{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:10:51Z","timestamp":1747185051228,"version":"3.40.5"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Haemophilias are X\u2010linked inherited bleeding disorders, due to <jats:italic>de novo<\/jats:italic> F8\/F9 gene variants in 30\u201350% of cases. The identification of causative variant in index cases (IC) is crucial for genetic counselling in related women. Over the last 20 years the Emilia\u2010Romagna Regional Haemophilia Registry documented high proportions of sporadic severe haemophilia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To clarify if carriers\u2019 reproductive choices influence the sporadic\/familial <jats:italic>ratio<\/jats:italic> of severe haemophilia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genetic counselling and genotyping in 221 relatives of severe IC were retrospectively reviewed, retrieving reproductive choices and pregnancy history of childbearing\u2010age carriers from familial and sporadic pedigrees and according to the IC degree of relationship (mothers, daughters, II\/other).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Carriers\u2019 identification rates were lower in sporadic women and in other\u2010degree relatives. Among childbearing age women (n\u00a0=\u00a0140), carriers were 37\/48 (77%) and 57\/92 (62%) of familial and sporadic relatives, respectively. Forty\u2010five\/57 sporadic carriers experienced 67 pregnancies, while 21\/37 familial carriers had 39 pregnancies (four voluntary terminations), with a significantly higher number of affected sons in the former (40\/67\u00a0vs. 12\/35, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.025). Prenatal diagnosis was chosen by 40% and 47% of sporadic and familial aware carriers, respectively. Sporadic mothers often avoided further pregnancies (17\/38, 45%) after a firstborn affected child, while familial mothers tended to face pregnancies without prenatal approaches (6\/10, 60%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this cohort sporadic offspring account for more than 70% of severe haemophilia cases. This increasing proportion is likely to reflect the influence in reproductive choices of awareness of carriers\u2019 status, particularly in sporadic mothers, and of prenatal diagnosis options.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14490","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T03:54:46Z","timestamp":1642737286000},"page":"308-315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The effect of carriers\u2019 reproductive choices and pregnancy history on sporadic severe haemophilia: A 20\u2010year retrospective study through a regional registry"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6308-6054","authenticated-orcid":false,"given":"Federica","family":"Riccardi","sequence":"first","affiliation":[{"name":"Regional Reference Centre for Inherited Bleeding Disorders University Hospital of Parma  Parma Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3697-706X","authenticated-orcid":false,"given":"Antonio","family":"Coppola","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Inherited Bleeding Disorders University Hospital of Parma  Parma Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1887-0154","authenticated-orcid":false,"given":"Gianna Franca","family":"Rivolta","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Inherited Bleeding Disorders University Hospital of Parma  Parma Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5154-4636","authenticated-orcid":false,"given":"Annalisa","family":"Matichecchia","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Inherited Bleeding Disorders University Hospital of Parma  Parma Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1999-4485","authenticated-orcid":false,"given":"Gabriele","family":"Quintavalle","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Inherited Bleeding Disorders University Hospital of Parma  Parma Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Biasoli","sequence":"additional","affiliation":[{"name":"Haemophilia and Transfusion Centre 'Bufalini\u2019 Hospital  Cesena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3532-8447","authenticated-orcid":false,"given":"Lelia","family":"Valdr\u00e8","sequence":"additional","affiliation":[{"name":"SSD Malattie Emorragiche Congenite IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Piscitelli","sequence":"additional","affiliation":[{"name":"SSD Malattie Emorragiche Congenite IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3268-6786","authenticated-orcid":false,"given":"Antonio","family":"Percesepe","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics University Hospital of Parma  Parma Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3529-6334","authenticated-orcid":false,"given":"Annarita","family":"Tagliaferri","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Inherited Bleeding Disorders University Hospital of Parma  Parma Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_9_2_1","DOI":"10.1016\/S0140-6736(15)01123-X"},{"doi-asserted-by":"publisher","key":"e_1_2_9_3_1","DOI":"10.1111\/j.1365-2516.2006.01397.x"},{"doi-asserted-by":"publisher","key":"e_1_2_9_4_1","DOI":"10.1111\/cge.12709"},{"doi-asserted-by":"publisher","key":"e_1_2_9_5_1","DOI":"10.1111\/j.1365-2516.2007.01623.x"},{"doi-asserted-by":"publisher","key":"e_1_2_9_6_1","DOI":"10.1111\/j.1365-2516.2008.01921.x"},{"issue":"3","key":"e_1_2_9_7_1","first-page":"19","article-title":"Prevalence of sporadic and familial severe hemophilia: has anything changed?","volume":"1","author":"Riccardi F","year":"2012","journal-title":"Haemophilia"},{"unstructured":"Istituto Nazionale di Statistica.https:\/\/www.istat.it\/it\/files\/\/2020\/12\/REPORT\u2010NATALITA\u20102019.pdf. 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