{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:18:54Z","timestamp":1791587934600,"version":"4.3.4"},"reference-count":181,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"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>Background\/Objectives: The first 1000 days of life represent a critical window for growth and neurodevelopment, during which nutrition strongly influences brain development and metabolic programming. In phenylketonuria (PKU), dietary management is essential to prevent neurological impairment and later-life risk of non-communicable diseases (NCDs). This review examines current evidence on PKU from pregnancy through complementary feeding, highlighting the impact of nutritional strategies on neurodevelopmental and metabolic outcomes. Methods: This narrative review, following PRISMA guidelines, used a systematic search of PubMed and Scopus with defined PICO questions. Original research, reviews, and guidelines on PKU nutrition during the first 1000 days were included, emphasizing neurological and metabolic outcomes. Results: Articles addressed prenatal and postnatal factors in PKU. Optimised metabolic control in women with PKU is critical to prevent maternal PKU syndrome, reducing risks of miscarriage, congenital heart defects, microcephaly, and neurocognitive impairment. Pre-conception dietary management, frequent blood Phe monitoring, supplementation with Phe-free protein substitutes (PSs), micronutrients, and emerging pharmacological therapies support maternal and foetal health. Following newborn screening, early dietary treatment in infants with PKU maintains plasma Phe within safe ranges, promoting growth and neurodevelopment. Breastfeeding, combined with Phe-free infant PSs, is feasible, and complementary feeding should be introduced carefully. Frequent monitoring and tailored dietary adjustments, including second-stage PSs, support metabolic control, while data on gut microbiota remain limited. Conclusions: Early multidisciplinary interventions are crucial to optimise metabolic and neurodevelopmental outcomes during this window of opportunity. Further research is needed to address remaining gaps and optimise PKU management across the first 1000 days.<\/jats:p>","DOI":"10.3390\/nu18020199","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:10:50Z","timestamp":1767867050000},"page":"199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The First 1000 Days of PKU: A Narrative Review of Maternal PKU and Early Life Management After Positive Newborn Screening"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2111-3111","authenticated-orcid":false,"given":"Elvira","family":"Verduci","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4859-5288","authenticated-orcid":false,"given":"Martina","family":"Tosi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milan, 20142 Milan, Italy"},{"name":"Department of Pediatrics, Vittore Buzzi Children\u2019s Hospital, 20154 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juri","family":"Zuvadelli","sequence":"additional","affiliation":[{"name":"Clinical Department of Pediatrics, San Paolo Hospital, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Giorda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Metabolic Diseases, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7441-9248","authenticated-orcid":false,"given":"Giacomo","family":"Biasucci","sequence":"additional","affiliation":[{"name":"Pediatrics and Neonatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy"},{"name":"Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2314-6139","authenticated-orcid":false,"given":"Vincenzo","family":"Leuzzi","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry, Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8894-350X","authenticated-orcid":false,"given":"Marco","family":"Spada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Metabolic Diseases, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-137X","authenticated-orcid":false,"given":"Alberto","family":"Burlina","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Department of Women\u2019s and Children\u2019s Health, Reference Centre Expanded Newborn Screening, University Hospital, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-3379","authenticated-orcid":false,"given":"Carlo","family":"Dionisi Vici","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jjcc.2020.02.003","article-title":"Developmental Origins of Health and Disease Theory in Cardiology","volume":"76","author":"Arima","year":"2020","journal-title":"J. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1159\/000496471","article-title":"Nutrition During Pregnancy, Lactation and Early Childhood and Its Implications for Maternal and Long-Term Child Health: The Early Nutrition Project Recommendations","volume":"74","author":"Koletzko","year":"2019","journal-title":"Ann. Nutr. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhou, Y., and Xu, Y. (2023). Nutrition and Metabolism in the First 1000 Days of Life. Nutrients, 15.","DOI":"10.3390\/nu15112554"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1080\/10408398.2012.745477","article-title":"Pregnancy and Infants\u2019 Outcome: Nutritional and Metabolic Implications","volume":"56","author":"Berti","year":"2016","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_5","unstructured":"World Health Organization (2023). WHO Guideline for Complementary Feeding of Infants and Young Children 6\u201323 Months of Age; WHO Guidelines Approved by the Guidelines Review Committee, World Health Organization."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Tain, Y.-L., Lin, Y.-J., and Hsu, C.-N. (2025). Breastfeeding and Future Cardiovascular, Kidney, and Metabolic Health-A Narrative Review. Nutrients, 17.","DOI":"10.3390\/nu17060995"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1017\/S2040174417000964","article-title":"Effects of Infant Formula Composition on Long-Term Metabolic Health","volume":"9","author":"Lemaire","year":"2018","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1159\/000439491","article-title":"Effects of Early Nutrition on the Infant Metabolome","volume":"85","author":"Hellmuth","year":"2016","journal-title":"Nestle Nutr. Inst. Workshop Ser."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1093\/nutrit\/nuaa143","article-title":"Complementary Feeding of Infants and Young Children 6 to 23 Months of Age","volume":"79","author":"Lutter","year":"2021","journal-title":"Nutr. