{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:08:45Z","timestamp":1792084125922,"version":"4.4.0"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants fed an exclusive human milk (HM) diet, either mother\u2019s own milk (MOM) or donor human milk (DHM). We searched PubMed, Embase, Google Scholar, CENTRAL and CINHAL between January 2015 and August 2023 for studies reporting outcomes in infants with \u226428 weeks gestation and\/or birthweight \u2264 1500 g on an exclusive human milk diet fortified with HMF versus BMF. The primary outcomes were death and NEC (stage \u2265 2). Four studies with a total of 681 infants were included. Mortality was significantly lower in infants fed with an HM-HMFs diet (four studies, 681 infants; RR = 0.50, 95% CI = 0.26\u20130.94; p = 0.03; I2 = 0%), NEC was similar between the two groups (four studies, 681 infants; RR = 0.48, 95% CI = 0.20\u20131.17; p = 0.11; I2= 39%). BPD was higher in the HM-BMFs group (four studies, 663 infants; RR = 0.83, 95% CI = 0.69\u20131.000; p = 0.05, I2 = 0%), although not statistically significant. No differences were found for sepsis (RR = 0.97, 95% CI = 0.66\u20131.42; p = 0.96; I2 = 26%) or combined ROP (four studies, 671 infants; RR = 0.64, 95% CI = 0.53\u20131.07; p = 0.28; I2 = 69%). An HM-HMFs diet could possibly be associated with decreased mortality with no association with NEC, BPD, sepsis, or ROP. This meta-analysis was limited by the small number of studies included. However, the results should not be refuted for this reason as they provide an impetus for subsequent clinical trials to assess the observed associations.<\/jats:p>","DOI":"10.3390\/nu16060910","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T11:37:22Z","timestamp":1711021042000},"page":"910","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Association of Fortification with Human Milk versus Bovine Milk-Based Fortifiers on Short-Term Outcomes in Preterm Infants\u2014A Meta-Analysis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4165-8816","authenticated-orcid":false,"given":"Radu","family":"Galis","sequence":"first","affiliation":[{"name":"Department of Neonatology, Emergency County Hospital Bihor, 50 Clujului Street, 410053 Oradea, Romania"},{"name":"Department of Neonatology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0967-9892","authenticated-orcid":false,"given":"Paula","family":"Trif","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Emergency County Hospital Bihor, 50 Clujului Street, 410053 Oradea, Romania"},{"name":"Doctoral School of Biomedical Sciences, University of Oradea, 1 University Street, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5225-1758","authenticated-orcid":false,"given":"Diana","family":"Mudura","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Emergency County Hospital Bihor, 50 Clujului Street, 410053 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Mazela","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy C.","family":"Daly","sequence":"additional","affiliation":[{"name":"Irish Neonatal Health Alliance (INHA), 26 Oak Glen View, Southern Cross, A98 Y234 Bray, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris W.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6259-3118","authenticated-orcid":false,"given":"Shivashankar","family":"Diggikar","sequence":"additional","affiliation":[{"name":"Oyster Woman and Child Hospital, Bengaluru 560043, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1055\/s-0042-1756677","article-title":"Bronchopulmonary Dysplasia and Impaired Neurodevelopment-What May Be the Missing Link?","volume":"39","author":"Kramer","year":"2022","journal-title":"Am. J. Perinatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kelly, C.E., Shaul, M., Thompson, D.K., Mainzer, R.M., Yang, J.Y.M., Dhollander, T., Cheong, J.L.Y., Inder, T.E., Doyle, L.W., and Anderson, P.J. (2023). Long-lasting effects of very preterm birth on brain structure in adulthood: A systematic review and meta-analysis. Neurosci. Biobehav. Rev., 147.","DOI":"10.1016\/j.neubiorev.2023.105082"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1055813","DOI":"10.3389\/fped.2023.1055813","article-title":"Retinopathy of prematurity and neurodevelopmental outcomes in preterm infants: A systematic review and meta-analysis","volume":"11","author":"Diggikar","year":"2023","journal-title":"Front. