title: A randomised controlled trial of high vs low volume initiation and rapid vs slow advancement of milk feeds in infants with birthweights ≤ 1000 g in a resource-limited setting.
abstract: BACKGROUND
  Optimal feeding regimens for infants ≤ 1000 g have not been established and are a global healthcare concern.
  
  
  OBJECTIVE
  A controlled trial to establish the safety and efficacy of high vs low volume initiation and rapid vs slow advancement of milk feeds in a resource-limited setting was undertaken.
  
  
  METHODS
  Infants ≤ 1000 g birthweight were randomised to one of four arms, either low (4 ml/kg/day) or high (24 ml/kg/day) initiation and either slow (24 ml/kg/day) or rapid (36 ml/kg/day) advancement of exclusive feeds of human milk (mother's or donor) until a weight of 1200 g was reached. After this point, formula was used to supplement insufficient mother's milk. The primary outcome was time to reach 1500 g.
  
  
  RESULTS
  infants were recruited (51: low/slow; 47: low/rapid; 52: high/slow; 50: high/rapid). Infants on rapid advancement regimens reached 1500 g most rapidly (hazard ratio 1.48, 95% CI 1.05-2.09, P=0.03). The rapid advancement groups also regained birthweight more rapidly (hazard ratio 1.77, 95% CI 1.26-2.50, P=0.001). There was no apparent effect of high vs low initiation volumes but there was some evidence of interaction between interventions. There were no significant differences in other secondary outcomes, including necrotising enterocolitis, feed intolerance and late-onset sepsis.
  
  
  CONCLUSIONS
  In this small pilot study, higher initiation feed volumes and larger daily increments appeared to be well tolerated and resulted in more rapid early weight gain. These data provide justification for a larger study in resource-limited settings to address mortality, necrotising enterocolitis and other important outcomes.
authors.affiliation: a Division of Neonatal Medicine, Department of Paediatrics , University of Cape Town , South Africa.
authors.forename: Shukri
authors.initials: S
authors.lastname: Raban
authors.affiliation: b Section of Neonatal Medicine, Department of Medicine , London School of Hygiene and Tropical Medicine , UK.
authors.forename: Shalini
authors.initials: S
authors.lastname: Santhakumaran
authors.affiliation: a Division of Neonatal Medicine, Department of Paediatrics , University of Cape Town , South Africa.
authors.forename: Quanitah
authors.initials: Q
authors.lastname: Keraan
authors.affiliation: a Division of Neonatal Medicine, Department of Paediatrics , University of Cape Town , South Africa.
authors.forename: Yaseen
authors.initials: Y
authors.lastname: Joolay
authors.affiliation: c Section of Neonatal Medicine, Department of Medicine , Imperial College , London , UK.
authors.forename: Sabita
authors.initials: S
authors.lastname: Uthaya
authors.affiliation: a Division of Neonatal Medicine, Department of Paediatrics , University of Cape Town , South Africa.
authors.forename: Alan
authors.initials: A
authors.lastname: Horn
authors.affiliation: c Section of Neonatal Medicine, Department of Medicine , Imperial College , London , UK.
authors.forename: Neena
authors.initials: N
authors.lastname: Modi
authors.affiliation: a Division of Neonatal Medicine, Department of Paediatrics , University of Cape Town , South Africa.
authors.forename: Michael
authors.initials: M
authors.lastname: Harrison
mesh_terms: D001942:Breast Feeding / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D008895:Milk, Human; D010865:Pilot Projects; D013997:Time Factors; D015430:Weight Gain
keywords: Enteral nutrition; Infant preterm; Infant very low birthweight; Necrotising enterocolitis