Tara Haelle

January 31, 2017

LAS VEGAS — For women with a history of pre-eclampsia, daily low-dose aspirin can lead to a 30% reduction in recurrence, new research shows, lending support to US Preventive Services Task Force (USPSTF) guidelines.

Pre-eclampsia affects 5% to 8% of all pregnancies, or approximately 10 million women globally. Each year, it causes the death of 76,000 mothers around the world, and accounts for 15% of preterm births in the United States.

Although the precise cause of pre-eclampsia is unclear, it is thought to be triggered by a combination of predisposing factors, including genetics and maternal comorbidities, immunologic and endothelial mediators, and a dysfunctional trophoblastic invasion, said Mary Catherine Tolcher, MD, a fellow in maternal–fetal medicine at the Baylor College of Medicine in Houston.

The resulting pathophysiology involves vascular and endothelial dysfunction, placental ischemia, and inflammatory and stress responses, she explained.

"The overproduction of thromboxanes plays a role in the vasoconstriction and platelet aggregation and contributes to placental ischemia," Dr Tolcher reported, so a medication that can prevent vasoconstriction might relieve ischemia.

Aspirin is a good candidate because of its safety profile and vasodilation activity, but results from previous research have been mixed.

Testing Aspirin

The USPSTF guidelines were implemented at Baylor in September 2014, with a particular emphasis on women with a history of pre-eclampsia, Dr Tolcher said here at Society for Maternal-Fetal Medicine 2017 Annual Pregnancy Meeting.

For their study, she and her colleagues assessed 284 deliveries that occurred before implementation and 133 that occurred after. The primary outcome of the study was recurrent pre-eclampsia, and secondary outcomes were the use of magnesium sulfate and preterm delivery.

The mean age of the mothers was 30 years, and there were fewer Hispanics in the after group than in the before group. Body mass index, smoking history, gestational age at the time of the previous pre-eclampsia episode and delivery, and rates of hypertension, type 2 diabetes, and previous preterm delivery were similar in the two groups. However, fewer women in the before group than in the after group were covered by private insurance (9.2% vs 37.6%), and there were slightly more women with type 1 diabetes in the after group.

Overall, there was a 49% reduction in risk, with more women in the before group than in the after group developing pre-eclampsia (32.4% vs 16.5%).

After adjustment for demographic characteristics and comorbidities, the risk was 30% lower in the after group (relative risk [RR], 0.70; 95% confidence interval [CI], 0.52 - 0.95). To prevent one case of recurrent pre-eclampsia, six women with a history would need to take low-dose aspirin, the researchers report.

The use of magnesium sulfate during labor was 29% lower in the after group than in the before group, but the difference was not significant (RR, 0.71; 95% CI, 0.46 - 1.10). The difference in the rate of preterm birth between the before and after groups was not significant (24.3% vs 23.3%).

The rate of pre-eclampsia had already begun to decline at Baylor before the guidelines were implemented, but after implementation, the overall trend was considerably lower and stayed steady without apparent seasonal variation.

Daily low-dose aspirin during the second and third trimesters would cost approximately $4, whereas the cost to treat one woman with pre-eclampsia is approximately $21,200, the researchers report.

"The most important clinical implication is that even a small benefit from aspirin is worth it because of the low cost and low risk of harm with the intervention," Dr Tolcher told Medscape Medical News. "Also, the benefit may be even greater in subsets of women, including those with a history of pre-eclampsia."

Limitations of this study are its retrospective design, the inclusion of only women with a history of pre-eclampsia, and the inability to determine compliance with aspirin use. However, unconfirmed compliance with the intervention is a reflection of actual clinical use, which is likely imperfect, she pointed out.

Comparing the Evidence

"Aspirin has not been shown to have a beneficial effect in terms of reducing the risk of pre-eclampsia in the two largest randomized trials — one from the United States and one an international study," Dr Tolcher told Medscape Medical News. "However, meta-analyses combining results from these and small studies show a benefit. But some clinicians are hesitant to make change based on meta-analyses."

 
Anything that's cost-effective and can prevent bad outcomes is fantastic.
 

In 2014, on the basis of findings from meta-analyses, the USPSTF began to recommend low-dose aspirin (81 mg/day) after 12 weeks of gestation to prevent morbidity and mortality from pre-eclampsia in women with a history of pre-eclampsia, multifetal gestation, chronic hypertension, type 1 or 2 diabetes, renal disease, or autoimmune disease. The American Congress of Obstetricians and Gynecologists followed with a similar recommendation last year. The level B evidence was based primarily on a meta-analysis showing a 24% reduction in the risk for pre-eclampsia.

"Anything that's cost-effective and can prevent bad outcomes is fantastic," said Daniele Feldman, MD, from the Perinatal, Obstetrics and Gynecology Health Center at Dignity Health in Santa Maria, California.

Although the results from this study are "consistent with what we have known about and been practicing," Dr Feldman said she finds them reassuring. "We've been looking for a way to prevent pre-eclampsia for a long, long time," she told Medscape Medical News. "It's nice to have something that looks like it works."

Dr Tolcher and Dr Feldman have disclosed no relevant financial relationships.

Society for Maternal-Fetal Medicine (SMFM) 2017 Annual Pregnancy Meeting. Presented January 27, 2017.

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