When should low‑dose aspirin be initiated in pregnancy for a woman with high‑risk preeclampsia, antiphospholipid syndrome, recurrent miscarriage, or other thrombophilic condition?

When to Start Aspirin in Pregnancy

Low-dose aspirin should be initiated between 12-16 weeks of gestation (optimally before 16 weeks) and continued daily until delivery for women at high risk of preeclampsia. 1, 2, 3

Optimal Timing Window

• Start aspirin between 12-16 weeks of gestation for maximum effectiveness, as this targets the critical period of placentation when defective spiral artery remodeling occurs 1, 3
• The window extends up to 28 weeks of gestation, but efficacy decreases significantly with later initiation 2, 3
• Evidence demonstrates that initiation before 16 weeks is significantly more effective than later initiation, particularly for doses ≥100 mg (RR 0.33,95% CI 0.19-0.57) 1

Earlier initiation (before 11 weeks) is safe but may not provide additional benefit. Recent evidence from 11,879 women shows no increased maternal, fetal, or neonatal adverse events when aspirin is started before 11 weeks, though the reduction in preeclampsia risk was not statistically significant (RR 0.52,95% CI 0.23-1.17, p=0.115) 4, 5

High-Risk Indications Requiring Aspirin

Single High-Risk Factor (start aspirin 12-16 weeks):

• History of preeclampsia, especially with delivery <34 weeks 2, 3
• Chronic hypertension 1, 2, 3
• Type 1 or type 2 diabetes 1, 2, 3
• Renal disease 2, 3
• Autoimmune disease (SLE, antiphospholipid syndrome) 6, 2, 3
• Multifetal gestation 2, 3

Multiple Moderate-Risk Factors (consider aspirin if ≥2 present):

• Nulliparity 1
• Maternal age ≥35 years 1, 2, 3
• 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 is 81-100 mg daily, but higher doses (100-150 mg daily) should be strongly considered for specific high-risk populations. 1, 7

Standard Dose (81 mg daily):

• Appropriate for most high-risk women 1, 8, 2, 3
• Supported by the American College of Obstetricians and Gynecologists and U.S. Preventive Services Task Force 2, 3

Higher Dose (100-150 mg daily) - Consider for:

• Chronic hypertension: Standard 81 mg has shown NO benefit in preventing superimposed preeclampsia (34.3% without aspirin vs 35.5% with aspirin, p=0.79), and severe features actually increased (21.7% vs 31.0%, p=0.03) 1
• Type 1 or type 2 diabetes: The American Diabetes Association recommends 100-150 mg daily 1
• BMI >40 kg/m²: Obesity increases platelet regeneration and reduces aspirin absorption, requiring higher doses for adequate platelet inhibition 6, 1
• Multifetal gestation 1

International guidelines increasingly favor 150 mg daily, with the International Federation of Gynecology and Obstetrics, Royal College of Obstetricians and Gynaecologists, and multiple European guidelines recommending this dose 1, 7

Special Populations

Antiphospholipid Syndrome:

• Combine low-dose aspirin (81-100 mg) with prophylactic-dose LMWH starting in first trimester for obstetric APS 6
• For thrombotic APS, use therapeutic-dose LMWH with aspirin 6
• Continue anticoagulation for 6-12 weeks postpartum 6
• Consider adding hydroxychloroquine to the regimen 6

Systemic Lupus Erythematosus:

• Start low-dose aspirin in the first trimester 6
• Combine with hydroxychloroquine throughout pregnancy 6
• Test for antiphospholipid antibodies early in pregnancy to guide additional therapy 6

Recurrent Miscarriage:

• Aspirin initiated before 11 weeks may reduce preterm delivery risk (RR 0.52,95% CI 0.27-0.97, p=0.04) but does not significantly reduce preeclampsia 4
• Consider preconception initiation for women with chronic conditions affecting placentation 1

Duration of Therapy

Continue aspirin daily until delivery—do not stop at 36 weeks. 1

• Preeclampsia risk persists throughout pregnancy and into the early postpartum period 1
• Low-dose aspirin (75-81 mg) does not increase risks of placental abruption, postpartum hemorrhage, or fetal intracranial bleeding when continued until delivery 1, 8, 2, 3
• The FDA warning about aspirin in third trimester refers to high doses (>100 mg), not prophylactic low doses 1

Exception for Planned Cesarean with Neuraxial Anesthesia:

• Consider discontinuing aspirin 7-10 days before scheduled cesarean to allow platelet recovery 9
• Verify platelet count >75 × 10⁹/L before spinal anesthesia 9

Common Pitfalls to Avoid

• Don't use 81 mg aspirin for chronic hypertension without considering dose escalation—this population shows no benefit at standard dosing and may require 150-162 mg daily 1
• Don't delay initiation beyond 16 weeks—effectiveness decreases significantly with later start 1, 3, 7
• Don't stop aspirin at 36 weeks "to be safe"—this removes protection during a high-risk period without evidence-based rationale 1
• Don't confuse low-dose (75-162 mg) with high-dose aspirin—safety data applies only to low doses 1
• Don't forget to combine aspirin with LMWH in antiphospholipid syndrome—aspirin alone is insufficient 6

Safety Profile

Low-dose aspirin in pregnancy has an excellent safety record: 8, 2, 3, 5

• No increased risk of placental abruption
• No increased risk of postpartum hemorrhage
• No increased risk of fetal intracranial bleeding
• No increased risk of perinatal mortality
• No increased risk of congenital anomalies
• Safe when initiated before 11 weeks of gestation

Expected Benefits

When initiated appropriately, low-dose aspirin provides: 1, 8

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