Promising stratagems for reducing the burden of neonatal sepsis

Two years ago we reviewed1 the rationale for the use of haemopoietic colony stimulating factors (CSFs) in preterm neonates. Two small pilot studies had shown that treatment with either granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) could increase the neutrophil count without apparent short term toxicity.2 3 Follow up at 2 years of age of the small cohort treated with G-CSF found no longer term adverse effects.4 However, there were no data on clinical efficacy. Whether CSFs could reduce morbidity and mortality from sepsis, and how they might be used to greatest effect, remained unaddressed. A number of studies have since been completed which point the way for future investigation.

All preterm neonates are at high risk of bacterial sepsis.5-7 Acute mortality from sepsis has remained constant at about 15% for two decades8 and increases to over 50% when associated with severe neutropenia.9 Of possibly greater importance is the fact that sepsis interacts with other pathologies, increasing the overall risk of disability. The preterm brain is believed to be developmentally vulnerable to damage as a consequence of infection remote from the brain.10Sepsis, by initiating endothelial injury, endotoxaemia, and uncontrolled inflammation/coagulation cascades is a prime candidate to cause white matter and other brain injury, including cerebral palsy. Infection provoked inflammation is also an important contributor to the multifactorial aetiology of chronic lung disease. These conditions are powerful determinants of outcome after preterm birth.

The high infection rates in preterm neonates are related to immaturity of both humoral and phagocyte immunity. Infants born before 30 weeks gestation are severely hypogammaglobulinaemic.11 The high incidence of postnatal neutropenia in both well and septic neonates12 13 is a consequence of the reduced total body neutrophil mass in infants born before 32 …