{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:03:24Z","timestamp":1760144604342,"version":"build-2065373602"},"reference-count":67,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>This retrospective cohort study evaluates the safety and efficacy of replacement therapy with regard to pregnancy outcomes in hemophilia carriers. Hemophilia carriers face elevated bleeding risks during pregnancy, necessitating meticulous management, including replacement therapy with clotting factors. This research examines the records of 64 pregnant hemophilia carriers at King Fahad Medical City, Riyadh, from January 2010 to December 2023, analyzing their demographic details, hemophilia type and severity, replacement therapy specifics, and pregnancy outcomes. The study found that 62.5% of the participants had hemophilia A, with 43.8% categorized as severe. Most subjects (87.5%) received recombinant factor VIII at a median dosage of 30 IU\/kg weekly. Adverse pregnancy outcomes included gestational hypertension (15.6%), preterm labor (18.8%), and postpartum hemorrhage (12.5%). The cesarean section rate was 28.1%. Neonatal outcomes were generally favorable, with median birth weights at 3100 g and mean Apgar scores of 8.2 and 9.1 at 1 and 5 min, respectively. Logistic regression analysis revealed no significant association between adverse events and therapy type or dosage, though a trend towards significance was noted with once-weekly administration (p = 0.082). The study concludes that replacement therapy is a viable method for managing hemophilia in pregnant carriers, leading to generally favorable maternal and neonatal outcomes. However, it underscores the importance of individualized treatment plans and close monitoring to effectively manage the risks associated with hemophilia during pregnancy.<\/jats:p>","DOI":"10.3390\/life14050623","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:59:37Z","timestamp":1715677177000},"page":"623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Replacement Therapy on Pregnancy Outcomes in Hemophilia Carriers: A Historical Cohort Study in Saudi Arabia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2564-8113","authenticated-orcid":false,"given":"Ebtisam","family":"Bakhsh","sequence":"first","affiliation":[{"name":"Internal Medicine Department, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 11564, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ijbiomac.2018.06.084","article-title":"Advancement in the Treatment of Haemophilia","volume":"118","author":"Bhardwaj","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/S0140-6736(03)13405-8","article-title":"Haemophilias A and B","volume":"361","author":"Pasi","year":"2003","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-021-00278-x","article-title":"Haemophilia","volume":"7","author":"Berntorp","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.mjafi.2011.12.007","article-title":"Factor IX Deficiency (Christmas Disease)","volume":"68","author":"Philip","year":"2012","journal-title":"Med. J. Armed Forces India"},{"key":"ref_5","unstructured":"Dunn, A.L. (2013). Transfusion Medicine and Hemostasis, Elsevier."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.blre.2019.03.002","article-title":"Factor VIII: Long-Established Role in Haemophilia A and Emerging Evidence beyond Haemostasis","volume":"35","author":"Recht","year":"2019","journal-title":"Blood Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.3324\/haematol.2019.221093","article-title":"Hemophilia A and B: Molecular and Clinical Similarities and Differences","volume":"104","author":"Castaman","year":"2019","journal-title":"Haematologica"},{"key":"ref_8","first-page":"e11216","article-title":"Skewed Inactivation of X Chromosome: A Cause of Hemophilia Manifestation in Carrier Females","volume":"12","author":"Shoukat","year":"2020","journal-title":"Cureus"},{"key":"ref_9","unstructured":"Mensink, K.A., and Highsmith, W.E. (2010). Essential Concepts in Molecular Pathology, Elsevier."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1055\/a-1945-9429","article-title":"Insights into the Molecular Genetic of Hemophilia A and Hemophilia B: The Relevance of Genetic Testing in Routine Clinical Practice","volume":"42","author":"Pezeshkpoor","year":"2022","journal-title":"Hamostaseologie"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1750-1172-5-14","article-title":"VD Expression of the Disease on Female Carriers of X-Linked Lysosomal Disorders: A Brief Review","volume":"5","author":"Pinto","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e5456","DOI":"10.1097\/MD.0000000000005456","article-title":"The Prevalence of Factor VIII and IX Inhibitors among Saudi Patients with Hemophilia","volume":"96","author":"Owaidah","year":"2017","journal-title":"Medicine"},{"key":"ref_13","first-page":"19","article-title":"Epidemiology & Social Costs of Haemophilia in India","volume":"140","author":"Kar","year":"2014","journal-title":"Indian J. Med. