How does Aspirin (acetylsalicylic acid) help in preventing Pregnancy-Induced Hypertension (PIH)?

How Aspirin Helps in Pregnancy-Induced Hypertension (PIH)

Mechanism of Action

Aspirin works by inhibiting cyclooxygenase-1 (COX-1) in the arachidonic acid pathway, which decreases production of thromboxane A2 (TxA2), a potent vasoconstrictor and platelet aggregator that contributes to the hypertensive state in preeclampsia. 1

The pathophysiology involves two key stages:

• Inadequate placental implantation: In normal pregnancy, trophoblasts invade the myometrium and remodel spiral arteries into low-resistance vessels. In preeclampsia, shallow invasion causes poor remodeling, leading to reduced uteroplacental perfusion and metabolic stress. 2

• Inflammatory cascade: The resulting placental hypoxia triggers release of inflammatory mediators including thromboxane A2, which causes endothelial dysfunction, vasoconstriction, and increased maternal blood pressure. 2

• Aspirin's protective effect: By inhibiting COX-1, aspirin reduces TxA2 production while preserving prostacyclin (a vasodilator), thereby improving the thromboxane/prostacyclin ratio and reducing vasoconstriction. 3, 4

Evidence for Efficacy

In High-Risk Populations (NOT Chronic Hypertension)

Meta-analysis of controlled trials demonstrates that low-dose aspirin reduces the risk of PIH by 65% (RR=0.35) in high-risk women, with a number needed to treat of 4-5 patients to prevent one case of PIH. 5

Additional benefits include:

• 44% reduction in severe low birth weight (RR=0.56) 5
• 66% reduction in cesarean section rates (RR=0.34) 5
• No increase in maternal or neonatal adverse effects 5

Critical Limitation: Chronic Hypertension

However, the most recent high-quality evidence shows that standard 81 mg aspirin does NOT prevent superimposed preeclampsia in women with chronic hypertension, despite ACOG recommendations. 2, 1

A 2020 retrospective cohort study of 457 women with chronic hypertension found:

• No difference in superimposed preeclampsia rates: 34.3% without aspirin vs 35.5% with 81 mg aspirin (p=0.79) 2
• Paradoxical increase in severe features: 21.7% vs 31.0% (p=0.03) 2
• No reduction in small-for-gestational-age infants or preterm birth 2

Recommended Dosing and Timing

Standard Recommendations

ACOG and USPSTF recommend 81 mg daily aspirin started between 12-16 weeks of gestation and continued until delivery for women at high risk of preeclampsia. 1

High-risk factors include:

• History of preeclampsia (especially delivery <34 weeks) 1
• Multifetal gestation 2
• Type 1 or type 2 diabetes 1
• Renal disease 2
• Autoimmune disease 2

Higher Doses for Specific Populations

For women with diabetes, the American Diabetes Association recommends 100-150 mg daily, as diabetes is an independent risk factor requiring higher dosing. 1

For women with chronic hypertension where standard 81 mg has failed, consider 150-162 mg daily as suggested by international guidelines (FIGO). 1

Additional considerations for higher dosing:

• BMI >40 kg/m² may reduce aspirin effectiveness and warrant dose adjustment 1
• Evidence suggests doses >100 mg initiated before 16 weeks may be more effective than standard dosing 1

Critical Timing Window

Aspirin must be initiated before 16 weeks of gestation for maximum effectiveness, as defective placentation and inadequate spiral artery remodeling occur in the first trimester. 1

• Starting aspirin early improves uteroplacental blood flow during the critical period of placentation 1
• Initiation after 16 weeks shows reduced efficacy 1

Safety Profile

Low-dose aspirin does not increase risks of placental abruption, postpartum hemorrhage, fetal intracranial bleeding, perinatal mortality, or congenital anomalies. 1, 5

Clinical Algorithm

For women presenting in early pregnancy:

1. Assess risk factors at first prenatal visit (before 12 weeks ideally) 6

2. High-risk factors present (history of preeclampsia, multifetal gestation, renal disease, autoimmune disease):

   • Start 81 mg aspirin at 12-16 weeks 1
   • Continue until delivery 1

3. Diabetes (type 1 or 2) present:

   • Start 100-150 mg aspirin at 12-16 weeks 1
   • Continue until delivery 1

4. Chronic hypertension present:

   • Caution: Standard 81 mg aspirin is NOT effective for preventing superimposed preeclampsia 2, 1
   • Consider higher dose (150-162 mg) based on FIGO recommendations 1
   • Counsel patient about limited evidence for efficacy in this population 2

5. BMI >40 kg/m²:

   • Consider dose adjustment above standard 81 mg 1

Common Pitfalls

• Starting aspirin too late (after 16 weeks) significantly reduces effectiveness 1
• Using standard 81 mg dose in chronic hypertension without recognizing it doesn't prevent superimposed preeclampsia 2
• Underdosing diabetic patients with standard 81 mg instead of recommended 100-150 mg 1
• Assuming aspirin works for all hypertensive disorders when evidence shows it fails in chronic hypertension 2