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The role of colony stimulating factors and immunoglobulin in the prevention and treatment of neonatal infection
  1. Robert Carr
  1. Department of Haematology, King's College London, Guy's and St Thomas’ Foundation Trust, London, UK
  1. Correspondence to Dr Robert Carr, Department of Haematology, King's College London, Guy's and St Thomas’ Foundation Trust, London SE1 9RT, UK; robert.carr{at}gstt.nhs.uk

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Introduction

Bacterial systemic infection (SI) remains one of the unresolved challenges of neonatal intensive care, directly and indirectly responsible for infant death and impaired neuro-developmental outcomes. The incidence increases with lower gestational age and birth weight. Reported rates of SI range from 21% in very low birth weight (VLBW) infants, 33% for infants <28 weeks and 41% in small for gestation preterm infants.1–3 Death is more frequent following gram negative than gram positive infection, and ranges from 18% mortality in VLBW infants to 31% in small for gestational age (SGA) infants following culture positive SI.1 ,3 Longer term outcomes of SI have been less frequently reported. The National Institute of Child Health and Development (NICHD) neonatal network reported significant impaired psychomotor development index in 26% of infants <1000 g surviving to 2 years following SI in contrast to 13% in those with no history of SI.4

Attempts to enhance the newborn infant's immature defences initially focused on the profound hypogammaglobulinaemia of babies born before the placental transfer of maternal immunoglobulin G (IgG) during the third trimester. From the mid-1990s, deficiencies of neutrophil production and function became therapeutic targets with recombinant haemopoietic colony stimulating factors (CSFs) available for therapeutic use. Both intravenous immunoglobulin (IvIg) replacement and CSFs have now been extensively investigated as adjunctive treatment for established SI or prophylaxis to prevent late onset newborn sepsis.

Immunoglobulin

Serum immunoglobulin levels at birth correlate with gestational age. A sequential study of immunoglobulin concentration in infants less than 1500 g birth weight recorded a mean birth IgG of 2.5 g/l, decreasing to <1 g/l by 3 months postnatal age in infants ≤28 weeks gestation.5 ,6 Increased infection risk is associated with IgG levels ≤4 g/dl.7 Against this background, there were a plethora of randomised studies published from 1986 and through the 1990s testing the ability of regular …

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