{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:04:39Z","timestamp":1789016679357,"version":"build-2803163510"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012759","name":"Ohio Department of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012759","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Sickle cell disease (SCD) is a group of related yet genetically complex hemoglobinopathies. Universal newborn screening (NBS) for SCD is performed in the United States and many other nations. Classical, protein-based laboratory methods are often adequate for the diagnosis of SCD but have specific limitations in the context of NBS. A particular challenge is the differentiation of sickle cell anemia (SCA) from the benign condition, compound heterozygosity for HbS and gene-deletion hereditary persistence of fetal hemoglobin (HbS\/HPFH). We describe a sequential cohort of 44 newborns identified over 4.5 years who had molecular genetic testing incorporated into NBS for presumed SCA (an \u201cFS\u201d pattern). The final diagnosis was something other than SCA in six newborns (12%). Three (7%) had HbS\/HPFH. All had a final, correct diagnosis at the time of their first scheduled clinic visit in our center (median 8 weeks of age). None received initial counseling for an incorrect diagnosis. In summary, genetic testing as a component of NBS for SCD is necessary to provide correct genetic counseling and education for all newborns' families at their first visit to a sickle cell center. Genetic testing also permits the use of early, pre-symptomatic hydroxyurea therapy by preventing infants with HbS\/HPFH from receiving unnecessary therapy. We argue that genetic testing should be incorporated into contemporary NBS for SCD.<\/jats:p>","DOI":"10.3389\/fmed.2021.734305","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T06:40:51Z","timestamp":1636526451000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Clinical Utility of the Addition of Molecular Genetic Testing to Newborn Screening for Sickle Cell Anemia"],"prefix":"10.3389","volume":"8","author":[{"given":"Lisa M.","family":"Shook","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deidra","family":"Haygood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles T.","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1136\/bmj.311.7020.1600","article-title":"Improved survival in homozygous sickle cell disease: lessons from a cohort study","volume":"311","author":"Lee","year":"1995","journal-title":"BMJ."},{"key":"B2","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1182\/blood.V86.2.776.bloodjournal862776","article-title":"Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease","volume":"86","author":"Gill","year":"1995","journal-title":"Blood."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.1182\/blood-2009-07-233700","article-title":"Improved survival of children and adolescents with sickle cell disease","volume":"115","author":"Quinn","year":"2010","journal-title":"Blood."},{"key":"B4","doi-asserted-by":"publisher","first-page":"4023","DOI":"10.1182\/blood-2003-11-3758","article-title":"Survival of children with sickle cell disease","volume":"103","author":"Quinn","year":"2004","journal-title":"Blood."},{"key":"B5","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1053\/j.semperi.2015.03.008","article-title":"Newborn screening for sickle cell diseases in the United States: a review of data spanning 2 decades","volume":"39","author":"Therrell","year":"2015","journal-title":"Semin Perinatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3390\/ijns6010007","article-title":"Clinical utility of confirmatory genetic testing to differentiate sickle cell trait from sickle-\u03b2+-thalassemia by newborn screening","volume":"6","author":"Shook","year":"2020","journal-title":"Int J Neonatal Screen."},{"key":"B7","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1080\/03630269.2017.1360336","article-title":"A plea for the newborn diagnosis of Hb S-hereditary persistence of fetal hemoglobin","volume":"41","author":"Serjeant","year":"2017","journal-title":"Hemoglobin."},{"key":"B8","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/j.1365-2141.1982.tb03915.x","article-title":"Post-natal decline of fetal haemoglobin in homozygous sickle cell disease: relationship to parenteral Hb F levels","volume":"52","author":"Mason","year":"1982","journal-title":"Br J Haematol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e27778","DOI":"10.1002\/pbc.27778","article-title":"Hydroxyurea for children with sickle cell anemia: prescribe it early and often","volume":"66","author":"Ware","year":"2019","journal-title":"Pediatr Blood Cancer."},{"key":"B10","unstructured":"National Heart, Lung, and Blood Institute2014"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/j.pcl.2013.09.006","article-title":"Sickle cell disease in childhood: from newborn screening through transition to adult medical care","volume":"60","author":"Quinn","year":"2013","journal-title":"Pediatr Clin N Am."},{"key":"B12","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1002\/ajh.25510","article-title":"Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia","volume":"94","author":"McGann","year":"2019","journal-title":"Am J Hematol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1111\/bjh.17663","article-title":"Early initiation of hydroxyurea (hydroxycarbamide) using individualised, pharmacokinetics-guided dosing can produce sustained and nearly pancellular expression of fetal haemoglobin in children with sickle cell anaemia","volume":"194","author":"Quinn","year":"2021","journal-title":"Brit J Haematol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.734305\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T06:40:55Z","timestamp":1636526455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.734305\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,10]]},"references-count":13,"alternative-id":["10.3389\/fmed.2021.734305"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.734305","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,10]]},"article-number":"734305"}}