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

IntroductionVery-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.MethodsWe designed a randomized controlled trial to determine whether...

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Main Authors: Chengsi Ong, Anng Anng Wong, Siew Tin Wong, Ying Zheng, Cynthia Pui Chan Pang, Pooja Agarwal Jayagobi, Joo Guan Yeo, Kee Thai Yeo, Mei Chien Chua
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Nutrition
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Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2025.1582519/full
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author Chengsi Ong
Anng Anng Wong
Siew Tin Wong
Ying Zheng
Cynthia Pui Chan Pang
Cynthia Pui Chan Pang
Pooja Agarwal Jayagobi
Pooja Agarwal Jayagobi
Joo Guan Yeo
Joo Guan Yeo
Joo Guan Yeo
Kee Thai Yeo
Kee Thai Yeo
Mei Chien Chua
Mei Chien Chua
Mei Chien Chua
author_facet Chengsi Ong
Anng Anng Wong
Siew Tin Wong
Ying Zheng
Cynthia Pui Chan Pang
Cynthia Pui Chan Pang
Pooja Agarwal Jayagobi
Pooja Agarwal Jayagobi
Joo Guan Yeo
Joo Guan Yeo
Joo Guan Yeo
Kee Thai Yeo
Kee Thai Yeo
Mei Chien Chua
Mei Chien Chua
Mei Chien Chua
author_sort Chengsi Ong
collection DOAJ
description IntroductionVery-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.MethodsWe 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).ResultsA 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.ConclusionAmong VLBW infants, EF did not improve weight gain, but reduced declines in HC and linear growth compared to SF.
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spelling doaj-art-da4b74b95468468097c2e40356782daa2025-08-20T03:47:02ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-08-011210.3389/fnut.2025.15825191582519Enhanced versus standard fortification of pasteurized donor human milk for growth in very low birth weight infants: a randomized controlled trialChengsi Ong0Anng Anng Wong1Siew Tin Wong2Ying Zheng3Cynthia Pui Chan Pang4Cynthia Pui Chan Pang5Pooja Agarwal Jayagobi6Pooja Agarwal Jayagobi7Joo Guan Yeo8Joo Guan Yeo9Joo Guan Yeo10Kee Thai Yeo11Kee Thai Yeo12Mei Chien Chua13Mei Chien Chua14Mei Chien Chua15Department of Nutrition and Dietetics, KK Women's and Children's Hospital, Singapore, SingaporeKK Human Milk Bank, Singapore, SingaporeKK Human Milk Bank, Singapore, SingaporeKK Human Milk Bank, Singapore, SingaporeKK Human Milk Bank, Singapore, SingaporeDivision of Nursing, Lactation Services, Singapore, SingaporeKK Human Milk Bank, Singapore, SingaporeDepartment of Neonatology, KK Women's and Children's Hospital, Singapore, SingaporeDuke-NUS Medical School, Singapore, SingaporeDivision of Medicine, KK Women's and Children's Hospital, Singapore, SingaporeSingHealth Duke-NUS Academic Medical Centre, Translational Immunology Institute, Singapore, SingaporeDepartment of Neonatology, KK Women's and Children's Hospital, Singapore, SingaporeDuke-NUS Medical School, Singapore, SingaporeKK Human Milk Bank, Singapore, SingaporeDepartment of Neonatology, KK Women's and Children's Hospital, Singapore, SingaporeDuke-NUS Medical School, Singapore, SingaporeIntroductionVery-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.MethodsWe 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).ResultsA 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.ConclusionAmong VLBW infants, EF did not improve weight gain, but reduced declines in HC and linear growth compared to SF.https://www.frontiersin.org/articles/10.3389/fnut.2025.1582519/fulldonor breast milkgrowthvery low birth weightpretermfortification
spellingShingle Chengsi Ong
Anng Anng Wong
Siew Tin Wong
Ying Zheng
Cynthia Pui Chan Pang
Cynthia Pui Chan Pang
Pooja Agarwal Jayagobi
Pooja Agarwal Jayagobi
Joo Guan Yeo
Joo Guan Yeo
Joo Guan Yeo
Kee Thai Yeo
Kee Thai Yeo
Mei Chien Chua
Mei Chien Chua
Mei Chien Chua
Enhanced versus standard fortification of pasteurized donor human milk for growth in very low birth weight infants: a randomized controlled trial
Frontiers in Nutrition
donor breast milk
growth
very low birth weight
preterm
fortification
title Enhanced versus standard fortification of pasteurized donor human milk for growth in very low birth weight infants: a randomized controlled trial
title_full Enhanced versus standard fortification of pasteurized donor human milk for growth in very low birth weight infants: a randomized controlled trial
title_fullStr Enhanced versus standard fortification of pasteurized donor human milk for growth in very low birth weight infants: a randomized controlled trial
title_full_unstemmed Enhanced versus standard fortification of pasteurized donor human milk for growth in very low birth weight infants: a randomized controlled trial
title_short Enhanced versus standard fortification of pasteurized donor human milk for growth in very low birth weight infants: a randomized controlled trial
title_sort enhanced versus standard fortification of pasteurized donor human milk for growth in very low birth weight infants a randomized controlled trial
topic donor breast milk
growth
very low birth weight
preterm
fortification
url https://www.frontiersin.org/articles/10.3389/fnut.2025.1582519/full
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