Target Versus Modified-Standard Fortification of Human Milk and Growth of Very Low Birth Weight Infants: A Double-Blind Randomized Trial

Background/Objectives: Individualized (“target”) fortification of human milk is promoted to improve growth and subsequent neurodevelopment in very low birth weight (VLBW) infants, because standard fortifiers may not provide sufficient protein given the considerable intra- and interindividual variability of human-milk composition. We compared modified-standard fortification (MSF), an optimized high-protein standard regimen, with high-protein target fortification (TFO). Methods: In a single-center, double-blind randomized trial, VLBW infants (24 + 0 – 31 + 6 weeks) receiving 100 mL/kg/d of standard fortified human milk were randomized to MSF (protein and medium-chain triglycerides added to standard fortifier) or TFO until 36 weeks postmenstrual age (PMA). The primary outcome was weight-gain velocity from randomization to 36 weeks PMA; the trial was powered to detect a difference of 0.666 standard deviations. Results: Weight-gain velocity did not differ between the groups (MSF n = 54, TFO n = 52; MSF − TFO − 0.18 g/kg/d, 95% CI −1.02 to +0.67, p = 0.68), nor did anthropometry, z-scores, skinfold thickness or cranial widths at 36 weeks PMA, or Bayley-III scores at 24 months. Conclusions: Compared with optimized high-protein standard fortification, high-protein target fortification did not improve growth or neurodevelopmental outcomes.