Stillbirth or pre-term birth outcomes linked to elevated risk of blood clots after pregnancy

(Press-News.org) (Washington)- Newly identified pregnancy-related events, such as stillbirth or pre-term birth, may dramatically increase a woman's risk of developing a potentially deadly blood clot immediately after pregnancy, according to the results of a large, population-based study published online today in Blood, the Journal of the American Society of Hematology (ASH).

Venous thromboembolism, or VTE, is a clotting disorder that includes both deep-vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a blood clot that typically forms in the deep veins of the leg. It can develop into PE, a life-threatening condition that occurs when the clot breaks free and becomes lodged in the arteries of the lung, blocking blood flow. VTE is a rare but serious complication in pregnancy, and remains one of the leading causes of pregnancy-related death in many parts of the world. One preventive measure for VTE includes a daily dose of the blood thinner heparin. However, because heparin may not be cost effective or safe, current U.K. obstetric VTE risk guidelines suggest administering the drug only to women considered to be at high risk based on specific sets of risk factors which may not fully capture the true "at risk" population.

"Preventing VTE in pregnancy remains a challenging topic for clinicians since there is still disagreement as to which clinical, lifestyle, and socio-demographic factors qualify women as high-risk, and data are lacking about the relative impact of those factors on their risk of VTE," said author Matthew Grainge, PhD, of the Division of Epidemiology and Public Health at the University of Nottingham in the U.K. "Moreover, many studies have made the incorrect assumption that any risk factors identified have a similar impact on VTE rates in both pregnant women and new moms."

To understand the relative risk of VTE in women in the period between conception and birth (antepartum) and for up to 12 weeks after birth (postpartum) with the goal of optimizing the preventive use of heparin in this population, Dr. Grainge and colleagues designed a study examining data from more than 375,000 pregnancies in women ages 15-44 between January 1995 and July 2009. Data analysis was conducted through a retrospective review of The Health Improvement Network (THIN), a large primary-care database with input from more than 1,500 general practitioners across the U.K. Of the 375,000 pregnancies documented, the overall incidence of VTE was low, but higher during the postpartum period (338 per 100,000 person-years, which represents an individual's risk of an event during a one-year period) than during the pregnancy (84 per 100,000 person-years).

During the antepartum period, Dr. Grainge and colleagues found that the risk of VTE was highest in women who had reported inflammatory bowel disease (incidence rate ratio compared to women without the risk factor, or IRR, of 3.5) or pre-existing diabetes (IRR 3.1).

In the postpartum period, the team discovered a significant correlation between VTE risk and stillbirth (a six-fold increased risk of VTE compared with women who did not have a stillbirth, IRR 6.2), a risk factor that is not currently addressed in VTE risk assessment guidelines. Importantly, obese women with a high body mass index (BMI) of 30 or above also had a significantly increased VTE risk (IRR 3.75). The team also determined other factors that led to an increased risk of VTE, including a caesarian section delivery ( IRR 1.99), three or more previous births (IRR 2.07), pre-term birth (prior to 37 weeks gestation, IRR 2.69), and obstetric hemorrhage (IRR 2.89).

"The higher overall risks in the postpartum period may be attributable to a number of pregnancy-related factors, including delivery-related trauma, sudden increases in cardiac output and blood flow during delivery, and the thickening of the blood that occurs during late pregnancy, all of which may trigger a greater risk of clotting immediately following delivery," said Dr. Grainge.

According to the team's findings, other factors currently included in U.K. risk guidelines, such as smoking status, maternal age (over 35 years), and current systemic infection were only moderately associated with VTE in both antepartum and postpartum periods.

"Our results provide valuable information to help clinicians identify high-risk pregnant women and new mothers who may require some form of intervention to prevent future clots. The findings support the use of heparin to prevent blood clots in the postpartum period, when the actual risk of VTE is highest, clear risk factors have been identified, and duration of care would likely be limited to a few weeks (as compared to treating throughout the pregnancy)," added Dr. Grainge.

### The study was carried out as part of a PhD project on VTE prevention in pregnancy being undertaken by Alyshah Abdul Sultan in collaboration with Professor Catherine Nelson-Piercy at the Women's Health Academic Centre at Guy's and St Thomas' Foundation Trust. Blood, the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH), the world's largest professional society concerned with the causes and treatment of blood disorders.

ASH's mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.

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