A new review in Pediatric Research is drawing attention to one of the most difficult questions in modern neonatal medicine: how to provide safe and effective nutrition to infants born at 22–23 weeks of gestation. These babies arrive at the edge of viability, often weighing little more than 500 grams, with organs that are still undergoing fundamental development. Their intestines may be immature, their metabolic reserves extremely limited, and their ability to coordinate sucking, swallowing, and breathing not yet established. In this setting, nutrition is not simply a matter of supplying calories. It is a carefully balanced medical intervention intended to support brain growth, lung development, immune function, and tissue repair while avoiding complications that can rapidly become life-threatening.
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
