{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:15:05Z","timestamp":1782738905638,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,26]],"date-time":"2020-07-26T00:00:00Z","timestamp":1595721600000},"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>Human milk (HM) must be accurately fortified for extremely low birth weight (ELBW) preterm infants with human milk fortifiers (HMFs). Powdered HMF has some limitations in terms of sterilization and accuracy. A concentrated preterm formula (CPF) may serve as a safe liquid HMF to facilitate growth. Hence, we launched a quality improvement project for fortification accuracy of minute volume HM. A CPF, Similac Special Care 30 (SSC30), was newly introduced as an HMF when daily feeding reached 100 cm3\/kg. CPF + HM (1:2 volume ratio), CPF + HM (1:1 volume ratio), and powdered HMF + HM (1 packet in 25 cm3) represented three fortification stages. Fortification shifted to powdered HMF while tolerable feeding reached 25 cm3\/meal. The outcome was compared before (Period-I, January 2015 to June 2016, n = 37) and after the new implement (Period-II, July 2016 to December 2017, n = 36). Compared with the Period-I group, the Period-II group had significantly higher daily enteral milk intake in the first 4 weeks of life, and higher percentages of fortification in the HM-fed infants in the first 8 weeks after birth. The Period-II group also significantly increased in body weight growth in terms of z-score at term equivalent age (p = 0.04) and had better language and motor performance at 24 months old (p = 0.048 and p = 0.032, respectively). Using the liquid CPF as a strategical alternative fortification of HM might be beneficial for extremely preterm infants in terms of growth as well as neurodevelopment.<\/jats:p>","DOI":"10.3390\/nu12082229","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T04:39:50Z","timestamp":1595824790000},"page":"2229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Concentrated Preterm Formula as a Liquid Human Milk Fortifier at Initiation Stage in Extremely Low Birth Weight Preterm Infants: Short Term and 2-year Follow-up Outcomes"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7698-8428","authenticated-orcid":false,"given":"Yung-Chieh","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng-Kung University, Tainan 70403, Taiwan"},{"name":"Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng-Kung University, Tainan 70403, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng-Kung University, Tainan 70403, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Ching","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng-Kung University, Tainan 70403, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Chang","family":"Shieh","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng-Kung University, Tainan 70403, Taiwan"},{"name":"Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng-Kung University, Tainan 70403, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1097\/MPG.0b013e3181adaee0","article-title":"Enteral nutrient supply for preterm infants: Commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition","volume":"50","author":"Agostoni","year":"2010","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.siny.2016.08.003","article-title":"Use of donor milk in the neonatal intensive care unit","volume":"22","author":"Pieltain","year":"2017","journal-title":"Semin. Fetal Neonatal. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.jpeds.2012.11.049","article-title":"Human milk and the nutritional needs of preterm infants","volume":"162","author":"Tudehope","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_4","first-page":"CD007137","article-title":"Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants","volume":"6","author":"Pammi","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7256","DOI":"10.3390\/nu7095334","article-title":"The role of immunonutrients in the prevention of necrotizing enterocolitis in preterm very low birth weight infants","volume":"7","author":"Zhou","year":"2015","journal-title":"Nutrients"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1089\/bfm.2017.0057","article-title":"Cost and cost-effectiveness of donor human milk to prevent necrotizing enterocolitis: Systematic review","volume":"12","author":"Buckle","year":"2017","journal-title":"Breastfeed. