Early Life Nutrition: From Milk Composition to Long-Term Growth Outcomes

This thesis aimed to optimize early-life nutrition in term and preterm infants by addressing three areas: the effects of reduced protein intake in formula-fed term infants, strategies to improve the nutritional consistency of donor human milk for very preterm infants, and the benefits of enriched post-discharge nutrition for moderate-to-late preterm infants. Together, these studies provide insight into how targeted nutritional interventions in early life may support healthy growth, body composition, and long-term health outcomes. Part I: Low-protein infant formula Breast milk is considered the optimal source of infant nutrition and is associated with a lower risk of overweight and improved metabolic health later in life compared with formula feeding. Its relatively lower protein content has led to interest in reducing protein levels in infant formula to improve long-term outcomes. Chapters 2 and 3 describe a randomized controlled trial in healthy term-born infants who received either a lower-protein formula, with protein content below current standards, or a standard-protein formula during the first six months of life. Growth, body composition, and metabolic markers were assessed up to six years of age. No significant differences were observed between the groups in growth, body composition, or metabolic outcomes. These findings indicate that reducing formula protein content below current recommendations does not provide additional benefits for growth or long-term metabolic health. Part II: Donor human milk composition For very preterm infants without access to their mother’s own milk, donor human milk is the preferred alternative to formula due to its protective effects, including a reduced risk of necrotizing enterocolitis. However, donor milk often contains lower protein and fat levels, partly due to later stages of lactation at donation and processing procedures such as pasteurization. Chapter 4 examined changes in milk composition over time within individual donors. Protein concentrations declined during the first months postpartum but later stabilized, while fat and energy content increased during the first eight months. Carbohydrate levels remained relatively stable, indicating that macronutrient composition becomes more consistent after early postpartum variation. Chapter 5 explored variability between donors and investigated data-driven pooling strategies to improve nutritional consistency. Using retrospective data and machine learning models, maternal characteristics such as body mass index and stage of lactation were identified as predictors of milk composition. Pooling strategies based on these predictors resulted in more nutritionally consistent donor milk batches. Together, these studies demonstrate that improved understanding of donor milk variability can enhance milk banking practices. Strategic pooling and broader acceptance of donations beyond the first postpartum year may improve both the quality and availability of donor human milk. Part III: Post-discharge nutrition Moderate-to-late preterm infants, born between 32 and 37 weeks of gestation, represent the largest group of preterm births, yet their nutritional needs after hospital discharge are not well established. Chapters 6 and 7 report a randomized controlled trial comparing a protein- and energy-enriched post-discharge formula with a standard term formula, provided until six months corrected age. Infants receiving the enriched formula showed modest but consistent improvements in early growth and bone mineral content. By 24 months corrected age, they also exhibited a more favorable body composition, with higher fat-free mass and lower fat mass. Conclusions This thesis highlights the importance of tailored, evidence-based nutritional strategies during infancy. While reducing formula protein content below current standards does not appear beneficial for term infants, data-informed donor milk pooling can improve nutrition for very preterm infants, and enriched post-discharge nutrition shows promise for moderate-to-late preterm infants. Breast milk remains the optimal source of nutrition whenever available.