Definitive estimate of rate of hemoglobin switching: measurement of percent hemoglobin F in neonatal reticulocytes.

The transition from fetal to adult erythropoiesis starts at 32-36 wk postconception. The rate of this switchover has been controversial. Studies of globin chain synthesis by reticulocytes in vitro have indicated gradual switching with a time for 50% reduction in fetal Hb synthesis ("half-time") of more than 6 wk. This may not accurately reflect fetal/adult Hb synthetic balance in vivo. By contrast, histochemical studies and also indirect mathematical analysis of postnatal changes in circulating fetal Hb and adult Hb may imply abrupt patterns of switching with half-times of less than 1 wk. We have resolved this discrepancy by direct measurement of the changing proportions of fetal and adult Hb in reticulocytes prepared by flourescence activated cell sorting from 10 full-term cord and 45 preterm postnatal blood samples. This method overcomes problems both of extrapolation from in vitro measurements and of mathematical analysis. We find a gradual transition from fetal Hb to adult Hb synthesis. The half-time is approximately 16-18 wk. Values of fetal Hb in reticulocytes were on average higher than predicted from in vitro synthesis studies. We find considerable individual variation. Infants differ in their switching behaviour, many showing prolonged dependence on fetal Hb.