Individualized Target Fortification of Breast Milk with Protein, Carbohydrates, and Fat for Preterm Infants: Effect on Neurodevelopment

Background/Objectives: Preterm infants are at high risk of extrauterine growth restriction and suboptimal neurological development due to cumulative nutrient deficits. Standard fortification (SF) of human milk does not account for individual macronutrient variability, potentially leading to inadequate intake. Target fortification (TFO) adjusts supplementation based on the measured macronutrient content, aimed at providing macronutrient intake aligned with ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) recommendations and optimize growth and development. This study aims to evaluate the effects of TFO compared to SF on growth, body composition, and neurological outcomes at 18 months corrected age. Methods: In this double-blind, randomized controlled trial, preterm infants (&lt:30 weeks gestation) received either SF or TFO for at least three weeks. Macronutrient levels in breast milk were analyzed three times per week, with modular adjustments in the TFO group. Growth parameters, body composition at 36 weeks postmenstrual age, and Bayley Scales of Infant and Toddler Development III (BSID-III) scores at 18 months corrected age were assessed (n = 69). Results: TFO significantly increased protein, fat, and carbohydrate intake compared to SF, leading to higher weight gain (2514 &plusmn: 289 g vs. 2283 &plusmn: 332 g, p &lt: 0.01) and growth velocity (21.7 &plusmn: 2.3 g/kg/d vs. 19.2 &plusmn: 2.2 g/kg/d, p &lt: 0.001). In infants whose mother&rsquo:s milk had low protein levels, fat-free mass was significantly higher with TFO compared to SF. BSID-III scores were higher in the TFO group across cognitive, language, and motor domains, with significant improvements in expressive language scores in infants whose mother&rsquo:s milk had high protein levels (p &lt: 0.05). The number of preterm infants with a motor BSID-III score of &le:70 was significantly lower in the TFO group compared to the SF group (0 vs. 3, p &lt: 0.05). Conclusions: TFO enhanced growth and body composition and may support better neurological outcomes in preterm infants. While most BSID-III differences were not statistically significant, the data suggest that TFO may reduce the risk of developmental delays. Larger, multicenter trials are needed to confirm these findings.