Unclear Benefits for Donor Milk Among Low-Risk Preterm Infants

Source: Rumbold AR, Lai MM, August D, et al. Supplemental donor milk vs infant formula in moderate to late preterm infants: a randomized clinical trial. Rumbold AR, et al. JAMA Pediatr. 2025;179(10):1065-1073; doi: 10.1001/jamapediatrics.2025.2365.Investigators from multiple institutions in Australia conducted a randomized clinical trial comparing the effect of donor human milk or formula used to supplement maternal milk in establishing full feeds in moderate to late preterm infants. Study participants were neonates born at 32 to <37 weeks’ gestation and a birth weight >1,500 grams who received care at 2 neonatal units in Australia. Only infants for whom the supply of maternal milk was insufficient to meet nutritional needs were enrolled. Study participants were randomized to the donor human milk or formula treatment group when they were ≤4 days old. The clinical staff added the donor milk or formula to feeds as needed until a study infant was 8 days old. The primary study outcome was time to full enteral feeds, defined as 150 mL/kg/d. Parents were contacted when their infants were 2, 4, and 6 months old to collect data on growth, hospital readmissions, and exclusive use of breast milk. Other secondary outcomes included time to regain birth weight, feeding intolerance (number of feedings held or reduced), and length of hospital stay (LOS). Outcomes were compared between patients in the 2 treatment groups with regression analyses.A total of 201 preterm infants were enrolled, with 99 randomized to donor human milk and 102 to the formula group. The mean gestational age at birth in study participants was 34.6 ±1.2 weeks, and mean birth weight was 2,267.1 ±450.8 grams. On average, infants were randomized when they were 1.4 days old. The median number of days that the treatment feedings were consumed was 6.0 days in both groups. The mean time to reach full enteral feeds was 5.7 ±2.6 days for infants randomized to donor human milk and 5.8 ±3.4 days for those in the control group (adjusted treatment effect, -0.07 days; 95% confidence interval [CI], -0.90, 0.76). There also were no significant differences between groups in LOS or incidence of feeding intolerance. Newborns randomized to formula regained birth weight significantly more quickly than those receiving donor human milk (mean, 8.4 ±4.4 and 10.7 ±5.7 days, respectively; hazard ratio, 0.65; 95% CI, 0.47, 0.88). During the 6-month follow-up, there were no significant differences between infants in the 2 treatment groups in growth, hospital readmission, or exclusive breast milk feeding.The authors conclude that, compared to formula, use of donor human milk did not reduce the time to full enteral feeds in moderate to late preterm infants.Dr King has received payment for work as an expert witness on legal cases that did not go to trial involving necrotizing enterocolitis and donor milk use. Dr King has no other conflicts to disclose. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Donor milk is a well-established intervention for very preterm infants to reduce necrotizing enterocolitis and is the recommended supplemental feeding for very preterm infants when mother’s own milk is unavailable.1,2 As a result, the prevalence of donor milk programs among advanced neonatal care facilities caring for very preterm infants is increasing, with a recent survey reporting 88% of level 3 and 4 units with associated programs.3However, inclusion criteria for infants to receive donor milk have been expanding beyond indications with high certainty of evidence. Among respondents in the same survey, 42% reported an inclusion criterion above 32 weeks’ gestational age.3 In a similar survey of level 1 nurses, nearly one-fifth reported routine donor milk use, and the number is likely to rise.4 A systematic review of donor milk among moderately preterm and early term infants identified only 1 small pilot randomized trial and 10 observational studies totaling more than 10,000 infants.5 Results were inconsistent, without any clear effect of donor milk on clinical outcomes or breastfeeding rates.The current researchers report results from the largest randomized trial to date of donor milk for moderate and late preterm infants. Donor milk was not associated with a shorter time to reach full enteral feeds, shorter LOS, or higher breastfeeding rates up to 6 months corrected age. Importantly, the exposure period was relatively short (8 days), with similar rates of formula use in both arms after exposure, which may have minimized differences between groups. While the largest trial to date, there were no cases of NEC, underscoring the much lower risk in this population. Though no harms were reported, these results question whether there are benefits justifying the expansion of donor milk programs toward lower-risk infants. Donor milk also is a costly and supply-limited resource, and while it has been associated with economic benefits among very preterm infants,6 this lower-risk population requires larger volumes of milk, resulting in greater costs for uncertain benefit. A large multicenter trial in this population (the GIFT trial), aiming to enroll more than 2,000 infants, is underway and may provide more definitive answers regarding benefits of donor milk in moderate and late preterm infants.In moderate to late preterm infants, short-term donor milk supplementation appears to offer no measurable clinical advantage over formula, questioning expansion of donor milk programs to this lower-risk group.