Powdered Human Milk-derived Versus Bovine Milk-derived Breastmilk Fortification: A Multi-centre Preterm Randomised Controlled Trial

Overview

Journal J Pediatr Gastroenterol Nutr

Publisher Wiley

Date 2024 Dec 11

PMID 39660504

Authors

Janet Berrington

Mark Johnson

Shalabh Garg

Christopher Stewart

Christopher Lamb

Jeremy Palmer

Nicholas Embleton

Affiliations

Soon will be listed here.

Abstract

Objective: To compare faecal calprotectin, plasma amino acids and clinical outcomes in preterm infants receiving powdered human milk-based fortifier (PHMF) compared to powdered bovine milk-based fortifier (PBMF) in preterm infants on an otherwise exclusive human milk diet.

Methods: A randomised controlled trial in infants <32 weeks of gestation or <1500 g who only received human milk and had reached full enteral feeds (150 mL/kg/day), without pre-existing gastrointestinal morbidity. Primary outcome was faecal calprotectin within 21 days of starting fortification; secondary outcomes were calprotectin at discharge, plasma amino acids and clinical outcomes, including growth and neonatal morbidities.

Results: The trial stopped early after the manufacturer's withdrawal of PHMF. Thirty-one infants were enroled, three without informative sampling, leaving 14 per group. No statistical differences were seen in faecal calprotectin on Day 7 (236 mcg/g PHMF vs. 303 mcg/g PBMF, p = 0.90) or 21 (135 mcg/g PHMF vs. 315 mcg/g PBMF, p = 0.21). Adjusting for gestation and day of life, and including all time points after enrolment to discharge, fortifier type did not impact faecal calprotectin (coefficient estimate -7.13, 95% confidence interval = -172 to 158, p = 0.93). Rates of key neonatal morbidities did not differ. PHMF infants grew more slowly reaching statistical significance in change in weight standard deviation score at discharge compared to PBMF infants (mean (standard deviation) -0.94 (0.7) PHMF vs. -0.24 (0.8) PBMF, p = 0.02).

Conclusions: We did not detect reduced gut inflammation as measured by faecal calprotectin in PHMF compared to PBMF but weight gain was slower, of potential clinical importance.

Citing Articles

Powdered human milk-derived versus bovine milk-derived breastmilk fortification: A multi-centre preterm randomised controlled trial.

Berrington J, Johnson M, Garg S, Stewart C, Lamb C, Palmer J J Pediatr Gastroenterol Nutr. 2024; 80(2):336-344.

PMID: 39660504 PMC: 11788938. DOI: 10.1002/jpn3.12431.

References

Embleton N, Sproat T, Uthaya S, Young G, Garg S, Vasu V . Effect of an Exclusive Human Milk Diet on the Gut Microbiome in Preterm Infants: A Randomized Clinical Trial. JAMA Netw Open. 2023; 6(3):e231165. PMC: 9978942. DOI: 10.1001/jamanetworkopen.2023.1165. View

Bach Jensen G, Ahlsson F, Domellof M, Elfvin A, Naver L, Abrahamsson T . Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial-the N-forte trial. BMJ Open. 2021; 11(11):e053400. PMC: 8611420. DOI: 10.1136/bmjopen-2021-053400. View

Leppanen M, Lapinleimu H, Lind A, Matomaki J, Lehtonen L, Haataja L . Antenatal and postnatal growth and 5-year cognitive outcome in very preterm infants. Pediatrics. 2013; 133(1):63-70. DOI: 10.1542/peds.2013-1187. View

Yoon J, Park J, Ko K, Lim J, Cheon E, Kim H . Fecal calprotectin concentration in neonatal necrotizing enterocolitis. Korean J Pediatr. 2014; 57(8):351-6. PMC: 4155179. DOI: 10.3345/kjp.2014.57.8.351. View

Menon G, Williams T . Human milk for preterm infants: why, what, when and how?. Arch Dis Child Fetal Neonatal Ed. 2013; 98(6):F559-62. DOI: 10.1136/archdischild-2012-303582. View

Panczuk J, Unger S, Francis J, Bando N, Kiss A, OConnor D . Introduction of Bovine-Based Nutrient Fortifier and Gastrointestinal Inflammation in Very Low Birth Weight Infants as Measured by Fecal Calprotectin. Breastfeed Med. 2016; 11(1):2-5. DOI: 10.1089/bfm.2015.0125. View

