Highlight
– In a blinded, multisite randomized clinical trial of 201 moderate to late preterm infants (32+0 to 36+6 weeks), supplemental pasteurized donor human milk did not reduce time to attainment of full enteral feeds (150 mL/kg/day) compared with term infant formula when used to supplement insufficient maternal milk.
– Secondary outcomes were largely similar between groups except for a slower time to regain birth weight in the donor milk group (median 10.7 vs 8.4 days; HR 0.65, 95% CI 0.47–0.88).
Background
Moderate to late preterm infants (born 32+0 to 36+6 weeks’ gestation) represent a large and heterogeneous segment of preterm births. Although their risk of severe prematurity-related complications is lower than that of very and extremely preterm infants, they frequently experience feeding immaturity, weight loss, and hospital stays that are influenced by adequacy of enteral intake. When maternal milk supply is insufficient in the neonatal period, clinicians commonly face the choice of supplementing with pasteurized donor human milk (donor milk) or with term infant formula. For very preterm and very low birth weight infants, randomized and observational data have supported donor milk use because of reductions in necrotizing enterocolitis (NEC) and other morbidities. However, evidence to guide the short-term use of donor milk in more mature preterm infants has been limited.
Study design
Rumbold et al. conducted a multisite, blinded, randomized clinical trial in two Australian neonatal units between July 6, 2021, and April 5, 2023, enrolling infants ≤4 days old, born between 32+0 and 36+6 weeks’ gestation, with birth weight ≥1500 g, clinically stable, ready to commence or already receiving enteral feeds, and with insufficient maternal milk. Infants were randomized to receive pasteurized donor human milk or term infant formula as supplemental feeds for up to 8 days. Randomization was stratified by site and gestational age. The trial was blinded. Infants were followed to 6 months’ corrected age (CA). Primary outcome was time (days) to full enteral feeds, defined as 150 mL/kg/day. Secondary outcomes included measures of feed intolerance, growth and body composition, breast milk feeding rates, and hospital readmissions through 6-month CA. The trial registration is ACTRN12621000529842. Full citation: Rumbold AR et al., JAMA Pediatrics. 2025;179(10):1065–1073.
Key findings
Population: 201 infants were randomized—99 to donor milk and 102 to formula. Mean (SD) gestational age at birth was 34.6 (1.2) weeks and mean (SD) birth weight 2267.1 (450.8) g. Forty-three percent were female and 37% were from multiple births.
Primary outcome
Mean (SD) time to reach full enteral feeds was similar between groups: donor milk 5.7 (2.6) days versus formula 5.8 (3.4) days. The adjusted mean difference was −0.07 days (95% CI −0.90 to 0.76), indicating no meaningful benefit of short-term donor milk supplementation in accelerating establishment of full enteral intake among these infants.
Secondary outcomes
Most secondary outcomes were comparable between groups. Notably:
- Feed intolerance and measures related to gastrointestinal tolerance did not differ meaningfully between donor milk and formula groups.
- Breast milk feeding rates and hospital readmissions to 6-month CA were similar in both arms.
- Growth and body composition outcomes showed no major differences over follow-up, with one exception: time to regain birth weight was longer in the donor milk group (mean [SD] 10.7 [5.7] days) than in the formula group (8.4 [4.4] days), with a hazard ratio for regaining birth weight of 0.65 (95% CI 0.47–0.88), favoring formula for earlier weight regain.
Safety
The trial reported no signal for increased adverse clinical events in either arm through 6 months’ corrected age. There were no reported excess hospital readmissions or serious complications attributable to the assigned supplemental feeding strategy in the studied population.
Interpretation and clinical significance
The principal result—that short-term supplementation with pasteurized donor human milk does not reduce the time to achieve full enteral feeds in stable moderate–late preterm infants when compared with term formula—has practical implications. The 95% confidence interval for the primary outcome excludes large clinically important reductions in time to full feeds, supporting the conclusion that donor milk confers no meaningful advantage for this specific outcome in this population under the conditions tested (up to 8 days of supplementation).
