Thrombotic Risk Raised in Stillbirths and Preterm Births

Yael Waknine

April 09, 2013

Stillbirth and preterm birth can increase a woman's risk for de novo postpartum venous thromboembolism (VTE), according to the results of a large epidemiologic study published online April 2 in Blood.

After adjusting for maternal age, body mass index, smoking status, and number of prior births, Alyshah Abdul Sultan, from the Division of Epidemiology and Public Health at the University of Nottingham in the United Kingdom, and colleagues found that stillbirth was linked to a 6-fold increased risk for VTE (vs live birth; incidence rate ratio [IRR], 6.24 [95% confidence interval (CI), 2.77 - 14.1]; absolute risk/100,000 person-years [AR], 2444 [95% CI, 109 - 5440]). Compared with full-term birth, preterm birth of 37 weeks or less was linked to a near tripling of risk (IRR, 2.69 [95% CI, 1.99 - 3.65]; AR, 854 [95% CI, 649 - 1124]).

"We believe the strong association between stillbirths and premature births, and VTE in particular, is a finding of real importance which has received only limited attention to date," senior author Matthew Grainge, PhD, also from the Division of Epidemiology and Public Health at the University of Nottingham, commented in a university news release, adding, "They are not currently incorporated in the guidelines for risk assessment for VTE and, if they were, then many cases associated with those risk factors could potentially be prevented."

376,000 Pregnancies

For the study, the researchers analyzed electronic medical records for 376,154 women aged 15 to 44 years whose pregnancies ended in live birth or stillbirth during a 14-year period from 1995 to 2009. Although the overall incidence of VTE was low, postpartum rates were higher than those in pregnancy (338 vs 84 per 100,000 person-years).

Additional pregnancy-related factors linked to an increased risk for postpartum VTE included cesarean delivery (IRR, 1.99 [95% CI, 1.52 - 2.58]; AR, 637 [95% CI, 513 - 790]), having 3 or more prior births (IRR, 2.07 [95% CI, 1.34 - 3.20; AR, 904 [95% CI, 611 - 608]), pregnancy bleeding (IRR, 2.89 [95% CI, 1.53 - 5.43]; AR, 963 [95% CI, 518 - 1791]), and urinary tract infections (IRR, 1.88 [95% CI, 1.28 - 2.77]; AR, 145 [95% CI, 102 - 206]).

Although gestational diabetes was linked to an increased risk for VTE, hypertension was not (gestational diabetes: IRR, 1.71 [95% CI, 0.54 - 5.41]; AR, 165 [95% CI, 53 - 514]; hypertension: IRR, 1.01 [95% CI, 0.37 - 2.76]; AR, 95 [95% CI, 35 - 254]).

Obesity (body mass index ≥ 30 kg/m2) was linked to an almost quadrupled risk for VTE (IRR, 3.75 [95% CI, 2.76 - 5.08]; AR, 926 [95% CI, 742 - 1554]), whereas other maternal characteristics had a more moderate effect, including advanced maternal age (≥35 years: IRR, 1.51 [95% CI, 1.15 - 1.98]; AR, 497 [95% CI, 399 - 618]) and smoking status (IRR, 1.31 [95% CI, 1.01 - 1.71]; AR, 403 [95% CI, 324 - 504]).

Certain medical comorbidities also showed a strong association with VTE, including systemic lupus erythematosus (IRR, 6.69 [95% CI, 0.95 - 47.0]; AR, 2374 [95% CI, 344 - 16,856]), cardiac disease (IRR, 6.58 [95% CI, 1.63 - 26.5]; AR, 2258 [95% CI, 646 - 10,335]), varicose veins (IRR, 3.83 [95% CI, 2.51 - 5.82]; AR, 1330 [95% CI, 899 - 1969]), and inflammatory bowel disease (IRR, 4.56 [95% CI, 1.88 - 11.0]; AR, 1514 [95% CI, 630 - 3638]).

Nothing New, Experts Say

According to Nancy Chescheir, MD, clinical professor of maternal-fetal medicine in the Department of Obstetrics and Gynecology at the University of North Carolina at Chapel Hill School of Medicine, the IRR analysis neglected to account for some important confounders.

"Both premature birth and stillbirth are often associated with infection, which might also increase risk for VTE. Also, some thrombophilias increase risk for stillbirth and, of course, risk for VTE," Dr. Chescheir told Medscape Medical News, noting that women with known risk factors for premature birth also may have been on bed rest for some time, which would increase VTE risk as well.

Jeffrey C. King, MD, professor and director of maternal-fetal medicine at the University of Louisville in Kentucky, concurs.

"Patients who have a preterm delivery may have been hospitalized and managed either as an inpatient or outpatient with varying periods of time with bedrest or modified bedrest, which would increase their risk for VTE," Dr. King told Medscape Medical News, noting that some of the conditions (or their treatments) underlying stillbirth are also known to increase the risk for VTE.

"I'm not sure that they discovered anything really new regarding the issues surrounding VTE and pregnancy," Dr. King added. "Multiparity, women of advanced age, patients undergoing cesarean delivery, obese patients, patients having operative delivery, and those suffering from obstetric-related injury or hemorrhage are well known to be at increased risk for VTE events."

One of the study coauthors has reported receiving honoraria for giving lectures from Leo Pharma and sanofi-aventis (makers of thromboprophylactic drugs) and has received funds from Leo Pharma for development of an electronic slide kit about obstetric thromboprophylaxis. The other authors, Dr. Chescheir, and Dr. King have disclosed no relevant financial relationships.

Blood. Published online April 2, 2013. Abstract