Effects of a Prolonged Exclusive Human Milk-Based Diet on Structural and Functional Brain Maturation in Very Preterm Infants: An Ancillary Analysis of the NEOVASC Trial

Background/Objectives: Early postnatal nutrition is a modifiable determinant of brain maturation in preterm infants. Exclusive human milk-based diets (EHMD) are associated with improved neurodevelopmental outcomes. The objective of this exploratory ancillary analysis of the NEOVASC randomized controlled trial was to determine whether prolonging an exclusive human milk-based diet, specifically through continued human milk-based fortification until 36 weeks postmenstrual age, is associated with differences in early brain structure and functional motor development compared with earlier introduction of bovine milk-based fortifier or formula at 32 weeks postmenstrual age. Methods: This ancillary study of the NEOVASC trial included preterm infants (<32 gestational weeks and birthweight of 500–1250 g) randomized to either prolonged EHMD until 36 weeks PMA or a diet introducing bovine milk-based fortifier or formula from 32 weeks. Quantitative brain metrics, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were analyzed at 40 weeks PMA. Functional maturation was assessed repetitively using the General Movement Optimality Score (GMOS) (34, 36, and 40 weeks PMA) and Motor Optimality Score (52 weeks PMA). Results: Fifty-four infants were included. Groups did not differ in brain growth metrics. After adjustment for imbalances in clinical characteristics, no FA or ADC differences remained statistically significant. GMOS at 40 weeks PMA was higher in the intervention group, with no differences at other time points. Conclusions: In this exploratory ancillary analysis of the NEOVASC trial, prolonging an exclusive EHMD until 36 weeks postmenstrual age was not associated with consistent differences in early brain maturation or motor performance. Given the high overall exposure to human milk in both groups, subtle effects may have been attenuated. These findings require confirmation in larger, adequately powered studies with long-term follow-up.