In a groundbreaking investigation into the long-term effects of neonatal nutrition, researchers from the NICHD Neonatal Research Network have presented compelling data comparing the growth outcomes of preterm infants fed donor milk versus those receiving preterm formula. This large-scale randomized trial, known as the MILK Trial, addresses a crucial question in neonatal care that has profound implications for infant health trajectories and clinical nutrition guidelines worldwide.
Premature infants, defined as those born before the completion of 37 weeks of gestation, face numerous health challenges, including susceptibility to infections and developmental delays. Among the most significant variables influencing their recovery and development during the vulnerable neonatal period is the type of nutritional support they receive. Human milk, especially donor milk, is often considered the gold standard due to its immunological and bioactive properties, though concerns about its ability to support optimal growth have persisted.
The MILK Trial is distinctive in design and scope. It randomized a cohort of preterm infants to receive either pasteurized donor human milk or preterm formula from the early days post-birth until discharge. Subsequently, the researchers conducted a longitudinal follow-up assessing growth parameters at two years of adjusted age, thereby enabling an understanding of not only immediate but also longer-term growth outcomes.
The fundamental hypothesis posited by the investigators was that there would be no significant differences in the anthropometric growth measures—weight, length, and head circumference—at the two-year follow-up, regardless of whether infants were fed donor milk or formula. This hypothesis emerged from prior, smaller studies suggesting equivalent growth patterns but lacked the statistical power to conclude definitively.
Upon evaluation, the data demonstrated that infants fed donor milk achieved growth metrics that paralleled their formula-fed counterparts at two years, thereby affirming the original hypothesis. Notably, these findings suggest that donor milk is a viable alternative to preterm formula without compromising growth in the critical early developmental window. This revelation challenges lingering biases favoring formula on the basis of growth promotion.
The trial meticulously accounted for confounding variables that could independently impact growth, including gestational age at birth, severity of neonatal complications, socioeconomic status, and access to post-discharge nutritional support. Adjusted analyses reinforced the robustness of the conclusion, underscoring that neonatal diet type itself did not differentially affect growth trajectories by the endpoint.
Importantly, the implications of these results extend beyond mere anthropometrics. Donor milk confers immunological benefits absent in formula, such as the transfer of maternal antibodies and prebiotic components that modulate the infant gut microbiome. The reassuring evidence of equal growth dispels concerns that opting for donor milk entails a trade-off between immunity and somatic growth, an issue that has long vexed neonatologists and dietitians.
While the infant brain’s development heavily relies on adequate nutrition, head circumference – a proxy for brain growth – was statistically indistinguishable between the two nutritional cohorts. This aspect addresses critical developmental concerns, broadly suggesting that donor milk supports neurodevelopmental programming as effectively as formula feeding under these controlled conditions.
These findings resonate strongly with ongoing efforts to optimize neonatal nutrition protocols, particularly within neonatal intensive care units (NICUs) where premature infants are managed. Donor milk banking systems, which have expanded globally, now gain further empirical justification as an essential resource that combines safety, nutrition, and ethical viability.
Furthermore, the trial’s follow-up at two years provides invaluable insight into medium-term developmental outcomes, extending the window of observation well beyond the initial hospitalization period. This approach illustrates the importance of longitudinal studies in neonatal nutrition research to capture the full spectrum of growth and developmental dynamics.
This rigorous clinical evidence is poised to inform clinical guidelines and policy decisions, potentially increasing advocacy for the use of donor milk in NICUs, reducing reliance on formula, and ultimately improving neonatal care standards. It also offers reassurance to parents grappling with feeding decisions in high-stress neonatal contexts.
Moreover, by conclusively demonstrating no deleterious growth impact attributable to donor milk, the MILK Trial opens avenues for exploring additional benefits donor milk may provide, such as reduced incidence of necrotizing enterocolitis and other inflammatory conditions prevalent in preterm infants.
The significance of these findings is amplified by the careful methodological rigor evident in the trial’s design, including randomization, blinding of assessors, and standardized growth measurement protocols, which collectively strengthen the validity and reliability of the conclusions drawn.
Future research inspired by these results may delve into nuanced nutritional compositions of donor milk, including fortification strategies aimed at optimizing macronutrient balance to further enhance both growth and functional outcomes.
In sum, the NICHD Neonatal Research Network’s MILK Trial constitutes a landmark study in neonatal nutrition, affirming that feeding preterm infants donor human milk achieves growth outcomes comparable to those observed with preterm formula. This evidence supports a paradigm shift in neonatal feeding practices, emphasizing the non-inferiority of donor milk with respect to growth, alongside its well-documented immunological advantages.
As the neonatal care community digests these findings, there is potential for widespread transformation in how vulnerable preterm infants are nourished during their most critical developmental phase. The MILK Trial’s robust evidence base will likely catalyze changes benefiting countless infants and families worldwide, underscoring that early nutrition remains central to lifelong health trajectories.
Subject of Research: Growth outcomes at two years of age in preterm infants based on neonatal diet: donor human milk versus preterm formula.
Article Title: Growth at 2 years in children born preterm: donor milk versus preterm formula.
Article References:
Brumbaugh, J.E., McDonald, S.A., Robinson, D.T. et al. Growth at 2 years in children born preterm: donor milk versus preterm formula. Pediatr Res (2026). https://doi.org/10.1038/s41390-025-04729-z
Image Credits: AI Generated
DOI: 19 January 2026
