1. Objectives

To assess the effect of feeding formula milk in comparison to maternal expressed breast milk on growth and development in preterm or low birth weight infants

2. How studies were identified

The following databases were searched in June 2007:

• CENTRAL (The Cochrane Library 2007, Issue 2)
• MEDLINE
• EMBASE
• CINAHL
• UK National Research Register
• Current Controlled Trials

Reference lists and relevant conference proceedings were also searched

3. Criteria for including studies in the review

3.1 Study type

Randomized controlled trials, including quasi-randomized trials

3.2 Study participants

Preterm (<37 weeks’ gestation) or low birth weight (<2500 g) infants

3.3 Interventions

Feeding with formula milk in comparison to maternal expressed breast milk

3.4 Primary outcomes

Growth

• Rates of growth during the trial period (weight gain per day, linear growth per week, head circumference growth per week, skinfold thickness growth per week)
• Long-term growth from six months of age (weight, height, head circumference, proportion of infants below the 10^th centile for the index population’s distribution)

Development

• Neurodevelopmental outcomes assessed from 12 months’ corrected age with validated tools
• Severe neurodevelopmental disability, including auditory and visual impairment, non-ambulant cerebral palsy, and developmental delay
• Cognitive and educational outcomes at >5 years, including intelligence quotient and educational attainment measured with validated tools

Secondary outcomes included neonatal death, death prior to hospital discharge, necrotising enterocolitis, time to establish full enteral feeding, feed intolerance (requirement to cease enteral feeds), and invasive infection

4. Main results

4.1 Included studies

No eligible trials were indentified for inclusion in this review

• Six studies were excluded, four because they were not randomized controlled trials and two because infants were randomized to receive either formula milk or a mixture of maternal and donor expressed breast milk

4.2 Study settings

How the data were analysed
Feeding with formula milk was to be compared to feeding with maternal expressed breast milk. Dichotomous data were to be summarized using relative risks, risk differences, and the number needed to treat, while continuous data were to be summarized with mean differences. Results were to be presented with 95% confidence intervals. Fixed effects models were planned for meta-analysis, and heterogeneity was to be investigated using subgroup analyses by study quality, participant characteristics, intervention regimens, and outcome assessments.

Results
Growth
No trials were indentified.

Development
No trials were indentified.

Additional outcomes
No trials were indentified.

5. Additional author observations*

In comparison with maternal breast milk, formula milk feeding has been associated with a higher incidence of necrotising enterocolitis in observational studies. In a meta-analysis of randomized controlled trials, rates of feed intolerance and necrotising enterocolitis were higher among preterm infants randomized to formula milk than those randomized to donor milk. Immunoprotective factors such as secretory immunoglobulin-A, lysozyme, lactoferrin, and epidermal growth factors may be responsible for the non-nutritive benefits of breast milk. These properties may also reduce the risk of infection in resource-constrained countries, as demonstrated by a randomized controlled trial in India in which serious infection was significantly reduced with expressed human milk in comparison to formula. Multi-nutrient fortification of maternal expressed breast milk can also be used to provide the benefits of breast milk along with additional nutrition to support the increased requirements of preterm and low birth weight infants.

Although there is currently no evidence from randomized controlled trials to assess the effect of formula milk versus maternal breast milk on growth and development in preterm and low birth weight infants, maternal breast milk continues to be the default feeding choice.

No studies comparing formula milk feeding to maternal expressed breast milk feeding were identified, likely due to the reluctance of researchers and potential study participants to deny infants the benefits of their mother’s milk. Nonetheless, mothers intending to breastfeed and health care practitioners would require convincing evidence that feeding with formula has benefits over breast milk before considering using formula to feed low birth weight and preterm infants.