<div>Pregnancy, childbirth and neonatal outcomes in women with inherited
bleeding disorders: a retrospective analysis.</div><div>Dr Lisa Clarke<sup>1,2</sup>, Dr Jennifer
Curnow,<sup>3,4</sup> Dr Briony Cutts<sup>5,6</sup> , Dr
Bryony Ross<sup>7,8</sup> and Dr Giselle
Kidson-Gerber<sup>9,10</sup>.</div><ol><li>Department of Haematology, Sydney Adventist Hospital, Sydney,
Australia</li><li>Transfusion Policy and Education, Australian Red Cross Lifeblood,
Sydney, Australia</li><li>Department of Haematology, Westmead Hospital, Sydney, Australia</li><li>Faculty of Medicine and Health, University of Sydney, Sydney,
Australia</li><li>Department of Obstetrics, Royal Women’s Hospital, Melbourne ,
Australia</li><li>Department of Obstetric Medicine, Joan Kirner Women’s and Children’s
at Sunshine Hospital, Melbourne, Australia.</li><li>Department of Haematology, Calvary Mater Newcastle, Australia</li><li>NSW Health Pathology, North (Hunter), Newcastle, Australia</li><li>Department of Haematology, Prince of Wales Hospital, Sydney, Australia</li><li>Royal Hospital for Woman, Sydney, Australia</li></ol><div>Corresponding author: Dr Lisa Clarke</div><div>Australia Red Cross Lifeblood</div><div>Sydney Processing Centre</div><div>17 O’Riordan street Alexandria 2015</div><div>LClarke@redcrossblood.org.au</div><div>+61411790679</div><div>Running title: Obstetric outcomes in inherited bleeding disorders</div><div>Abstract</div><div>Objective</div><div>To describe the characteristics and outcomes of women with inherited
bleeding disorder during pregnancy and birth.</div><div>Design</div><div>Retrospective cohort study.</div><div>Setting</div><div>Tertiary care hospitals, NSW and Victoria Australia.</div><div>Population</div><div>100 women with inherited bleeding disorders, who birthed 134 live
infants from 132 pregnancies.</div><div>Methods</div><div>Data was retrospectively obtained from the patient and neonatal medical
records. Descriptive analysis was used to report maternal and pregnancy
characteristics, birth and neonatal outcomes.</div><div>Main outcome measures</div><div>Factor replacement, neuraxial analgesia use and complications,
post-partum haemorrhage and neonatal complications.</div><div>Results</div><div>PPH occurred in 22% of deliveries with primary PPH occurring in 20%
and secondary PPH in 4% of births. 48% of PPHs were classified as
major. PPHs occurred across the spectrum of IBD and was evenly
distributed between women who had “normalised” their factor levels in
pregnancy compared to those requiring factor at the time of birth. An
obstetric cause was identified in more than half of PPHs.</div><div>Conclusions</div><div>Women with inherited bleeding disorders can deliver safely and receive
neuraxial analgesia without complication when best practices are adhered
to. PPH appears to occur at higher rates than the general population
despite adequate factor levels or planned replacement. Whilst an
obstetric cause was demonstrable in the many cases, these findings raise
concern over the current definition of “adequate” factor levels at the
time of birth.</div><div>Keywords</div><div>Inherited bleeding disorders, pregnancy, post-partum haemorrhage</div><div>Tweetable abstract:</div><div>Women with inherited bleeding disorders can deliver without complication
when best practices are maintained.</div><div>Disclosures of interest.</div><div>Nil.</div><div>Contribution to authorship.</div><div>LJC collected data, analysed the data and wrote the manuscript.</div><div>JC critically appraised the manuscript.</div><div>BC collected data and critically appraised the manuscript.</div><div>BR collected data and critically appraised the manuscript</div><div>GKG conceived the idea, collected data and critically appraised the
manuscript.</div><div>Ethics</div><div>Ethics approval was obtained through the human research ethics committee
(SESLHD HREC 15/294).</div><div>Introduction</div><div>Pregnancy and childbirth pose unique haemostatic challenges. The
