{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:28:58Z","timestamp":1792718938141,"version":"4.5.0"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>The currently recommended technologies of HPLC and isoelectric focusing for newborn blood spot screening for sickle cell disease (SCD) identify both the disease and carrier states, resulting in large numbers of infants being followed up unnecessarily. Analysis of blood spot tryptic peptides performed by using tandem mass spectrometry (MS\/MS) is an alternative technology to detect hemoglobin (Hb) variant disorders.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We analyzed 2154 residual newborn blood spots and 675 newborn blood spots from infants with Hb variants by using MS\/MS after trypsin digestion. Screening cutoffs were developed by using the ratio between the variant peptide\u2013to\u2013wild-type peptide abundance for HbS, C, DPunjab, OArab, Lepore, and E peptides. A postanalytical data analysis protocol was developed using these cutoffs to detect only the disease states of SCD and not to identify carrier states. A parallel study of 13 249 newborn blood spots from a high-prevalence SCD area were analyzed by both MS\/MS and HPLC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Screening cutoffs developed distinguished the infants with the disease states of SCD, infants who were carriers of SCD, and infants with normal Hb. In the parallel study no false-negative results were identified, and all clinically relevant cases were correctly identified using the MS\/MS protocol. Unblinding the data revealed a total of 328 carrier infants that were successfully excluded by the protocol.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>The screening protocol developed correctly identified infants with the disease states of SCD. Furthermore, large numbers of sickle cell carrier infants were successfully not identified, thereby avoiding unnecessary follow-up testing and referral for genetic counseling.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1373\/clinchem.2013.210948","type":"journal-article","created":{"date-parts":[[2013,10,25]],"date-time":"2013-10-25T08:20:01Z","timestamp":1382689201000},"page":"373-380","source":"Crossref","is-referenced-by-count":41,"title":["Newborn Blood Spot Screening for Sickle Cell Disease by Using Tandem Mass Spectrometry: Implementation of a Protocol to Identify Only the Disease States of Sickle Cell Disease"],"prefix":"10.1093","volume":"60","author":[{"given":"Stuart J","family":"Moat","sequence":"first","affiliation":[{"name":"Wales Newborn Screening Laboratory, Department of Medical Biochemistry, Immunology & Toxicology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Rees","sequence":"first","affiliation":[{"name":"Wales Newborn Screening Laboratory, Department of Medical Biochemistry, Immunology & Toxicology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"King","sequence":"first","affiliation":[{"name":"Department of Haematology, University Hospital Wales, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeboye","family":"Ifederu","sequence":"first","affiliation":[{"name":"Newborn Screening Laboratory, Department of Chemical Pathology, Great Ormond Street Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Harvey","sequence":"first","affiliation":[{"name":"Newborn Screening Laboratory, Department of Chemical Pathology, Great Ormond Street Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Hall","sequence":"first","affiliation":[{"name":"Newborn Screening & Biochemical Genetics, Birmingham Children's Hospital, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoff","family":"Lloyd","sequence":"first","affiliation":[{"name":"Wales Newborn Screening Laboratory, Department of Medical Biochemistry, Immunology & Toxicology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Morrell","sequence":"first","affiliation":[{"name":"Directorate for Public Health and Health Professions, Welsh Government, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Hillier","sequence":"first","affiliation":[{"name":"Screening Division, Public Health Wales, Cathedral Road, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,1]]},"reference":[{"key":"2020022705433216500_B1","unstructured":"National Health Service (NHS) Sickle Cell and Thalassaemia Screening Programme. Sickle cell and thalassaemia: handbook for laboratories, third edition, 2012. http:\/\/sct.screening.nhs.uk\/getdata.php?id=10756 (Accessed May 2013)."},{"key":"2020022705433216500_B2","unstructured":"NHS Sickle Cell and Thalassaemia Screening Programme. Data report 2011\/12: trends and performance analysis. http:\/\/sct.screening.nhs.uk\/data-report (Accessed May 2013)."},{"key":"2020022705433216500_B3","article-title":"Screening for hemoglobinopathies in newborns: reaffirmation update for the U.S. Preventive Services Task Force","author":"Lin","year":"2007"},{"issue":"4","key":"2020022705433216500_B4","first-page":"CD003859","article-title":"Disclosing to parents newborn carrier status identified by routine blood spot screening","author":"Oliver","year":"2004","journal-title":"Cochrane Database Syst Rev"},{"key":"2020022705433216500_B5","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/j.1365-2141.2005.05646.x","article-title":"Rapid and specific detection of clinically significant haemoglobinopathies using electrospray mass spectrometry-mass spectrometry","volume":"2130","author":"Daniel","year":"2005","journal-title":"Br J Haematol"},{"key":"2020022705433216500_B6","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1006\/bcmd.2001.0430","article-title":"Rapid identification of hemoglobin variants by electrospray ionization mass spectrometry","volume":"27","author":"Wild","year":"2001","journal-title":"Blood Cells Mol Dis"},{"key":"2020022705433216500_B7","unstructured":"Daniel\n              YA\n            , TurnerC, FarrarL, DaltonRN. A comparison of IEF and MSMS for clinical hemoglobinopathy screening in 40,000 newborns. 50th American Society of Hematology annual meeting; 2008 Dec 6\u20139; San Francisco, CA. http:\/\/ash.confex.com\/ash\/2008\/webprogram\/Paper9728.html (Accessed May 2013)."},{"key":"2020022705433216500_B8","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1373\/clinchem.2008.106369","article-title":"Newborn screening for sickle cell disease using tandem mass spectrometry","volume":"54","author":"Boemer","year":"2008","journal-title":"Clin Chem"},{"key":"2020022705433216500_B9","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.cca.2011.04.031","article-title":"3-years experience review of neonatal screening for haemoglobin disorders using tandem mass spectrometry","volume":"412","author":"Boemer","year":"2011","journal-title":"Clin Chim Acta"},{"key":"2020022705433216500_B10","doi-asserted-by":"crossref","unstructured":"The Human Genetics Commission. Making babies: reproductive decisions and genetic technologies, 2006. http:\/\/centronuclear.org.uk\/theinformationpoint\/documents\/research\/articles\/making_babies.pdf (Accessed August 2013).","DOI":"10.1515\/9783110186406.485"},{"key":"2020022705433216500_B11","unstructured":"SpOtOn Clinical Diagnostics. Protocol for haemoglobinopathy screening using mass spectrometry. http:\/\/spotoncd.com\/spoton_protocol_for_haemoglobinopathy_screening.pdf (Accessed May 2013)."},{"key":"2020022705433216500_B12","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1373\/clinchem.2007.088682","article-title":"Quantification of hemoglobin A2 by tandem mass spectrometry","volume":"53","author":"Daniel","year":"2007","journal-title":"Clin Chem"},{"key":"2020022705433216500_B13","unstructured":"UK National Screening Committee (UK NSC). Note of the meeting held on March 20th 2013 and UK NSC March 2013 briefing. http:\/\/www.screening.nhs.uk\/meetings. (Accessed August 2013)."}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/60\/2\/373\/32662140\/clinchem0373.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/60\/2\/373\/32662140\/clinchem0373.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T10:44:34Z","timestamp":1582800274000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/60\/2\/373\/5621732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,1]]},"references-count":13,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,2,1]]},"published-print":{"date-parts":[[2014,2,1]]}},"URL":"https:\/\/doi.org\/10.1373\/clinchem.2013.210948","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,2,1]]},"published":{"date-parts":[[2014,2,1]]}}}