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

Chengsi Ong^1*Anng Anng Wong²Siew Tin Wong²Ying Zheng²Cynthia Pui Chan Pang^2,3Pooja Agarwal Jayagobi^2,4Joo Guan Yeo^5,6,7Kee Thai Yeo^4,6Mei Chien Chua^2,4,6

• ¹Department of Nutrition and Dietetics, KK Women's and Children's Hospital, Singapore, Singapore
• ²KK Human Milk Bank, Singapore, Singapore
• ³Lactation Services, KK Women's and Children's Hospital, Singapore, Singapore
• ⁴Department of Neonatology, KK Women's and Children's Hospital, Singapore, Singapore
• ⁵Division of Medicine, KK Women's and Children's Hospital, Singapore, Singapore
• ⁶Duke-NUS Medical School, Singapore, Singapore
• ⁷Translational Immunology Institute, Singhealth Duke-NUS Academic Medical Centre, Singapore, Singapore

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. 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 ≥3.8g/dL) with bovine powdered HMF and a liquid protein fortifier providing an additional 0.67g/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) zscores from birth, requirement for high calorie formula, and rates of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP). A total of 61 infants were randomized (31 SF, 30 EF). Impaired weight gain was not significantly different between SF and EF groups (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 (interquartile range (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. Among VLBW infants, EF did not improve weight gain, but reduced declines in HC and linear growth compared to SF.