associated risks and severity of potential bleeding complications are
increased in women with inherited bleeding disorders (IBD) however
appropriate measures can limit adverse outcomes. Guidelines are
available to direct management of such women but there remains a paucity
of published outcome data.</div><div>IBD affect approximately 1% of the population(1). In Australia 2643
women are registered with the Australian Bleeding Disorders Registry,
with approximately 2/3 of reproductive age.(2)</div><div>Haemophilia A (HA) and B (HB) are X linked disorders, resulting in
deficiencies of factors VIII (FVIII) and IX (FIX) respectively.(1) Most
women are asymptomatic (carriers), however women with levels
&lt;40U/dL are classified as having mild disease.(3) In contrast
to FIX levels, FVIII levels increase significantly throughout pregnancy
and exceed recommended thresholds for birth in the majority of women.(3,
4) Maintaining factor levels &gt;50U/dL are currently
recommended for birth and 3-7 days post-partum depending on mode of
birth(4). Neuraxial analgesia is deemed safe when levels are above this
threshold.(4) Recombinant FVIII or FIX concentrates are the treatments
of choice when factor levels are inadequate in HA and HB.(5)</div><div>von Willebrand disease (VWD) is the most common IBD and can be divided
into 3 types(5). Types 1 and 3 represent quantitative defects of
increasing magnitude whereas Type 2 represents a qualitative defect and
can be further classified into Types 2A, B, M and N depending on the
mechanism of disordered haemostasis. VWD has autosomal dominant
inheritance in the less severe forms and autosomal recessive inheritance
in the more severe types.(5) von Willebrand Factor (VWF) levels also
rise in pregnancy. This increase is generally adequate in women with
Type 1, fails to overcome the functional impairment in Type 2 and is
insufficient in Type 3.(4) VWF levels (or activity) &gt;50U/dL
are recommended for birth, neuraxial analgesia, and 3-7 days
post-partum.(4) Desmopressin, which releases endogenous VWF, or VWF
containing concentrates can be administered to increase VWF levels.(5)</div><div>Rare bleeding disorders include disorders of prothrombin, fibrinogen,
Factor V, VII, X, XI, XIII and functional platelet disorders. There is
limited data to guide management of these woman. In many, pregnancy does
not improve the bleeding risk<sup>(3)</sup> and factor
replacement is achieved with transfusion of plasma, factor concentrates
or platelets.(5)</div><div>Objective</div><div>We aim to describe the characteristics and outcomes of pregnancies and
births of a cohort of Australian women with IBD.</div><div>Methods</div><div>All women with a known history of an IBD, who received care throughout
their pregnancy or birth at either Prince of Wales Hospital Sydney, The
Royal Hospital for Women Sydney, Westmead Hospital Sydney, John Hunter
Hospital Newcastle, Calvary Mater Newcastle, Royal Women’s Hospital
Melbourne and Joan Kirner Women’s and Children’s at Sunshine Hospital
Melbourne between 2011 and 2020 were included. Ethics approval was
obtained through the human research ethics committee (SESLHD HREC
15/294).</div><div>Data was retrospectively obtained from the patient and neonatal medical
records. Descriptive analysis was used to report maternal
characteristics, factor levels, factor replacement, pregnancy, birth and
neonatal outcomes for each pregnancy. Data analysis was performed using
SAS studio.</div><div>Funding was not received for this study.</div><div>Results:</div><div>The study captured 100 women with 132 pregnancies and 134 live births</div><div>Figure 1 demonstrates the normalisation of mean VWF levels in women with
Type 1 VWD (VWF antigen level) compared to women with Type 2B and 2N VWD
(VWF activity level); and mean factor levels in women with mild HA
compared to mild HB, FXI deficiency and hypofibrinogenaemia. The mean
factor levels for both HA and HB carriers were above recommended levels
throughout all stages of pregnancy.</div>