The review by Romero-Lopez, Naik, Thoene and colleagues examines the evidence available for nutritional management in this exceptionally premature population and highlights how much of current practice is still based on extrapolation, expert consensus, or studies involving infants born at later gestational ages. Babies born at 22 or 23 weeks differ biologically from those born at 25 or 27 weeks: they have less mature gastrointestinal barriers, lower protein and energy stores, greater fluid instability, and a higher risk of respiratory and circulatory complications. As a result, nutritional strategies that appear safe in more mature preterm infants may not have the same effects in infants born at the limits of viability.

Immediately after birth, many of these infants cannot safely receive sufficient nutrition through the gastrointestinal tract. Parenteral nutrition, delivered directly into the bloodstream, therefore becomes central to early care. It can provide amino acids for protein synthesis, glucose for energy, lipid emulsions for essential fatty acids and concentrated calories, as well as electrolytes, vitamins, and trace elements. The technical challenge is to start these nutrients early enough to reduce catabolism—the breakdown of the infant’s own tissues—without worsening metabolic instability. Clinicians must continuously monitor blood glucose, triglycerides, acid-base status, electrolytes, kidney function, and liver markers, adjusting the composition of the infusion as the infant’s physiology changes.

Protein delivery is particularly important because extremely preterm infants can lose nitrogen rapidly when their intake is inadequate. Protein is required not only for muscle growth but also for the formation of enzymes, hormones, immune molecules, and structural components of the developing brain and lungs. At the same time, excessive or poorly balanced nutrient administration may contribute to metabolic disturbances. The review emphasizes that the ideal doses, timing, and progression of amino acids and other macronutrients remain uncertain for infants born at 22–23 weeks. Many existing recommendations are derived from fetal growth estimates or trials in broader preterm populations, rather than from direct evidence in the most immature infants.

Human milk remains a central component of nutritional care whenever it is available. A mother’s own milk contains proteins, enzymes, growth factors, immune cells, antibodies, and complex carbohydrates that may help protect the immature intestine and support microbial development. Colostrum, the early milk produced after birth, is especially concentrated in immunological components, although the very small volumes available during the first days may make its nutritional contribution limited. Donor human milk is often used when a mother’s milk is insufficient, but it can differ in composition and may require fortification to meet the high protein, mineral, and energy needs of an extremely premature infant.

Feeding milk through the gastrointestinal tract is generally introduced cautiously, often in small volumes known as trophic or minimal enteral feeds. The purpose is not initially to provide all required nutrition but to stimulate intestinal activity and expose the gut to milk-derived signals. As tolerance improves, feeds may be advanced while parenteral nutrition is reduced. Yet determining whether an infant is ready for faster advancement is difficult. Abdominal distension, residual stomach contents, changes in stool, blood in the stool, or alterations in vital signs can raise concern about feeding intolerance or necrotizing enterocolitis, a severe inflammatory disease in which intestinal tissue can become damaged. The review identifies the balance between promoting gut maturation and minimizing intestinal risk as one of the most important unresolved issues.

Fortification presents another complex problem. Human milk alone may not supply enough protein, calcium, phosphorus, sodium, and energy to support the growth expected during late fetal development. Fortifiers are added to increase nutrient density, but the composition and timing of fortification may need to be adapted for infants born at 22–23 weeks. These babies can have unusually high nutritional requirements, while also being vulnerable to fluid overload and biochemical abnormalities. Standard fortification protocols may not account for individual variation in milk composition or changes in an infant’s renal function, growth rate, and illness severity. More individualized approaches, including targeted or adjustable fortification based on laboratory and growth data, are promising but require stronger validation.

Nutrition is also closely linked to the major complications of extreme prematurity. Insufficient protein and energy may restrict postnatal growth and contribute to impaired neurodevelopment, while excessive carbohydrate delivery can worsen hyperglycemia and increase osmotic stress. Lipid emulsions supply dense energy and essential fatty acids needed for neural and retinal development, but their formulations may influence inflammation, liver function, and immune responses. Poor mineral balance can weaken bones and contribute to metabolic bone disease, while inadequate sodium intake may limit growth even when calories appear sufficient. These interactions mean that nutrition cannot be evaluated in isolation from respiratory support, infection, fluid management, medication exposure, and the infant’s evolving organ function.