Rouge C, Butel M, Piloquet H, Ferraris L, Legrand A, Vodovar M . Fecal calprotectin excretion in preterm infants during the neonatal period. PLoS One. 2010; 5(6):e11083. PMC: 2884033. DOI: 10.1371/journal.pone.0011083. View

Fenton T, Merlino Barr S, Elmrayed S, Alshaikh B . Expected and Desirable Preterm and Small Infant Growth Patterns. Adv Nutr. 2024; 15(6):100220. PMC: 11251411. DOI: 10.1016/j.advnut.2024.100220. View

Brown J, Lin L, Embleton N, Harding J, McGuire W . Multi-nutrient fortification of human milk for preterm infants. Cochrane Database Syst Rev. 2022; 6:CD000343. PMC: 7268980. DOI: 10.1002/14651858.CD000343.pub4. View

10.

Pergialiotis V, Konstantopoulos P, Karampetsou N, Koutaki D, Gkioka E, Perrea D . Calprotectin levels in necrotizing enterocolitis: a systematic review of the literature. Inflamm Res. 2016; 65(11):847-852. DOI: 10.1007/s00011-016-0963-9. View

11.

OConnor D, Kiss A, Tomlinson C, Bando N, Bayliss A, Campbell D . Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing <1250 g: a randomized clinical trial. Am J Clin Nutr. 2018; 108(1):108-116. DOI: 10.1093/ajcn/nqy067. View

12.

MacQueen B, Christensen R, Yost C, Gordon P, Baer V, Schlaberg R . Reference intervals for stool calprotectin in preterm neonates and their utility for the diagnosis of necrotizing enterocolitis. J Perinatol. 2018; 38(10):1379-1385. DOI: 10.1038/s41372-018-0108-9. View

13.

Lucas A, Boscardin J, Abrams S . Preterm Infants Fed Cow's Milk-Derived Fortifier Had Adverse Outcomes Despite a Base Diet of Only Mother's Own Milk. Breastfeed Med. 2020; 15(5):297-303. PMC: 7232708. DOI: 10.1089/bfm.2019.0133. View

14.

Qu Y, Xu W, Han J, Zhou W, Wu H . Diagnostic value of fecal calprotectin in necrotizing enterocolitis: A meta-analysis. Early Hum Dev. 2020; 151:105170. DOI: 10.1016/j.earlhumdev.2020.105170. View

15.

Sullivan S, Schanler R, Kim J, Patel A, Trawoger R, Kiechl-Kohlendorfer U . An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr. 2009; 156(4):562-7.e1. DOI: 10.1016/j.jpeds.2009.10.040. View

16.

Corpeleijn W, Kouwenhoven S, Paap M, van Vliet I, Scheerder I, Muizer Y . Intake of own mother's milk during the first days of life is associated with decreased morbidity and mortality in very low birth weight infants during the first 60 days of life. Neonatology. 2012; 102(4):276-81. DOI: 10.1159/000341335. View

17.

Ananthan A, Balasubramanian H, Rao S, Patole S . Response to comments by Prof Abrams and Prof Lucas on "Human Milk-Derived Fortifiers Compared with Bovine Milk-Derived Fortifiers in Preterm Infants: A Systematic Review and Meta-Analysis". Adv Nutr. 2020; 11(6):1713-1715. PMC: 7666968. DOI: 10.1093/advances/nmaa099. View

18.

Uthaya S, Jeffries S, Andrzejewska I, Vasu V, Embleton N, Modi N . Randomised controlled trial of human derived breast milk fortifier versus bovine milk fortifier on body composition in very preterm babies. Early Hum Dev. 2022; 171:105619. DOI: 10.1016/j.earlhumdev.2022.105619. View

19.

Embleton N, Moltu S, Lapillonne A, van den Akker C, Carnielli V, Fusch C . Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts. J Pediatr Gastroenterol Nutr. 2023; 76(2):248-268. DOI: 10.1097/MPG.0000000000003642. View

20.

Bach Jensen G, Domellof M, Ahlsson F, Elfvin A, Naver L, Abrahamsson T . Effect of human milk-based fortification in extremely preterm infants fed exclusively with breast milk: a randomised controlled trial. EClinicalMedicine. 2024; 68:102375. PMC: 10965410. DOI: 10.1016/j.eclinm.2023.102375. View