Aspirin Use for the Prevention of Morbidity and Mortality from Preeclampsia: Preventive Medication--Pregnant Women who are at High Risk for Preeclampsia


General

Grade: B The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Offer or provide this service.

Specific Recommendations

The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication after 12 weeks of gestation in women who are at high risk for preeclampsia.

Frequency of Service

Use of low-dose aspirin was initiated between 12 and 28 weeks of gestation. Evidence did not suggest additional benefit when use of aspirin was started earlier (12 to 16 weeks) rather than later (≥16 weeks) in pregnancy in women at increased risk for preeclampsia.

Risk Factor Information

No information available.


Clinical

There are no validated methods of identifying women at high risk for preeclampsia on the basis of biomarkers, clinical diagnostic tests, or medical history. Most clinicians use medical history to identify women at high risk. Risk factors, based on medical history, may help guide clinicians and their patients in the decision to begin aspirin use.

Although clinical risk assessments were not systematically reviewed for this recommendation, a pragmatic approach is described in the Table. This approach may help to identify a patient population with an absolute risk for preeclampsia of at least 8%, which is consistent with the lowest preeclampsia incidence observed in control groups in studies reviewed by the USPSTF. Women with 1 or more high-risk factors should receive low-dose aspirin. Women with several moderate-risk factors may also benefit from low-dose aspirin (Table), but the evidence is less certain for this approach. Clinicians should use clinical judgment in assessing the risk for preeclampsia and talk with their patients about the benefits and harms of low-dose aspirin use.  

Table. Clinical Risk Assessment for Preeclampsia*

Risk LevelRisk FactorsRecommendation
High History of preeclampsia, especially when accompanied by an adverse outcome
Multifetal gestation
Chronic hypertension
Type 1 or 2 diabetes
Renal disease
Autoimmune disease (systemic lupus erythematous, antiphospholipid syndrome)
Recommend low-dose aspirin if the patient has ≥1 of these high-risk factors
Moderate Nulliparity
Obesity (body mass index >30 kg/m2)
Family history of preeclampsia (mother or sister)
Sociodemographic characteristics (African American race, low socioeconomic status)
Age ≥35 years
Personal history factors (e.g., low birthweight or small for gestational age, previous adverse pregnancy outcome, >10-year pregnancy interval)
Consider low-dose aspirin if the patient has several of these moderate-risk factors§
Low Previous uncomplicated full-term delivery Do not recommend low-dose aspirin
*Includes only risk factors that can be obtained from the patient medical history. Clinical measures, such as uterine artery Doppler ultrasonography, are not included.
†Single risk factors that are consistently associated with the greatest risk for preeclampsia. The preeclampsia incidence rate would be approximately ≥8% in a pregnant woman with ≥1 of these risk factors.
‡ A combination of multiple moderate-risk factors may be used by clinicians to identify women at high risk for preeclampsia. These risk factors are independently associated with moderate risk for preeclampsia, some more consistently than others.
§ Moderate-risk factors vary in their association with increased risk for preeclampsia.

Assessment of Risk for Adverse Effects

Low-dose aspirin use in women at increased risk for preeclampsia has not been shown to increase the occurrence of placental abruption; postpartum hemorrhage; or fetal harms, such as intracranial bleeding and congenital anomalies.

Use of Preventive Medication

The dosage and timing of initiation of low-dose aspirin varied across studies. However, the beneficial effects and small harms of low-dose aspirin were consistent across dosages and timing of initiation. It was not possible to determine from the evidence whether a specific dosage or timing of aspirin use conferred greater benefit over other dosages or intervals.

Dosage

Low-dose aspirin at dosages between 60 and 150 mg/d reduced the occurrence of preeclampsia, preterm birth, and IUGR in women at increased risk for preeclampsia in several randomized trials. The most commonly used dosage was 100 mg/d, but the 2 largest trials contributing to the estimates of benefit used 60 mg/d. Although studies did not evaluate a dosage of 81 mg/d, low-dose aspirin is available in the United States as 81-mg tablets, which is a reasonable dosage for prophylaxis in women at high risk for preeclampsia.

