title: Multicomponent fortified human milk for promoting growth in preterm infants.
abstract: BACKGROUND
  For term infants, human milk provides adequate nutrition to facilitate growth, as well as potential beneficial effects on immunity and the maternal-infant emotional state. However, the role of human milk in premature infants is less well defined as it contains insufficient quantities of some nutrients to meet the estimated needs of the infant. There are potential short term and long term benefits from human milk, although observational studies have suggested that infants fed formula have a higher rate of growth than infants who are breast fed. Commercially-produced multicomponent fortifiers provide additional nutrients to human milk (in the form of protein, calcium, phosphate, and carbohydrate, as well as vitamins and trace minerals).
  
  
  OBJECTIVE
  The main objective was to determine if addition of multiple dietary supplements to human milk leads to improved growth, bone metabolism and neurodevelopmental outcomes without significant adverse effects in premature infants.
  
  
  METHODS
  The standard search strategy of the Neonatal Review Group was used. This includes searches of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language.
  
  
  METHODS
  All trials utilising random or quasi-random allocation to supplementation of human milk with multiple nutrients or no supplementation in premature infants within a nursery setting were eligible.
  
  
  METHODS
  Data were extracted using the standard methods of the Cochrane Collaboration and its Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk and weighted mean difference.
  
  
  RESULTS
  Supplementation of human milk with multicomponent fortifiers is associated with short term increases in weight gain, linear and head growth. There is no effect on serum alkaline phosphatase levels. Bone mineral content and nitrogen retention appear to be increased. There are insufficient data to evaluate long term neurodevelopmental and growth outcomes. Adverse effects of fortification do not appear to be significantly increased, although the total number of infants studied and the unavailability of results for some infants randomized and subsequently withdrawn reduces confidence in this conclusion. Blood urea levels are increased and blood pH levels minimally decreased, but the significance of this is uncertain.
  
  
  CONCLUSIONS
  Multicomponent fortification of human milk is associated with short-term improvements in weight gain, linear and head growth. Despite the absence of evidence of long-term benefit and insufficient evidence to be reassured that there are no deleterious effects, it is unlikely that further studies evaluating fortification of human milk versus no supplementation will be performed. Further research should be directed toward comparisons between different proprietary preparations and evaluating both short-term and long-term outcomes in search of the "optimal" composition of fortifiers.
authors.affiliation: Newborn Services, National Women's Hospital, Private Bag 92 189, Auckland, New Zealand. CarlK@ahsl.co.nz
authors.forename: C A
authors.initials: CA
authors.lastname: Kuschel
authors.forename: J E
authors.initials: JE
authors.lastname: Harding
mesh_terms: D005527:Food, Fortified; D006128:Growth; D006801:Humans; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007234:Infant, Premature; D008895:Milk, Human