357 - Individually targeted macronutrient fortification of human milk for hospitalized preterm infants <31 weeks of gestation: a single-center randomized, controlled trial.

Publication Number: 3344.357

Mandy Belfort, Harvard Medical School, Boston, MA, United States; Banu Ahtam, Boston Children's Hospital, Boston, MA, United States; Katherine A. Bell, Harvard Medical School, Boston, MA, United States; Paige K. Berger, Brigham and Women's Hospital, Boston, MA, United States; Sara Cherkerzian, Brigham and Women's Hospital, Boston, MA, United States; Deirdre M. Ellard, Brigham and Women's Hospital, Boston, MA, United States; Laurie P. Foster, 0100, Boston, MA, MA, United States; Christoph Fusch, Paracelsus Medical University, Nuremberg, Bayern, Germany; Borjan Gagoski, Boston Children's Hospital, Boston, MA, United States; P. Ellen grant, Boston Children's Hospital, Boston, MA, United States; Manasa Kuncham, Brigham and Women's Hospital, Allston, MA, United States; Hunter L. Pepin, Brigham and Women's Hospital, Boston, MA, United States; Tina Steele, Brigham and Won=men's Hospital, North Billerica, MA, United States; Lianne J. Woodward, University of Canterbury, Christchurch, Canterbury, New Zealand; Terrie E. Inder, CHOC Children's Hospital of Orange County, Orange, CA, United States

Background: Human milk is the recommended diet for hospitalized preterm infants, but variable milk composition may cause gaps in macronutrient delivery despite routine fortification. Point-of-care macronutrient analysis of milk allows for individually targeted fortification, but its effectiveness is not well-studied.

Objective: To conduct a pragmatic randomized, controlled trial comparing effects of individually targeted human milk fortification (intervention) with standard-of-care fortification (control), on 1) macronutrient delivery, 2) in-hospital growth and body composition, and 3) neonatal brain size and maturity assessed with magnetic resonance imaging (MRI).

Design/Methods: From 2020-2025, we randomized 130 infants born at 24-30 completed weeks’ gestation 1:1 to intervention and control groups. All participants received maternal and/or pasteurized donor human milk fortified according to a local guideline (standard of care). The intervention group received added protein and/or fat fortification guided by 5x per week milk analysis with mid infrared spectroscopy and targeting ≥1 g/dL true protein and ≥20 kcal/ounce in the base milk through 36 weeks’ postmenstrual age. Clinicians were blinded to study arm. We compared macronutrient intakes and outcomes of anthropometry, body composition with air displacement plethysmography, and total brain volume and fractional anisotropy of the posterior limb of the internal capsule by MRI at term equivalent age between groups. We used generalized linear models to adjust for covariates and account for twins.

Results: Mean (SD) gestational age was 28.5 (1.9) weeks and birth weight was 1165 (298) grams (Table 1). Median true protein content of base milk (1.25 vs. 1.18 g/dL, p=0.08) and total protein intake from base milk and all fortifiers (4.58 vs. 4.46 g/kg/day, p=0.008) were unexpectedly higher in the control group; fat and energy content and intakes were similar between groups (Table 2). In intention to treat analyses, z-score changes from study diet start to end in weight, length, and head circumference; body composition; and brain MRI indices did not differ between groups (Table 3). Length z-score change from study diet start to discharge was less negative in the intervention vs. control group (adjusted difference, 0.25; 95% CI, 0.03, 0.48).

Conclusion(s): Individually targeted human milk fortification did not increase macronutrient delivery or improve most outcomes when compared with standard-of-care fortification. Body length z-score declined less through discharge in the intervention group, suggesting a possible benefit to linear growth.

Table 1. Participant characteristics and clinical outcomes
Table 1.pdf

Table 2. Macronutrient content of base milk and daily macronutrient intakes
Table 2.pdf

Table 3. Anthropometry, body composition, and brain MRI outcomes
Table 3.pdf