The observed slower regain of birth weight among infants receiving donor milk is biologically plausible. Pasteurization and pooling of donor milk reduce some bioactive components and can alter nutrient density; donor milk provided as unfortified supplemental feeds may have lower energy and protein content per unit volume than term formula. In very preterm or very low birth weight infants, fortification of human milk is standard to meet high nutrient requirements; in moderate–late preterm infants where requirements are lower and supplementation brief, potential differences in caloric/protein intake are likely to manifest as modest differences in early weight recovery.
Strengths
- Randomized, blinded design across two neonatal units increases internal validity and reduces selection and ascertainment biases.
- Pragmatic enrollment of clinically stable, moderate–late preterm infants mirrors a common clinical dilemma: short-term supplementation when maternal milk is insufficient.
- Follow-up to 6 months’ corrected age allows assessment of short-term growth and early clinical outcomes beyond hospital discharge.
Limitations and generalizability
- The trial enrolled infants who were clinically stable and primarily moderate–late preterm; results should not be extrapolated to very preterm (<32 weeks) or extremely low birth weight infants, where donor milk benefits for NEC and other outcomes are established.
- Supplementation was limited to a maximum of 8 days. Different durations of donor milk exposure or use with systematic fortification could yield different growth outcomes.
- The study was conducted at two Australian centers and used commercially available pasteurized donor milk; variations in donor milk processing, fortification practices, and local clinical pathways may affect external applicability.
- Only a single trial of this specific population is available; replication and larger multicenter studies could further refine effect estimates for less frequent outcomes.
Implications for practice and policy
For neonatal clinicians and units faced with limited donor milk supplies and the competing needs of very preterm infants, this trial provides evidence to support judicious allocation of donor human milk. In clinically stable moderate–late preterm infants with short-term need for supplementation, term formula appears to achieve similar time to full enteral feeds and earlier weight regain compared with pasteurized donor milk. These data suggest that routine use of limited donor milk resources for stable moderate–late preterm infants to accelerate enteral feeding may not be warranted.
That said, individual clinical circumstances matter: maternal preference, concerns about allergy or formula intolerance, ethical and cultural considerations, and efforts to support breastfeeding should all influence feeding decisions. Where donor milk is abundant and family-centered care favors its use, clinicians can still reasonably offer donor milk knowing no safety signal was observed in this trial. Conversely, when donor milk is scarce, reserving it for the highest-risk very preterm infants is a defensible policy supported by the current evidence base.
Research gaps and future directions
Open questions remain. These include whether:
- Longer courses of donor milk or fortified donor milk would alter growth or other outcomes in this population.
- Specific subgroups of moderate–late preterm infants (for example, those with feeding intolerance, respiratory disease, or maternal contraindications to breastfeeding) may differentially benefit from donor milk.
- Cost-effectiveness and health systems implications of routine donor milk supplementation in this population would justify policy changes.
Future multicenter trials or pooled analyses that examine fortified versus unfortified donor milk, longer supplementation durations, and patient-centered outcomes—including breastfeeding duration and parental satisfaction—would be valuable.
Conclusion
In this randomized clinical trial, short-term supplementation with pasteurized donor human milk did not shorten time to full enteral feeds compared with term formula among clinically stable moderate–late preterm infants. Donor milk was associated with a modest delay in regaining birth weight. These findings support targeted use of scarce donor milk resources for infants at highest risk of severe complications of prematurity, while allowing individualized decision-making for moderate–late preterm infants based on clinical context and parental preferences.
Funding and trial registration
Trial registration: ACTRN12621000529842. Funding sources are reported in the original manuscript (Rumbold AR et al., JAMA Pediatrics. 2025).
Reference
Rumbold AR, Lai MM, August D, Koorts P, Donovan T, Yelland L, Makrides M, Cuthbert AR, Klein LD, Ginis T, Al Gharram A, Jones S, Summers L, McPhee A, Keir A. Supplemental Donor Milk vs Infant Formula in Moderate to Late Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2025 Oct 1;179(10):1065-1073. doi: 10.1001/jamapediatrics.2025.2365. PMID: 40758360; PMCID: PMC12322819.