The authors describe major gaps in the evidence base, including the absence of large, adequately powered trials focused specifically on infants born at 22–23 weeks. Researchers still need clearer answers about the safest initial doses of parenteral amino acids and lipids, the optimal speed of enteral feeding advancement, the comparative effects of mother’s milk and donor milk, and the best methods for fortifying human milk. Long-term outcomes also require greater attention. A feeding strategy may appear successful if it produces short-term weight gain, yet its true value must also be judged by survival without severe intestinal disease, lung injury, eye disease, impaired brain development, or later disability. Standardized definitions and consistent outcome measures will be essential for comparing future studies.

The review ultimately presents nutritional care at 22–23 weeks as a field moving faster than its evidence. Advances in neonatal intensive care have enabled more infants born at the limits of viability to survive, but survival alone does not define success. The next generation of research will need to connect precise nutrient delivery with developmental biology, intestinal microbiology, inflammation, and long-term neurodevelopment. Until those data are available, clinicians must combine careful monitoring with individualized decisions, recognizing that the smallest premature infants may respond differently from older preterm populations. Their nutritional treatment is therefore both a daily clinical calculation and a major scientific frontier: providing enough of what a developing body needs, without overwhelming organs that have only just begun to function outside the womb.

Subject of Research: Nutritional management of infants born at 22–23 weeks of gestational age

Article Title: Nutritional management at 22–23 weeks gestational age: evidence and knowledge gaps

Article References: Romero-Lopez, M., Naik, M., Thoene, M. et al. Nutritional management at 22–23 weeks gestational age: evidence and knowledge gaps. Pediatr Res (2026). https://doi.org/10.1038/s41390-026-05370-0

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05370-0

Keywords: extreme prematurity, periviability, neonatal nutrition, parenteral nutrition, human milk, enteral feeding, necrotizing enterocolitis, infant growth, neonatal intensive care, gestational age

Extremely preterm infants—those born before 28 weeks of gestation—face enormous challenges in achieving optimal postnatal growth and avoiding life-threatening complications such as NEC, a severe inflammatory disease of the intestine. The timing and composition of enteral nutrition—feeding directly into the gastrointestinal tract—have long been contentious subjects, with clinicians balancing the need to stimulate gut maturation against the risks of feeding intolerance and intestinal injury. This study’s dual cohort design allowed researchers to decisively link early nutrition protocols with measurable clinical outcomes, shining a light on best practices that could transform neonatal care worldwide.

A central aspect of the investigation was the timing of enteral nutrition initiation. The study meticulously compared outcomes between infants who began minimal enteral feeding within the first 24 hours of life versus those whose feeds were delayed beyond this critical window. Statistical analyses revealed that earlier initiation of feeding was positively correlated with improved weight gain patterns by discharge and a reduced overall incidence of NEC. These findings support the hypothesis that early enteral nutrition serves not only a nutritional function but also acts as a pivotal stimulus for gut motility, mucosal integrity, and immunological development.

The complexity of feeding regimens examined in this study underscores the nuanced decision-making required in neonatal intensive care units. Researchers segregated nutritional strategies into categories based on the volume and type of milk—mother’s own milk, donor human milk, or formula—and their respective roles in fostering growth while mitigating gastrointestinal risk. Notably, exclusive human milk diets were associated with the most favorable outcomes, consistent with prior evidence suggesting its protective effect against NEC. Conversely, mixed feeding protocols involving formula showed a statistically significant increase in NEC risk, emphasizing the importance of human milk components in early gut health.

Beyond timing and composition, the study also explored the role of feeding advancement rates—the speed at which feeding volumes were increased over the first weeks of life. Rapid advancement has historically been feared to exacerbate feeding intolerance and intestinal damage; however, the dual cohort data suggests that carefully monitored incremental increases in enteral nutrition can promote catch-up growth without elevating NEC risk. This challenges entrenched clinical conservatism and opens dialogues on refining nutrition protocols to better balance risk and reward in these fragile patients.

One of the most compelling dimensions of this study is its cross-national design, integrating data from distinct healthcare systems with differing protocols, demographics, and resource availabilities. This methodology permitted a robust comparative framework and enhanced the generalizability of the results. Researchers were able to delineate how institutional practices, including the use of standardized feeding guidelines and lactation support programs, significantly influence neonatal outcomes. This highlights systemic factors beyond individualized care, inviting a broader perspective on improving neonatal nutrition worldwide.

The research also examined secondary outcomes related to neurological development and metabolic stability, assessing whether early enteral feeding practices might influence these domains indirectly through improved growth metrics. Preliminary data from neurodevelopmental assessments at corrected ages suggest a trend toward better cognitive and motor outcomes associated with earlier and exclusively human milk enteral feeding. While longitudinal follow-up is ongoing, these findings point toward the profound implications of neonatal nutrition extending far beyond immediate survival.

