LAS VEGAS – Using low-dose aspirin during pregnancy significantly reduced the risk of recurrent preeclampsia, according to results of a new study.

“The net benefit of aspirin is substantial,” Mary Catherine Tolcher, MD, the study’s lead author said. “The number needed to treat to prevent one case of recurrent preeclampsia is six... The cost of daily low-dose aspirin for the duration of one pregnancy is about $4.00. Comparatively, the cost to prevent one case of eclampsia is approximately $21,000.”

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In the retrospective study, the investigators examined 17,256 deliveries at a single academic medical center, including deliveries before and after implementation of the U.S. Preventive Services Task Force (USPSTF) recommendation that women at high risk for preeclampsia receive a daily low-dose aspirin, beginning at 12 weeks of gestation. The USPSTF guidelines carry a recommendation grade of B, meaning that there is “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.”

Dr. Tolcher, a postdoctorate fellow in ob.gyn. at Baylor College of Medicine, Houston, and her colleagues found a total of 417 at-risk women in the institution’s labor and delivery database during the August 2011–June 2016 study period; 284 were identified before the guidelines were implemented in 2014, while 133 women were identified as high-risk after guideline implementation.

While nearly one-third (32.4%) of women with a history of preeclampsia had a recurrence in the before group, the recurrence rate fell to 16.5% in the after group, who had been instructed to take low-dose aspirin in accordance with the guidelines. When the investigators calculated the fully adjusted odds ratio for recurrent preeclampsia, they found a reduction of about 30% in recurrent preeclampsia [aOR, 0.71; 95% confidence interval, 0.52-0.95].

“This decrease is greater than the approximately 10 to 15 percent reduction that has been previously reported in clinical trials, and different from the meta-analysis that prompted the national recommendations,” Dr. Tolcher said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

She and her colleagues hypothesize that the greater effect size may be attributable to limiting the study population to the higher-risk group of women with a history of preeclampsia. Alternatively, she said, aspirin’s pharmacodynamics can differ by race, so racial differences between study populations may also be at play.

One of the causative mechanisms for preeclampsia is thought to be impaired trophoblastic remodeling that impedes development of the low-resistance vascular system of the maternal-fetal unit. “The resulting pathophysiology is multisystemic and includes vascular and endothelial dysfunction, placental ischemia, and an inflammatory and stress response,” Dr. Tolcher said. Overproduction of thromboxanes, she said, plays a role in this process. Aspirin’s inhibition of cyclooxygenase-2 (COX-2) enzymes and thromboxanes is thought to mitigate the vasoconstriction and endothelial dysfunction seen in preeclampsia, she said.

A secondary outcome measure in the study was use of magnesium sulfate, and after guideline implementation “there was a trend toward reduced use of magnesium sulfate, which we reserved for preeclampsia with severe features,” Dr. Tolcher said.

There was no difference in the incidence of preterm deliveries, another secondary outcome measure, after the aspirin guidelines were implemented.

There were some differences in characteristics between the before and after groups: the ratio of Hispanic women with preeclampsia was significantly lower in the after group (P less than .0001). The distribution of method of payment shifted, with more private pay patients, fewer Children’s Health Insurance Program (CHIP) patients, and fewer “other” payment method patients in the after group. Though Dr. Tolcher reported that type 1 diabetes was seen more often in the after group, the rates of any kind of pre-pregnancy diabetes were similar between the groups (6.33% before; 4.26% after).

Potentially confounding variables were controlled by means of logistic regression analysis. Women with multiple gestations were excluded, and only the first pregnancy after a previous episode of preeclampsia was studied.

Otherwise, demographics and other patient characteristics – including rates of chronic hypertension, were similar between the before and after groups. About a quarter of the patients in each group had a history of preterm delivery, and the median age at delivery for both was 38 years.

Within the total group that had recurrent preeclampsia, “maternal age greater than 35, type 2 diabetes, chronic hypertension, and a history of preterm preeclampsia were significantly associated with recurrent preeclampsia,” Dr. Tolcher said.

Study limitations included the retrospective nature, the inclusion of only women who had a prior history of preeclampsia, and the investigators’ inability to determine whether patients were adherent to recommendations for aspirin use. However, the study represents actual clinical use, Dr. Tolcher said, and addresses a real need. “Preeclampsia is responsible for 75,000 maternal deaths annually, and accounts for 15% of the preterm births in the U.S.,” she said.

Dr. Tolcher reported having no relevant financial disclosures.

koakes@frontlinemedcom.com

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Aspirin reduces recurrent preeclampsia in real-world study