Optimizing Enteral Nutrition in the NICU: Early Feeding Strategies, Fortification Approaches, and Long-Term Growth Outcomes in Preterm and High-Risk Infants

Preterm infants, particularly those born at very low birthweight, face profound nutritional challenges from the earliest days of extrauterine life. They enter a critical window of somatic growth and neurodevelopment abruptly deprived of the continuous placental nutrient supply that would have supported their maturation in utero. Human milk, whether maternal or donor, is widely recognized as the optimal enteral substrate for these infants, providing macronutrients alongside immunological, bioactive, and microbiological components that confer protection against necrotizing enterocolitis, late‑onset sepsis, and retinopathy of prematurity. Yet human milk alone, even when fortified, rarely meets the markedly elevated energy and micronutrient requirements of very preterm infants, making multinutrient fortification a cornerstone of contemporary neonatal intensive care.

Despite broad consensus on the importance of early and adequate nutrition, substantial variation persists in clinical practice worldwide. The timing of feed initiation, the rate of advancement, and the choice of fortification strategy remain areas of active debate, with recent randomised trials often underpowered or inconclusive and international surveys revealing striking discrepancies in feeding protocols, fortification thresholds, and monitoring tools. Similar uncertainties extend to high‑risk term and late‑preterm infants requiring intensive care whose feeding strategies frequently adapt preterm paradigms but remain under‑studied as a distinct population. These inconsistencies underscore the need for unified, evidence‑based frameworks to optimise enteral nutrition in neonatal intensive care units across diverse settings.

This Research Topic seeks to consolidate and advance knowledge on enteral nutrition practices in the NICU, focusing primarily on preterm and very low birthweight infants, while also welcoming selected contributions related to high‑risk term and late‑preterm infants whose clinical course necessitates intensive care and/or specialized feeding strategies. Its primary aim is to clarify how early feeding initiation, feeding advancement strategies, and fortification approaches, whether standard, targeted, adjustable, or enhanced, affect short‑term growth trajectories, nutrition‑related morbidities, and long‑term neurodevelopmental and metabolic outcomes. A further goal is to characterize the broader “nutritional ecosystem” of the NICU, including the comparative roles of maternal and donor human milk, their interactions with various fortification protocols, and the clinical and logistical barriers to implementing precision nutrition at the bedside. The Topic will also explore the potential of emerging technologies, such as point‑of‑care human milk analysis, including near‑infrared spectroscopy, bedside calorimetry, and body composition monitoring, to guide individualized nutritional management and reduce extrauterine growth failure. Importantly, it will foreground health equity dimensions in neonatal nutrition, examining how maternal education, health insurance coverage, socioeconomic status, and geographic region influence access to optimal nutritional care, human milk, donor milk banking, and advanced fortification strategies, including exclusive human milk diets. Studies that integrate mechanistic biology with clinical outcomes, that link nutrient delivery and gut development to systemic inflammation and neurodevelopment, or that translate nutritional innovation into pragmatic quality‑improvement and implementation‑science initiatives will be particularly valued. By bridging physiology, clinical practice, implementation science, and policy, this Topic aims to inform the development of robust, scalable strategies that improve survival, growth, and neurodevelopment for preterm infants and other high‑risk NICU populations globally.

To gather further insights into optimising enteral nutrition in the NICU and its influence on infant health and development, we welcome contributions addressing, but not limited to, the following themes:

• Timing of enteral feed initiation and rate of advancement in preterm and very low birthweight infants, including strategies to minimize feed interruptions and support early achievement of full enteral feeds.
• Comparative evaluation of standard, adjustable, targeted, and enhanced human milk fortification strategies, including their operational feasibility, safety, and cost‑effectiveness.
• Clinical outcomes of maternal versus donor human milk and their interactions with fortification protocols, including exclusive human milk diets and human‑milk‑based fortifiers.
• Neurodevelopmental outcomes and long‑term growth trajectories following early nutritional interventions, with attention to critical windows of nutrient delivery and body‑composition changes.
• Necrotizing enterocolitis, late‑onset sepsis, bronchopulmonary dysplasia, cholestasis, and other morbidities associated with feeding practices, diet type, and fortification decisions.
• Bedside tools and imaging modalities for monitoring body composition, energy expenditure, bone health, and overall nutritional response in NICU populations.
• Technology‑assisted approaches to precision and individualized neonatal nutrition, including point‑of‑care milk composition analysis, algorithm‑based decision support, and digital dashboards for nutrient delivery and growth monitoring.
• Transition strategies from parenteral to enteral feeding in the NICU and their impact on cholestasis, growth, length of stay, and readiness for discharge.
• Influence of social determinants of health and regional resource disparities on nutritional practices and outcomes, including access to human milk banks, donor milk, lactation support, and specialized fortifiers.
• Quality‑improvement and implementation‑science initiatives aimed at standardizing feeding protocols, enhancing guideline adherence, reducing extrauterine growth restriction, and improving post‑discharge follow‑up.
• Feeding strategies and human‑milk‑based nutrition for high‑risk term and late‑preterm infants requiring NICU care, including initial fluid strategies, fluid‑restricted diets, fortification decisions, and transition to oral feeding.
• Post‑discharge nutritional management for former preterm and high‑risk infants, including human milk use, preterm and transitional formulas, micronutrient supplementation, and their association with later metabolic, bone, and cognitive development.

We welcome many different article types, including Original Research, Systematic Reviews and Meta-Analyses, Clinical Trial Reports, Narrative Reviews, Perspectives, and Case Reports that contribute to a deeper understanding of how early nutrition can optimise survival, growth, and neurodevelopment for preterm infants worldwide.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Enteral nutrition, Neonatal intensive care unit (NICU), Preterm infants, Human milk fortification, Very low birth weight (VLBW), Neurodevelopmental outcomes, Donor human milk, Necrotizing enterocolitis, Precision nutrition, Extrauterine growth restriction

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.