What are the indications for low-dose aspirin (acetylsalicylic acid) in pregnancy, particularly for women with a history of preeclampsia, chronic hypertension, or low PAPP-A (Pregnancy-Associated Plasma Protein-A) levels?

Indications for Low-Dose Aspirin in Pregnancy

Low-dose aspirin (81-150 mg daily) should be initiated between 12-16 weeks of gestation and continued until delivery in pregnant women with any high-risk factor for preeclampsia, including history of preeclampsia, chronic hypertension, type 1 or type 2 diabetes, renal disease, autoimmune disease, or multifetal gestation. 1, 2, 3

High-Risk Factors (Any Single Factor Warrants Aspirin)

One high-risk factor is sufficient to initiate aspirin prophylaxis: 2, 3

• History of preeclampsia, especially early-onset preeclampsia with delivery <34 weeks 1, 4, 2, 3
• Chronic hypertension 1, 2, 3
• Type 1 or type 2 diabetes mellitus 1, 2, 3
• Renal disease 1, 2, 3
• Autoimmune disease (including systemic lupus erythematosus or antiphospholipid syndrome) 1, 2, 3
• Multifetal gestation (twins or higher-order multiples) 1, 2, 3

Moderate-Risk Factors (Two or More Warrant Aspirin)

Aspirin prophylaxis should be initiated when two or more moderate-risk factors are present: 1, 2, 3

• Nulliparity (first pregnancy) 1, 2, 3
• Maternal age ≥35 years 1, 2, 3
• Body mass index (BMI) >30 kg/m² 1, 2, 3
• Family history of preeclampsia 1, 2, 3
• Low socioeconomic status 1
• Interpregnancy interval ≥10 years 1

Dosing Recommendations

Standard Dosing

• 81-100 mg daily is the traditional U.S. recommendation for most high-risk women 1, 2, 3

Higher Dosing for Specific Populations

Consider 100-150 mg daily for: 1

• Women with type 1 or type 2 diabetes (100-150 mg daily specifically recommended by the American Diabetes Association) 1
• Women with chronic hypertension (standard 81 mg has shown no benefit in preventing superimposed preeclampsia in this population) 5, 1
• Women with BMI >40 kg/m² (higher doses needed to overcome altered pharmacokinetics in obesity) 1
• Multifetal gestation 1

The evidence increasingly supports that doses ≥100 mg initiated before 16 weeks are significantly more effective than lower doses, with risk reduction of RR 0.33 for preeclampsia. 1

Timing

Initiation

• Start between 12-16 weeks of gestation (optimally before 16 weeks) 1, 2, 3
• Aspirin may be initiated up to 28 weeks, but efficacy decreases with later initiation 1, 2, 3
• Early initiation is critical because defective placentation occurs in the first trimester, and aspirin improves uteroplacental blood flow during this critical period 1

Duration

• Continue daily until delivery 1, 2, 3
• Do not stop at 36 weeks—this removes protection during a high-risk period without evidence-based rationale 1
• Preeclampsia risk persists throughout pregnancy and into the early postpartum period 1

Clinical Benefits

Low-dose aspirin in high-risk women provides: 1, 4

• 24% reduction in preeclampsia risk 1, 4
• 14% reduction in preterm birth 1, 4
• 20% reduction in intrauterine growth restriction (IUGR) 1, 4
• Increased mean birthweight by approximately 130g 4
• Number needed to treat: 42 women to prevent one case of preeclampsia 4

Safety Profile

Low-dose aspirin does NOT increase risks of: 1, 4

• Placental abruption 1, 4
• Postpartum hemorrhage 1, 4
• Fetal intracranial bleeding 1, 4
• Perinatal mortality 1, 4
• Congenital anomalies 1, 4

Critical Pitfalls to Avoid

Do not use aspirin for preeclampsia prevention in women without risk factors—current evidence does not support prophylactic aspirin for prevention of early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth in low-risk women. 2, 3

Do not confuse low-dose aspirin (75-162 mg) with high-dose aspirin—the FDA warning about aspirin in the third trimester refers to high doses (>100 mg therapeutic doses), not prophylactic low doses. 1, 6

Do not underdose women with chronic hypertension—the standard 81 mg dose has been shown ineffective in this population, with one study showing no difference in superimposed preeclampsia rates (34.3% without aspirin vs. 35.5% with aspirin, p=0.79). 5, 1

Do not start aspirin too late—initiation after 16 weeks significantly reduces efficacy, as the critical window for improving placentation has passed. 1, 7

Special Consideration: Low PAPP-A

While low PAPP-A (Pregnancy-Associated Plasma Protein-A) levels are associated with increased risk of placental insufficiency and adverse outcomes, the current ACOG and USPSTF guidelines do not specifically list isolated low PAPP-A as an indication for aspirin prophylaxis. 2, 3 However, if low PAPP-A is accompanied by abnormal first-trimester uterine artery Doppler studies or other high-risk factors, aspirin is indicated. 7