{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:31:27Z","timestamp":1790983887551,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dietmar Hopp Foundation","award":["2311221"],"award-info":[{"award-number":["2311221"]}]},{"name":"Dietmar Hopp Foundation","award":["DH2011117"],"award-info":[{"award-number":["DH2011117"]}]},{"name":"Dietmar Hopp Foundation","award":["2311220"],"award-info":[{"award-number":["2311220"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin B12 deficiency, mostly of maternal origin in newborns, is a well-treatable condition but can cause severe neurologic sequelae in infants. Early detection of vitamin B12 deficiency allows the pre-symptomatic treatment of affected children. This evaluation assesses the characteristics of maternal vitamin B12 deficiency detected by newborn screening. In a prospective single-center study, a systematic screening strategy for vitamin B12 deficiency using a combination of two second-tier strategies was applied. In addition to confirmatory diagnostics in children, the systematic work-up of vitamin B12 status was also performed for their mothers. Maternal characteristics were assessed including ethnic origin, diet, and vitamin supplementation during pregnancy. For affected mothers, a work-up by internal medicine was recommended. In total, 121 mother\u2013infant couples were analyzed. 66% of mothers adhered to a balanced diet including meat. The cause of maternal vitamin B12 deficiency was unknown in 56% of cases, followed by dietary causes in 32%, and organic causes in 8%. All mothers following a vegan diet and most mothers with a vegetarian diet took vitamin preparations during pregnancy, whereas only 55.8% of mothers with a balanced diet took folic acid or other vitamins. Maternal vitamin B12, folic acid, and homocysteine levels were significantly correlated with the child\u2019s folic acid levels, and with homocysteine, methylmalonic, and methylcitric acid levels in first and second NBS dried blood spots. Most children had normal blood counts and showed normocytosis. Although 36.7% of mothers showed anemia, only one presented with macrocytosis. Adherence to vitamin supplementation in pregnancy is low despite the recommendation for supplementation of folic acid. Ideally, the evaluation of mothers for vitamin B12 levels and appropriate therapy should be initiated in early pregnancy. In infants detected through newborn screening, the multidisciplinary assessment and therapy of both children and mothers should be performed.<\/jats:p>","DOI":"10.3390\/nu14183767","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T22:37:28Z","timestamp":1663108648000},"page":"3767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Maternal Vitamin B12 Deficiency Detected by Newborn Screening\u2014Evaluation of Causes and Characteristics"],"prefix":"10.3390","volume":"14","author":[{"given":"Anna T.","family":"Reischl-Hajiabadi","sequence":"first","affiliation":[{"name":"Division of Neuropediatrics and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7420-4757","authenticated-orcid":false,"given":"Sven F.","family":"Garbade","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Feyh","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl Heinz","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, Gastroenterology and Hepatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4251-7257","authenticated-orcid":false,"given":"Ulrike","family":"M\u00fctze","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-9477","authenticated-orcid":false,"given":"Stefan","family":"K\u00f6lker","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg F.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7596-6529","authenticated-orcid":false,"given":"Gwendolyn","family":"Gramer","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany"},{"name":"University Medical Center Hamburg-Eppendorf, University Children\u2019s Hospital, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lyon, P., Strippoli, V., Fang, B., and Cimmino, L. (2020). B vitamins and one-carbon metabolism: Implications in human health and disease. Nutrients, 12.","DOI":"10.3390\/nu12092867"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1056\/NEJMcp1113996","article-title":"Vitamin B12 deficiency","volume":"368","author":"Stabler","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrgastro.2012.76","article-title":"Vitamin B12 transport from food to the body\u2019s cells\u2014A sophisticated, multistep pathway","volume":"9","author":"Nielsen","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1146\/annurev.nutr.24.012003.132440","article-title":"Vitamin B12 deficiency as a worldwide problem","volume":"24","author":"Stabler","year":"2004","journal-title":"Annu. Rev. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17040","DOI":"10.1038\/nrdp.2017.40","article-title":"Vitamin B 12 deficiency","volume":"3","author":"Green","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1177\/15648265080292S107","article-title":"Review of the magnitude of folate and vitamin B12 deficiencies worldwide","volume":"29","author":"McLean","year":"2008","journal-title":"Food Nutr. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"693S","DOI":"10.3945\/ajcn.2008.26947A","article-title":"How common is vitamin B-12 deficiency?","volume":"89","author":"Allen","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e011247","DOI":"10.1136\/bmjopen-2016-011247","article-title":"Vitamin B12 status in women of childbearing age in the UK and its relationship with national nutrient intake guidelines: Results from two National Diet and Nutrition Surveys","volume":"6","author":"Sukumar","year":"2016","journal-title":"BMJ Open"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"971","DOI":"10.3945\/an.117.015628","article-title":"Cobalamin status from pregnancy to early childhood: Lessons from global experience","volume":"8","author":"Obeid","year":"2017","journal-title":"Adv. