Do advanced maternal age and nulliparity (having no previous births) qualify for low-dose Aspirin (acetylsalicylic acid) to decrease the risk of preeclampsia?

From the Guidelines

Advanced maternal age and nulliparity are recognized as moderate risk factors for preeclampsia, and low-dose aspirin prophylaxis is recommended to decrease this risk. According to the U.S. Preventive Services Task Force recommendation statement published in the Annals of Internal Medicine 1, women with a history of hypertension in a previous pregnancy, chronic kidney disease, autoimmune disease, type 1 or 2 diabetes, or chronic hypertension are considered high-risk, and those with more than one moderate-risk factor, such as first pregnancy, age ≥40 years, pregnancy interval >10 years, body mass index ≥35 kg/m2, family history of preeclampsia, or multifetal pregnancies, are also eligible for low-dose aspirin.

Key Points to Consider

• The recommended dose of aspirin for preeclampsia prevention is 75-81 mg per day, started between 12 weeks of gestation and continued until delivery 1.
• The American Heart Association and the American Stroke Association also recommend low-dose aspirin for women with chronic primary or secondary hypertension or previous pregnancy-related hypertension 1.
• The American Academy of Family Physicians suggests low-dose aspirin (81 mg/d) after 12 weeks of gestation in women at high risk for preeclampsia 1.
• The mechanism behind aspirin's protective effect involves its anti-inflammatory properties and ability to improve placental blood flow by inhibiting thromboxane production while preserving prostacyclin, thereby reducing placental ischemia that contributes to preeclampsia development.
• Low-dose aspirin can reduce preeclampsia risk by approximately 10-15% in women with moderate risk factors, such as advanced maternal age and nulliparity.

Important Considerations for Clinical Practice

• Women should use the low-dose (81 mg) formulation of aspirin specifically, not regular-strength aspirin.
• If starting after 16 weeks, low-dose aspirin may still be beneficial but may have reduced effectiveness.
• Patients should inform all healthcare providers about their low-dose aspirin use during pregnancy.
• The medication is generally well-tolerated with minimal side effects at this low dose.

From the Research

Preeclampsia Risk Factors and Aspirin Use

• Advanced maternal age and nulliparity are considered risk factors for preeclampsia 2, 3
• The American College of Obstetricians and Gynecologists recommends daily low-dose aspirin beginning in the late first trimester for women with a history of early-onset preeclampsia and preterm delivery at less than 34 0/7 weeks of gestation, or for women with more than one prior pregnancy complicated by preeclampsia 2
• Low-dose aspirin prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery 2

Aspirin Dosage and Timing

• The optimal dosage of aspirin for preeclampsia prevention is 81 mg/day 2
• Aspirin should be initiated at ≤16 weeks of gestation and at a daily dose of ≥100 mg to reduce the risk of preterm preeclampsia 4
• Administration of aspirin was associated with reduction in the risk of preterm preeclampsia, but there was no significant effect on term preeclampsia 4

Benefits and Harms of Aspirin Use

• Daily low-dose aspirin during pregnancy was associated with lower risks of serious perinatal outcomes for individuals at increased risk for preeclampsia, without evident harms 3
• Aspirin use was significantly associated with lower risk of preeclampsia, perinatal mortality, preterm birth, and intrauterine growth restriction 3
• There were no significant associations of aspirin use with risk of postpartum hemorrhage and other bleeding-related harms, or with rare perinatal or longer-term harms 3