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Objective: To evaluate a systematic newborn screening (NBS) strategy for vitamin B 12 deficiency., Study Design: In a prospective single-center NBS study, a systematic screening strategy for vitamin B 12 deficiency was developed and evaluated. Tandem-mass spectrometry screening was complemented by 2 second-tier strategies, measuring methylmalonic/3-OH-propionic/methylcitric acid, and homocysteine from dried blood spots., Results: In a cohort of 176 702 children screened over 27 months, 33 children were detected by NBS in whom (maternal) vitamin B 12 deficiency was confirmed. Homocysteine was the most sensitive marker for vitamin B 12 deficiency, but only combination with a second-tier strategy evaluating methylmalonic acid allowed for detection of all 33 children. Mothers were of various ethnic origins, and 89% adhered to a balanced diet. Treatment in children was performed predominantly by oral vitamin B 12 supplementation (84%), and all children remained without clinical symptoms at short-term follow-up., Conclusions: Vitamin B 12 deficiency is a treatable condition but can cause severe neurologic sequelae in infants if untreated. The proposed screening strategy is feasible and effective to identify moderate and severe cases of vitamin B 12 deficiency. With an incidence of 1:5355 newborns, vitamin B 12 deficiency is more frequent than inborn errors of metabolism included in NBS panels. Treatment of vitamin B 12 deficiency is easy, and additional benefits can be achieved for previously undiagnosed affected mothers. This supports inclusion of vitamin B 12 deficiency into NBS but also stresses the need for increased awareness of vitamin B 12 deficiency in caregivers of pregnant women., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Newborn screening (NBS) in Germany currently includes 15 target disorders. Recent diagnostic improvements suggest an extension of the screening panel., Methods: Since August 2016, a prospective study evaluating 26 additional target disorders (25 metabolic disorders and vitamin B 12 -deficiency) in addition to the German screening panel is performed at the Newborn Screening Center Heidelberg. First-tier results from tandem-MS screening are complemented by second-tier strategies for 15 of the additional target disorders. NBS results of seven patients diagnosed symptomatically with one of the additional target disorders by selective screening since August 2016 are retrospectively evaluated., Results: Over a 13-month period, 68,418 children participated in the study. Second-tier analyses were performed in 5.4% of samples. Only 59 (0.1%) of study participants had abnormal screening results for one of the additional target disorders. Target disorders from the study panel were confirmed in 12 children: 1 3-hydroxy-3-methylglutaryl coenzyme A (CoA)-lyase deficiency, 1 citrullinemia type I, 1 multiple acyl-CoA dehydrogenase-deficiency, 1 methylenetetrahydrofolate reductase-deficiency, and 8 children with maternal vitamin B 12 -deficiency. In addition, six of seven patients diagnosed symptomatically outside the study with one of the target disorders would have been identified by the study strategy in their NBS sample., Conclusions: Within 13 months, the study "Newborn Screening 2020" identified additional 12 children with treatable conditions while only marginally increasing the recall rate by 0.1%. Maternal vitamin B 12 -deficiency was the most frequent finding. Even more children could benefit from screening for the additional target disorders by extending the NBS panel for Germany and/or other countries.