Timing

Use of low-dose aspirin was initiated between 12 and 28 weeks of gestation. Evidence did not suggest additional benefit when use of aspirin was started earlier (12 to 16 weeks) rather than later (≥16 weeks) in pregnancy in women at increased risk for preeclampsia.

Research Needs and Gaps

Research is needed on the effect of low-dose aspirin on the development of preeclampsia and how the magnitude of response to low-dose aspirin varies with individual or combined risk factors for preeclampsia. Research on how to improve clinicians' ability to identify women at increased risk for preeclampsia, particularly those who would receive the greatest benefit from aspirin as preventive medication, is also needed. Efforts to validate the effectiveness of risk assessment tools using clinical history alone or combined with clinical testing may help clinicians better identify high-risk women who will benefit from aspirin as preventive medication, and help reduce the incidence of preeclampsia and its consequent outcomes.

Further research in populations that bear the highest disease burden for preeclampsia, including African American and nulliparous women, is needed. Multivariable risk prediction models that identify healthy nulliparous women who are likely to develop preeclampsia are in development, but further refinement and validation are needed. Additional research to further assess preeclampsia risk in pregnant women with 1 or more moderate-risk factors is needed. Future trials should recruit adequate numbers of women from racial/ethnic populations that are at disproportionate risk, such as African American women, in order to have sufficient power to determine the effectiveness of different aspirin dosages and timing of initiation in these high-risk groups.

Larger studies investigating aspirin use in the first or early second trimester may improve the evidence base on optimal timing of low-dose aspirin as preventive medication. Other areas of research include optimal therapies that individualize the aspirin dosage and timing of administration (e.g., morning vs. bedtime).

In addition, studies that explore less well-established risk factors that may better identify women at high risk for preeclampsia are needed. Further research should also investigate whether preeclampsia prevention with low-dose aspirin affects women's long-term risk for cardiovascular disease and whether there are benefits to continuing low-dose aspirin after delivery in women with 1 or more high-risk factors.

Other Approaches to Prevention

The USPSTF recommends that all women planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400 to 800 µg) of folic acid. More information is available at www.uspreventiveservicestaskforce.org.

Rationale

No information available.


Others

The American College of Obstetricians and Gynecologists recommends initiating use of low-dose aspirin (60 to 80 mg/d) during the late first trimester to prevent preeclampsia in women with a medical history of early-onset preeclampsia and preterm delivery (<34 weeks) or history of preeclampsia in more than 1 previous pregnancy. The World Health Organization recommends the use of low-dose aspirin (75 mg/d) starting as early as 12 to 20 weeks of gestation for high-risk women (i.e., those with a history of preeclampsia, diabetes, chronic hypertension, renal or autoimmune disease, or multifetal pregnancies). It states that there is limited evidence regarding the benefits of low-dose aspirin in other subgroups of high-risk women. The National Institute for Health and Clinical Excellence recommends that women at high risk for preeclampsia (i.e., women with a history of hypertension in a previous pregnancy, chronic kidney disease, autoimmune disease, type 1 or 2 diabetes, or chronic hypertension) take 75 mg/d of aspirin from 12 weeks until delivery. It recommends the same for women with more than 1 moderate-risk factor (first pregnancy, age ≥40 years, pregnancy interval >10 years, body mass index ≥35 kg/m2, family history of preeclampsia, or multifetal pregnancies).The American Heart Association and the American Stroke Association recommend that women with chronic primary or secondary hypertension or previous pregnancy-related hypertension take low-dose aspirin from 12 weeks until delivery. The American Academy of Family Physicians recommends low-dose aspirin (81 mg/d) after 12 weeks of gestation in women who are at high risk for preeclampsia.


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