麻豆传媒

When it comes to whether or not to treat women at high risk for preeclampsia with low-dose aspirin therapy, the U.S. Preventive Services Task Force (USPSTF) guidelines are spot on, experts in the field agree.

After reviewing 23 studies -- 21 of which were randomized controlled trials -- in which women at a high risk for preeclampsia were given low-dose aspirin, the USPSTF found aspirin therapy yielded risk reductions of 24% for preeclampsia, 20% for intrauterine growth restriction (IUGR), and 14% for preterm birth, according to , of the Kaiser Permanente Center for Health Research in Portland, Ore., and colleagues.

"No harms were identified, but long-term evidence was limited," Henderson and colleagues wrote in the guidelines, which were published Monday in the .

Results from the 23 studies showed:

• An absolute risk reduction (aRR) of 2% to 5% for preeclampsia (relative risk [RR] 0.76, 95% CI 0.62-0.95)
• An aRR of 1% to 5% for intrauterine growth restriction (RR 0.80, 95% CI 0.65-0.99)
• An aRR of 2% to 4% for preterm birth (RR 0.86, 95% CI 0.76-0.98)

Among the trials, 10 included women at high risk for preeclampsia. When the researchers calculated the risks for harms associated with aspirin therapy, they included average-risk populations, and found no evidence to suggest potential for perinatal mortality (RR 0.92, 95% CI 0.76-1.11, P=0.65).

Henderson and colleagues noted their findings were tempered by evidence of small-study effects and modest findings in the two largest trials, so the risk reduction for preeclampsia, IUGR, and preterm birth was really closer to 10%. The timing and dosage of the aspirin therapy had no consistent effect on outcomes, they wrote. However, the preterm birth benefit was better in studies where the patients were given at least 75 mg of aspirin.

ACOG Gives Thumbs Up

"These guidelines are exactly consistent with ours," , of the University of Mississippi Medical Center in Jackson, and past president of the American Congress of Obstetricians and Gynecologists (ACOG), told 麻豆传媒, referring to ACOG's guidelines.

Quoting from the , Martin said, "For women with a medical history of early-onset preeclampsia and preterm delivery at less than 34 weeks of gestation, or preeclampsia in more than one prior pregnancy, initiating the administration of daily low-dose aspirin beginning in the late first trimester is suggested."

Martin said the USPSTF guidelines used similar verbiage to the ACOG guidelines. However, Martin said, "The use of low-dose aspirin is not a panacea for every patient. There are some who respond and some who don't.

"Research continues to try to identify between the lines where it may work and where it may not work. But in general, we are advocating from ACOG, and they are from the USPSTF, that patients at risk for recurrent, preterm preeclampsia take low-dose aspirin.

"We know of no harms with this, and that is exactly what they found too," he continued. "There was a question about possible increased risk of abruption, but that has not been validated."

SMFM Looks At Broader Picture

"We absolutely would recommend these guidelines," , president of the Society of Maternal Fetal Medicine (SMFM), told 麻豆传媒.

"[However], the clinical issue goes farther. Here, they say that daily low-dose aspirin prevents clinically important outcomes. [But] the issue is who to give it to," said Berghella, who is also with Jefferson University Hospital in Philadelphia.

"They talk about women at high risk for preeclampsia, but any pregnant woman is at risk for preeclampsia, so the issue is whom, which they don't go over in detail," he said. "For example, the American Heart Association guidelines [released in February 2014 without consulting ACOG or SMFM] suggested that women with chronic hypertension in pregnancy should take low-dose aspirin, which went against what we had recommended at ACOG.

"They [USPSTF guidelines] are not specific, so they're certainly in line, but the specific recommendation from the most recent hypertension recommendation from ACOG is to give it to women with prior preeclampsia that was severe enough to lead to a delivery before 34 weeks in the prior pregnancy," Berghella said.

"If everyone is technically at risk for preeclampsia, then the definition of high risk would fall to women who had preeclampsia in a prior pregnancy and had to deliver prior to 34 weeks because of preeclampsia. Low-dose aspirin is not recommended for first pregnancies," Berghella emphasized.

He agreed that there really are no risks with baby aspirin therapy. "This has been studied now in hundreds of thousands of women, dozens of different studies, and we know that much for certain, that baby aspirin is not been associated with risks," he said.

"If you are going to take a baby aspirin, you should start it before 16 weeks of gestation, to be precise. If you take the aspirin later, it's not as effective," Berghella said.

An Expert Looks at More Research

"Different organizations have somewhat different recommendations, but overall these recommendations seem reasonable and in line with other organizations," , chief, obstetrical anesthesiology at Cedars-Sinai Medical Center in Los Angeles, told 麻豆传媒. "Therapy of 60-80 mg aspirin should begin in the late first trimester."

According to Zakowski, the American Heart Association (AHA) recommends that women with chronic hypertension or previous pregnancy-related hypertension should take low-dose aspirin starting at 12 weeks of gestation. The AHA also suggests calcium supplementation of more than 1 gram per day in women with low dietary intake of calcium to further help prevent preeclampsia.

The European NICE guideline suggests low-dose aspirin for women with at least one high level risk factor for preeclampsia (chronic hypertension, diabetes, autoimmune disease, hypertension in prior pregnancy) or two moderate level risk factors (age 40 years old or greater, first pregnancy, multiple gestation, greater then 10 years between pregnancy, body mass index greater then 35, family history of preeclampsia), Zakowski told 麻豆传媒.

"One study found an increased risk of abruption when aspirin was used -- 0.7% compared to 0.1%. However, subsequent studies have not found a statistically significant increased risk of abruption," Zakowski said.

Zakowski referenced a study by Subtil and colleagues, which found that "Maternal complications were more common in women taking low-dose aspirin for preeclampsia prevention, 19.5% aspirin group versus 15.8% control group, with minor bleeding (epistaxis, metrorrhagia, GI bleeding) being more common, 11.6% compared with 9.3%, and major bleeding (postpartum hemorrhage, abruption, transfusion) 4.6% versus 3.5% which did not reach statistical significance.

"Meta-analyses have not found a statistically significant increase in these complications. Fortunately, no study, even one with 18-month follow-up of the infant, showed adverse effects on the baby," Zakowski said.

He noted that preeclampsia is a complex disease, with potentially different origins.

"Most studies that show benefits of low-dose aspirin have started treatment by the end of the first trimester. Ideally, screening for those at risk for developing preeclampsia would enable better individualizing of therapy. Abnormal uterine artery Doppler studies in mid-pregnancy can predict who will develop preeclampsia, but routine screening by ACOG has not been recommended," Zakowski said.

A recent meta-analysis showed abnormal flow velocity waveform in the first trimester as having a sensitivity of 48% and good specificity (93%) for early-onset preeclampsia, Zakowski noted.

"There are also blood tests that may be useful," Zakowski said. "For example, placenta protein 13 shows great promise as a predictor of the development of preeclampsia. One study showed low placenta protein 13 in the first trimester as being the best predictor of who develops preeclampsia and low-dose aspirin was beneficial in this group.

"Perhaps with better patient selection criteria, the prevention of preeclampsia can be improved. Patient outcomes are being improved with interdisciplinary efforts among obstetricians, physician anesthesiologists, nurses, and midwives," Zakowski said.

From the American Heart Association:

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