{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:30:29Z","timestamp":1790983829091,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"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: Vitamin B12 (B12) is essential for the provision of methyl groups for numerous essential pathways. Infant B12 deficiency (B12D) can lead to severe, even irreversible neurological abnormalities. Maternal B12 status in pregnancy and during the breastfeeding period correlates significantly with the child\u2019s B12 status. B12D is a target disease in some newborn screening (NBS) programs. This study investigates whether infants that were clinically symptomatic and diagnosed with B12D in their first year of life could be retrospectively detected by the Austrian NBS algorithm. Methods: Data from infants with clinically diagnosed B12D in their first year of life between 2012 and 2022 were retrospectively collected in Austria (B12-related NBS implemented in 2018) and Switzerland (B12-related NBS not implemented). NBS data were retrospectively analysed, and clinical information was collected by a survey. Correlations between clinical symptoms, NBS data, biochemical parameters at diagnosis, maternal medical history and B12 status were analysed. Results: Four\/forty-eight cases were retrospectively detected by the first-tier NBS parameters. From two children material for second-tier testing was available and B12D was confirmed by elevated total homocysteine (tHcy), resulting in a detection rate between 4.3 and 9.3%. The numbers of neurological and haematological symptoms correlated with low B12 and elevated levels of tHcy and methylmalonic acid. Although the detection rate of symptomatic B12D by NBS was low, fewer infants with symptomatic B12D were observed in the period after implementation of B12-related NBS (Austria). A history of B12D-relevant maternal disease such as pernicious anaemia was reported in 12 cases. Conclusions: B12D causes severe clinical symptoms in infants. NBS has a very limited retrospective detection rate of infants with severe B12D but seems to correlate with a reduction in cases due to not yet precisely quantified mechanisms. The workup triggered by NBS recalls is costly and often challenging for families. Maternal B12D increases the risk of infant B12D but also of other pregnancy-related health risks. To increase the efficacy of the prevention of infant B12D, to promote a healthy pregnancy and breastfeeding period, and to reduce the frequency of NBS recalls, pregnant women should be screened for B12D to be counselled and treated.<\/jats:p>","DOI":"10.3390\/nu17223583","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T11:05:31Z","timestamp":1763463931000},"page":"3583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Newborn Screening Alone Cannot Prevent Most Cases of Severe Vitamin B12 Deficiency in the First Year of Life"],"prefix":"10.3390","volume":"17","author":[{"given":"Christina","family":"Kaufman","sequence":"first","affiliation":[{"name":"Division of Metabolism and Children\u2019s Research Center, University Children\u2019s Hospital of Zurich, University of Zurich, 8008 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9678-8096","authenticated-orcid":false,"given":"Julian","family":"Margreitter","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health, Division of Pediatrics I\u2014Inherited Metabolic Disorders, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0702-4374","authenticated-orcid":false,"given":"Marion","family":"Herle","sequence":"additional","affiliation":[{"name":"Austrian Newborn Screening, Comprehensive Center for Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6797-7604","authenticated-orcid":false,"given":"Walter","family":"Bonfig","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Klinikum Wels, 4600 Wels, Austria"},{"name":"Department of Pediatrics, Technical University Munich, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"D\u00e4ster","sequence":"additional","affiliation":[{"name":"Neonatology, Kantonsspital Aarau, 5001 Aarau, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianka","family":"Heinrich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stadtspital Z\u00fcrich Triemli, 8063 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4846-1047","authenticated-orcid":false,"given":"Daniela","family":"Karall","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health, Division of Pediatrics I\u2014Inherited Metabolic Disorders, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-3387","authenticated-orcid":false,"given":"Hubert","family":"Kogler","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, St. Anna Children\u2019s Hospital, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki","family":"Konstantopoulou","sequence":"additional","affiliation":[{"name":"Austrian Newborn Screening, Comprehensive Center for Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9191-1886","authenticated-orcid":false,"given":"Alexander","family":"Laemmle","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reta","family":"Mal\u00e4r","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cantonal Hospital Graubuenden, 7000 Chur, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition, Children\u2019s Hospital of Eastern Switzerland, 9006 St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"P\u00f6ll","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, St. Anna Children\u2019s Hospital, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-314X","authenticated-orcid":false,"given":"Martin","family":"Poms","sequence":"additional","affiliation":[{"name":"Newborn Screening Switzerland, University Children\u2019s Hospital Zurich, University of Zurich, 8008 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5762-8681","authenticated-orcid":false,"given":"Franziska","family":"Righini-Grunder","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children\u2019s Hospital of Central Switzerland, 6000 Lucerne, Switzerland"},{"name":"Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University Children\u2019s Hospital Zurich, 8008 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0726-7459","authenticated-orcid":false,"given":"Rotraud K.","family":"Saurenmann","sequence":"additional","affiliation":[{"name":"Center of Pediatrics, Cantonal Hospital Winterthur, 8401 Winterthur, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Sluka","sequence":"additional","affiliation":[{"name":"Newborn Screening Switzerland, University Children\u2019s Hospital Zurich, University of Zurich, 8008 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9555-3817","authenticated-orcid":false,"given":"Nicolas","family":"von der Weid","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital Basel (UKBB), University of Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5000-1974","authenticated-orcid":false,"given":"Maximilian","family":"Zeyda","sequence":"additional","affiliation":[{"name":"Austrian Newborn Screening, Comprehensive Center for Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias R.","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children\u2019s Research Center, University Children\u2019s Hospital of Zurich, University of Zurich, 8008 Zurich, Switzerland"},{"name":"Newborn Screening Switzerland, University Children\u2019s Hospital Zurich, University of Zurich, 8008 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Huemer","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children\u2019s Research Center, University Children\u2019s Hospital of Zurich, University of Zurich, 8008 Zurich, Switzerland"},{"name":"Department of Pediatrics, LKH Bregenz, 6900 Bregenz, Austria"},{"name":"Vorarlberg University of Applied Sciences, Competence Area Healthcare and Nursing, 6850 Dornbirn, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1002\/jimd.12593","article-title":"The complex machinery of human cobalamin metabolism","volume":"46","author":"McCorvie","year":"2023","journal-title":"J. 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