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

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.

Keywords: Cyanosis in newborn; Cyanotic congenital heart disease; Cyanotic respiratory disease; Nucleated red blood cells.