Clinical trial NCT00856076: Venous Thromboembolism in Pregnancy Study
Official title: Venous Thromboembolism and Intrauterine Fetal Death in Pregnancy - Epidemiology and Pathogenic Mechanisms
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Venous Thromboembolism
Intrauterine Fetal Death
Keywords: Venous thromboembolism
Intrauterine fetal death
Risk factor
Thrombophilia
Venous thromboembolism (in pregnancy)
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2009-03-05
Enrollment: 1200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cases: women with first-time validated venous thromboembolism in pregnancy or women who had experienced intrauterine fetal death, either all cases with validated data from medical records or cases meeting for blood sampling.

Controls: women from the source population; either population based with data from the Norwegian Patient Registry or Norwegian Birth Registry, or hospital-based and randomly drawn from the source population and with validated data, or subset of the latter group meeting for blood sampling

Brief summary: The purpose of this study is to investigate clinical, biochemical and genetic risk factors for venous thromboembolism in pregnancy and pregnancy related vascular complications, and the long-term outcome of such complications including implications for quality of life.

Detailed description: Background: Venous thromboembolism (VTE) in pregnancy is a serious, but rare condition. There is no epidemiological data on this patient group from Norway, and there is generally little literature on the immediate and long-term outcome after such pregnancies. Approximately 50% of the women with VTE in pregnancy have known thrombophilia. These women also carry a considerably increased risk for intrauterine fetal death (IUFD). In this project we want to identify new thrombophilias as risk factors for VTE and IUFD in pregnancy.

Aims:

Using a case-control design we will investigate the following issues:

* Risk factors for VTE in pregnancy and IUFD
* Association between thrombophilia, VTE, and other vascular pregnancy complications including IUFD
* Association between thrombophilia and IUFD
* Long term effects of VTE in pregnancy and IUFD on future health including quality of life
* Association between "single nucleotide polymorphisms" (SNP) in genes coding for specific coagulation-, fibrinolysis-, inflammatory, and other relevant proteins and their phenotypic expression
* Association between relevant phenotypes of coagulation, fibrinolysis, inflammation, and other relevant pathways and their risk of disease
* Association between the frequency of specific SNPs that codes for coagulation-, fibrinolysis-, inflammatory, and other relevant proteins and risk for VTE

Materials and Methods:

* 300 women with a history of VTE in their pregnancy and 150 women with IUFD will be identified by the Norwegian patient registry (NPR) and the Medical Birth Registry (MFR). The medical records of these patients will be checked. The epidemiological data will be collected with the help of questionnaires that the patients will fill out and blood samples will be collected. Blood samples will be analyzed with the aim to check for known coagulation factors and thrombophilias as well as new gene polymorphisms.
* 600 control women, from the maternity wards at Ullevål/Aker University Hospitals in the same time period, matched for age and ethnicity, will also answer questionnaires and donate blood samples. The medical records for these women will be checked.

Ethical problems: This study raises no new ethical problems. The study is based on voluntary participation from the invited and informed consent for all analyzes of biological test material. The study design, data procedures and storing of biological material, will use methods that assure the patients privacy at all levels.

The participants are invited to fill out a questionnaire concerning information of thrombosis in pregnancy and take one simple blood test. Women with symptoms of post thrombotic syndrome (PTS) will be offered a clinical examination of their lower extremities to verify the condition. The data will be de-identified and the individuals will not be able to be identify by other than those that have concession to the patient register established for this study.

Blood tests will be stored in a biobank at Ullevål University Hospital (UUS) established for this study, and will only be used for research related problems that have to do with this study.

Some patients could have a psychological reaction of the illness they experienced many years ago. The project leader or co-workers from the Hematology Department/Research Laboratory will handle this problem. These patients will be offered additional information on thrombosis in pregnancy.

Eligibility criteria: Inclusion Criteria:

* women with first-time objectively verified venous thromboembolism in pregnancy.
* women with history of intrauterine fetal death.

Exclusion Criteria:

* recurrent venous thromboembolism in pregnancy.
* non-validated venous thromboembolism in pregnancy.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital Ullevaal (formerly Ullevaal University Hospital)
city: Oslo
country: Norway
facility: Oslo University Hospital (formerly Ullevaal University Hospital)
Study officials:
affiliation: Oslo University Hospital Ullevål and University of Oslo
name: Per Morten Sandset, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Bergrem A, Jacobsen EM, Skjeldestad FE, Jacobsen AF, Skogstad M, Sandset PM. The association of antiphospholipid antibodies with pregnancy-related first time venous thrombosis--a population-based case-control study. Thromb Res. 2010 May;125(5):e222-7. doi: 10.1016/j.thromres.2009.12.006. Epub 2010 Jan 6.
citation: Jacobsen AF, Skjeldestad FE, Sandset PM. Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium--a register-based case-control study. Am J Obstet Gynecol. 2008 Feb;198(2):233.e1-7. doi: 10.1016/j.ajog.2007.08.041. Epub 2007 Nov 12.
citation: Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost. 2008 Jun;6(6):905-12. doi: 10.1111/j.1538-7836.2008.02961.x. Epub 2008 Mar 21.
citation: Gravensteen IK, Helgadottir LB, Jacobsen EM, Radestad I, Sandset PM, Ekeberg O. Women's experiences in relation to stillbirth and risk factors for long-term post-traumatic stress symptoms: a retrospective study. BMJ Open. 2013 Oct 22;3(10):e003323. doi: 10.1136/bmjopen-2013-003323.
citation: Gravensteen IK, Helgadottir LB, Jacobsen EM, Sandset PM, Ekeberg O. Long-term impact of intrauterine fetal death on quality of life and depression: a case-control study. BMC Pregnancy Childbirth. 2012 Jun 7;12:43. doi: 10.1186/1471-2393-12-43.
citation: Jacobsen AF, Dahm A, Bergrem A, Jacobsen EM, Sandset PM. Risk of venous thrombosis in pregnancy among carriers of the factor V Leiden and the prothrombin gene G20210A polymorphisms. J Thromb Haemost. 2010 Nov;8(11):2443-9. doi: 10.1111/j.1538-7836.2010.04038.x.