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"151694","DOI":"10.1016\/j.semperi.2022.151694","article-title":"Neurodevelopmental outcome of infants who develop necrotizing enterocolitis: The gut-brain axis","volume":"47","author":"Lu","year":"2023","journal-title":"Semin. Perinatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.siny.2018.08.005","article-title":"Neurodevelopmental outcomes following necrotizing enterocolitis","volume":"23","author":"Hickey","year":"2018","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"088","DOI":"10.23937\/2474-3658\/1510088","article-title":"Neurodevelopmental Outcome in Very Low Birth Weight Preterm Newborns: The Role of Neonatal Sepsis","volume":"5","author":"Martina","year":"2019","journal-title":"J. Infect. Dis. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2167074","DOI":"10.1080\/14767058.2023.2167074","article-title":"The association between bronchopulmonary dysplasia grade and risks of adverse neurodevelopmental outcomes among preterm infants born at less than 30 weeks of gestation","volume":"36","author":"Oluwole","year":"2023","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fnut.2017.00020","article-title":"Optimizing Nutrition in Preterm Low Birth Weight Infants-Consensus Summary","volume":"4","author":"Kumar","year":"2017","journal-title":"Front. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.clp.2016.11.004","article-title":"Neurodevelopmental Outcomes of Preterm Infants Fed Human Milk: A Systematic Review","volume":"44","author":"Lechner","year":"2017","journal-title":"Clin. Perinatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1097\/MPG.0000000000003642","article-title":"Enteral Nutrition in Preterm Infants (2022): A Position Paper from the ESPGHAN Committee on Nutrition and Invited Experts","volume":"76","author":"Embleton","year":"2022","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fped.2019.00076","article-title":"Fortification of Human Milk for Preterm Infants: Update and Recommendations of the European Milk Bank Association (EMBA) Working Group on Human Milk Fortification","volume":"7","author":"Arslanoglu","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/0140-6736(90)93304-8","article-title":"Breast milk and neonatal necrotising enterocolitis","volume":"336","author":"Lucas","year":"1990","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1016\/j.jpeds.2013.07.011","article-title":"Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants","volume":"163","author":"Cristofalo","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Jensen, G.B., Domell\u00f6f, M., Ahlsson, F., Elfvin, A., Nav\u00e9r, L., and Abrahamsson, T. (2023, August 31). Effect of Human Milk-Based Fortification in Extremely Preterm Infants Fed Exclusively with Breast Milk: A Randomised Controlled Trial. Available at SSRN. Available online: https:\/\/papers.ssrn.com\/sol3\/papers.cfm?abstract_id=4529245.","DOI":"10.1016\/j.eclinm.2023.102375"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1093\/ajcn\/nqy067","article-title":"Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing <1250 g: A randomized clinical trial","volume":"108","author":"Kiss","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1089\/bfm.2019.0133","article-title":"Preterm Infants Fed Cow\u2019s Milk-Derived Fortifier Had Adverse Outcomes Despite a Base Diet of Only Mother\u2019s Own Milk","volume":"15","author":"Lucas","year":"2020","journal-title":"Breastfeed Med."},{"key":"ref_17","first-page":"3","article-title":"Safety of Cow\u2019s Milk-Derived Fortifiers Used with an All-Human Milk Base Diet in Very Low Birthweight Preterm Infants","volume":"15","author":"Lucas","year":"2020","journal-title":"Neonatol. Today"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/jp.2015.168","article-title":"Decreased cost and improved feeding tolerance in VLBW infants fed an exclusive human milk diet","volume":"36","author":"Assad","year":"2016","journal-title":"J. Perinatol."},{"key":"ref_19","first-page":"ED000142","article-title":"Updated guidance for trusted systematic reviews: A new edition of the Cochrane Handbook for Systematic Reviews of Interventions","volume":"10","author":"Cumpston","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_20","unstructured":"Wells, G.A., Shea, B., O\u2019Connell, D., Peterson, J., Welch, V., Losos, M., and Tugwell, P. (2023, October 30). The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. Available online: https:\/\/web.archive.org\/web\/20210716121605id_\/http:\/\/www3.med.unipmn.it\/dispense_ebm\/2009-2010\/Corso%20Perfezionamento%20EBM_Faggiano\/NOS_oxford.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e053400","DOI":"10.1136\/bmjopen-2021-053400","article-title":"Nordic study on human milk fortification in extremely preterm infants: A randomised controlled trial\u2014The N-forte trial","volume":"11","author":"Fredrik","year":"2021","journal-title":"BMJ Open"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.jpeds.2009.10.040","article-title":"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","volume":"156","author":"Sullivan","year":"2010","journal-title":"J. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1136\/adc.28.141.416","article-title":"A history of infant feeding. IV. Nineteenth century continued","volume":"28","author":"Wickes","year":"1953","journal-title":"Arch. Dis. Child."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1213\/ANE.0000000000000705","article-title":"Outcomes for extremely premature infants","volume":"120","author":"Glass","year":"2015","journal-title":"Anesth. Analg."},{"key":"ref_25","first-page":"CD013145","article-title":"Human milk-derived fortifier versus bovine milk-derived fortifier for prevention of mortality and morbidity in preterm neonates","volume":"11","author":"Premkumar","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fped.2019.00053","article-title":"Recommendations for the Establishment and Operation of Human Milk Banks in Europe: A Consensus Statement from the European Milk Bank Association (EMBA)","volume":"7","author":"Weaver","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1093\/pch\/15.9.595","article-title":"Human milk banking","volume":"15","author":"Kim","year":"2010","journal-title":"Paediatr. Child Health"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Swanson, J.R., Becker, A., Fox, J., Horgan, M., Moores, R., Pardalos, J., Pinheiro, J., Stewart, D., and Robinson, T. (2023). Implementing an exclusive human milk diet for preterm infants: Real-world experience in diverse NICUs. BMC Pediatr., 23.","DOI":"10.1186\/s12887-023-04047-5"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1089\/bfm.2011.0002","article-title":"Costs of Necrotizing Enterocolitis and Cost-Effectiveness of Exclusively Human Milk-Based Products in Feeding Extremely Premature Infants","volume":"7","author":"Ganapathy","year":"2011","journal-title":"Breastfeed. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1007\/s12144-018-0018-1","article-title":"The interpretation of statistical power after the data have been gathered","volume":"39","author":"Dziak","year":"2020","journal-title":"Curr. Psychol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/d41586-019-00857-9","article-title":"Scientists rise up against statistical significance","volume":"567","author":"Amrhein","year":"2019","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e189","DOI":"10.1542\/neo.20-4-e189","article-title":"Prevention of Bronchopulmonary Dysplasia: A Summary of Evidence-Based Strategies","volume":"20","author":"Jensen","year":"2019","journal-title":"NeoReviews"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/s41372-019-0507-6","article-title":"The importance of shared decision-making in the neonatal intensive care unit","volume":"40","author":"Soltys","year":"2020","journal-title":"J. Perinatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e217","DOI":"10.1542\/neo.21-4-e217","article-title":"Historical Perspectives: Shared Decision Making in the NICU","volume":"21","author":"Sullivan","year":"2020","journal-title":"NeoReviews"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Modi, N. (2024). Repeating the errors of the past: The hazards of a commercial human milk industry. Pediatr. Res., 1\u20133.","DOI":"10.1038\/s41390-023-03004-3"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100668","DOI":"10.1016\/j.waojou.2022.100668","article-title":"Diagnosis and Rationale for Action against Cow\u2019s Milk Allergy (DRACMA) Guidelines update-III-Cow\u2019s milk allergens and mechanisms triggering immune activation","volume":"15","author":"Jensen","year":"2022","journal-title":"World Allergy Organ. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s41043-021-00258-7","article-title":"Socio-cultural beliefs influence feeding practices of mothers and their children in Grand Popo, Benin","volume":"40","author":"Lokossou","year":"2021","journal-title":"J. Health Popul. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1126\/science.293.5539.2392","article-title":"Short-Term Trials and Long-Term Effects","volume":"293","author":"Daniels","year":"2001","journal-title":"Science"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/6\/910\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:17:35Z","timestamp":1760105855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/6\/910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,21]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["nu16060910"],"URL":"https:\/\/doi.org\/10.3390\/nu16060910","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,21]]}}}