73
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy Danish nationwide historical cohort 1995–2009 Jesper Friis Petersen1; Thomas Bergholt1; Anne Kristine Nielsen1; Michael J. Paidas2; Ellen Christine L. Løkkegaard1 1Department
of Gynecology and Obstetrics, Hillerød Hospital, Hillerød, University of Copenhagen, Denmark; 2Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale Women and Children’s Center for Blood Disorders, Yale University School of Medicine, New Haven, Conneticut, USA
Summary Estimating the risk of venous thromboembolism (VTE) associated with combined hormonal contraceptives following early terminated pregnancies or birth, a Danish nationwide retrospective cohort observing a one-year follow-up was defined using three unique registries. All Danish women with confirmed pregnancies aged 15–49 during the period of 1995–2009 were included. The main outcomes were relative and absolute risks of first time venous thromboembolism in users as well as non-users of combined hormonal contraceptives. In 985,569 person-years, 598 venous thromboembolisms were recorded. After early terminated pregnancies and births, respectively, 113 and 485 events occurred in 212,552 and 773,017 person-years. After early terminated pregnancies, the crude VTE incidence ratios were similar, and the numbers needed to harm were equal between groups that did or did Correspondence to: Jesper Friis Petersen, MD Department of Gynecology and Obstetrics University of Copenhagen, Hillerød Hospital Dyrehavevej 29, 3400 Hillerød, Denmark Tel.: + 45 21 84 84 89 E-mail: [email protected]
not use combined hormonal contraceptives throughout the follow-up year. After childbirth, individuals that used combined hormonal contraceptives were more likely than non-users to experience VTE depicted by crude incidence ratios; however, the difference was only significant after 14 weeks. This implied that the numbers needed to harm were lower for those that used compared to those that did not use combined oral contraceptives in the initial 14 weeks postpartum. In conclusion, the use of combined hormonal contraceptives after early terminated pregnancies was not detrimental, but during the puerperal period, they should be used with caution.
Keywords Venous thromboembolism, early termination of pregnancy, birth, puerperal period Financial support: The study was funded by the research foundation at Hillerød Hospital. The funding organisation had no role in the study planning, data collection, analysis, writing of the article, or in the decision to submit the article for publication. All authors held positions independent from funding organisation. Received: September 30, 2013 Accepted after major revision: January 25, 2014 Epub ahead of print: February 6, 2014 http://dx.doi.org/10.1160/TH13-09-0797 Thromb Haemost 2014; 112: 73–78
Introduction
Materials and methods
Venous thromboembolism (VTE) is the leading cause of maternal mortality in the developed world (1-3). Both pregnancy and the use of combined hormonal contraceptives are established as independent risk factors (4). An interaction between these separate risks has been suggested; however, research addressing the matter is limited (5). Recently, the World Health Organization (WHO) changed its recommendation on the time to initiate oral contraceptives following birth; they postponed the commencement time from three to six weeks postpartum (5, 6). The aim of the present study was to estimate the risk of VTE associated with the use of any type of combined hormonal contraceptives over one year following pregnancy in two settings; first, after early terminated pregnancies (terminated before 22 weeks of gestation), and second, after childbirth.
All Danish women aged 15-49 in the period of 1995-2009 were included in a nationwide historical cohort. From the Danish Central Person Registry, women were identified by a unique personal tendigit identification number. This number was used to link to other registries to acquire individual information. From the National Registry of Patients, pregnancies were identified by the discharge diagnosis encoded with ICD-10 criteria. Women were excluded when they had been diagnosed with prior VTE, cardiovascular disease, cancer, or gynaecological surgery that had impaired fertility. From the National Registry of Medical Products Statistics, information was retrieved on women that had filled prescriptions for combined hormonal contraceptives. This registry records all prescriptions filled by Danish citizens, coded according to anatomictherapeutic-chemical categories. The use of combined hormonal contraceptives was considered a time-varying covariate
© Schattauer 2014
Thrombosis and Haemostasis 112.1/2014 Downloaded from www.thrombosis-online.com on 2015-01-16 | ID: 1000471717 | IP: 132.174.255.116 For personal or educational use only. No other uses without permission. All rights reserved.
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Petersen et al. Risk of VTE by contraceptives following pregnancy
Table 1: Characteristics of populations with different pregnancy outcomes: childbirth or early terminated pregnancy. Results indicate the numbers of person years (PY) and venous thromboembolisms (VTE); the incidence rate (IR) was calculated: VTE/(PY/1000).
