Low-Dose Aspirin Recommended for Prevention of Preeclampsia in High-Risk Pregnant Women

Pregnancy and childbirth sometimes have substantial health risks for the mother and baby. High among those risks is a condition that occurs during pregnancy known as preeclampsia, which is characterized by hypertension (high blood pressure) and signs of kidney, liver or other organ damage in the mother.[1]

Because it occurs so frequently and can be so devastating to pregnant women and their developing babies, measures to prevent preeclampsia are an essential component of good prenatal and perinatal care. One extensively studied method to prevent preeclampsia is maternal ingestion of daily low-dose aspirin (BAYER ASPIRIN, ECOTRIN, VAZALORE).

The U.S. Preventive Services Task Force (USPSTF) — a federally supported volunteer panel of national experts in evidence-based medicine and disease prevention that works independently of the pharmaceutical and medical-device industries — recently issued an updated recommendation regarding the use of low-dose aspirin to prevent preeclampsia in expectant mothers at high risk for the disorder.[2]

Background on preeclampsia

Preeclampsia is a disorder of pregnancy defined by the development of high blood pressure after 20 weeks’ gestation in a patient with previously normal blood pressure — or worsening hypertension or hypertension resistant to treatment in an individual with existing chronic hypertension — and new onset of one or more of the following:

• Proteinuria (protein in the urine)
• Low blood platelet (disc-shaped structures involved in blood clotting) count
• Decreased kidney function
• Liver damage
• Pulmonary edema (fluid in the lungs)
• New-onset and persistent headache not due to a recognizable cause and unresponsive to analgesics
• Visual symptoms (for example, blurred vision or sensation of flashing lights)[3]

Preeclampsia is believed to be related to abnormal development of the blood vessels in the placenta.[4]

The disorder’s severity and course are difficult to predict, but in extreme cases it can cause maternal seizures, stroke, organ damage and death. It also poses serious risks to the developing baby, including growth retardation, preterm birth, stillbirth and neonatal death.[5] Delivery of the baby is the definitive treatment for preeclampsia and the best approach for minimizing these serious complications, but such action depends on many factors including preeclampsia severity, the broader condition of the mother and fetus, and gestational age.[6]

In the U.S., the overall incidence of preeclampsia is about 5% of all deliveries.[7] In Black women, that incidence is higher at approximately 7%, compared with about 4% among White women.[8] Preeclampsia accounts for 6% of all preterm births and nearly 20% of medically induced preterm births in the U.S.[9]

Low-dose aspirin has been shown to reduce the frequency of preeclampsia and related adverse pregnancy outcomes in women at risk for the disease. The beneficial effects of aspirin in reducing the risk of preeclampsia are thought to be due to its antiplatelet and anti-inflammatory properties.[10]

USPSTF recommendation update

In the Sept. 28, 2021, issue of the Journal of the American Medical Association (JAMA), the USPSTF published its updated recommendation in favor of “the use of low-dose aspirin (81 mg/d) as preventive medication after 12 weeks of gestation in persons who are at high risk for preeclampsia.”[11] Pregnant women are considered to be at high risk if they have one or more of the following risk factors:

• A history of preeclampsia during a prior pregnancy
• Pregnant with more than one fetus (for example, twins or triplets)
• Chronic hypertension prior to the pregnancy
• Diabetes prior to the pregnancy
• Kidney disease
• Autoimmune disease (for example, systemic lupus erythematosus)

Pregnant women also are considered to be at high risk for preeclampsia if they have two or more the following risk factors:

• Nulliparity (no prior live births)
• Obesity (defined as a body-mass index, which is based on weight and height, of more than 30)
• Having a mother or sister who had preeclampsia
• Black race (this is due to social, rather than biological, factors)
• Lower income
• Age 35 years or older
• In vitro conception
• Other personal history factors (for example, low birth weight, previous adverse pregnancy outcome or more than 10 years since last pregnancy)

This recommendation is essentially the same as that issued by the USPSTF in 2014 but is strengthened by new evidence from additional clinical trials demonstrating reduced perinatal mortality with low-dose aspirin use.

Prior to updating its 2014 recommendation, the USPSTF commissioned a systematic review of randomized, placebo-controlled clinical trials that enrolled pregnant women and assessed the benefits and risks of low-dose aspirin for preventing preeclampsia or related adverse outcomes (maternal or child).[12] Sixteen trials together enrolled just over 14,000 high-risk subjects to assess the effect of low doses of aspirin (50 mg to 150 mg daily) on the incidence of preeclampsia. The incidence of preeclampsia across these 16 trials ranged from 4% to 30%. The relative risk of preeclampsia across the 16 trials decreased by 15% with the use of low-dose aspirin, with an overall absolute risk reduction of approximately 4%. The systematic review also found a relative 21% reduction in the risk of perinatal mortality and a relative 20% reduction in preterm birth. The review revealed no increased risk of bleeding post-delivery in the mothers or other bleeding complications with low-dose aspirin use.

Based on the systematic review, the USPSTF concluded “with moderate certainty that there is a substantial net benefit of daily low-dose aspirin to reduce the risk for preeclampsia, preterm birth, small for gestational age/intrauterine growth restriction, and perinatal mortality in pregnant persons at high risk for preeclampsia.”[13]

What You Can Do

If you are pregnant, consult with an obstetrician early in your pregnancy regarding your risk of preeclampsia to decide whether you should be treated with low-dose aspirin starting at 12 weeks of gestation.

Regardless of your preeclampsia risk, seek regular prenatal care to monitor and manage your blood pressure and other important vital signs carefully throughout your pregnancy and during the period immediately following your child’s delivery.

If you experience any of the following symptoms during your pregnancy, consult with your doctor right away as these may be signs of preeclampsia:[14]

• Swelling of the hands and face or eyes
• Sudden weight gain over one to two days or more than 2 pounds in a week
• Persistent or intensifying headache
• Difficulty breathing
• Abdominal pain on your right side, below the ribs or in your right shoulder
• Marked reduction in urination frequency
• Nausea and vomiting
• Vision changes, temporary blindness, flashing lights or spots, light sensitivity or blurriness
• Feeling lightheaded or faint

References

[1] August P, Sibai BM. Preeclampsia: Clinical features and diagnosis. UpToDate. February 18, 2022.

[2] US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;326(12):1186-1191.

[3] August P, Sibai BM. Preeclampsia: Clinical features and diagnosis. UpToDate. February 18, 2022.

[4] Karumanchi SA, Lim KH, August P. Preeclampsia: Pathogenesis. UpToDate. September 10, 2021.

[5] Henderson JT, Vesco KK, Senger CA, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021; 326(12):1192-1206.

[6] Norwitz ER. Preeclampsia: Management and prognosis. UpToDate. February 18, 2022.

[7] Henderson JT, Vesco KK, Senger CA, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021; 326(12):1192-1206.

[8] Ibid.

[9] US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;326(12):1186-1191.

[10] August P, Jeyabalan A. Preeclampsia: Prevention. UpToDate. December 21, 2021.

[11] US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;326(12):1186-1191.

[12] Henderson JT, Vesco KK, Senger CA, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021; 326(12):1192-1206.

[13] US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;326(12):1186-1191.

[14] MedlinePlus. Preeclampsia. February 18, 2022. https://medlineplus.gov/ency/article/000898.htm. Accessed March 8, 2022.