Estimating the nucleated red blood cell 'emergence time' in neonates

The time between onset of fetal hypoxia and first appearance of nucleated red blood cells (NRBCs) in the blood can conceptually be divided into two periods; (1) the 'erythropoietin (EPO) generation time', which previous fetal studies suggest is 4 to 5 h, and (2) the 'NRBC emergence time'. In this study, we estimated the latter as the time required for NRBC to appear in the blood after administering a dose of recombinant EPO.

This was a retrospective analysis of data from a multihospital healthcare system (Intermountain Healthcare). Data were included only for neonates born ≥34 weeks gestation between the dates 1 January 2005 and 31 October 2012 and only if they received a dose of darbepoetin during their neonatal intensive care unit stay and had one or more complete blood cell counts (CBCs) obtained during the 3-day period before the dose was given and one or more CBCs in the 7-day period after the dose.

The study involved 31 neonates who received 34 doses of darbepoetin. Seven doses were 4 μg kg(-1) and twenty-seven doses were 10 μg kg(-1). Twenty-six CBCs were obtained during the 24-h period following the darbepoetin dose and none had NRBC identified. NRBC first appeared in the blood between 24 and 36 h after the dose. Recipients of the higher dose generally had a higher peak NRBC count but the NRBC 'emergence time' did not appear to depend on dose.

Following fetal hypoxia, transcription and translation of the EPO gene result in an elevation in plasma EPO concentration. Previous fetal studies suggest this process requires 4 to 5 h. The present studies suggest that, following the increase in plasma EPO, NRBC emerge into the circulation in ≥24 h. If this model serves as a reasonable estimate, it suggests that neonates with an elevated NRBC count at birth had the onset of hypoxia at least 28 to 29 h before birth.