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s13023-020-01391-y","article-title":"PKU Dietary Handbook to Accompany PKU Guidelines","volume":"15","author":"MacDonald","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109125","DOI":"10.1016\/j.ymgme.2025.109125","article-title":"European Guidelines on Diagnosis and Treatment of Phenylketonuria: First Revision","volume":"145","author":"MacDonald","year":"2025","journal-title":"Mol. Genet. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107583","DOI":"10.1016\/j.ymgme.2023.107583","article-title":"Phenylketonuria and the Brain","volume":"139","author":"Rovelli","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1016\/j.ymgme.2013.08.013","article-title":"Neurocognitive Functioning in Adults with Phenylketonuria: Results of a Long Term Study","volume":"110","author":"Weglage","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1037\/neu0000337","article-title":"Cognitive Outcomes in Early-Treated Adults with Phenylketonuria (PKU): A Comprehensive Picture across Domains","volume":"31","author":"Palermo","year":"2017","journal-title":"Neuropsychology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s40200-025-01631-7","article-title":"The Association of Plasma Level of Phenylalanine with Inflammatory Markers, Insulin Resistance, and Atherosclerotic Indexes in Patients with Phenylketonuria","volume":"24","author":"Moghimi","year":"2025","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"109068","DOI":"10.1016\/j.ymgme.2025.109068","article-title":"Protein Intake and Prevalence of Overweight in Patients with Phenylketonuria: A 10-Year Longitudinal Study","volume":"144","author":"Rodrigues","year":"2025","journal-title":"Mol. Genet. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Montanari, C., Parolisi, S., Borghi, E., Putignani, L., Bassanini, G., Zuvadelli, J., Bonfanti, C., Tummolo, A., Dionisi Vici, C., and Biasucci, G. (2021). Dysbiosis, Host Metabolism, and Non-Communicable Diseases: Trialogue in the Inborn Errors of Metabolism. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.716520"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Moher, D., Liberati, A., Tetzlaff, J., and Altman, D.G. (2009). PRISMA Group Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000097"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1152\/physrev.00029.2013","article-title":"Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?","volume":"94","author":"Hanson","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/S0140-6736(18)30312-X","article-title":"Origins of Lifetime Health around the Time of Conception: Causes and Consequences","volume":"391","author":"Fleming","year":"2018","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1017\/S0029665112000596","article-title":"Early Nutrition Project Early Nutrition Programming of Long-Term Health","volume":"71","author":"Koletzko","year":"2012","journal-title":"Proc. Nutr. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1097\/MPG.0000000000003075","article-title":"Role of Dietary Factors, Food Habits, and Lifestyle in Childhood Obesity Development: A Position Paper from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition","volume":"72","author":"Verduci","year":"2021","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mand\u00f2, C., Novielli, C., Nuzzo, A.M., Parisi, F., Moretti, L., Lisso, F., Revelli, A., Savasi, V.M., Laoreti, A., and Anelli, G.M. (2025). Maternal BMI and Diet Quality Modulate Pregnancy Oxidative and Inflammatory Homeostasis. Nutrients, 17.","DOI":"10.3390\/nu17162590"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1183\/13993003.00643-2015","article-title":"Hypertensive Disorders of Pregnancy, Respiratory Outcomes and Atopy in Childhood","volume":"47","author":"Shaheen","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Beluska-Turkan, K., Korczak, R., Hartell, B., Moskal, K., Maukonen, J., Alexander, D.E., Salem, N., Harkness, L., Ayad, W., and Szaro, J. (2019). Nutritional Gaps and Supplementation in the First 1000 Days. Nutrients, 11.","DOI":"10.3390\/nu11122891"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tosi, M., Tagi, V.M., Colombo, A., Cecchini, A., Zobele, M., Montanari, C., Ferraro, S., Bosetti, A., Bonaventura, E., and Bruschi, F. (2025). Dietary Pattern and Nutritional Assessment in a Cohort of Mothers Identified by Neonatal Screening for Cobalamin Deficiency in Offspring: An Italian Single Center Experience. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1604336"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/s12967-015-0690-y","article-title":"Short and Long Term Health Effects of Parental Tobacco Smoking during Pregnancy and Lactation: A Descriptive Review","volume":"13","author":"Banderali","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gould, G.S., Havard, A., Lim, L.L., The Psanz Smoking in Pregnancy Expert Group, and Kumar, R. (2020). Exposure to Tobacco, Environmental Tobacco Smoke and Nicotine in Pregnancy: A Pragmatic Overview of Reviews of Maternal and Child Outcomes, Effectiveness of Interventions and Barriers and Facilitators to Quitting. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17062034"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1123\/jpah.2019-0348","article-title":"Maternal Physical Activity During Pregnancy and the Effect on the Mother and Newborn: A Systematic Review","volume":"18","year":"2021","journal-title":"J. Phys. Act. Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2165\/11532290-000000000-00000","article-title":"Physical Activity and Pregnancy: Cardiovascular Adaptations, Recommendations and Pregnancy Outcomes","volume":"40","author":"Melzer","year":"2010","journal-title":"Sports Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s13679-025-00629-9","article-title":"When Weight Matters: How Obesity Impacts Reproductive Health and Pregnancy-A Systematic Review","volume":"14","author":"Barbouni","year":"2025","journal-title":"Curr. Obes. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1001\/jama.2014.2269","article-title":"Maternal Body Mass Index and the Risk of Fetal Death, Stillbirth, and Infant Death: A Systematic Review and Meta-Analysis","volume":"311","author":"Aune","year":"2014","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"j1","DOI":"10.1136\/bmj.j1","article-title":"Obesity and Pregnancy: Mechanisms of Short Term and Long Term Adverse Consequences for Mother and Child","volume":"356","author":"Catalano","year":"2017","journal-title":"BMJ"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1093\/nutrit\/nuae027","article-title":"The Association of Maternal Gestational Weight Gain with Cardiometabolic Risk Factors in Offspring: A Systematic Review and Meta-Analysis","volume":"83","author":"Wen","year":"2025","journal-title":"Nutr. