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Impact of Inherited Bleeding Disorders and Iron Deficiency Anemia on Maternal Bleeding and Other Pregnancy Outcomes: A Population-based Cohort Study from Alberta, Canada

  • Author / Creator
    Alam, Arafat Ul
  • Background: Inherited bleeding disorders are caused by quantitative and qualitative alterations of coagulation proteins or platelets involved in hemostasis. The most frequent inherited bleeding disorders are hemophilia, von Willebrand disease (VWD) and inherited platelet function disorder. Women with inherited bleeding disorders are at increased risk of pregnancy related bleeding, especially postpartum hemorrhage (PPH). In addition, women may develop new onset or worsening of pre-existing iron deficiency (ID) or iron deficiency anemia (IDA).
    Aim: In this population based retrospective cohort study using linked administrative data we aimed to examine 1) the recent trends of PPH in women with inherited bleeding disorders compared with the general population in the province of Alberta, Canada; 2) the impact of inherited bleeding disorders and IDA on pregnancy outcomes; 3) the quality of care in relation to: a) coagulation workup in pregnant women with inherited bleeding disorders and b) rates of ID and IDA screening and correction during pregnancy.
    Methods: We initially developed and validated case definitions for identifying hemophilia A , hemophilia B and VWD from administrative data using a combination of International Classification of Diseases diagnostic codes and coagulation factor levels. Subsequently, we performed two population-based retrospective cohort studies based on linked administrative data. The first study evaluated the trend of PPH in all pregnancies associated with hospitalized live births in Alberta, from 2010-2018 and examined the incidence of PPH in women with bleeding disorders compared with matched controls. Next, we examined the rates of ID and IDA detection and correction in pregnant women with or without bleeding disorders and the independent effect of IDA on pregnancy outcomes during 2014-2017. Multivariable logistic regression was used to compute odds of pregnancy outcomes along with generalized estimating equations to account for multiple pregnancies in the same woman.
    Results: Our case definitions had a sensitivity of 93.7% and specificity of 99.4% for identifying hemophilia A, a sensitivity of 90.9% and specificity of 99.8% for identifying hemophilia B and a sensitivity of 99.2% and specificity of 88.2% for identifying VWD. We identified 311,330 women with a total of 454,400 pregnancies during 2010-2018. The rate of PPH did not have any significant change from 10.13/100 deliveries (95% CI 10.10-10.16) in 2010 to 10.72/100 deliveries (95% CI 10.69-10.75) in 2018 (P for trend =0.35). We identified 93 (0.03%) women with inherited bleeding disorders with a total of 140 pregnancies. We observed increased odds of PPH (odds ratio [OR] 2.3; 95% CI 1.5-3.6), antepartum hemorrhage (OR 2.9; 95% CI 1.5-5.9) and red cell transfusion (OR 2.8; 95% CI 1.1-7.0) in women with bleeding disorders. Only 49.5% pregnancies in women with bleeding disorders had third trimester coagulation factor levels checked. Among the 207,355 pregnancies associated with hospitalized live births from 2014-2017, 36,500 (17.6%) had anemia at least once during pregnancy. Only 1 in 3 pregnancies with anemia had concurrent ferritin screening within the same trimester, and 83% of those had IDA. Inherited bleeding disorder was associated with higher odds of ID (OR 2.1 95% CI 1.02-4.5) and IDA (OR 3.5, 95% CI 1.3-9.7). ID screening was suboptimal (79.3%) even among women with bleeding disorders. Among tested, only 8% IDA from both first and third trimester achieved normalization for hemoglobin and ferritin during third trimester. Third-trimester IDA was associated with significantly higher odds of PPH and red cell transfusion compared with those without IDA. The association between third-trimester IDA and PPH disappeared in the subgroup who achieved correction of IDA.
    Conclusion: We observed no significant change in the rate of PPH in Alberta between 2010-2018. Despite increased risk of pregnancy related bleeding among them, screening of coagulation factor levels and ferritin as well as correction of IDA during third trimester remained suboptimal in pregnant women with inherited bleeding disorders.

  • Subjects / Keywords
  • Graduation date
    Spring 2023
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/r3-b1rs-ts59
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.