{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:14:54Z","timestamp":1760145294645,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"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>The long-term efficacy and use of phenylalanine-free infant amino acid formula (PFIF) is understudied. This retrospective, longitudinal study evaluated PFIF (PKU Start: Vitaflo International) in children with phenylketonuria, collecting data on metabolic control, growth, dietary intake, and symptoms and the child\u2019s experience with PFIF. Twenty-five children (12 males, 48%) with a median age of 3.6 years (2.0\u20136.2 years) were included. During 24 months follow-up, children maintained normal growth and satisfactory metabolic control. The protein intake from protein substitutes increased from 2.7 at 6 months to 2.8 g\/kg\/day at 24 months, while natural protein decreased from 0.6 to 0.4 g\/kg\/day. By 24 months, most children (n = 16, 64%) had stopped PFIF, while nine (36%) continued with a median intake of 450 mL\/day (Q1:300 mL, Q3: 560 mL). Children who continued PFIF after 24 months of age had higher energy and fat intakes with higher weight\/BMI z-scores compared with those who stopped earlier (p &lt; 0.05). Constipation was reported in 44% of infants but improved with age. Initial difficulty with PFIF acceptance was reported in 20% of infants but also improved with time. Prolonged use of PFIF in pre-school children may contribute to poor feeding patterns and overweight; thus, replacing the majority of the protein equivalent provided by PFIF with a weaning protein substitute by 12 months and discontinuing PFIF before 2 years is recommended.<\/jats:p>","DOI":"10.3390\/nu16142204","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T13:34:38Z","timestamp":1720618478000},"page":"2204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenylalanine-Free Infant Formula in Patients with Phenylketonuria: A Retrospective Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Ozlem","family":"Yilmaz Nas","sequence":"first","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"},{"name":"Department of Nutrition and Dietetics, Ankara Yildirim Beyazit University, Ankara 06760, Turkey"},{"name":"Department of Nutrition and Dietetics, Ankara University, Ankara 06760, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Ashmore","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-3621","authenticated-orcid":false,"given":"Sharon","family":"Evans","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Pinto","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2579-8699","authenticated-orcid":false,"given":"Anne","family":"Daly","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurcan","family":"Yabanc\u0131 Ayhan","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, Ankara University, Ankara 06760, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13023-017-0685-2","article-title":"The complete European guidelines on phenylketonuria: Diagnosis and treatment","volume":"12","author":"MacDonald","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(10)60961-0","article-title":"Phenylketonuria","volume":"376","author":"Blau","year":"2010","journal-title":"Lancet"},{"key":"ref_3","first-page":"8","article-title":"Phenylketonuria (PKU): A problem solved?","volume":"6","author":"Brown","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ajhg.2020.06.006","article-title":"The genetic landscape and epidemiology of phenylketonuria","volume":"107","author":"Hillert","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Blanchard, E., Zhu, P., and Schuck, P. (2024). Infant formula powders. Handbook of Food Powders, Elsevier.","DOI":"10.1016\/B978-0-323-98820-9.00073-9"},{"key":"ref_6","first-page":"1","article-title":"Proteins, peptides and amino acids: Role in infant nutrition","volume":"Volume 86","author":"Nutten","year":"2016","journal-title":"Protein in Neonatal and Infant Nutrition: Recent Updates"},{"key":"ref_7","unstructured":"European Commission (2016). Commission Delegated Regulation (EU) 2016\/127 of 25 September 2015 supplementing Regulation (EU) No 609\/2013 of the European Parliament and of the Council as regards the specific compositional and information requirements for infant formula and follow-on formula and as regards requirements on information relating to infant and young child feeding. OJEC, 59, 1\u201329."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1016\/j.ymgme.2011.09.015","article-title":"Specific prebiotics in a formula for infants with Phenylketonuria","volume":"104","author":"MacDonald","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bakshi, S., Paswan, V.K., Yadav, S.P., Bhinchhar, B.K., Kharkwal, S., Rose, H., Kanetkar, P., Kumar, V., Al-Zamani, Z.A.S., and Bunkar, D.S. (2023). A comprehensive review on infant formula: Nutritional and functional constituents, recent trends in processing and its impact on infants\u2019 gut microbiota. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1194679"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2019272","DOI":"10.1590\/1981-6723.27219","article-title":"How the heat treatment affects the constituents of infant formulas: A review","volume":"23","author":"Francisquini","year":"2020","journal-title":"Braz. J. Food Technol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jfoodeng.2019.02.023","article-title":"Effect of lactose-to-maltodextrin ratio on emulsion stability and physicochemical properties of spray-dried infant milk formula powders","volume":"254","author":"Masum","year":"2019","journal-title":"J. Food Eng."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13052-015-0141-7","article-title":"Flavor, relative palatability and components of cow\u2019s milk hydrolysed formulas and amino acid-based formula","volume":"41","author":"Peroni","year":"2015","journal-title":"Ital. J. Pediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.2147\/JMDH.S330845","article-title":"Food Regime for Phenylketonuria: Presenting Complications and Possible Solutions","volume":"15","author":"Adlakha","year":"2022","journal-title":"J. Multidiscip. Healthc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1651-2227.1994.tb13454.x","article-title":"Protein intake affects phenylalanine requirements and growth of infants with phenylketonuria","volume":"83","author":"Acosta","year":"1994","journal-title":"Acta Paediatr."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Daly, A., Evans, S., Pinto, A., Ashmore, C., and MacDonald, A. (2021). Protein substitutes in PKU; their historical evolution. Nutrients, 13.","DOI":"10.3390\/nu13020484"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13023-023-02621-9","article-title":"Phenylalanine free infant formula in the dietary management of phenylketonuria","volume":"18","author":"Yilmaz","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S2213-8587(16)30320-5","article-title":"Key European guidelines for the diagnosis and management of patients with phenylketonuria","volume":"5","author":"Ahring","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_18","unstructured":"World Health Organization (2018). WHO Anthro Survey Analyser: Software for Analysing Survey Anthropometric Data for Children under 5 Years of Age, WHO. Built-in Software Edition."},{"key":"ref_19","unstructured":"World Health Organization (2008). WHO Child Growth Standards: Training Course on Child Growth Assessment, WHO."},{"key":"ref_20","unstructured":"Nutritics (2024, May 26). Research Edition (v5. 09) [Computer Software]. Available online: https:\/\/www.nutritics.com."},{"key":"ref_21","unstructured":"Scientific Advisory Committee on Nutrition (2012). Dietary Reference Values for Energy."},{"key":"ref_22","unstructured":"(Microsoft Excel, 2023). Microsoft Excel, version 16.71 (Build 23031200)."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"(IBM SPSS Statistics for Macintosh, 2019). IBM SPSS Statistics for Macintosh, version 26.0.","DOI":"10.4324\/9780429056765-3"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Evans, S., Daly, A., Wildgoose, J., Cochrane, B., Chahal, S., Ashmore, C., Loveridge, N., and MacDonald, A. (2019). How does feeding development and progression onto solid foods in PKU compare with non-PKU children during weaning?. Nutrients, 11.","DOI":"10.3390\/nu11030529"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1365-277X.2011.01199.x","article-title":"Weaning infants with phenylketonuria: A review","volume":"25","author":"MacDonald","year":"2012","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.jpeds.2011.02.037","article-title":"Prolonged bottle use and obesity at 5.5 years of age in US children","volume":"159","author":"Gooze","year":"2011","journal-title":"J. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1177\/000992280404300605","article-title":"Is late bottle-weaning associated with overweight in young children? Analysis of NHANES III data","volume":"43","author":"Bonuck","year":"2004","journal-title":"Clin. Pediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1017\/S1368980010002156","article-title":"Factors associated with exclusive breast-feeding and breast-feeding in Norway","volume":"13","author":"Kristiansen","year":"2010","journal-title":"Public Health Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/mcn.12152","article-title":"Childcare arrangements and infant feeding practices by family structure and household income among US children aged 0 to 2 years","volume":"12","author":"Kim","year":"2016","journal-title":"Matern. Child Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1515\/jpem-2019-0439","article-title":"Oral health status of children with phenylketonuria","volume":"33","author":"Ballikaya","year":"2020","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109","DOI":"10.15644\/asc56\/2\/2","article-title":"Dental Status and Periodontal Health of Patients with Phenylketonuria in Latvia","volume":"56","author":"Brinkmane","year":"2022","journal-title":"Acta Stomatol. Croat."