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gavriilaki, E., Huang, C.-L., and Nayak, L. (2022). Editorial: Women in Science\u2014Hematology 2021. Front. Med., 9.","DOI":"10.3389\/fmed.2022.926204"},{"key":"ref_15","first-page":"004695801984528","article-title":"Epidemiological Profile of Hemophilia in Baghdad-Iraq","volume":"56","author":"Kadhim","year":"2019","journal-title":"Inq. J. Health Care Organ. Provis. Financ."},{"key":"ref_16","first-page":"11","article-title":"Clinical Profile of Adult Hemophilia Patients with Special Reference to FISH and WFHPE Score: An Observational Cross-Sectional Study","volume":"71","author":"Shastri","year":"2023","journal-title":"J. Assoc. Physicians India"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1177\/1753495X15624307","article-title":"Update on Inherited Disorders of Haemostasis and Pregnancy","volume":"9","author":"Lavee","year":"2016","journal-title":"Obstet. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E246","DOI":"10.1503\/cjs.005922","article-title":"Preoperative Diagnosis and Management of Inherited Bleeding Disorders in Female Adolescents and Adults","volume":"66","author":"Wilson","year":"2023","journal-title":"Can. J. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1111\/jth.14825","article-title":"The Experiences and Attitudes of Hemophilia Carriers around Pregnancy: A Qualitative Systematic Review","volume":"18","author":"Punt","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.hoc.2021.07.007","article-title":"Acquired Hemophilia A","volume":"35","author":"Pai","year":"2021","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Shaban, M.M., Sharaa, H.M., Amer, F.G.M., and Shaban, M. (2024). Effect of Digital Based Nursing Intervention on Knowledge of Self-Care Behaviors and Self-Efficacy of Adult Clients with Diabetes. BMC Nurs., 23.","DOI":"10.1186\/s12912-024-01787-2"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1097\/AOG.0000000000005083","article-title":"Von Willebrand Disease, Hemophilia, and Other Inherited Bleeding Disorders in Pregnancy","volume":"141","author":"Pacheco","year":"2023","journal-title":"Obstet. Gynecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3329\/jhpn.v30i2.11294","article-title":"Maternal Morbidity and Disability and Their Consequences: Neglected Agenda in Maternal Health","volume":"30","author":"Koblinsky","year":"2012","journal-title":"J. Health Popul. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"CMPed.S40070","DOI":"10.4137\/CMPed.S40070","article-title":"Intrauterine Growth Restriction: Antenatal and Postnatal Aspects","volume":"10","author":"Sharma","year":"2016","journal-title":"Clin. Med. Insights Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1365-2516.2009.02142.x","article-title":"The Optimal Mode of Delivery for the Haemophilia Carrier Expecting an Affected Infant Is Caesarean Delivery","volume":"16","author":"James","year":"2010","journal-title":"Haemophilia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.2147\/IJWH.S273043","article-title":"Managing Pregnant Women with Hemophilia and von Willebrand Disease: How Do We Provide Optimum Care and Prevent Complications?","volume":"14","author":"Janbain","year":"2022","journal-title":"Int. J. Women\u2019s Health"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Okaygoun, D., Oliveira, D.D., Soman, S., and Williams, R. (2021). Advances in the Management of Haemophilia: Emerging Treatments and Their Mechanisms. J. Biomed. Sci., 28.","DOI":"10.1186\/s12929-021-00760-4"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2147\/BTT.S252580","article-title":"Recent Advances in the Treatment of Hemophilia: A Review","volume":"15","author":"Marchesini","year":"2021","journal-title":"Biol. Targets Ther."},{"key":"ref_29","first-page":"575","article-title":"Principles of Treatment and Update of Recommendations for the Management of Haemophilia and Congenital Bleeding Disorders in Italy","volume":"12","author":"Rocino","year":"2014","journal-title":"Blood Transfus."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9759","DOI":"10.1080\/14767058.2022.2051699","article-title":"Management and Outcomes of Mild Hemophiliacs and Hemophilia Carriers during Pregnancy and Peripartum Period: A Hemophilia Treatment Center Experience in the United States","volume":"35","author":"Lim","year":"2024","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1055\/s-0042-1758117","article-title":"Planning Pregnancy and Birth in Women with Inherited Bleeding Disorders","volume":"49","author":"Malinowski","year":"2023","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/14712598.2022.2002842","article-title":"Hemophilia A Gene Therapy: Current and next-Generation Approaches","volume":"22","author":"Pipe","year":"2022","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Merch\u00e1n, E.C., De Pablo-Moreno, J.A., and Liras, A. (2021). Gene Therapy in Hemophilia: Recent Advances. