{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:30:06Z","timestamp":1789399806283,"version":"build-2803163510"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Natural Science Foundation Project of Chongqing","award":["cstc2021jcyj-msxmX0003"],"award-info":[{"award-number":["cstc2021jcyj-msxmX0003"]}]},{"name":"Joint project of Chongqing Health Commission and Science and Technology Bureau","award":["2025MSXM031"],"award-info":[{"award-number":["2025MSXM031"]}]},{"name":"Chongqing Fuling District Science and Health Joint Medical Scientific research Project","award":["2023KWLH010"],"award-info":[{"award-number":["2023KWLH010"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["World J Pediatr"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Screening and pre-symptomatic diagnosis in newborns allows early treatment of thalassemia and abnormal hemoglobin (Hb) disorders in childhood. However, there remains a lack of efficient methods to screen for hemoglobinopathies in newborns.\u00a0This study aimed to\u00a0establish a bottom-up mass spectrometry\u00a0(MS)-based method for efficient screening of hemoglobinopathies in newborns using dried blood spot (DBS) samples.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We developed LC\u2013MS methodology using high-performance liquid chromatography (HPLC) combined with high-resolution mass spectrometry (HRMS). DBS samples from patients covering the most common types of hemoglobinopathies and normal controls were collected. We extracted Hb from a 3.2\u00a0mm disc punched from the DBS sample, which was then digested with trypsin to release a series of Hb-specific peptides. Using HPLC\u2013HRMS, we identified disease-related peptides for biomarker design. Using this methodology, we built a prediction model using binary logistic regression to facilitate efficient screening.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>This new method costs less than $1 per test and can process at least 192 samples per batch. Our methodology is fast with a sampling and analysis time of 2.6\u00a0minutes and inter- and intra-assay coefficients of variation below 14.67%. Moreover, we report low limits of quantification for the proteo-specific peptides (0.50\u201360.00\u00a0\u03bcg\/L). No significant matrix effects or carryover were observed. Our method could give reliable results even with DBS samples stored for one month. Prospective application of this method to 2726 newborns identified 87 patients with hemoglobinopathies and achieved high screening sensitivity and specificity for deletional \u03b1-thalassemia (--<jats:sup>SEA<\/jats:sup>) (100.00% and 100.00%), <jats:italic>\u03b2<\/jats:italic>-thalassemia (97.50% and 89.63%) and other abnormal Hb disorders.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We have developed a low-cost, high-throughput method for reliable screening of thalassemia and abnormal Hb disorders in newborns. This could be deployed as a first-line screening test.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s12519-025-00962-y","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T16:45:49Z","timestamp":1756745149000},"page":"889-901","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of a low-cost and high-throughput LC\u2013MS method for newborn screening of thalassemia and abnormal hemoglobin disorders"],"prefix":"10.1007","volume":"21","author":[{"given":"Wen-Xia","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Xin","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Rong","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Xing","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5636-1866","authenticated-orcid":false,"given":"Chao-Wen","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"962_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2023.117685","volume":"552","author":"A Sani","year":"2024","unstructured":"Sani A, Idrees Khan M, Shah S, Tian Y, Zha G, Fan L, et al. 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The paper was handled by the other Editor and has undergone rigrous peer review process. Author Chao-Wen Yu\u00a0was not involved in the journal\u2019s review of, or decisions related to, this manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}},{"value":"This study was approved by the Institutional Ethical Review Boards of the Children\u2019s Hospital of the Chongqing Medical University (No. 2018-64).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}