Key messages
• Feeding very preterm or very low-birthweight infants donor human milk rather than formula reduces the risk of necrotising enterocolitis by about half.
• There is probably little or no effect on infection or death rates during the infant's hospital stay.
What is necrotising enterocolitis?
Very preterm infants (those born more than eight weeks early) and very low-birthweight infants (those weighing less than 1.5 kg at birth) are at risk of developing necrotising enterocolitis, a severe condition where tissues in the lining of the infant's bowel become inflamed and die. This condition can lead to serious infection, death, and disability or developmental problems.
What is donor milk?
One way to help prevent necrotising enterocolitis in very preterm or very low-birthweight infants might be to feed them donor human milk (donated by other women) rather than artificial formula (usually adapted from cow milk) when the infant's own mother's milk is not available.
What did we want to find out?
We wanted to know if when a mother's own milk is not available, feeding her very preterm or very low-birthweight infant donor human milk rather than formula reduces the risk of necrotising enterocolitis, serious infection, and death.
What did we do?
We searched for studies and compared and summarised the results of the studies we found. We rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We found 12 trials involving a total of 2296 infants. Feeding very preterm or very low-birthweight infants donor human milk rather than formula reduces the risk of necrotising enterocolitis by about half. There is probably little or no effect on infection or death rates during the infant's hospital stay.
What are the limitations of the evidence?
We are confident in the evidence for an effect on necrotising enterocolitis. We are only moderately confident in the evidence for serious infection and death because there were not enough studies to be certain about the effects, and it is possible that people in the studies knew which treatment they were getting, which could have influenced the results.
How up-to-date is the evidence?
The evidence is current to February 2024.
The evidence shows that donor human milk reduces the risk of NEC by about half in very preterm or VLBW infants. There is probably little or no effect on late-onset invasive infection or all-cause mortality before hospital discharge.
When sufficient maternal milk is not available, donor human milk or formula are the alternative forms of enteral nutrition for very preterm or very low-birthweight (VLBW) infants. Donor human milk may retain the non-nutritive benefits of maternal milk and has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or VLBW infants.
To assess the effectiveness of donor human milk compared with formula for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants when sufficient maternal milk is not available.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care (MIC) database, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to February 2024. We searched clinical trials registries and examined the reference lists of included studies.
Randomised or quasi-randomised controlled trials comparing feeding with donor human milk versus formula in very preterm (< 32 weeks' gestation) or VLBW (< 1500 g) infants.
Two review authors evaluated the risk of bias in the trials, extracted data, and synthesised effect estimates using risk ratio, risk difference, and mean difference, with associated 95% confidence intervals. The primary outcomes were NEC, late-onset invasive infection, and all-cause mortality before hospital discharge. The secondary outcomes were growth parameters and neurodevelopment. We used the GRADE approach to assess the certainty of the evidence for our primary outcomes.
Twelve trials with a total of 2296 infants fulfilled the inclusion criteria. Most trials were small (average sample size was 191 infants). All trials were performed in neonatal units in Europe or North America. Five trials were conducted more than 40 years ago; the remaining seven trials were conducted in the year 2000 or later. Some trials had methodological weaknesses, including concerns regarding masking of investigators and selective reporting.
Meta-analysis showed that donor human milk reduces the risk of NEC (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.37 to 0.76; I² = 4%; risk difference (RD) −0.03, 95% CI −0.05 to −0.01; 11 trials, 2261 infants; high certainty evidence). Donor human milk probably has little or no effect on late-onset invasive infection (RR 1.12, 0.95 to 1.31; I² = 27%; RD 0.03, 95% CI −0.01 to −0.07; 7 trials, 1611 infants; moderate certainty evidence) or all-cause mortality (RR 1.00, 95% CI 0.76 to 1.31; I² = 0%; RD −0.00, 95% CI −0.02 to 0.02; 9 trials, 2116 infants; moderate certainty evidence).