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147647"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/hematology.2019000007","article-title":"Gene Therapy for Hemophilia","volume":"2019","author":"Nathwani","year":"2019","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1182\/blood.2019000964","article-title":"How I Manage Pregnancy in Carriers of Hemophilia and Patients with von Willebrand Disease","volume":"136","author":"Leebeek","year":"2020","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.bjae.2020.10.003","article-title":"Venous Thromboembolism in Pregnancy\u2014Diagnosis, Management, and Treatment","volume":"21","author":"Kearsley","year":"2021","journal-title":"BJA Educ."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bakhsh, E., Shaban, M., Al Subaie, S., Al Moshary, M., and AlSheef, M. (2023). Exploring the Clinical Efficacy of Venous Thromboembolism Management in Saudi Arabian Hospitals: An Insight into Patient Outcomes. J. Pers. Med., 13.","DOI":"10.3390\/jpm13040612"},{"key":"ref_38","first-page":"112","article-title":"Patient Blood Management in Obstetrics: Prevention and Treatment of Postpartum Haemorrhage. A NATA Consensus Statement","volume":"17","author":"Stensballe","year":"2019","journal-title":"Blood Transfus."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bakhsh, E., Alkhaldi, M., and Shaban, M. (2023). Exploring the Link between Maternal Hematological Disorders during Pregnancy and Neurological Development in Newborns: Mixed Cohort Study. Life, 13.","DOI":"10.3390\/life13102014"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1111\/j.1365-2516.2012.02909.x","article-title":"Guidelines for the Management of Hemophilia","volume":"19","author":"Srivastava","year":"2013","journal-title":"Haemophilia"},{"key":"ref_41","unstructured":"Kaya, Z., Safarian, N., Pezeshkpoor, B., and Adcock, D.M. (2023). Congenital Bleeding Disorders, Springer International Publishing."},{"key":"ref_42","unstructured":"Hayward, C.P.M. (2018). Hematology, Elsevier."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/ejh.13193","article-title":"Inhibitors in Haemophilia A and B: Management of Bleeds, Inhibitor Eradication and Strategies for Difficult-to-treat Patients","volume":"102","author":"Ljung","year":"2019","journal-title":"Eur. J. Haematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/bjh.15053","article-title":"How I Manage Patients with Inherited Haemophilia A and B and Factor Inhibitors","volume":"180","author":"Ljung","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_45","first-page":"292","article-title":"Plasma-Derived versus Recombinant Factor VIII Concentrates for the Treatment of Haemophilia A: Recombinant Is Better","volume":"8","author":"Franchini","year":"2010","journal-title":"Blood Transfus."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"183","DOI":"10.2147\/JBM.S6885","article-title":"Treatment of Hemophilia: A Review of Current Advances and Ongoing Issues","volume":"1","author":"Coppola","year":"2010","journal-title":"J. Blood Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/j.1365-2125.2010.03899.x","article-title":"Inhibitors of Propagation of Coagulation (Factors VIII, IX and XI): A Review of Current Therapeutic Practice","volume":"72","author":"Franchini","year":"2011","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Godby, R.C., Gangaraju, R., May, J.E., Kommalapati, A., Paschal, R., and Marques, M.B. (2022). Congenital and Acquired Disorders of Secondary Hemostasis. Ann. Blood, 7, Available online: https:\/\/aob.amegroups.org\/article\/view\/6852\/html.","DOI":"10.21037\/aob-21-78"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"391","DOI":"10.2147\/TCRM.S4412","article-title":"Recombinant Factor VIII in the Management of Hemophilia A: Current Use and Future Promise","volume":"5","author":"Powell","year":"2009","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"fmac039","DOI":"10.1093\/tropej\/fmac039","article-title":"Twice Weekly Vs. Thrice Weekly Low-Dose Prophylactic Factor VIII Therapy in Children with Hemophilia A: An Open Label Randomized Trial","volume":"68","author":"Gomber","year":"2022","journal-title":"J. Trop. Pediatr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"545","DOI":"10.3324\/haematol.2019.232132","article-title":"Hemophilia Therapy: The Future Has