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Multinutrient fortification of human breast milk for preterm infants following hospital discharge

  1. Lauren Young1,
  2. Nicholas D Embleton2,
  3. Felicia M McCormick3,
  4. William McGuire1,*

Editorial Group: Cochrane Neonatal Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 10 SEP 2012

DOI: 10.1002/14651858.CD004866.pub4


How to Cite

Young L, Embleton ND, McCormick FM, McGuire W. Multinutrient fortification of human breast milk for preterm infants following hospital discharge. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD004866. DOI: 10.1002/14651858.CD004866.pub4.

Author Information

  1. 1

    Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, UK

  2. 2

    Royal Victoria Infirmary, Newcastle Neonatal Service, Newcastle upon Tyne, UK

  3. 3

    University of York, Mother and Infant Research Unit, Department of Health Sciences, York, UK

*William McGuire, Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, Y010 5DD, UK. William.McGuire@hyms.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 28 FEB 2013

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Characteristics of included studies [ordered by study ID]
O'Connor 2008

MethodsRandomised controlled trial


Participants39 preterm infants born < 33 weeks' gestation with birthweight 750-1800 g

Enrolled when receiving 80% of enteral feedings orally as human milk (fortified or unfortified) 3 days before planned hospital discharge

Exclusion criteria: infants with serious anomalies affecting growth; grade 3 or 4 periventricular haemorrhage; receipt of oral steroids within 14 days of randomisation; Apgar score < 5 at 5 minutes; known maternal alcohol or drug abuse; family habitat outside study area; mother unable to communicate verbally in English; infant needed nutrient enrichment incompatible with the intervention


InterventionsIntervention (N = 19): feeding after hospital discharge with human milk, half of which to be fortified with 3.6 g commercially-available powdered multinutrient human milk fortifier per 100 mL fresh or thawed human milk for 12 weeks following discharge

Control (N = 20): "Standard care" - feeding after hospital discharge with unfortified human milk

Both groups received standard vitamins and iron supplements post-discharge

Both groups had access to intensive lactation support from the study co-ordinator, a certified lactation consultant, who also performed the study measures during home visits


Outcomes1. Growth: weight , length and head circumference up to completion of intervention period (12 weeks post-discharge) and up to 12 months corrected age

2. Bayley II mental and psychomotor development index scores at 18 months corrected age

3. Bone mineral content and density at 4 months and 12 months corrected age

4. Nutrient intake up to completion of intervention period

5. Duration of breast milk feeding (at least one human milk feed per day) and proportion of daily feeds provided as human milk up to 12 weeks

6. Visual development: Grating acuity (i.e., visual acuity) and contrast sensitivity were assessed using sweep visual-evoked potential tests at 4 and 6 months corrected age


NotesAim with fortification of half of the daily human milk intake was to provide milk with an overall average calorie content of 74 kcal/100 mL and protein content of 1.8 g/100 mL; that is, about the same nutrient density as commercially-available "post-discharge" formula

Infants in the intervention group did receive about 50% fortified feeds as planned. Infants in the control group received about 8% fortified feeds at each data collection point

The investigators estimated that "energy intakes did not differ between the groups, suggesting human milk-fed infants are able to compensate to some degree for the energy and/or nutrient density of their feeding."

The authors acknowledge that the human milk fortifier and disposable supplies to collect and store human milk, were donated by Abbott Nutrition and Mead Johnson Nutritionals


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated

Allocation concealment (selection bias)Low riskSequence stored in sealed envelopes

Blinding (performance bias and detection bias)
All outcomes
High riskParents or other caregivers were not blind to intervention

Unclear whether assessors (e.g. developmental assessment) were aware of intervention group

Incomplete outcome data (attrition bias)
All outcomes
High riskOutcome data not reported for five infants withdrawn post-randomisation (from total N = 39)

Zachariassen 2011

MethodsRandomised controlled trial


Participants207 preterm infants born < 33 weeks' gestation

Enrolled 'shortly' before planned hospital discharge

Exclusion criteria: infants with serious diseases or circumstances influencing feeding ability at discharge


InterventionsIntervention (N = 105): once daily addition of a commercially available breast-milk fortifier containing 17.5 kCal and 1.375 g of protein to 20-50 mL of expressed breast milk. The fortified milk was fed via bottle or cup. The intervention was planned to continue until 4 months post term

Control (N = 102): breast feeding after hospital discharge with unfortified human milk

Use of vitamins or iron not described, level of lactation support not described


Outcomes1. Growth: weight , length and head circumference up to 12 months corrected age

2. Duration of breast milk feeding (at least one human milk feed per day) and proportion of daily feeds provided as human milk up to 12 weeks

3. Haemoglobin concentration, serum phosphate and urea level at end of 4 months intervention period


NotesIf breast feeding was discontinued (or insufficient for all feeds) infants received either a formula milk (during first two months protein and mineral enriched milk, for the following two months, a standard 'term' formula was used)

By 2 months post term, 54 of 105 intervention group infants had changed nutrition, and 24 of 102 controls, and by 4 months post term, 85 of 105 intervention group infants had changed nutrition, and 57 of 102 controls

Multiple birth siblings were randomised together: 42 of 105 (intervention) versus 27 of 102 (controls) were multiples

The authors acknowledge that Mead Johnson Nutritionals donated nutritional products used in the trial


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated

Allocation concealment (selection bias)Low riskSequence stored in sealed envelopes

Blinding (performance bias and detection bias)
All outcomes
High riskUnblinded to parents, caregivers, and investigators

Incomplete outcome data (attrition bias)
All outcomes
Low riskNear complete follow-up (97%)

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Hall 1993The intervention group received only mineral supplements. The trial did not report growth as an outcome

 
Comparison 1. Multinutrient fortification vs. no fortification of human breast milk

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Weight (g)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    1.1 3-4 months corrected age
2236Mean Difference (IV, Fixed, 95% CI)138.26 [-89.87, 366.40]

    1.2 12 months corrected age
2211Mean Difference (IV, Fixed, 95% CI)255.25 [-93.40, 603.90]

 2 Head circumference (cm)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    2.1 3-4 months corrected age
2235Mean Difference (IV, Fixed, 95% CI)0.22 [-0.15, 0.58]

    2.2 12 months corrected age
2197Mean Difference (IV, Fixed, 95% CI)0.16 [-0.27, 0.60]

 3 Length (cm)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    3.1 3-4 months corrected age
2236Mean Difference (IV, Fixed, 95% CI)0.60 [-0.14, 1.33]

    3.2 12 months corrected age
2211Mean Difference (IV, Fixed, 95% CI)0.88 [0.01, 1.74]

 4 Visual acuity (cycles/degree)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 4 months corrected age
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 6 months corrected age
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Contrast sensitivity (log)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 4 months corrected age
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 6 months corrected age
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Bone mineral content (g)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 4 months corrected age
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 12 months corrected age
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Bone mineral density (g/cm2)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 4 months corrected age
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 12 months corrected age
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Duration of human milk feeding2Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 Postnatal weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.2 Post discharge weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Proportion of infants fed with breast milk at end of intervention period2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    9.1 Exclusively fed with human milk
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 At least partially fed with human milk
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]