No abstract

HbF, optimal for oxygen transport in utero, is progressively replaced by HbA from about 32-36 wk of gestation (1). This maturational phenomenon is clinically important and shows marked individual variation. Prolonged postnatal dependence on HbF impairs oxygen transport and has been associated with clinicallv significant anaemia and with the sudden infant death on acid elution (5), and on indirect mathematical analysis of circulating fetal and adult Hb (6, 7). Studies of Hb actively synthesized by reticulocytes in vitroimply a gradual decline of HbF synthesis after a sigmoid curve, the "steep" part starting at about 32 wk gestation and proceding such that the "half-time" for 50% reduction in HbF synthesis is >6 wk. There is a corresponding increase in HbA production. This technique, which assesses HbF/A synthetic balance at the end of erythroid maturation in vitro, may not accurately reflect events in vivo.Studies using the acid elution method of Betke and Kleihauer for detecting HbF in erythrocytes point to the sudden appearance of a distinct subpopulation of cells containing predominantly HbA at about the time of resumption of erythropoiesis after the postnatal erythropoietic shut-down. This suggests a fairly rapid process followed by the appearance of a new population of erythroid cells containing HbA (1, 5).A similiar pattern can be inferred from mathematical analyses of the changing proportion of HbF and HbA in the circulation of individual infants studied postnatally. Mathematical analyses could be taken to imply that, on resumption of erythropoiesis after the postnatal shut-down, HbF synthesis has completely ceased (6, 7). The histo-chemical and mathematical findings could be reconciled with the in vitro observations by assuming that the switchover occurs gradually during a period of relatively inactive erythropoiesis and that, when erythropoiesis resumes, any residual HbF synthesis is insufficient to be detected by these techniques. However, this hypothesis has not been proven and the controversy between rapid and slower rates of switching has not yet been satisfactorily resolved.The discrepancies relating to the time course of the switching process prompted us to develop a direct means of assessing HbF to HbA switching patterns in infants by measurement of the %HbF in reticulocytes harvested from the peripheral blood at different postconceptual stages. We consider that the %HbF of reticulocytes accurately reflects the balance of HbF/A synthesis in the bone marrow in the 2-3 days immediately preceding sampling. This direct approach overcomes the shortcomings associated with the indirect nature of the previous studies. syndroie T2, 3). Despite its biological importance the time course of switching has remained controversial (1). There are PATIENTS theoretical reservations about the validity of methods previously used to study Hb switching. These depend respectively on in Thirty preterm infants of gestation at birth 26-33 wk (mean vitro globin chain synthesis (4), on histochemical studies based 29.5 + 1.74 ...