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1515\/ijamh-2021-0058","article-title":"Correlation between Obesity, Gestational Diabetes Mellitus, and Pregnancy Outcomes: An Overview","volume":"33","author":"Zehravi","year":"2021","journal-title":"Int. J. Adolesc. Med. Health"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/AOG.0b013e3182245d49","article-title":"Effect of Prepregnancy Maternal Overweight and Obesity on Pregnancy Outcome","volume":"118","author":"Ovesen","year":"2011","journal-title":"Obstet. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1111\/obr.12455","article-title":"Association between Perinatal Outcomes and Maternal Pre-Pregnancy Body Mass Index","volume":"17","author":"Liu","year":"2016","journal-title":"Obes. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.ecl.2019.05.008","article-title":"Type 1 Diabetes in Pregnancy","volume":"48","author":"McCance","year":"2019","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1001\/jama.2019.4981","article-title":"Management of Preexisting Diabetes in Pregnancy: A Review","volume":"321","author":"Alexopoulos","year":"2019","journal-title":"JAMA"},{"key":"ref_40","first-page":"23","article-title":"Maternal Phenylketonuria: Long-Term Outcomes in Offspring and Post-Pregnancy Maternal Characteristics","volume":"21","author":"Waisbren","year":"2015","journal-title":"JIMD Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.2105\/AJPH.72.12.1320","article-title":"Maternal PKU: Control of an Emerging Problem","volume":"72","author":"Levy","year":"1982","journal-title":"Am. J. Public Health"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Leone, G., Meli, C., Falsaperla, R., Gullo, F., Licciardello, L., La Spina, L., Messina, M., Lo Bianco, M., Sapuppo, A., and Pappalardo, M.G. (2025). Maternal Phenylketonuria and Offspring Outcome: A Retrospective Study with a Systematic Review of the Literature. Nutrients, 17.","DOI":"10.3390\/nu17040678"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Donarska, J., Szablewska, A.W., and Wierzba, J. (2025). Maternal Phenylketonuria: Consequences of Dietary Non-Adherence and Gaps in Preconception Care\u2014A Case Report. J. Clin. Med., 14.","DOI":"10.3390\/jcm14041102"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0022-3476(00)90050-7","article-title":"Maternal Phenylketonuria Syndrome: Congenital Heart Defects, Microcephaly, and Developmental Outcomes","volume":"136","author":"Rouse","year":"2000","journal-title":"J. Pediatr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rohde, C., Thiele, A.G., Tomm, A., Lier, D., Eschrich, K., Baerwald, C., and Beblo, S. (2024). The Prevention of Maternal Phenylketonuria (PKU) Syndrome: The Development and Evaluation of a Specific Training Program. Nutrients, 16.","DOI":"10.3390\/nu16234111"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1007\/s10545-008-0910-1","article-title":"Phenylalanine Tolerance in Three Phenylketonuric Women Pregnant with Fetuses of Different Genetic PKU Status","volume":"32","author":"Ellerbrok","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1542\/peds.112.S4.1534","article-title":"Role of Nutrition in Pregnancy with Phenylketonuria and Birth Defects","volume":"112","author":"Matalon","year":"2003","journal-title":"Pediatrics"},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1177\/02601060241248522","article-title":"Benefits of a Prolonged-Release Amino Acid Mixture in Four Pregnant Women with Phenylketonuria","volume":"31","author":"Sestito","year":"2025","journal-title":"Nutr. Health"},{"key":"ref_50","first-page":"105","article-title":"Dietary Management of Maternal Phenylketonuria with Glycomacropeptide and Amino Acids Supplements: A Case Report","volume":"13","author":"Pinto","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Dong, J., Yin, L.-L., Deng, X.-D., Ji, C.-Y., Pan, Q., Yang, Z., Peng, T., Wu, J.-N., Wu, G.-H., and Zhou, L.-Y. (2023). Initiation and Duration of Folic Acid Supplementation in Preventing Congenital Malformations. BMC Med., 21.","DOI":"10.1186\/s12916-023-03000-8"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1017\/S1368980015000555","article-title":"Folate and Folic Acid in the Periconceptional Period: Recommendations from Official Health Organizations in Thirty-Six Countries Worldwide and WHO","volume":"19","author":"Gomes","year":"2016","journal-title":"Public Health Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Cetin, I., Devlieger, R., Isolauri, E., Obeid, R., Parisi, F., Pilz, S., van Rossem, L., Maternal Nutrition Delphi Study Group, and Steegers-Theunissen, R. (2025). International Expert Consensus on Micronutrient Supplement Use during the Early Life Course. BMC Pregnancy Childbirth, 25.","DOI":"10.1186\/s12884-024-07123-5"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/nbu.70016","article-title":"Diet in Pregnancy: A Review of Current Challenges and Recommendations. A British Nutrition Foundation Briefing Paper","volume":"50","author":"Hart","year":"2025","journal-title":"Nutr. Bull."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3945\/ajcn.115.109108","article-title":"Folate and Long-Chain Polyunsaturated Fatty Acid Supplementation during Pregnancy Has Long-Term Effects on the Attention System of 8.5-y-Old Offspring: A Randomized Controlled Trial","volume":"103","author":"Catena","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1880S","DOI":"10.3945\/ajcn.110.001107","article-title":"Effects of Prenatal Fish-Oil and 5-Methyltetrahydrofolate Supplementation on Cognitive Development of Children at 6.5 y of Age","volume":"94","author":"Campoy","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Green, B., Browne, R., Firman, S., Hill, M., Rahman, Y., Kaalund Hansen, K., Adam, S., Skeath, R., Hallam, P., and Herlihy, I. (2019). Nutritional and Metabolic Characteristics of UK Adult Phenylketonuria Patients with Varying Dietary Adherence. Nutrients, 11.","DOI":"10.3390\/nu11102459"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Green, B., Rahman, Y., Firman, S., Adam, S., Jenkinson, F., Nicol, C., Adams, S., Dawson, C., Robertson, L., and Dunlop, C. (2019). Improved Eating Behaviour and Nutrient Intake in Noncompliant Patients with Phenylketonuria after Reintroducing a Protein Substitute: Observations from a Multicentre Study. Nutrients, 11.","DOI":"10.3390\/nu11092035"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/ejcn.2013.218","article-title":"PKU Patients