Haemopoietic colony stimulating factors for preterm neonates
- aDepartment of Haematology, United Medical and Dental School of Guy’s and St Thomas’s, St Thomas’s Hospital, Lambeth Palace Road, London SE1 7EH, bNeonatal Paediatrics, Royal Postgraduate Medical School, Hammersmith Hospital, London
- to: Dr R Carr.
Bacterial and fungal sepsis is a major cause of morbidity and mortality in neonates. Infection rates are high in infants treated in intensive care units, with the highest rates, of around 30%, occurring in extremely immature preterm neonates.1-3 A survey of neonatal infection at Yale University, ongoing since 1928,4 has documented a decline in neonatal septic deaths commensurate with the establishment of neonatal intensive care units and the liberal use of increasingly effective antibiotics. Mortality from sepsis declined steadily until the early 1980s, but since then it has remained constant at near 15%. This plateau of mortality most likely reflects the poor host defences of immature, preterm neonates.5
Neutrophil leucocytes are central to the defences against bacterial infection,6 and in neonates both neutrophil production and function are immature. Neutropenia, defined as a neutrophil count below the normal range for neonates established by Monroe,7occurs in up to 35% of preterm neonates8 9 and in 50% of all infants born to mothers with pregnancy induced hypertension.10 The development of sepsis together with neutropenia carries a high mortality of 39%, and two out of every three septic infants whose neutrophils fall below 0.5 × 109/l will die.9
Kinetics of neutrophil production
It is impossible to measure directly the total neutrophil cell mass in a human neonate. There is a good deal of circumstantial evidence to suggest that neonatal bone marrow has a reduced capacity to produce neutrophils in adequate numbers.11 Neutrophils develop from multipotent haemopoietic stem cells through lineage-committed progenitors (granulocyte-macrophage colony forming units, CFU-GM). These give rise to a proliferative pool, identified morphologically in the bone marrow as promyelocytes and myelocytes, and a storage pool comprising metamyelocytes, bands, and segmented neutrophils, before being released into the circulation. Mature neutrophils circulate with a peripheral blood half life …
