood cell counts (nRBC). We hypothesized that hypoxia due to congenital heart disease (CHD) is chronic and is better tolerated than hypoxia due to respiratory disease (RD), which is an acute stress in newborns leading to higher nRBC. This study assesses the utility of nRBC as a marker to differentiate hypoxia due to CHD vs RD in term neonates. This was a single-center, retrospective study of term neonates with cyanosis from 2015 to 2022. Neonates < 37 weeks of gestation, with hypoxic-ischemic encephalopathy, and those with other causes of cyanosis were excluded. The patients were divided into 2 groups: cyanotic CHD and cyanotic RD. Clinical and laboratory data done within 12 h and 24–36 h after birth were collected. Data are represented as median and Interquartile range. Of 189 patients with cyanosis, 80 had CHD and 109 had RD. The absolute nRBC count at ≤ 12 h of age was lower in the CHD (360 cells/mm3) compared to RD group (2340 cells/mm3) despite the CHD group having significantly lower baseline saturations. A value of 1070 cells/mm3 was highly sensitive and specific for differentiating CHD from RD. The positive predictive value for this cut-off value of 1070 cells/mm3 was 0.94 and the negative predictive value was 0.89. The absolute nRBC is a simple screening test and is available worldwide. A nRBC < 1070 cells/mm3 in cyanotic newborns should hasten the search for CHD etiology with the possible need for prostaglandin therapy.

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Abbreviations

CHD:

Congenital Heart Disease

RD:

Respiratory Disease

nRBC:

Nucleated Red Blood Cells

HIE:

Hypoxic-Ischemic Encephalopathy

IQR:

Interquartile range

ROC:

Receiver Operating Characteristic

TGA:

Transposition of the Great Arteries

HLHS:

Hypoplastic Left Heart Syndrome

DORV:

Double Outlet Right Ventricle

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Acknowledgements

We thank Dr. Yaddanapudi Ravindranath for his input on the hematological data.

Funding

This project was done with no financial support.

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Authors and Affiliations

  1. Division of Cardiology, Central Michigan University College of Medicine, Children’s Hospital of Michigan, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA

    Deepank Sahni, Yamuna Sanil & Robert D. Ross

  2. Carman and Ann Adams Department of Pediatrics, Central Michigan University College of Medicine, Children’s Hospital of Michigan, Detroit, USA

    Ronald Thomas

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  1. Deepank Sahni
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  2. Yamuna Sanil
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  3. Ronald Thomas
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  4. Robert D. Ross
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Contributions

Dr DS conceptualized and designed the study, drafted the initial manuscript, collected the data, and critically reviewed and revised the manuscript. Dr YS helped with the study design, collected the data, and critically reviewed and revised the manuscript. Dr RT carried out the initial data analyses and critically reviewed and revised the manuscript. Dr RDR conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Yamuna Sanil.

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We report that nucleated red blood cells (nRBC) can be used as a marker to differentiate a cardiac vs. respiratory etiology of cyanosis at birth.

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Sahni, D., Sanil, Y., Thomas, R. et al. Nucleated Red Blood Cell Counts Differentiate Cardiac from Respiratory Causes of Cyanosis at Birth. Pediatr Cardiol 45, 513–519 (2024). https://doi.org/10.1007/s00246-024-03409-9

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  • DOI: https://doi.org/10.1007/s00246-024-03409-9

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