on a Relaxed Diet May Be at Risk for Micronutrient Deficiencies","volume":"68","author":"Rohde","year":"2014","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s10545-011-9277-9","article-title":"A Cross-Sectional Study of Docosahexaenoic Acid Status and Cognitive Outcomes in Females of Reproductive Age with Phenylketonuria","volume":"34","author":"Yi","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Verduci, E., Carbone, M.T., Borghi, E., Ottaviano, E., Burlina, A., and Biasucci, G. (2020). Nutrition, Microbiota and Role of Gut-Brain Axis in Subjects with Phenylketonuria (PKU): A Review. Nutrients, 12.","DOI":"10.3390\/nu12113319"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jhn.12054","article-title":"Body Mass Index in Adult Patients with Diet-Treated Phenylketonuria","volume":"26","author":"Robertson","year":"2013","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Rodrigues, C., Pinto, A., Faria, A., Teixeira, D., van Wegberg, A.M.J., Ahring, K., Feillet, F., Calhau, C., MacDonald, A., and Moreira-Ros\u00e1rio, A. (2021). Is the Phenylalanine-Restricted Diet a Risk Factor for Overweight or Obesity in Patients with Phenylketonuria (PKU)? A Systematic Review and Meta-Analysis. Nutrients, 13.","DOI":"10.3390\/nu13103443"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Gama, M.I., Pinto, A., Daly, A., Rocha, J.C., and MacDonald, A. (2022). The Impact of the Quality of Nutrition and Lifestyle in the Reproductive Years of Women with PKU on the Long-Term Health of Their Children. Nutrients, 14.","DOI":"10.3390\/nu14051021"},{"key":"ref_65","first-page":"57","article-title":"Living with Phenylketonuria: Lessons from the PKU Community","volume":"17","author":"Ford","year":"2018","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Petersohn, I., Hellinga, A.H., van Lee, L., Keukens, N., Bont, L., Hettinga, K.A., Feskens, E.J.M., and Brouwer-Brolsma, E.M. (2023). Maternal Diet and Human Milk Composition: An Updated Systematic Review. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1320560"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1111\/apa.16263","article-title":"Environmental Determinants of Human Milk Composition in Relation to Health Outcomes","volume":"111","author":"Gridneva","year":"2022","journal-title":"Acta Paediatr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/jimd.12724","article-title":"Efficacy and Safety of Sapropterin before and during Pregnancy: Final Analysis of the Kuvan\u00ae Adult Maternal Paediatric European Registry (KAMPER) Maternal and Phenylketonuria Developmental Outcomes and Safety (PKUDOS) PKU-MOMs Sub-Registries","volume":"47","author":"Feillet","year":"2024","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s10545-014-9716-5","article-title":"Use of Sapropterin Dihydrochloride in Maternal Phenylketonuria. A European Experience of Eight Cases","volume":"37","author":"Feillet","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e1881","DOI":"10.1542\/peds.2012-3291","article-title":"Long-Term Follow-up and Outcome of Phenylketonuria Patients on Sapropterin: A Retrospective Study","volume":"131","author":"Keil","year":"2013","journal-title":"Pediatrics"},{"key":"ref_71","first-page":"31","article-title":"Nutritional Changes and Micronutrient Supply in Patients with Phenylketonuria Under Therapy with Tetrahydrobiopterin (BH(4))","volume":"9","author":"Thiele","year":"2013","journal-title":"JIMD Rep."},{"key":"ref_72","unstructured":"(2017). Dietary Treatment for Phenylketonuria. Clinical Review Report: Sapropterin Dihydrochloride (Kuvan) [Internet], Canadian Agency for Drugs and Technologies in Health."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Evers, R.A.F., van Wegberg, A.M.J., MacDonald, A., Huijbregts, S.C.J., Leuzzi, V., and van Spronsen, F.J. (2022). Dietary Liberalization in Tetrahydrobiopterin-Treated PKU Patients: Does It Improve Outcomes?. Nutrients, 14.","DOI":"10.3390\/nu14183874"},{"key":"ref_74","first-page":"101181","article-title":"Lessons Learned from 5 Years of Pegvaliase in US Clinics: A Case Series","volume":"42","author":"Cooney","year":"2025","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"108152","DOI":"10.1016\/j.ymgme.2024.108152","article-title":"Outcomes in 14 Live Births Resulting from Pegvaliase-Treated Pregnancies in PKU-Affected Females","volume":"141","author":"Bier","year":"2024","journal-title":"Mol. Genet. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/s13023-025-03840-y","article-title":"Current State of the Treatment Landscape of Phenylketonuria","volume":"20","author":"Nulmans","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_77","unstructured":"(2025, October 28). Global Strategy for Infant and Young Child Feeding. Available online: https:\/\/www.who.int\/publications\/i\/item\/9241562218."},{"key":"ref_78","unstructured":"World Health Organization (2017). Executive Summary. Guideline: Protecting, Promoting and Supporting Breastfeeding in Facilities Providing Maternity and Newborn Services, World Health Organization."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Yi, D.Y., and Kim, S.Y. (2021). Human Breast Milk Composition and Function in Human Health: From Nutritional Components to Microbiome and MicroRNAs. Nutrients, 13.","DOI":"10.3390\/nu13093094"},{"key":"ref_80","unstructured":"(2025, October 28). Maternal Nutrition and Body Composition During Breastfeeding: Association with Human Milk Composition\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/30262786\/."},{"key":"ref_81","unstructured":"CDC (2025, October 28). Contraindications to Breastfeeding, Available online: https:\/\/www.cdc.gov\/breastfeeding-special-circumstances\/hcp\/contraindications\/index.html."},{"key":"ref_82","unstructured":"(2025, October 28). Delegated Regulation\u20142016\/127\u2014EN\u2014EUR-Lex. Available online: https:\/\/eur-lex.europa.eu\/eli\/reg_del\/2016\/127\/oj\/eng."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1177\/147323000503300601","article-title":"Closer to the Gold Standard: An Appraisal of Formulae Available in Italy for Use in Formula-Fed Infants","volume":"33","author":"Riva","year":"2005","journal-title":"J. Int. Med. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.3945\/ajcn.2008.27091","article-title":"Lower Protein in Infant Formula Is Associated with Lower Weight up to Age 2 y: A Randomized Clinical Trial","volume":"89","author":"Koletzko","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1920S","DOI":"10.3945\/ajcn.110.001123","article-title":"Sex Differences in the Endocrine System in Response to Protein Intake Early in Life","volume":"94","author":"Luque","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1210\/jc.2014-3157","article-title":"Dietary Protein Intake Affects Amino Acid and Acylcarnitine Metabolism in Infants Aged 6 Months","volume":"100","author":"Kirchberg","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e12961","DOI":"10.1111\/ijpo.12961","article-title":"Different Protein Intake in the First Year and Its Effects on Adiposity Rebound and Obesity throughout Childhood: 11\u2009Years Follow-up of a Randomized Controlled Trial","volume":"17","author":"Totzauer","year":"2022","journal-title":"Pediatr. Obes."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/MPG.0000000000000818","article-title":"Lipid Quality in Infant Nutrition: Current Knowledge and Future Opportunities","volume":"61","author":"Delplanque","year":"2015","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00394-009-0067-1","article-title":"Dietary Intake and Plasma Concentrations of PUFA and LC-PUFA in Breastfed and Formula Fed Infants under Real-Life Conditions","volume":"49","author":"Schwartz","year":"2010","journal-title":"Eur. J. Nutr."},{"key":"ref_90","first-page":"1101","article-title":"Controversy about the critical role of long-chain polyunsaturated fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), during infancy","volume":"38","author":"Campoy","year":"2021","journal-title":"Nutr. Hosp."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Chong, H.-Y., Tan, L.T.-H., Law, J.W.-F., Hong, K.-W., Ratnasingam, V., Ab Mutalib, N.-S., Lee, L.-H., and Letchumanan, V. (2022). Exploring the Potential of Human Milk and Formula Milk on Infants\u2019 Gut and Health. Nutrients, 14.","DOI":"10.3390\/nu14173554"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.chom.2015.04.004","article-title":"Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life","volume":"17","author":"Roswall","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Thompson, A.L., Monteagudo-Mera, A., Cadenas, M.B., Lampl, M.L., and Azcarate-Peril, M.A. (2015). Milk- and Solid-Feeding Practices and Daycare Attendance Are Associated with Differences in Bacterial Diversity, Predominant Communities, and Metabolic and Immune Function of the Infant Gut Microbiome. Front. Cell. Infect. Microbiol., 5.","DOI":"10.3389\/fcimb.2015.00003"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Salvatore, S., Dinleyici, E.C., Szajewska, H., Canani, R.B., Gutierrez-Castrell\u00f3n, P., Hojsak, I., Indrio, F., Mihatsch, W., Orel, R., and van Goudoever, J.B. (2025). Technical Review by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications on the Health Outcomes of Infant Formula Supplemented with Synbiotic. J. Pediatr. Gastroenterol. Nutr., 1\u201312.","DOI":"10.1002\/jpn3.70031"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Boswell, N. (2021). Complementary Feeding Methods-A Review of the Benefits and Risks. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18137165"},{"key":"ref_96","unstructured":"World Health Organization (WHO) (2025, October 28). Guideline on the Complementary Feeding of Infants and Young Children Aged 6\u201323 Months 2023: A Multisociety Response\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/38743631\/."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Capra, M.E., Decarolis, N.M., Monopoli, D., Laudisio, S.R., Giudice, A., Stanyevic, B., Esposito, S., and Biasucci, G. (2024). Complementary Feeding: Tradition, Innovation and Pitfalls. Nutrients, 16.","DOI":"10.3390\/nu16050737"},{"key":"ref_98","unstructured":"(2025, October 28). Strengthening Action to Improve Feeding of Infants and Young Children 6\u201323 Months of Age in Nutrition and Child Health Programmes. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241597890."},{"key":"ref_99","unstructured":"(2025, October 28). Appropriate Age Range for Introduction of Complementary Feeding into an Infant\u2019s Diet\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/32626427\/."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/MPG.0000000000001454","article-title":"Complementary Feeding: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition","volume":"64","author":"Fewtrell","year":"2017","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1007\/s00394-013-0560-4","article-title":"Nutrition and Neurodevelopment in Children: Focus on NUTRIMENTHE Project","volume":"52","author":"Anjos","year":"2013","journal-title":"Eur. J. Nutr."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"56","DOI":"10.12944\/CRNFSJ.2.2.02","article-title":"Importance of Exclusive Breastfeeding and Complementary Feeding among Infants","volume":"2","author":"Motee","year":"2014","journal-title":"Curr. Res. Nutr. Food Sci. J."},{"key":"ref_103","unstructured":"Dewey, K. (2003). Guiding Principles for Complementary Feeding of the Breastfed Child, World Health Organization."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1017\/S0029665100000021","article-title":"Essential Fatty Acids in Early Life: Structural and Functional Role","volume":"59","author":"Uauy","year":"2000","journal-title":"Proc. Nutr. Soc."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1007\/s00394-015-0982-2","article-title":"Fatty Acid Supply with Complementary Foods and LC-PUFA Status in Healthy Infants: Results of a Randomised Controlled Trial","volume":"55","author":"Libuda","year":"2016","journal-title":"Eur. J. Nutr."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1097\/MOP.0000000000000203","article-title":"Long-Chain Polyunsaturated Fatty Acids Supplementation in Preterm Infants","volume":"27","author":"Uauy","year":"2015","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_107","first-page":"CD000376","article-title":"Long Chain Polyunsaturated Fatty Acid Supplementation in Infants Born at Term","volume":"3","author":"Jasani","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1740-8709.2010.00284.x","article-title":"Association between Timing of Introducing Solid Foods and Obesity in Infancy and Childhood: A Systematic Review","volume":"7","author":"Moorcroft","year":"2011","journal-title":"Matern. Child. Nutr."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000543126","article-title":"Feeding Practices in the Introduction of Complementary Feeding and Implications for Future Healthy Eating","volume":"81","author":"Verduci","year":"2025","journal-title":"Ann. Nutr. Metab."