The occurrence and risk factors for first venous thromboembolism in and around pregnancy: population based cohort studies using primary and secondary care data from the United Kingdom

Abdul Sultan, Alyshah (2013) The occurrence and risk factors for first venous thromboembolism in and around pregnancy: population based cohort studies using primary and secondary care data from the United Kingdom. PhD thesis, University of Nottingham.

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Background: Venous thromboembolism (VTE) in one of the leading causes of maternal morbidity and mortality in high income countries. However there is a surprising shortage of evidence which allows us to accurately predict which women are at high risk which has hindered prevention to date. Therefore the aim of this thesis is to measure the occurrence of and risk factors for VTE during the antepartum and postpartum periods.

Methods: Electronic health records from women of childbearing age (15-44 years) were identified from two separate databases; The Health Improvement Network (THIN) between 1995 and 2009 and the Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) between 1997 and 2010. Five separate studies were then carried out to study the incidence and risk factors for VTE during antepartum and postpartum periods. In studies 1 and 2 I used the THIN database to assess the incidence of and risk factors for VTE during antepartum and postpartum periods separately. Studies 3, 4 and 5 incorporated the CPRD-HES linked data which enabled me to get better ascertainment of VTE and its potential risk factors. Using these data I externally validated my VTE definition which was followed by investigating the impact of non-delivery related hospitalisations on the incidence of antepartum VTE. I also examined the risk factors for postpartum VTE using a conceptual hierarchical analysis approach along with their impact on the timing of VTE during specific periods of postpartum. All results were presented in the form of absolute rates (AR) per 100,000 person-years and incidence rate ratios (IRR) were calculated using Poisson regression with adjustment for relevant covariates.

Results: In THIN, there were a total of 1.7 million women of which 280,451 experienced 376,154 pregnancies resulting in live or stillbirths whereas the CPRD-HES linked data contained information on over 240,000 pregnancies among 204,929 women. Overall VTE rates were highest in the first few weeks postpartum. Women in their third trimester of antepartum were at a 5 fold increased risk of first VTE compared to their time outside pregnancy whereas in the first and second trimesters this rate was only marginally higher. However the use of CPRD-HES linked database gave me estimates of VTE risk with better precision in and around pregnancy that were comparable to the existing literature. For my risk factor analysis I found that the strongest risk factor for VTE during the antepartum period was hospitalisation corresponding to a 17-fold increase (IRR=17.7 95%CI=7.7-39.6) compared to time outside hospital. The rate of VTE was also high during the 28 days post-discharge (IRR=5.9; 95%CI=3.5-10.0; AR=646). These factors were not confounded by pregnancy related characteristics and complications, pre-existing medical co-morbidities or demographic or life style related characteristics. I also found that postpartum, women whose pregnancies resulted in stillbirth were at a 6- fold (IRR=6; 95%CI 3.17-14.6; AR=2570) increased risk of VTE. Those with caesarean delivery (elective or emergency), pre-term birth or postpartum haemorrhage had a 2-fold or higher risk of postpartum VTE compared to their respective baseline (AR>600/100,000 person-years). These findings were consistent across both the THIN and CPRD-HES linked data bases with respect women's risk factors for VTE. Finally the risk of VTE remains consistently high up to first six weeks postpartum (>700/100,000 person-years) for pregnancies of women complicated with BMI>30kg/m2 or caesarean delivery whereas risk of VTE was only high in the first three weeks postpartum (>1300/100,000 person-years) In those with pre-term birth or postpartum haemorrhage.

Conclusion: I have provided some of the most precise estimates of absolute rates of VTE In and around pregnancy for better understanding of risks. The overall rate of antepartum VTE is substantially increased during non-delivery related hospitalisations and this increase is sustained in the 28 days post-discharge. Postpartum, delivery associated characteristics and complications including, stillbirth, caesarean delivery, BMI>30Kg/m2 postpartum haemorrhage are important risk factors for VTE particularly during the first three weeks postpartum. My analysis provides valuable information to clinicians for better decision making in terms of identifying high risk pregnant and postpartum women who may require some form of thromboprophylaxis.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Grainge, M.J.
Tata, L.
West, J.
Keywords: Risk factors for thromboembolism, Pregnancy complications, Prediction of risk, Postpartum complications
Subjects: W Medicine and related subjects (NLM Classification) > WQ Obstetrics
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 29086
Depositing User: Blore, Mrs Kathryn
Date Deposited: 15 Jun 2015 07:57
Last Modified: 15 Sep 2016 18:52

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