An Aspirin a Day... Keeps Preeclampsia at Bay?

Women carrying twins. Women who begin pregnancy with diabetes, or hypertension, or lupus. African-American women who become pregnant after age 35.

What do these different groups of pregnant women have in common?

The American College of Obstetricians and Gynecologists (ACOG) now considers them candidates for early aspirin therapy—a daily baby aspirin starting at the end of the first trimester—to reduce their risk of preeclampsia.

Preeclampsia is a serious pregnancy complication involving high blood pressure and problems with other organs, such as the kidney or liver. It affects 2-8% of all pregnancies in the U.S.

Until last year, ACOG reserved aspirin therapy for women with a history of severe preeclampsia in earlier pregnancies. These women were indeed at very high risk of having preeclampsia again. But they represent only a tiny fraction of the women who would develop the condition. In fact, preeclampsia is most common in first pregnancies.

Then, in 2018, ACOG vastly expanded the number of women eligible for aspirin therapy during pregnancy. (See the box below for the full list.)

Why the Change in Guidelines?

Whether aspirin helps prevent preeclampsia has long been one of the more controversial questions in pregnancy research.

Then in 2017, the results of the ASPRE trial gave a clear answer: Early aspirin therapy helps prevent preterm preeclampsia (preeclampsia beginning before 37 weeks).

(Daily aspirin unfortunately does not help prevent term preeclampsia (preeclampsia starting after 37 weeks).)

In ASPRE, a large, double-blind, placebo-controlled trial, researchers tracked 1776 pregnant women from 13 maternal hospital in Europe and Israel. All women were carrying singletons (no twins or higher order multiples) and were considered at high-risk for preterm preeclampsia*. The women were randomly assigned to receive either 150 mg of aspirin per day or a placebo from 11 weeks to 36 weeks of gestation. 

Preterm preeclampsia occurred in 4.3% of the placebo group, but only 1.6% of the aspirin group—a 60% reduction. Aspirin benefited women no matter their age or education background. And the more consistent women were with taking a daily aspirin, the lower their risk.

There was one group, however, whom aspirin did not benefit: Women with pre-existing hypertension (high blood pressure prior to becoming pregnant). If anything, women with pre-existing hypertension were more likely to develop preterm preeclampsia if they received aspirin rather than the placebo.**

However, for women without pre-existing high blood pressure, the risk reduction was truly staggering: Daily aspirin reduced their risk of preterm preeclampsia by over 95%.

This alone is a tremendous victory. Preterm preeclampsia tends to be more severe than term preeclampsia, and it is a major cause of induced preterm births. 

Aspirin Therapy, Best Practices

After years of careful study, we now have a reasonably clear picture how to use aspirin to help prevent preterm preeclampsia:  

1. Start early: An aspirin regimen works best if initiated early—ideally before 16 weeks.
2. Take a modest amount, daily. The right dosage is still being worked out. Studies suggest that 150 mg/day is more effective than 60 mg/day. However, ACOG currently recommends 81 mg/day because of limited safety data for higher doses and because this is the amount found in baby aspirin in the U.S.
3. Take aspirin at night: Our circadian rhythm affects how we respond to aspirin. To lower blood pressure, aspirin must be taken at night. (Incidentally, this is true for everyone, not just pregnant women).

How Does Aspirin Therapy Work?

We do not know for sure, but there are two leading theories.

1. Aspirin inhibits thromboxane, a hormone that raises blood pressure and is known to be elevated in women with preeclampsia.
2. Aspirin improves blood flow across the placenta, by dilating uterine arteries. Inadequate placental blood supply is thought to play a key role in initiating preeclampsia. 

The Limits of Aspirin Therapy

Studies find that aspirin does not help prevent term preeclampsia (preeclampsia occurring after 37 weeks). And, in the ASPRE trial, it failed to help women who start pregnancy with hypertension, over 1 in 5 of whom will develop preeclampsia during pregnancy.

Aspirin is a new and important tool in our arsenal for preventing preeclampsia. We sincerely hope the expanded guidelines rapidly make their way into clinical practice, and that all women eligible for aspirin therapy receive it. But it is no cure.

We Still Need a Cure

In researching this article, I read through hundreds of women sharing preeclampsia stories on social media—of early labors, long NIUC stays, and losing their babies. Heartbreaking stories of women in the prime of their lives suffering strokes and liver damage. Even those that ultimately ended “happily”—in a healthy baby and a healthy mother—were harrowing.

Preeclampsia’s health consequences may also extend well beyond birth. Women who have had preeclampsia face a greatly elevated risk of chronic high blood pressure and heart disease.

“Preterm preeclampsia is a stronger risk factor than smoking for the development of stroke and other cardiovascular diseases in women” 

– Basky Thilaganathan, Professor and Director of Fetal Medicine at St George’s Hospital in the United Kingdom, noted in a recent editorial.

Despite these serious harms, preeclampsia research has proceeded at a snail’s pace—bogged down by safety concerns, logistical challenges, and a lack of funding. From 1996-2006, the National Institutes of Health (NIH) funded only 40 research projects on preeclampsia, despite preeclampsia’s growing toll on pregnant women in the U.S. 

Fortunately, this situation has finally begun to turn around. The NIH is currently funding over 100 funded research projects on preeclampsia. Let’s hope women don’t have to wait much longer for a real cure.

*How best to determine a woman’s risk of preterm preeclampsia remains unclear. Thus far, the American College of Gynecologists (ACOG) has declined to endorse any clinical algorithms for predicting preeclampsia, including the one used in ASPRE trial. For now, ACOG continues to rely on a risk factor based approach. This may change soon. The latest data suggests that algorithms which incorporate ultrasound measurements, blood flow across the umbilical cord, and maternal hormone levels in the first trimester (like the one used in ASPRE ) predict preeclampsia better than risk factors alone. 

**Despite the ASPRE trial showing no benefit for women who start pregnancy with chronic high blood pressure, ACOG recommends these women (who are at high risk of preeclampsia) receive early aspirin therapy. If this applies to you, we recommend talking with your doctor about the risks and benefits of early daily aspirin.