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1542\/peds.2011-3838","article-title":"Timing of the Introduction of Complementary Foods in Infancy: A Randomized Controlled Trial","volume":"130","author":"Jonsdottir","year":"2012","journal-title":"Pediatrics"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1093\/nutrit\/nuad019","article-title":"Optimal Timing of Introduction of Complementary Feeding: A Systematic Review and Meta-Analysis","volume":"81","author":"Padhani","year":"2023","journal-title":"Nutr. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/ijo.2013.99","article-title":"Timing of the Introduction of Complementary Feeding and Risk of Childhood Obesity: A Systematic Review","volume":"37","author":"Pearce","year":"2013","journal-title":"Int. J. Obes."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1046\/j.1365-277x.2001.00264.x","article-title":"Avon Longitudinal Study of Pregnancy and Childhood the Effect of Age of Introduction to Lumpy Solids on Foods Eaten and Reported Feeding Difficulties at 6 and 15 Months","volume":"14","author":"Northstone","year":"2001","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1740-8709.2008.00153.x","article-title":"Delayed Introduction of Lumpy Foods to Children during the Complementary Feeding Period Affects Child\u2019s Food Acceptance and Feeding at 7 Years of Age","volume":"5","author":"Coulthard","year":"2009","journal-title":"Matern. Child. Nutr."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1097\/MPG.0000000000003892","article-title":"Developmental Feeding Stages and Their Impact on Child Feeding Behavior","volume":"77","author":"Sdravou","year":"2023","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1056\/NEJMoa1514210","article-title":"Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants","volume":"374","author":"Perkin","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1016\/S0140-6736(22)00687-0","article-title":"Early Food Intervention and Skin Emollients to Prevent Food Allergy in Young Children (PreventADALL): A Factorial, Multicentre, Cluster-Randomised Trial","volume":"399","author":"Skjerven","year":"2022","journal-title":"Lancet"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/j.jaci.2016.06.045","article-title":"Randomized Placebo-Controlled Trial of Hen\u2019s Egg Consumption for Primary Prevention in Infants","volume":"139","author":"Bellach","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1001\/jamapediatrics.2023.0142","article-title":"Timing of Allergenic Food Introduction and Risk of Immunoglobulin E-Mediated Food Allergy: A Systematic Review and Meta-Analysis","volume":"177","author":"Scarpone","year":"2023","journal-title":"JAMA Pediatr."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.appet.2014.06.008","article-title":"Maternal Feeding Self-Efficacy and Fruit and Vegetable Intakes in Infants. Results from the SAIDI Study","volume":"81","author":"Koh","year":"2014","journal-title":"Appetite"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.appet.2013.08.011","article-title":"Parenting style and dietary behaviour of young children. Findings from the Healthy Beginnings Trial","volume":"71","author":"Xu","year":"2013","journal-title":"Appetite"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1007\/s00394-022-02822-1","article-title":"The Establishment of the Gut Microbiota in 1-Year-Aged Infants: From Birth to Family Food","volume":"61","author":"Vacca","year":"2022","journal-title":"Eur. J. Nutr."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Noles, D.L., Matzeller, K.L., Frank, D.N., Krebs, N.F., and Tang, M. (2025). Complementary Feeding and Infant Gut Microbiota: A Narrative Review. Nutrients, 17.","DOI":"10.3390\/nu17050743"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1159\/000517912","article-title":"Gut Microbiota Development: Influence of Diet from Infancy to Toddlerhood","volume":"77","author":"Laursen","year":"2021","journal-title":"Ann. Nutr. Metab."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e12642","DOI":"10.1111\/ijpo.12642","article-title":"Potential Interaction between Timing of Infant Complementary Feeding and Breastfeeding Duration in Determination of Early Childhood Gut Microbiota Composition and BMI","volume":"15","author":"Differding","year":"2020","journal-title":"Pediatr. Obes."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Differding, M.K., Benjamin-Neelon, S.E., Hoyo, C., \u00d8stbye, T., and Mueller, N.T. (2020). Timing of Complementary Feeding Is Associated with Gut Microbiota Diversity and Composition and Short Chain Fatty Acid Concentrations over the First Year of Life. BMC Microbiol., 20.","DOI":"10.1186\/s12866-020-01723-9"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1136\/adc.65.5.472","article-title":"Intelligence and Quality of Dietary Treatment in Phenylketonuria","volume":"65","author":"Smith","year":"1990","journal-title":"Arch. Dis. Child."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/s41390-021-01728-8","article-title":"Metabolic Control during the Neonatal Period in Phenylketonuria: Associations with Childhood IQ","volume":"91","author":"Liemburg","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/s13023-019-1236-9","article-title":"Reducing Complexity: Explaining Inborn Errors of Metabolism and Their Treatment to Children and Adolescents","volume":"14","author":"Zeltner","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1186\/s13023-021-02094-8","article-title":"Improving Phenylalanine and Micronutrients Status of Children with Phenylketonuria: A Pilot Randomized Study","volume":"16","author":"Zamani","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Kaloteraki, E., Pardali, E.C., Poulimeneas, D., Mylona, V., Fotiadou, E., Papa, K., Gioxari, A., Spilioti, M., Bogdanos, D.P., and Grammatikopoulou, M.G. (2025). Nutritional Practices and Knowledge of Patients with Phenylketonuria. Nutrients, 17.","DOI":"10.3390\/nu17213351"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/1750-1172-8-191","article-title":"Requirements for a Minimum Standard of Care for Phenylketonuria: The Patients\u2019 Perspective","volume":"8","author":"Hagedorn","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1186\/s13023-021-02086-8","article-title":"Italian National Consensus Statement on Management and Pharmacological Treatment of Phenylketonuria","volume":"16","author":"Burlina","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/humu.22980","article-title":"Genetics of Phenylketonuria: Then and Now","volume":"37","author":"Blau","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgme.2019.04.004","article-title":"International Best Practice for the Evaluation of Responsiveness to Sapropterin Dihydrochloride in Patients