{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:23:36Z","timestamp":1783995816798,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2021YFC2700705"],"award-info":[{"award-number":["2021YFC2700705"]}]},{"name":"National Key Research and Development Program of China","award":["BYSYDL2022008"],"award-info":[{"award-number":["BYSYDL2022008"]}]},{"name":"Peking University Third Hospital Clinical Queue Construction Project","award":["2021YFC2700705"],"award-info":[{"award-number":["2021YFC2700705"]}]},{"name":"Peking University Third Hospital Clinical Queue Construction Project","award":["BYSYDL2022008"],"award-info":[{"award-number":["BYSYDL2022008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: The clinical characteristics and outcomes of hemolytic disease of the newborn (HDN) caused by irregular antibodies remain unclear. Herein, we analyzed the clinical features and prognosis of HDN. Methods: Children admitted to our institution between June 2009 and December 2022 with a definite diagnosis of HDN were evaluated. Patients with irregular antibodies were matched in a 1:3 ratio to those with ABO incompatibility. Children with confirmed Rh-incompatibility hemolytic disease were divided into the RhD subgroup (hemolysis induced by Rh anti-D) and the non-RhD group (hemolysis induced by other Rh antibodies). Results: The irregular antibody and ABO incompatibility group included 32 and 96 patients, respectively. Compared to the ABO incompatibility group, the irregular antibody group showed earlier jaundice; higher incidence of liver and spleen enlargement and anemia; higher direct antiglobulin test (DAT) positivity; earlier and more severe anemia; higher rates of enhanced phototherapy, blood transfusion, and blood exchange; and longer hospital stay (all p &lt; 0.05). Compared to the non-RhD group, the RhD subgroup showed an earlier occurrence of jaundice and a higher incidence of liver and spleen enlargement (both p &lt; 0.05). The multiple irregular antibody subgroup further showed earlier occurrence of jaundice and a higher rate of enhanced phototherapy, blood transfusion, and blood exchange than the single-antibody group (both p &lt; 0.05). Conclusions: HDN caused by irregular red blood cell antibodies is rare, but clinical manifestations are serious. It is important to pay attention to the screening of irregular antibodies during pregnancy, to strengthen monitoring, and to provide intrauterine treatment and early intervention as necessary.<\/jats:p>","DOI":"10.3390\/children11121409","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T04:46:11Z","timestamp":1732164371000},"page":"1409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Characteristics and Prognosis of Hemolytic Disease of the Newborn Caused by Irregular Antibodies: A 13-Year Retrospective Analysis"],"prefix":"10.3390","volume":"11","author":[{"given":"Hui","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongling","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3275-1461","authenticated-orcid":false,"given":"Weiwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"ref_1","unstructured":"International Society of Blood Transfusion (2023, January 26). Red Cell Immunogenetics and Blood Group Terminology. Available online: https:\/\/www.isbtweb.org\/isbt-working-parties\/rcibgt.html."},{"key":"ref_2","first-page":"44","article-title":"Research progress in immune hemolytic disease of the fetus and newborn","volume":"1","author":"Yuanjun","year":"2020","journal-title":"Chin. J. Perinat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1080\/17474086.2022.2138853","article-title":"Identification and management of fetal anemia due to hemolytic disease","volume":"15","author":"Zwiers","year":"2022","journal-title":"Expert Rev. Hematol."},{"key":"ref_4","unstructured":"Neonatology group of the pediatric society of the Chinese Medical Association, editorial board of the Chinese journal of pediatrics (2014). Expert consensus on the diagnosis and treatment of neonatal hyperbilirubinemia. Chin. J. Pediatr., 52, 745\u2013748."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"(2000). Noninvasive diagnosis of fetal anemia by Doppler ultrasonography. N. Engl. J. Med., 343, 66\u201368. author reply 67\u201368.","DOI":"10.1056\/NEJM200007063430114"},{"key":"ref_6","first-page":"1330","article-title":"Investigation and analysis of non-ABO hemolytic disease of the newborn","volume":"29","author":"Zheng","year":"2021","journal-title":"J. Exp. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Alsaleem, M. (2020). Intravenous immune globulin uses in the fetus and neonate: A review. Antibodies, 9.","DOI":"10.3390\/antib9040060"},{"key":"ref_8","first-page":"986","article-title":"Research on the correlation between intravenous immunoglobulin therapy for hemolytic disease of the newborn and the incidence of necrotizing enterocolitis in full-term infants","volume":"20","author":"Li","year":"2021","journal-title":"J. Clin. Exp. Med."},{"key":"ref_9","first-page":"CD3313","article-title":"Immunoglobulin for alloimmune hemolytic disease in neonates","volume":"3","author":"Zwiers","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1080\/17474086.2017.1331124","article-title":"Neonatal management and outcome in alloimmune hemolytic disease","volume":"10","author":"Ree","year":"2017","journal-title":"Expert Rev. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1002\/pd.5674","article-title":"Red cell alloimmunization: A 2020 update","volume":"40","author":"Castleman","year":"2020","journal-title":"Prenat. Diagn."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1111\/trf.15154","article-title":"Identification of red blood cell antibodies in maternal breast milk implicated in prolonged hemolytic disease of the fetus and newborn","volume":"59","author":"Leonard","year":"2019","journal-title":"Transfusion"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1111\/trf.14171","article-title":"Persistent hemolytic disease of the fetus and newborn (HDFN) associated with passive acquisition of anti-D in maternal breast milk","volume":"57","author":"Li","year":"2017","journal-title":"Transfusion"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.tjog.2022.04.006","article-title":"Polyhydramnios as a sole ultrasonographic finding for detecting fetal hemolytic anemia caused by anti-c alloimmunization","volume":"61","author":"Wang","year":"2022","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/trf.16252","article-title":"Hemolytic disease and reticulocytopenia of the newborn attributable to maternal immunoglobulin G anti-M reacting optimally at cold temperatures","volume":"61","author":"Andersen","year":"2021","journal-title":"Transfusion"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1111\/trf.16350","article-title":"Hyporegenerative anemia in anti-M-associated hemolytic disease of the fetus","volume":"61","author":"Li","year":"2021","journal-title":"Transfusion"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.mjafi.2021.05.004","article-title":"Early-onset hypoproliferative anemia in an intrauterine-transfused neonate with severe Rh hemolytic disease","volume":"79","author":"Subramaniyan","year":"2023","journal-title":"Med. J. Armed Forces India"},{"key":"ref_18","first-page":"267","article-title":"Research on the role of reticulocyte count in guiding IVIG therapy for ABO hemolytic disease of the newborn","volume":"42","author":"Duan","year":"2021","journal-title":"Sichuan Med. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.2174\/1871530321666201229152019","article-title":"Study of cord blood levels of erythropoietin, bilirubin and reticulocyte count as early predictors of neonatal hyperbilirubinemia","volume":"21","author":"Elfarargy","year":"2021","journal-title":"EMIDDT"},{"key":"ref_20","first-page":"393","article-title":"Application value of reticulocyte parameters in the treatment of hemolytic disease of the newborn","volume":"33","author":"Yang","year":"2018","journal-title":"Lab. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3233\/CH-221388","article-title":"Value of red cell distribution width-to-platelet ratio as a predictor for morbidity and mortality in neonatal intensive care unit","volume":"81","author":"Wang","year":"2022","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4274\/tjod.galenos.2021.68822","article-title":"The combined effect of anti-D and non-D Rh antibodies in maternal alloimmunization","volume":"18","year":"2021","journal-title":"Turk. J. Obstet. Gynecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102958","DOI":"10.1016\/j.transci.2020.102958","article-title":"Effect of multiple maternal red cell alloantibodies on the occurrence and severity of hemolytic disease of the fetus and newborn","volume":"60","author":"Singh","year":"2021","journal-title":"Transfus. Apher. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1056\/NEJMe068071","article-title":"Diagnosing hemolytic disease of the fetus\u2014Time to put the needles away?","volume":"355","author":"Moise","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1182\/asheducation-2009.1.185","article-title":"Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn","volume":"2009","author":"Brinc","year":"2009","journal-title":"Hematology"},{"key":"ref_26","first-page":"28","article-title":"Expert consensus on laboratory testing for hemolytic disease of the fetus and newborn","volume":"20\u201323","author":"Li","year":"2021","journal-title":"J. Clin. Transfus. Lab. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.4049\/jimmunol.1601736","article-title":"Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion","volume":"198","author":"Arthur","year":"2017","journal-title":"J. Immunol."},{"key":"ref_28","unstructured":"Shao, X., Ye, H., and Qiu, X. (2019). Practical Neonatology, People\u2019s Medical Publishing House. [5th ed.]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1182\/asheducation-2015.1.146","article-title":"Hemolytic disease of the fetus and newborn: Managing the mother, fetus, and newborn","volume":"2015","author":"Delaney","year":"2015","journal-title":"Hematology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0140-6736(88)90466-7","article-title":"What is the best predictor of the severity of ABO-hemolytic disease of the newborn?","volume":"44","author":"Brouwers","year":"1988","journal-title":"Lancet"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/11\/12\/1409\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:36:35Z","timestamp":1760114195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/11\/12\/1409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,21]]},"references-count":30,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["children11121409"],"URL":"https:\/\/doi.org\/10.3390\/children11121409","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,21]]}}}