Moreover, the study delves into the pathophysiological mechanisms underlying NEC, illuminating how early enteral nutrition modulates gut microbiota composition and immune responses. The investigators utilized sequencing technologies to profile intestinal microbial communities, revealing that early feeding with human milk fosters colonization by beneficial bacteria such as Bifidobacteria, while delayed or formula-heavy protocols were linked to dysbiosis and increased gut inflammation. These microbiological insights provide a biological rationale for the clinical associations observed, bridging neonatal nutrition with emerging fields of microbiome research.

The paper meticulously discusses limitations inherent to observational cohort studies, including potential confounders such as varying degrees of illness severity and socioeconomic status. To mitigate these, the authors employed advanced statistical controls and sensitivity analyses, lending robustness to their conclusions. They underscore the urgent need for randomized controlled trials to validate these observational findings and refine clinical guidelines accordingly, advocating for collaboration across neonatal centers worldwide.

Ethical considerations are addressed in the context of striking the appropriate balance between necessary nutritional interventions and the avoidance of harm. The study’s findings reinforce the ethical imperative for neonatologists to re-examine conservative feeding practices that may inadvertently delay gut stimulation and growth progress, emphasizing evidence-based policy changes to enhance care quality and equity for vulnerable preterm populations.

In terms of translational impact, this research paves the way for standardized feeding protocols emphasizing early initiation and exclusive use of human milk when possible, alongside prudent advancement rates. Such protocols could dramatically improve survival rates, reduce NEC incidence, and support healthier growth patterns, ultimately improving long-term health trajectories for preterm infants. The findings also bolster advocacy for increased availability and support for donor human milk programs globally, especially in regions where maternal milk supply may be compromised.

This pivotal study aligns with emerging trends in neonatology prioritizing personalized nutrition and microbiota-focused interventions. The integration of clinical nutrition with immunological and microbiological research highlights a multidisciplinary approach becoming increasingly necessary to tackle complex neonatal conditions. The team’s collaborative model and data transparency set a benchmark for future studies aiming to optimize neonatal outcomes through targeted nutritional strategies.

Experts not involved in the study have lauded its comprehensive approach and its potential to reshape clinical paradigms, observing that the dual cohort methodology offers unprecedented clarity on a hotly debated topic. The broader medical community stands to benefit from these insights as they navigate the delicate challenges faced by premature infants and their families. Furthermore, the study’s implications extend beyond neonatology, potentially informing nutritional science and care strategies in other vulnerable pediatric populations.

In summation, Challis and colleagues have delivered a landmark contribution to neonatal nutrition science, providing eloquent evidence that early, carefully managed enteral nutrition is a cornerstone in promoting growth and preventing devastating intestinal complications in extremely preterm infants. Their work not only advances academic understanding but also equips clinicians with actionable knowledge to improve bedside care during the most critical phases of neonatal intensive care.

Moving forward, the integration of molecular and clinical data to personalize neonatal nutrition regimes will likely become standard practice, guided by studies like this which illustrate the profound interplay between nutrition, gut biology, and infant development. This research heralds a new era where feeding strategies are scientifically tailored to harness the full potential of early nutrition, setting the stage for healthier beginnings for the most fragile patients.

As neonatal care continues to evolve, the findings presented here emphasize the crucial role that precision nutrition and systemic healthcare factors play in optimizing preterm infant outcomes. The widespread adoption of evidence-based early enteral feeding protocols promises to transform prognoses for these high-risk newborns, offering hope to clinicians and families alike for better growth, fewer complications, and improved lifespans.

Subject of Research: Early enteral nutrition practices and their association with growth and necrotizing enterocolitis in extremely preterm infants.

Article Title: Early enteral nutrition practices and their association with growth and necrotising enterocolitis in extremely preterm infants—A dual national cohort study.

Article References:
Challis, P., Stoltz Sjöström, E., Elfvin, A. et al. Early enteral nutrition practices and their association with growth and necrotising enterocolitis in extremely preterm infants—A dual national cohort study. Pediatr Res (2026). https://doi.org/10.1038/s41390-026-04849-0

Image Credits: AI Generated

DOI: 10.1038/s41390-026-04849-0

Keywords: enteral nutrition, extremely preterm infants, necrotizing enterocolitis, neonatal growth, human milk, neonatal intensive care, gut microbiota, feeding protocols