{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:02:25Z","timestamp":1790766145760,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004331","name":"Johnson and Johnson","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pregnancy"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Severe fetal anemia developing at \u226424\u00a0weeks gestational age (GA) in pregnancies complicated by early\u2010onset severe hemolytic disease of the fetus and newborn (EOS\u2010HDFN) is managed by intrauterine erythrocyte transfusions (IUTs). Evidence of off\u2010label intravenous immunoglobulin (IVIG) for preventing\/reducing fetal hydrops, fetal anemia, and IUT(s) remains limited to retrospective studies and case series.\u00a0The prospective, global, multicenter, observational CLARITY study characterized standard\u2010of\u2010care management and outcomes for high\u2010risk pregnancies complicated by EOS\u2010HDFN and their offspring at expert referral centers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CLARITY enrolled individuals with singleton pregnancies at \u22658\u00a0weeks GA and high risk for EOS\u2010HDFN, defined by prior severe fetal anemia, fetal hydrops, or stillbirth at \u226424\u00a0weeks GA with indicative fetal\/placental HDFN pathology, and current titers \u226532 anti\u2010Rhesus D (RhD) or \u22654 anti\u2010Kell with a confirmed antigen\u2010positive fetus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 15 pregnant participants, two (13%) achieved the primary endpoint of a live birth at \u226532\u00a0weeks GA without IUT, indicating the absence of clinically relevant fetal anemia and low disease burden. Fourteen (93%) pregnancies resulted in a live birth (median GA, 36\n                      <jats:sup>2\/7<\/jats:sup>\n                      \u00a0weeks; range, 31\n                      <jats:sup>4\/7<\/jats:sup>\n                      \u201338\n                      <jats:sup>0\/7<\/jats:sup>\n                      ), including seven (50%) preterm births and 12 (86%) cesarean deliveries. Thirteen (87%) participants required IUTs (median IUTs\/pregnancy, 4; range, 1\u201311), with median GA at first IUT of 24\n                      <jats:sup>0\/7<\/jats:sup>\n                      \u00a0weeks (range, 13\n                      <jats:sup>0\/7<\/jats:sup>\n                      \u201328\n                      <jats:sup>2\/7<\/jats:sup>\n                      ). One (7%) fetal death occurred at 16\n                      <jats:sup>5\/7<\/jats:sup>\n                      \u00a0weeks, following early IUT (13\n                      <jats:sup>0\/7<\/jats:sup>\n                      \u00a0weeks) and serial IVIG treatment (13\n                      <jats:sup>1\/7<\/jats:sup>\n                      \u201314\n                      <jats:sup>6\/7<\/jats:sup>\n                      \u00a0weeks). IUT complications occurred in four (31%) pregnant participants who received IUTs. In an exploratory, post hoc analysis, eight (53%) pregnant participants received IVIG starting between 10\n                      <jats:sup>6\u20447<\/jats:sup>\n                      and 19\n                      <jats:sup>3\u20447<\/jats:sup>\n                      \u00a0weeks (median administrations\/pregnancy, 12.5; range, 1\u201320); IVIG\u2010related complications were reported in three (38%), and two (25%) met the primary endpoint. Of 14 live\u2010born neonates followed through 12\u00a0weeks of life, three (21%) received exchange transfusion(s), nine (64%) received simple transfusion(s) (one required both types of transfusions), while three (21%) required no transfusions (one required no IUTs during the pregnancy).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Outcomes of this prospective study of high\u2010risk EOS\u2010HDFN pregnant participants and their offspring are consistent with previous retrospective studies, indicating a high risk of early IUT, neonatal transfusions, and fetal\/neonatal morbidity and mortality. The results underscore the unmet medical need for effective treatments for EOS\u2010HDFN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov Identifier: NCT03755128.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pmf2.70352","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:48:15Z","timestamp":1783925295000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of the clinical course of early\u2010onset severe hemolytic disease of the fetus and newborn"],"prefix":"10.1002","volume":"2","author":[{"given":"Dick","family":"Oepkes","sequence":"first","affiliation":[{"name":"Department of Obstetrics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Kenneth J.","family":"Moise","sequence":"additional","affiliation":[{"name":"Dell Medical School The University of Texas at Austin  Austin Texas USA"},{"name":"Comprehensive Fetal Care Center at Dell Children's Medical Center  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-5066","authenticated-orcid":false,"given":"Enrico","family":"Lopriore","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonor","family":"Tiblad","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division Department of Medicine, Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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(Joanne)","family":"Verweij","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Windrim","sequence":"additional","affiliation":[{"name":"Ontario Fetal Centre Mount Sinai Hospital University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav","family":"Pandya","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit University College London Hospitals NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5794-3152","authenticated-orcid":false,"given":"Robert M.","family":"Silver","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Utah School of Medicine  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Emery","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Gynecology, and Reproductive Sciences UPMC Magee\u2010Womens Hospital  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Smoleniec","sequence":"additional","affiliation":[{"name":"Feto\u2010Maternal Unit Liverpool Hospital  Liverpool New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-3651","authenticated-orcid":false,"given":"Olga","family":"Oc\u00f3n\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit San Cecilio University Hospital and ibs.GRANADA  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1247-429X","authenticated-orcid":false,"given":"Rachel K.","family":"Morris","sequence":"additional","affiliation":[{"name":"Fetal Medicine Centre Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"},{"name":"Department of Applied Health Sciences, School of Health Sciences, College of Medicine and Health University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell S.","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine Department of Obstetrics and Gynecology Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Streisand","sequence":"additional","affiliation":[{"name":"Streisand Biomedical Consulting  Wayland Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane D.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Johnson &amp; 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