Arch Dis Child Fetal Neonatal Ed 98:F2-F4 doi:10.1136/archdischild-2011-301273
  • Leading article

Lactoferrin immunoprophylaxis for very preterm infants

  1. The ELFIN Trial Investigators Group
  1. Correspondence to Professor William McGuire, NIHR Centre for Reviews and Dissemination, University of York, York YO10 5DD, UK; william.mcguire{at}
  • Received 9 March 2012
  • Accepted 11 July 2012
  • Published Online First 15 August 2012

Late-onset infection in very preterm infants

Late-onset invasive infection (occurring >72 h after birth) is the most common serious complication associated with intensive care for newborn infants. The incidence is >20% in very preterm or very low birth weight infants reflecting their level and duration of exposure to invasive procedures and intensive care.1–3 Coagulase-negative staphylococci cause about half of all bloodstream infections.4 Other pathogens include Gram-negative bacilli (mainly enteric bacilli), Gram-positive cocci (Staphylococcus aureus, enterococci), and fungi (predominantly Candida spp.).3 ,5 ,6

Very preterm infants with late-onset invasive infection have a higher risk of mortality and a range of important morbidities including necrotising enterocolitis (NEC), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and the need for intensive care and mechanical ventilation.1 ,7 ,8 These higher rates of mortality and serious morbidity are usually associated with Gram-negative bacterial or fungal infection. Coagulase-negative staphylococcal infection, although common, is generally associated with a more benign clinical course. However, even ‘low grade’ coagulase-negative staphylococcal bloodstream infection may generate inflammatory cascades associated with both acute morbidity (metabolic, respiratory or thermal instability) and long-term white matter and other brain damage that may result in neurodevelopmental disability.9 As a consequence of these associated morbidities, very preterm infants with invasive infection spend about 20 more days in hospital than their peers without infection.2 Late-onset infection therefore has major consequences for perinatal health care and service management, delivery and costs.

Diagnosis of late-onset invasive infection

Clinical signs of invasive infection in very preterm infants individually have limited sensitivity. Similarly, laboratory measures (biomarkers) are insensitive and have low predictive value for bloodstream infection.10 Most neonates who undergo ‘sepsis evaluation’ and are treated empirically with antibiotics do not have infection confirmed subsequently. Since individual clinical signs and laboratory markers are generally unreliable predictors of true invasive infection, a policy of …

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