Begun","volume":"105","author":"Mannucci","year":"2020","journal-title":"Haematologica"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1182\/blood-2006-11-056317","article-title":"Recombinant versus Plasma-Derived Factor VIII Products and the Development of Inhibitors in Previously Untreated Patients with Severe Hemophilia A: The CANAL Cohort Study","volume":"109","author":"Gouw","year":"2007","journal-title":"Blood"},{"key":"ref_53","first-page":"e26015","article-title":"The Impact of Recombinant Versus Plasma-Derived Factor VIII Concentrates on Inhibitor Development in Previously Untreated Patients with Hemophilia A: A 2021 Update of a Systematic Review and Meta-Analysis","volume":"14","author":"Kohar","year":"2022","journal-title":"Cureus"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41392-023-01619-w","article-title":"Drug-Microbiota Interactions: An Emerging Priority for Precision Medicine","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/rth2.12301","article-title":"Hemophilia Prophylaxis Adherence and Bleeding Using a Tailored, Frequency-escalated Approach: The Canadian Hemophilia Primary Prophylaxis Study","volume":"4","author":"Dover","year":"2020","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1111\/j.1538-7836.2006.01953.x","article-title":"Tailored Prophylaxis in Severe Hemophilia A: Interim Results from the First 5 Years of the Canadian Hemophilia Primary Prophylaxis Study","volume":"4","author":"Feldman","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/j.1365-2516.2008.01950.x","article-title":"Replacement Therapy for Invasive Procedures in Patients with Haemophilia: Literature Review, European Survey and Recommendations","volume":"15","author":"Hermans","year":"2009","journal-title":"Haemophilia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"204062072311658","DOI":"10.1177\/20406207231165857","article-title":"Considerations for Shared Decision Management in Previously Untreated Patients with Hemophilia A or B","volume":"14","author":"Astermark","year":"2023","journal-title":"Ther. Adv. Hematol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"668447","DOI":"10.3389\/fendo.2021.668447","article-title":"Prevalence of Gestational Diabetes Mellitus in the Middle East and North Africa, 2000-2019: A Systematic Review, Meta-Analysis, and Meta-Regression","volume":"12","author":"Abdo","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2147\/JBM.S43734","article-title":"Barriers and Perceived Limitations to Early Treatment of Hemophilia","volume":"4","author":"Saxena","year":"2013","journal-title":"J. Blood Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.3324\/haematol.2018.209619","article-title":"Mode of Delivery in Hemophilia: Vaginal Delivery and Cesarean Section Carry Similar Risks for Intracranial Hemorrhages and Other Major Bleeds","volume":"104","author":"Andersson","year":"2019","journal-title":"Haematologica"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1365-2516.2010.02238.x","article-title":"What Is the Optimal Mode of Delivery for the Haemophilia Carrier Expecting an Affected Infant-vaginal Delivery or Caesarean Delivery?","volume":"16","author":"Madan","year":"2010","journal-title":"Haemophilia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/job.4030020205","article-title":"The Measurement of Experienced Burnout","volume":"2","author":"Maslach","year":"1981","journal-title":"J. Organ. Behav."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"29S","DOI":"10.1177\/1076029618807583","article-title":"A Practical Guide to the Management of the Fetus and Newborn with Hemophilia","volume":"24","author":"Moorehead","year":"2018","journal-title":"Clin. Appl. Thromb."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6338","DOI":"10.4081\/pr.2015.6338","article-title":"Neonatal Hemophilia: A Rare Presentation","volume":"7","author":"Ferreira","year":"2015","journal-title":"Pediatr. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1182\/asheducation-2016.1.663","article-title":"Treatment of Rare Factor Deficiencies in 2016","volume":"2016","author":"Peyvandi","year":"2016","journal-title":"Hematology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1161\/01.CIR.103.24.2994","article-title":"Guide to Anticoagulant Therapy: Heparin","volume":"103","author":"Hirsh","year":"2001","journal-title":"Circulation"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/5\/623\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:40:58Z","timestamp":1760107258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/5\/623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,11]]},"references-count":67,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["life14050623"],"URL":"https:\/\/doi.org\/10.3390\/life14050623","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2024,5,11]]}}}