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/jp.2017.149","article-title":"Maternal milk feedings reduce sepsis, necrotizing enterocolitis and improve outcomes of premature infants","volume":"38","author":"Cortez","year":"2018","journal-title":"J. Perinatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Villamor-Martinez, E., Pierro, M., Cavallaro, G., Mosca, F., Kramer, B.W., and Villamor, E. (2018). Donor human milk protects against bronchopulmonary dysplasia: A systematic review and meta-analysis. Nutrients, 10.","DOI":"10.20944\/preprints201801.0107.v1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.earlhumdev.2016.01.011","article-title":"Very low birth weight infant care: Adherence to a new nutrition protocol improves growth outcomes and reduces infectious risk","volume":"94","author":"Stefanescu","year":"2016","journal-title":"Early Hum. Dev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0140-6736(92)91329-7","article-title":"Breast milk and subsequent intelligence quotient in children born preterm","volume":"339","author":"Lucas","year":"1992","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e645","DOI":"10.1542\/neo.19-11-e645","article-title":"Enteral feeding of the preterm infant","volume":"19","author":"Brune","year":"2018","journal-title":"NeoReviews"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/jp.2016.85","article-title":"Growth failure among preterm infants due to insufficient protein is not innocuous and must be prevented","volume":"36","author":"Hay","year":"2016","journal-title":"J. Perinatol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Arslanoglu, S., Boquien, C.-Y., King, C., Lamireau, D., Tonetto, P., Barnett, D., Bertino, E., Gaya, A., Gebauer, C., and Grovslien, A. (2019). Fortification of human milk for preterm infants: Update and recommendations of the European Milk Bank Association (EMBA) Working Group on human milk fortification. Front. Pediatrics, 7.","DOI":"10.3389\/fped.2019.00076"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fnut.2018.00076","article-title":"Best practices for handling and administration of expressed human milk and donor human milk for hospitalized preterm infants","volume":"5","author":"Steele","year":"2018","journal-title":"Front. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1056\/NEJMoa1816654","article-title":"Controlled trial of two incremental milk-feeding rates in preterm infants","volume":"381","author":"Dorling","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/MPG.0000000000002589","article-title":"Effect of target fortification on osmolality and microbiological safety of human milk over time","volume":"70","author":"Piemontese","year":"2020","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_17","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_18","unstructured":"(2011). Neofax 2011, Thomson Reuters. [24th ed.]."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Pillai, A., Albersheim, S., Matheson, J., Lalari, V., Wei, S., Innis, S.M., and Elango, R. (2018). Evaluation of a concentrated preterm formula as a liquid human milk fortifier in preterm babies at increased risk of feed intolerance. Nutrients, 10.","DOI":"10.3390\/nu10101433"},{"key":"ref_20","unstructured":"Taiwan Society of Neonatology (2015). Recommendation on Nutritional Care of Taiwan Preterm Infants, Taiwan Society of Neonatology."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.pedneo.2013.07.003","article-title":"Optimizing nutrition in preterm infants","volume":"55","author":"Su","year":"2014","journal-title":"Pediatr. Neonatol."},{"key":"ref_22","unstructured":"Health Promotion Administration, Ministry of Health and Welfare (2017). Children\u2019s Health Booklet."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"American Academy of Pediatrics (2019). Caring for Your Baby and Young Child: Birth to Age 5, Bantam. [7th ed.].","DOI":"10.1542\/9781610023443"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.pedneo.2011.08.008","article-title":"Growth and neurodevelopmental outcomes of extremely low birth weight infants: A single center\u2019s experience","volume":"52","author":"Lin","year":"2011","journal-title":"Pediatr. Neonatol."},{"key":"ref_25","unstructured":"Abbott Nutrition (2016). Pediatric Nutrition Product Guide 2016, Abbott Laboratories."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1159\/000448615","article-title":"Isolated cystic periventricular leukomalacia differs from cystic periventricular leukomalacia with intraventricular hemorrhage in prevalence, risk factors and outcomes in preterm infants","volume":"111","author":"Wang","year":"2017","journal-title":"Neonatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1159\/000487505","article-title":"Identifying risk factors shared by bronchopulmonary dysplasia, severe retinopathy, and cystic periventricular leukomalacia in very preterm infants for targeted intervention","volume":"114","author":"Wang","year":"2018","journal-title":"Neonatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa1605566","article-title":"Survival and neurodevelopmental outcomes among periviable infants","volume":"376","author":"Younge","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fenton, T.R., and Kim, J.H. (2013). A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr., 13.","DOI":"10.1186\/1471-2431-13-59"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Anderson, J.G., Baer, R.J., Partridge, J.C., Kuppermann, M., Franck, L.S., Rand, L., Jelliffe-Pawlowski, L.L., and Rogers, E.E. (2016). Survival and major morbidity of extremely preterm infants: A population-based study. Pediatrics, 138.","DOI":"10.1542\/peds.2015-4434"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00000658-197801000-00001","article-title":"Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging","volume":"187","author":"Bell","year":"1978","journal-title":"Ann. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1542\/peds.2005-0249","article-title":"Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia","volume":"116","author":"Ehrenkranz","year":"2005","journal-title":"Pediatrics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000323381","article-title":"Meeting the nutritional needs of the low-birth-weight infant","volume":"58","author":"Ziegler","year":"2011","journal-title":"Ann. Nutr. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1097\/PCC.0000000000001221","article-title":"Oropharyngeal colostrum administration in very low birth weight infants: A randomized controlled trial","volume":"18","author":"Zhang","year":"2017","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/NNR.0000000000000093","article-title":"Factors associated with feeding progression in extremely preterm infants","volume":"64","author":"Park","year":"2015","journal-title":"Nurs. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/jp.2009.149","article-title":"Impact of prematurity and co-morbidities on feeding milestones in neonates: A retrospective study","volume":"30","author":"Jadcherla","year":"2010","journal-title":"J. Perinatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/ajcn\/nqy012","article-title":"Early progressive feeding in extremely preterm infants: A randomized trial","volume":"107","author":"Salas","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/nure.12110","article-title":"Early optimal nutrition improves neurodevelopmental outcomes for very preterm infants","volume":"72","author":"Hsiao","year":"2014","journal-title":"Nutr. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.pedneo.2012.11.004","article-title":"Characteristics of the first human milk bank in Taiwan","volume":"54","author":"Chang","year":"2013","journal-title":"Pediatr. Neonatol."},{"key":"ref_40","first-page":"762","article-title":"Growth, biochemical status, and mineral metabolism in very-low-birth-weight infants receiving fortified preterm human milk","volume":"5","author":"Modanlou","year":"1986","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_41","first-page":"65","article-title":"Human milk fortifiers","volume":"1","author":"Thompson","year":"1987","journal-title":"J. Pediatr. Perinat. Nutr."},{"key":"ref_42","first-page":"157","article-title":"Human milk fortification strategies for improved in-hospital growth of preterm infants","volume":"29","author":"Kemp","year":"2016","journal-title":"S. Afr. J. Clin. Nutr."},{"key":"ref_43","unstructured":"(2020, July 18). Preparation of Small Volumes (10mL) Standard Strength Fortified M\/DEBM. Available online: http:\/\/swmnodn.org.uk\/wp-content\/uploads\/2020\/05\/additon-of-HMF-less-than-50ml-EBM-1.pdf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1097\/MPG.0000000000001638","article-title":"Highly concentrated preterm formula as an alternative to powdered human milk fortifier: A randomized controlled trial","volume":"65","author":"Willeitner","year":"2017","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_45","first-page":"203","article-title":"The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems","volume":"28","author":"Carabotti","year":"2015","journal-title":"Ann. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s41574-018-0066-5","article-title":"Breast milk, formula, the microbiome and overweight","volume":"14","author":"Mueller","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fcimb.2012.00094","article-title":"Effect of breast and formula feeding on gut microbiota shaping in newborns","volume":"2","author":"Guaraldi","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ho, N.T., Li, F., Lee-Sarwar, K.A., Tun, H.M., Brown, B.P., Pannaraj, P.S., Bender, J.M., Azad, M.B., Thompson, A.L., and Weiss, S.T. (2018). Meta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations. Nat. Commun., 9.","DOI":"10.1038\/s41467-018-06473-x"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/8\/2229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:51:53Z","timestamp":1760176313000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/8\/2229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,26]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["nu12082229"],"URL":"https:\/\/doi.org\/10.3390\/nu12082229","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,26]]}}}