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1093\/jn\/137.8.1863","article-title":"Longitudinal study of the effect of pregnancy on maternal and fetal cobalamin status in healthy women and their offspring","volume":"137","author":"Murphy","year":"2007","journal-title":"J. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s11596-020-2260-7","article-title":"Vitamin B12 deficiency in newborns and their mothers","volume":"40","author":"Gramer","year":"2020","journal-title":"Curr. Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.clinbiochem.2014.08.020","article-title":"Maternal vitamin B12 deficiency detected in expanded newborn screening","volume":"47","author":"Scolamiero","year":"2014","journal-title":"Clin. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.3945\/ajcn.115.123083","article-title":"Prevalence of vitamin B-12 insufficiency during pregnancy and its effect on offspring birth weight: A systematic review and meta-analysis","volume":"103","author":"Sukumar","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1017\/S0007114517002331","article-title":"Pregnant women of South Asian ethnicity in Canada have substantially lower vitamin B12 status compared with pregnant women of European ethnicity","volume":"118","author":"Schroder","year":"2017","journal-title":"Br. J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"552","DOI":"10.3945\/an.115.008201","article-title":"Vitamin B-12 and perinatal health","volume":"6","author":"Finkelstein","year":"2015","journal-title":"Adv. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1093\/jn\/nxy028","article-title":"Maternal serum cobalamin at 18 weeks of pregnancy predicts infant cobalamin status at 6 months\u2014A prospective, observational study","volume":"148","author":"Varsi","year":"2018","journal-title":"J. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/S0022-3476(05)81897-9","article-title":"Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants","volume":"121","author":"Graham","year":"1992","journal-title":"J. Pediatrics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1177\/0883073813516194","article-title":"Vitamin B12 deficiency in children: A treatable cause of neurodevelopmental delay","volume":"30","author":"Jain","year":"2015","journal-title":"J. Child Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/pbc.25828","article-title":"Vitamin B12 deficiency in infancy: The case for screening","volume":"63","author":"Singh","year":"2016","journal-title":"Pediatric Blood Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s00112-014-3297-0","article-title":"Neue zielerkrankungen im neugeborenenscreening","volume":"163","author":"Sonnenschein","year":"2015","journal-title":"Mon. Kinderheilkd."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jpeds.2021.02.009","article-title":"Health outcomes of infants with Vitamin B12 deficiency identified by newborn screening and early treated","volume":"235","author":"Walter","year":"2021","journal-title":"J. Pediatrics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jpeds.2019.07.052","article-title":"Newborn screening for Vitamin B(12) deficiency in Germany\u2014Strategies, results, and public health implications","volume":"216","author":"Gramer","year":"2020","journal-title":"J. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgmr.2017.11.002","article-title":"High incidence of low vitamin B12 levels in Estonian newborns","volume":"15","author":"Reinson","year":"2018","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1001\/jama.2011.310","article-title":"Expanded newborn screening for detection of vitamin B12 deficiency","volume":"305","author":"Sarafoglou","year":"2011","journal-title":"JAMA"},{"key":"ref_25","unstructured":"(2022). Richtlinie des Gemeinsamen Bundesausschusses \u00fcber die Fr\u00fcherkennung von Krankheiten bei Kindern (Kinder-Richtlinie), Gemeinsamer Bundesausschuss."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Monostori, P., Klinke, G., Richter, S., Bar\u00e1th, A., Fingerhut, R., Baumgartner, M.R., K\u00f6lker, S., Hoffmann, G.F., Gramer, G., and Okun, J.G. (2017). Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS\/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184897"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.jpeds.2009.09.054","article-title":"Newborn population screening for classic homocystinuria by determination of total homocysteine from guthrie cards","volume":"156","author":"Kebbewar","year":"2010","journal-title":"J. Pediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3389\/fmolb.2016.00027","article-title":"Biomarkers and algorithms for the diagnosis of vitamin B12 deficiency","volume":"3","author":"Hannibal","year":"2016","journal-title":"Front. Mol. Biosci."},{"key":"ref_29","unstructured":"Bundesamt, S. (2022, February 20). Bev\u00f6lkerung Migration und Integration 2022. Available online: https:\/\/www.destatis.de\/DE\/Themen\/Gesellschaft-Umwelt\/Bevoelkerung\/Migration-Integration\/_inhalt.html."