Enhanced versus standard fortification of pasteurized donor human milk for growth in very low birth weight infants: a randomized controlled trial

Abstract

Introduction: Very-low-birthweight (VLBW) infants on pasteurized donor human milk (PDHM) have poorer growth compared to infants on fortified mother's milk, suggesting that standard fortification methods for PDHM are inadequate. Methods: We designed a randomized controlled trial to determine whether an enhanced method of fortification (EF) improved growth in VLBW infants compared to standard fortification (SF). VLBW infants admitted to our tertiary-level neonatal intensive care unit were randomized to receive a bovine powdered human milk fortifier (HMF) added to PDHM (SF), or specially selected high-fat PDHM (fat concentration ≥3.8 g/dL) with bovine powdered HMF and a liquid protein fortifier providing an additional 0.67 g/dL protein (EF). Primary outcome was impaired weight gain defined as weight z-score drop of ≥0.8 from birth at 37 weeks or hospital discharge, whichever earlier. Secondary outcomes included change in length and head circumference (HC) z-scores from birth, requirement for high calorie formula, and rates of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP). Results: A total of 61 infants were randomized (31 SF, 30 EF). Impaired weight gain was not significantly different (SF 83.9% vs. EF 73.3%, p = 0.347), with similar declines in weight z-scores from birth in both groups SF −1.27 [interquartile range (IQR) −1.71, −0.87] vs. EF −1.13 (IQR −1.46, −0.78), p = 0.403. However, the EF group had a smaller decline in length and HC z-scores from birth to discharge compared to the SF group [Length z-score change: −0.92 (IQR −1.64, −0.48) vs. −1.64 (IQR −2.21, −0.89), p = 0.007; HC z-score change: −0.08 (IQR −0.74,0.58) vs. −0.86 (IQR −1.81, −0.21), p = 0.014]. The EF group also required less high calorie formula supplementation [0% (IQR 0-4.1) vs. 3.8% (IQR 0 −16.9), p = 0.032]. Rates of BPD and ROP were not significantly different between groups. Conclusion: Among VLBW infants, EF did not improve weight gain, but reduced declines in HC and linear growth compared to SF.