with Phenylketonuria","volume":"127","author":"Muntau","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"11229","DOI":"10.1073\/pnas.1902639116","article-title":"Structure of Full-Length Human Phenylalanine Hydroxylase in Complex with Tetrahydrobiopterin","volume":"116","author":"Flydal","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.earlhumdev.2015.08.013","article-title":"Human Breast Milk: A Review on Its Composition and Bioactivity","volume":"91","author":"Andreas","year":"2015","journal-title":"Early Hum. Dev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.pcl.2012.10.002","article-title":"Human Milk Composition: Nutrients and Bioactive Factors","volume":"60","author":"Ballard","year":"2013","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e002066","DOI":"10.1136\/bmjpo-2023-002066","article-title":"Breast Feeding in Infants Diagnosed with Phenylketonuria (PKU): A Scoping Review","volume":"7","author":"Kalvala","year":"2023","journal-title":"BMJ Paediatr. Open"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Mej\u00eda, L., Guill\u00e9n-L\u00f3pez, S., Vela-Amieva, M., Fern\u00e1ndez-Lainez, C., and Castro-Monroy, L. (2025). Positive Impact of Breastfeeding on Nutritional Status and Metabolic Control in Infants with PKU: A Retrospective Study. Nutrients, 17.","DOI":"10.3390\/nu17172851"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Zuvadelli, J., Paci, S., Salvatici, E., Giorgetti, F., Cefalo, G., Re Dionigi, A., Rovelli, V., and Banderali, G. (2022). Breastfeeding in Phenylketonuria: Changing Modalities, Changing Perspectives. Nutrients, 14.","DOI":"10.3390\/nu14194138"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e70001","DOI":"10.1002\/jimd.70001","article-title":"Human Milk Feeding in Inherited Metabolic Disorders: A Systematic Review of Growth, Metabolic Control, and Neurodevelopment Outcomes","volume":"48","author":"Ilgaz","year":"2025","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Verduci, E., Tosi, M., Montanari, C., Gambino, M., Eletti, F., Bosetti, A., Costanzo, M.D., Carbone, M.T., Biasucci, G., and Fiori, L. (2023). Are Phe-Free Protein Substitutes Available in Italy for Infants with PKU All the Same?. Nutrients, 16.","DOI":"10.3390\/nu16010030"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Natividad, J.M., Marsaux, B., Rodenas, C.L.G., Rytz, A., Vandevijver, G., Marzorati, M., Van den Abbeele, P., Calatayud, M., and Rochat, F. (2022). Human Milk Oligosaccharides and Lactose Differentially Affect Infant Gut Microbiota and Intestinal Barrier In Vitro. Nutrients, 14.","DOI":"10.3390\/nu14122546"},{"key":"ref_145","unstructured":"(2025, December 10). Nutritional Support of Neurodevelopment and Cognitive Function in Infants and Young Children-An Update and Novel Insights\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/33435231\/."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1177\/15598276221116052","article-title":"A Systematic Review of Omega-3 Fatty Acid Consumption and Cognitive Outcomes in Neurodevelopment","volume":"17","author":"Sherzai","year":"2022","journal-title":"Am. J. Lifestyle Med."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Carr, L.E., Virmani, M.D., Rosa, F., Munblit, D., Matazel, K.S., Elolimy, A.A., and Yeruva, L. (2021). Role of Human Milk Bioactives on Infants\u2019 Gut and Immune Health. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.604080"},{"key":"ref_148","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_149","doi-asserted-by":"crossref","unstructured":"Evans, S., Daly, A., Wildgoose, J., Cochrane, B., Chahal, S., Ashmore, C., Loveridge, N., and MacDonald, A. (2019). Growth, Protein and Energy Intake in Children with PKU Taking a Weaning Protein Substitute in the First Two Years of Life: A Case-Control Study. Nutrients, 11.","DOI":"10.3390\/nu11030552"},{"key":"ref_150","first-page":"39","article-title":"Weaning Practices in Phenylketonuria Vary between Health Professionals in Europe","volume":"18","author":"Pinto","year":"2019","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_151","first-page":"E454","article-title":"Dietary management practices in phenylketonuria: Results of an Italian multicentric survey and comparison with the European guidelines","volume":"1","author":"Giorda","year":"2024","journal-title":"JIM"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/jhn.12510","article-title":"Fifteen Years of Using a Second Stage Protein Substitute for Weaning in Phenylketonuria: A Retrospective Study","volume":"31","author":"Evans","year":"2018","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Yilmaz Nas, O., Ashmore, C., Evans, S., Pinto, A., Daly, A., Yabanc\u0131 Ayhan, N., and MacDonald, A. (2025). Global Clinical Practice in Transitioning Protein Substitutes for Children with Phenylketonuria. Nutrients, 17.","DOI":"10.3390\/nu17162650"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1159\/000363391","article-title":"The Micronutrient Status of Patients with Phenylketonuria on Dietary Treatment: An Ongoing Challenge","volume":"65","author":"Evans","year":"2014","journal-title":"Ann. Nutr. Metab."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.clnu.2018.01.034","article-title":"Vitamin\/Mineral and Micronutrient Status in Patients with Classical Phenylketonuria","volume":"38","author":"Kose","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Bokayeva, K., Jamka, M., Walkowiak, D., Du\u015b-\u017buchowska, M., Herzig, K.-H., and Walkowiak, J. (2024). Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105065"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Evans, S., Daly, A., Wildgoose, J., Cochrane, B., Ashmore, C., Kearney, S., and MacDonald, A. (2019). Mealtime Anxiety and Coping Behaviour in Parents and Children During Weaning in PKU: A Case-Control Study. Nutrients, 11.","DOI":"10.3390\/nu11122857"},{"key":"ref_158","unstructured":"Edwards, M.J. (2014). Comparison of Gut Microbial Community in Infants and Toddlers with and Without Phenylketonuria. [Master\u2019s Thesis, University of Washington]."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Ostrowska, M., Nowosad, K., Mikoluc, B., Szczerba, H., and Komon-Janczara, E. (2024). Changes in the Gut and Oral Microbiome in Children with Phenylketonuria in the Context of Dietary Restrictions\u2014A Preliminary Study. Nutrients, 16.","DOI":"10.3390\/nu16223915"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Bassanini, G., Ceccarani, C., Borgo, F., Severgnini, M., Rovelli, V., Morace, G., Verduci, E., and Borghi, E. (2019). Phenylketonuria Diet Promotes Shifts in Firmicutes Populations. Front. Cell. Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00101"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Ubaldi, F., Frangella, C., Volpini, V., Fortugno, P., Valeriani, F., and Romano Spica, V. (2023). Systematic Review and Meta-Analysis of Dietary Interventions and Microbiome in Phenylketonuria. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417428"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Pinto, A., Ilgaz, F., Evans, S., van Dam, E., Rocha, J.C., Karabulut, E., Hickson, M., Daly, A., and MacDonald, A. (2023). Phenylalanine Tolerance over Time in Phenylketonuria: A Systematic Review and Meta-Analysis. Nutrients, 15.","DOI":"10.3390\/nu15163506"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Pinto, A., Almeida, M.F., MacDonald, A., Ramos, P.C., Rocha, S., Guimas, A., Ribeiro, R., Martins, E., Bandeira, A., and Jackson, R. (2019). Over Restriction of Dietary Protein Allowance: The Importance of Ongoing Reassessment of Natural Protein Tolerance in Phenylketonuria. Nutrients, 11.","DOI":"10.3390\/nu11050995"},{"key":"ref_164","first-page":"E532","article-title":"Special low protein foods in the management of Inborn Errors of Metabolism: Overview on availability, composition and comparison with regular foods in Italy","volume":"1","author":"Salera","year":"2024","journal-title":"JIM"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Leal-Witt, M.J., Rojas-Agurto, E., Mu\u00f1oz-Gonz\u00e1lez, M., Pe\u00f1aloza, F., Arias, C., Fuenzalida, K., Bunout, D., Cornejo, V., and Acevedo, A. (2023). Risk of Developing Insulin Resistance in Adult Subjects with Phenylketonuria: Machine Learning Model Reveals an Association with Phenylalanine Concentrations in Dried Blood Spots. Metabolites, 13.","DOI":"10.3390\/metabo13060677"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.arr.2016.08.003","article-title":"Nutrition in Early Life and Age-Associated Diseases","volume":"39","author":"Ozanne","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"107625","DOI":"10.1016\/j.ymgme.2023.107625","article-title":"Health Status and Comorbidities of Adult Patients with Phenylketonuria (PKU) in France with a Focus on Early-Diagnosed Patients\u2014A Nationwide Study of Health Insurance Claims Data","volume":"139","author":"Maillot","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/jimd.12186","article-title":"Phenylketonuria, Co-Morbidity, and Ageing: A Review","volume":"43","author":"Vardy","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Daly, A., Evans, S., Pinto, A., Ashmore, C., Rocha, J.C., and MacDonald, A. (2020). A 3 Year Longitudinal Prospective Review Examining the Dietary Profile and Contribution Made by Special Low Protein Foods to Energy and Macronutrient Intake in Children with Phenylketonuria. Nutrients, 12.","DOI":"10.3390\/nu12103153"},{"key":"ref_170","first-page":"148","article-title":"Promoting Psychological Well-Being in Women with Phenylketonuria: Pregnancy-Related Stresses, Coping Strategies and Supports","volume":"1","author":"Roberts","year":"2014","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Cassidy, S., Evans, S., Pinto, A., Daly, A., Ashmore, C., Ford, S., Buckley, S., and MacDonald, A. (2023). Parent\u2019s Perception of the Types of Support Given to Families with an Infant with Phenylketonuria. Nutrients, 15.","DOI":"10.20944\/preprints202304.0606.v1"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"350","DOI":"10.17712\/nsj.2015.4.20150319","article-title":"Depression and Anxiety among Parents of Phenylketonuria Children","volume":"20","author":"Gunduz","year":"2015","journal-title":"Neurosciences"},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Pinto, A., Gerrard, A., Vijay, S., Evans, S., Daly, A., Ashmore, C., Gama, M.I., Rocha, J.C., Singh, R., and Jackson, R. (2025). Point-of-Care Testing in PKU: A New ERA of Blood Phenylalanine Monitoring. Nutrients, 17.","DOI":"10.3390\/nu17233800"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1186\/s13023-025-03989-6","article-title":"Performance of the Egoo Test for Phenylalanine Measurement in Females with Phenylketonuria","volume":"20","author":"Schoen","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.numecd.2020.02.003","article-title":"Maternal PKU: Defining Phenylalanine Tolerance and Its Variation during Pregnancy, According to Genetic Background","volume":"30","author":"Caletti","year":"2020","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_176","first-page":"e70042","article-title":"Metabolic Control and Frequency of Clinical Monitoring Among Canadian Children with Phenylalanine Hydroxylase Deficiency: A Retrospective Cohort Study","volume":"66","author":"Yuskiv","year":"2025","journal-title":"JIMD Rep."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1080\/03007995.2024.2337662","article-title":"Unmet Needs in Phenylketonuria: An Exploratory Italian Survey among Patients and Caregivers","volume":"40","author":"Rovelli","year":"2024","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/cch.12727","article-title":"Psychosocial Functioning in Children with Phenylketonuria: Relationships between Quality of Life and Parenting Indicators","volume":"46","author":"Morawska","year":"2020","journal-title":"Child. Care Health Dev."},{"key":"ref_179","first-page":"107","article-title":"Demographic and Psychosocial Influences on Treatment Adherence for Children and Adolescents with PKU: A Systematic Review","volume":"39","author":"Medford","year":"2018","journal-title":"JIMD Rep."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"109705","DOI":"10.1016\/j.ymgme.2025.109705","article-title":"Dietetic Guidance for Nutritional Management of People with Phenylketonuria Receiving Sepiapterin","volume":"147","author":"MacDonald","year":"2025","journal-title":"Mol. Genet. Metab."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/s13023-023-02751-0","article-title":"Nutrition Management of PKU with Pegvaliase Therapy: Update of the Web-Based PKU Nutrition Management Guideline Recommendations","volume":"18","author":"Cunningham","year":"2023","journal-title":"Orphanet J. Rare Dis."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/2\/199\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:17:12Z","timestamp":1767867432000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/2\/199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":181,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["nu18020199"],"URL":"https:\/\/doi.org\/10.3390\/nu18020199","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]}}}