Formula milk versus term human milk for feeding preterm or low birth weight infants

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Abstract
Term (mature) human breast milk, compared with artificial formula milks, may provide insufficient nutrition for growth and development in preterm or low birth weight infants. However, human milk may confer advantages to infants in terms of a decreased incidence of adverse outcomes. To determine if formula milk compared with term human breast milk leads to improved growth and development without significant adverse effects in low birth weight or preterm infants. The standard search strategy of the Cochrane Neonatal Review Group was used. This included electronic searches of the Cochrane Controlled Trials Register, MEDLINE, EMBASE and previous reviews including cross references. Randomised controlled trials comparing feeding with formula milk versus term human milk in low birth weight or preterm infants. Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk, risk difference and weighted mean difference. Six trials, all initiated more than 20 years ago, fulfilled the pre-specified inclusion criteria. Four small trials compared feeding with standard calorie formula milk versus unfortified term human milk. Two trials compared feeding with calorie-enriched formula milk versus unfortified term human milk. No trials comparing feeding with formula milk versus nutrient-fortified term human milk were found. Only one trial reported longer term follow up of growth and development. In preterm and low birth weight infants, enteral feeding with formula milk compared with unfortified term human milk resulted in a greater rate of growth in the short term. We did not find a statistically significant difference in the incidence of necrotising enterocolitis, but this was evaluated as a pre-defined outcome in only one trial. The single trial that evaluated longer-term outcomes did not find evidence of an effect on longer-term growth and neurodevelopment. In preterm and low birth weight infants, feeding with formula milk, compared with unfortified term human milk, leads to a greater rate of growth in the short term. The limited data available do not allow definite conclusions on whether adverse outcomes, including necrotising enterocolitis, are increased in infants who receive formula milk compared with term human milk. There are no data from randomised trials on the comparison of feeding with formula milk versus nutrient-fortified breast milk. This limits the implications for practice of this review as nutrient fortification of breast milk is now a common practice in neonatal care. Future trials may compare growth, development and adverse outcomes in infants who receive adapted "preterm" formula milks versus nutrient-fortified human breast milk.