Estimating the nucleated red blood cell ‘emergence time’ in neonates

Objective: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.study design: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.result: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.conclusion: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.