Childbirth PY
VTE
IR
Early terminated pregnancy PY VTE IR
Age (years)
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy Danish nationwide historical cohort 1995–2009 Jesper Friis Petersen1; Thomas Bergholt1; Anne Kristine Nielsen1; Michael J. Paidas2; Ellen Christine L. Løkkegaard1 1Department
of Gynecology and Obstetrics, Hillerød Hospital, Hillerød, University of Copenhagen, Denmark; 2Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale Women and Children’s Center for Blood Disorders, Yale University School of Medicine, New Haven, Conneticut, USA
Summary Estimating the risk of venous thromboembolism (VTE) associated with combined hormonal contraceptives following early terminated pregnancies or birth, a Danish nationwide retrospective cohort observing a one-year follow-up was defined using three unique registries. All Danish women with confirmed pregnancies aged 15–49 during the period of 1995–2009 were included. The main outcomes were relative and absolute risks of first time venous thromboembolism in users as well as non-users of combined hormonal contraceptives. In 985,569 person-years, 598 venous thromboembolisms were recorded. After early terminated pregnancies and births, respectively, 113 and 485 events occurred in 212,552 and 773,017 person-years. After early terminated pregnancies, the crude VTE incidence ratios were similar, and the numbers needed to harm were equal between groups that did or did Correspondence to: Jesper Friis Petersen, MD Department of Gynecology and Obstetrics University of Copenhagen, Hillerød Hospital Dyrehavevej 29, 3400 Hillerød, Denmark Tel.: + 45 21 84 84 89 E-mail: [email protected]
not use combined hormonal contraceptives throughout the follow-up year. After childbirth, individuals that used combined hormonal contraceptives were more likely than non-users to experience VTE depicted by crude incidence ratios; however, the difference was only significant after 14 weeks. This implied that the numbers needed to harm were lower for those that used compared to those that did not use combined oral contraceptives in the initial 14 weeks postpartum. In conclusion, the use of combined hormonal contraceptives after early terminated pregnancies was not detrimental, but during the puerperal period, they should be used with caution.
Keywords Venous thromboembolism, early termination of pregnancy, birth, puerperal period Financial support: The study was funded by the research foundation at Hillerød Hospital. The funding organisation had no role in the study planning, data collection, analysis, writing of the article, or in the decision to submit the article for publication. All authors held positions independent from funding organisation. Received: September 30, 2013 Accepted after major revision: January 25, 2014 Epub ahead of print: February 6, 2014 http://dx.doi.org/10.1160/TH13-09-0797 Thromb Haemost 2014; 112: 73–78
Introduction
Materials and methods
Venous thromboembolism (VTE) is the leading cause of maternal mortality in the developed world (1-3). Both pregnancy and the use of combined hormonal contraceptives are established as independent risk factors (4). An interaction between these separate risks has been suggested; however, research addressing the matter is limited (5). Recently, the World Health Organization (WHO) changed its recommendation on the time to initiate oral contraceptives following birth; they postponed the commencement time from three to six weeks postpartum (5, 6). The aim of the present study was to estimate the risk of VTE associated with the use of any type of combined hormonal contraceptives over one year following pregnancy in two settings; first, after early terminated pregnancies (terminated before 22 weeks of gestation), and second, after childbirth.
All Danish women aged 15-49 in the period of 1995-2009 were included in a nationwide historical cohort. From the Danish Central Person Registry, women were identified by a unique personal tendigit identification number. This number was used to link to other registries to acquire individual information. From the National Registry of Patients, pregnancies were identified by the discharge diagnosis encoded with ICD-10 criteria. Women were excluded when they had been diagnosed with prior VTE, cardiovascular disease, cancer, or gynaecological surgery that had impaired fertility. From the National Registry of Medical Products Statistics, information was retrieved on women that had filled prescriptions for combined hormonal contraceptives. This registry records all prescriptions filled by Danish citizens, coded according to anatomictherapeutic-chemical categories. The use of combined hormonal contraceptives was considered a time-varying covariate
© Schattauer 2014
Thrombosis and Haemostasis 112.1/2014 Downloaded from www.thrombosis-online.com on 2015-01-16 | ID: 1000471717 | IP: 132.174.255.116 For personal or educational use only. No other uses without permission. All rights reserved.
74
Petersen et al. Risk of VTE by contraceptives following pregnancy
Table 1: Characteristics of populations with different pregnancy outcomes: childbirth or early terminated pregnancy. Results indicate the numbers of person years (PY) and venous thromboembolisms (VTE); the incidence rate (IR) was calculated: VTE/(PY/1000).
Childbirth PY
VTE
IR
Early terminated pregnancy PY VTE IR
Age (years)
