1. Multinutrient fortification of human breast milk for preterm infants following hospital discharge: systematic review Lauren Young1, Felicia M McCormick2, William McGuire1, Nicholas D Embleton3 1Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, UK 2Mother and Infant Research Unit, Department of Health Sciences, University of York, York, UK 3Newcastle Neonatal Service, Royal Victoria Infirmary, Newcastle upon Tyne, UK
Background
• Preterm infants are often growth restricted at the time of hospital discharge, having accumulated significant protein, mineral and energy deficiencies during their prolonged hospital stay.
Feeding preterm infants after hospital discharge with multinutrient fortified breast milk rather than unfortified breast milk may facilitate more rapid catch-up growth and improve neurodevelopmental outcomes.
• Slow postnatal growth has been associated with long term growth restriction, neuro-developmental impairment and poorer educational outcomes in later childhood, and cardiovascular disease, obesity and insulin resistance in later life.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Results: outcomes
Growth: The trials did not provide statistically significant evidence that multinutrient fortification of breast milk for 3 to 4 months after hospital discharge affected rates of growth during infancy (both during the intervention period and post intervention period). All of the meta-analyses contained statistically significant heterogeneity, in each case O'Connor 2008 found a larger (and statistically significant) mean difference than Zachariassen 2011.
Development: One trial assessed infants at 18 months post term and did not find any statistically significant effects on neurodevelopmental outcomes.
Long term outcomes: There are not yet any data on growth or development through later childhood.
Aim
To determine the effect of feeding preterm (< 37 weeks' gestation at birth) and low birth weight infants (< 2.5 kg), with multinutrient fortified breast milk compared with unfortified human breast milk, on growth and development for preterm infants following hospital discharge.
Methods
• Cochrane systematic review:
Search: CENTRAL (The Cochrane Library, Issue 3, 2012), MEDLINE, EMBASE, and CINAHL (until July 2012), conference proceedings, and previous reviews.
Data collection and analysis: Standard method of the Cochrane Neonatal Group, with separate evaluation of trial quality and data extraction by two authors, and synthesis using a fixed effect model for meta-analysis. We calculated the I² statistic for each analysis to quantify inconsistency across studies.
Discussion and implications
The limited available data do not provide consistent evidence that feeding preterm infants following hospital discharge with multinutrient fortified breast milk compared with unfortified breast milk affects growth rates during infancy. The effect on long term growth and development has not been assessed.
Current recommendations to provide multinutrient fortifier for preterm infants post hospital discharge are not supported by the available evidence.
Since fortifying breast milk for infants fed directly from the breast is logistically difficult and has the potential to interfere with breast feeding, it’s important to determine if mothers would support further trials of this intervention.
Results: trials
Participants: A total of 246 infants included, in two trials – mostly very preterm and very low birth weight infants.
Interventions: Both trials compared multinutrient fortifier mixed with expressed breast milk or unfortified human milk feeding for 3 – 4 months post-discharge.
Risk of bias: allocation generation and concealment, and loss to follow-up was adequate. Blinding of intervention was not attempted but blinding of some assessments (including developmental assessment) was possible.
This is a summary of independent research funded in part by the National Institute for Health Research (NIHR)’s Academic Clinical Fellowship programme (L. Young is an Academic Clinical Fellow).  The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.