},{"key":"ref_32","first-page":"43","article-title":"Evaluation of oral health status in children with phenylketonuria","volume":"43","author":"Pires","year":"2015","journal-title":"Int. J. Clin. Dent."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s00784-015-1564-7","article-title":"Investigation of the oral status and microorganisms in children with phenylketonuria and type 1 diabetes","volume":"20","author":"Meissner","year":"2016","journal-title":"Clin. Oral Investig."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cheng, H., Chen, R., Milosevic, M., Rossiter, C., Arora, A., and Denney-Wilson, E. (2021). Interventions targeting bottle and formula feeding in the prevention and treatment of early childhood caries, overweight and obesity: An integrative review. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph182312304"},{"key":"ref_35","first-page":"909","article-title":"Infant oral health","volume":"65","author":"Brecher","year":"2018","journal-title":"Pediatr. Clin."},{"key":"ref_36","unstructured":"Green, M. (1994). Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents."},{"key":"ref_37","unstructured":"American Academy of Pediatric Dentistry (2023). Policy on Early Childhood Caries (ECC): Consequences and Preventive Strategies, American Academy of Pediatric Dentistry. The Reference Manual of Pediatric Dentistry."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1136\/adc.68.3_Spec_No.317","article-title":"Development of bowel habit in preterm infants","volume":"68","author":"Weaver","year":"1993","journal-title":"Arch. Dis. Child."},{"key":"ref_39","first-page":"568","article-title":"The bowel habit of milk-fed infants","volume":"7","author":"Weaver","year":"1988","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_40","first-page":"81","article-title":"The relationship between stool hardness and stool composition in breast-and formula-fed infants","volume":"20","author":"Quinlan","year":"1995","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1097\/MPG.0000000000000209","article-title":"Early-life factors associated with pediatric functional constipation","volume":"58","author":"Turco","year":"2014","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.cegh.2018.03.005","article-title":"Fat structure and composition in human milk and infant formulas: Implications in infant health","volume":"7","author":"Mehrotra","year":"2019","journal-title":"Clin. Epidemiol. Glob. Health"},{"key":"ref_43","first-page":"553","article-title":"Structural position and amount of palmitic acid in infant formulas: Effects on fat, fatty acid, and mineral balance","volume":"23","author":"Carnielli","year":"1996","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/ajcn\/70.5.920","article-title":"Double-blind, randomized trial of a synthetic triacylglycerol in formula-fed term infants: Effects on stool biochemistry, stool characteristics, and bone mineralization","volume":"70","author":"Kennedy","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/MPG.0000000000000443","article-title":"Effects of term infant formulas containing high sn-2 palmitate with and without oligofructose on stool composition, stool characteristics, and bifidogenicity","volume":"59","author":"Yao","year":"2014","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.clnu.2018.05.015","article-title":"Growth, stool consistency and bone mineral content in healthy term infants fed sn-2-palmitate-enriched starter infant formula: A randomized, double-blind, multicentre clinical trial","volume":"38","author":"Marchandise","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/1475-2891-13-105","article-title":"Stool fatty acid soaps, stool consistency and gastrointestinal tolerance in term infants fed infant formulas containing high sn-2 palmitate with or without oligofructose: A double-blind, randomized clinical trial","volume":"13","author":"Nowacki","year":"2014","journal-title":"Nutr. J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Litmanovitz, I., Bar-Yoseph, F., Lifshitz, Y., Davidson, K., Eliakim, A., Regev, R.H., and Nemet, D. (2014). Reduced crying in term infants fed high beta-palmitate formula: A double-blind randomized clinical trial. 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