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.ejpn.2009.12.003","article-title":"Clinical presentation and metabolic consequences in 40 breastfed infants with nutritional vitamin B12 deficiency\u2014What have we learned?","volume":"14","author":"Honzik","year":"2010","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.jpeds.2010.03.006","article-title":"Maternal and neonatal vitamin B12 deficiency detected through expanded newborn screening\u2014United States, 2003\u20132007","volume":"157","author":"Hinton","year":"2010","journal-title":"J. Pediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1055\/a-0713-1058","article-title":"Diet and lifestyle before and during pregnancy\u2013practical recommendations of the Germany-wide healthy start\u2013young family network","volume":"78","author":"Koletzko","year":"2018","journal-title":"Geburtshilfe Frauenheilkd."},{"key":"ref_33","first-page":"S55","article-title":"Der bundes-gesundheits-survey 1998\u2014Erfahrungen, ergebnisse, perspektiven","volume":"61","author":"Schaefer","year":"1999","journal-title":"Gesundheitswesen"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.3945\/jn.115.211300","article-title":"Pregnant Canadian women achieve recommended intakes of one-carbon nutrients through prenatal supplementation but the supplement composition, including choline, requires reconsideration","volume":"145","author":"Masih","year":"2015","journal-title":"J. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0387-7604(02)00163-8","article-title":"Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid","volume":"25","author":"Karabiber","year":"2003","journal-title":"Brain Dev."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Karaoglu, L., Pehlivan, E., Egri, M., Deprem, C., Gunes, G., Genc, M.F., and Temel, I. (2010). The prevalence of nutritional anemia in pregnancy in an east Anatolian province, Turkey. BMC Public Health, 10.","DOI":"10.1186\/1471-2458-10-329"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ejogrb.2006.04.026","article-title":"Hemolysis, elevated liver enzymes and low platelets during pregnancy due to vitamin B12 and folate deficiencies","volume":"131","author":"Hartong","year":"2007","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.biochi.2015.12.003","article-title":"Early pregnancy B vitamin status, one carbon metabolism, pregnancy outcome and child development","volume":"126","author":"Murphy","year":"2016","journal-title":"Biochimie"},{"key":"ref_39","unstructured":"Eidgenossenschaft, S. (2014, November 28). Gesundheit von M\u00fcttern und Kindern mit Migrationshintergrund. Available online: https:\/\/www.bfs.admin.ch\/bfs\/portal\/de\/index\/news\/00\/06.html."},{"key":"ref_40","unstructured":"Centers for Disease Control and Prevention (2003). Neurologic impairment in children associated with maternal dietary deficiency of cobalamin\u2014Georgia, 2001. MMWR Morb. Mortal. Wkly. Rep., 52, 61\u201364."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e23388","DOI":"10.1002\/ajhb.23388","article-title":"Trends of folate, vitamin B12, and homocysteine levels in different trimesters of pregnancy and pregnancy outcomes","volume":"32","author":"Mishra","year":"2020","journal-title":"Am. J. Hum. Biol."},{"key":"ref_42","first-page":"212","article-title":"Associations of maternal vitamin B12 concentration in pregnancy with the risks of preterm birth and low birth weight: A systematic review and meta-analysis of individual participant data","volume":"185","author":"Rogne","year":"2017","journal-title":"Am. J. Epidemiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2399\/prn.15.0232003","article-title":"The effect of vitamin B12 level on fetal birth weight","volume":"23","author":"Keskin","year":"2015","journal-title":"Perinat. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"572.e1","DOI":"10.1016\/j.ajog.2010.01.045","article-title":"Maternal homocysteine and related B vitamins as risk factors for low birthweight","volume":"202","author":"Hogeveen","year":"2010","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1017\/S0007114521000581","article-title":"Maternal vitamin B12 status in early pregnancy and its association with birth outcomes in Canadian mother\u2013newborn Dyads","volume":"126","author":"Tan","year":"2021","journal-title":"Br. J. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ymgme.2007.12.002","article-title":"Genetic and lifestyle factors related to the periconception vitamin B12 status and congenital heart defects: A Dutch case-control study","volume":"94","author":"Lindemans","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1016\/j.jacc.2011.08.025","article-title":"Birth prevalence of congenital heart disease worldwide: A systematic review and meta-analysis","volume":"58","author":"Konings","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/chd.12515","article-title":"Changing prevalence of severe congenital heart disease: Results from the National Register for Congenital Heart Defects in Germany","volume":"12","author":"Pfitzer","year":"2017","journal-title":"Congenit. Heart Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/jpc.12652","article-title":"Oral vitamin B 12 treatment is effective for children with nutritional vitamin B 12 deficiency","volume":"50","author":"Bahadir","year":"2014","journal-title":"J. Paediatr. Child Health"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/18\/3767\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:30:13Z","timestamp":1760142613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/18\/3767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,13]]},"references-count":49,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["nu14183767"],"URL":"https:\/\/doi.org\/10.3390\/nu14183767","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,13]]}}}