What are the new promising strategies for preventing preeclampsia in high‑risk pregnant women?

New Promising Strategies for Preeclampsia Prevention

Low-dose aspirin (100-150 mg daily) started before 16 weeks gestation remains the cornerstone of preeclampsia prevention, while emerging therapies including metformin, dextran sulfate apheresis, and advanced multiomics-based risk stratification show promise but require validation in large randomized trials. 1

Established Prevention: Low-Dose Aspirin

The most robust evidence supports low-dose aspirin as the primary preventive strategy for high-risk women. 1

• Initiate aspirin at 100-150 mg daily (81-162 mg acceptable) before 16 weeks gestation, ideally by 12 weeks, and continue until delivery to achieve maximal reduction in preterm preeclampsia risk. 2, 3, 4
• Aspirin started before 16 weeks reduces preterm preeclampsia by approximately 62%, with the protective window closing at 20 weeks. 2, 3
• Evening dosing may offer superior efficacy compared to morning administration. 1
• High-risk criteria include: prior preeclampsia (including postpartum), chronic hypertension, diabetes (type 1 or 2), renal disease, autoimmune disease, or multiple gestation. 2, 4
• Women with multiple moderate-risk factors (nulliparity, age >35-40 years, BMI >30-35, family history, pregnancy interval >10 years) should also receive aspirin prophylaxis. 2, 3, 4

Calcium Supplementation as Adjunct Therapy

Calcium supplementation provides substantial benefit in women with low dietary calcium intake but is not a substitute for aspirin. 1, 3

• Provide 1.2-2.5 g elemental calcium daily when dietary intake is <600-800 mg/day, which reduces preeclampsia risk by 36-64% in this population. 1, 3, 5
• Calcium carbonate in divided doses of ≤500 mg per dose optimizes absorption. 5
• Continue calcium supplementation even if placental calcification is detected on ultrasound, as supplements do not cause or worsen calcification. 3

Emerging Pharmacologic Interventions

Metformin

Metformin shows preliminary promise for extending gestation and targeting molecular pathways in preeclampsia, but requires confirmation in larger trials. 1

• Recent studies suggest metformin may prolong pregnancy by approximately 1 week in women with established preeclampsia and mediate pathways implicated in both preeclampsia and fetal growth restriction. 1
• This intervention remains investigational and should not be used outside research protocols until validated. 1

Dextran Sulfate Apheresis

Exploratory pilot studies suggest dextran sulfate apheresis may reduce circulating sFlt-1 and proteinuria in early preterm preeclampsia without major adverse effects. 1

• This therapy targets the antiangiogenic imbalance characteristic of preeclampsia by removing soluble fms-like tyrosine kinase-1 (sFlt-1). 1
• Interpret these results cautiously—this strategy has not been evaluated in larger randomized trials and remains experimental. 1

Statins and Other Antiangiogenic Therapies

Pravastatin did not demonstrate efficacy in treating preeclampsia in recent trials, but other antiangiogenic approaches remain under investigation. 1, 6

• Emerging management approaches include hypoxia-inducible factor suppression, CoQ10, nitric oxide donors, and hydrogen sulfide donors, though none are ready for clinical implementation. 6

Advanced Prediction and Risk Stratification

Multiomics and Machine Learning

Comprehensive genomic, proteomic, and metabolomic approaches combined with machine learning are identifying novel mechanisms and molecular targets for intervention. 1

• Genome-wide association studies have identified maternal and fetal genetic variations associated with increased preeclampsia risk. 1
• Machine learning algorithms are being developed for early detection and identification of preeclampsia subtypes to enable targeted interventions. 1

Biomarker-Based Screening

First-trimester screening combining maternal risk factors, blood pressure, placental growth factor (PlGF), and uterine artery Doppler refines risk stratification but does not reliably predict all cases. 1, 2

• Biomarkers including uterine artery pulsatility index, mean arterial pressure, pregnancy-associated plasma protein A (PAPP-A), PlGF, and sFlt-1 show promise for predicting early- and late-onset preeclampsia. 1
• Do not rely solely on biomarker testing for clinical decision-making, as routine use outside clinical trials is not recommended. 2

Lifestyle and Non-Pharmacologic Interventions

Regular exercise and weight management provide modest benefit without significant adverse effects. 1, 3

• Encourage at least 50 minutes of combined aerobic, strength, and flexibility training 3 times weekly, which reduces gestational hypertension and preeclampsia while limiting excessive weight gain. 1, 3
• Maintain ideal body weight and avoid excessive gestational weight gain. 3, 5
• Do not recommend bed rest, salt restriction, or vitamin C/E supplementation—these interventions are ineffective or potentially harmful. 1, 3, 7

Critical Gaps and Future Directions

Many interventions showing promise in preclinical or small pilot studies have failed in large randomized controlled trials, highlighting the need for rigorous validation. 1

• Future trials must include adequate numbers of women from high-risk racial/ethnic populations (particularly Black women who face disproportionate disease burden) and stratify by preeclampsia subtype. 1, 6
• Research is needed to understand how aspirin response varies with individual risk factors and to develop personalized dosing strategies. 1
• Interventions must be designed to meet the needs of low- and middle-income countries where preeclampsia burden is highest. 1

Common Pitfalls to Avoid

• Do not delay aspirin initiation beyond 16 weeks—the optimal benefit window closes at 20 weeks. 2, 3
• Do not prescribe low-molecular-weight heparin for preeclampsia prevention, even in women with early-onset disease history—it is not indicated. 2, 8
• Do not assume postpartum preeclampsia carries lower recurrence risk—treat it equivalently to antepartum preeclampsia for risk stratification. 2
• Do not use NSAIDs for postpartum analgesia in women with preeclampsia, especially those with renal involvement—use acetaminophen instead. 5

Health Equity Considerations

Addressing systemic and community-level factors that limit access to care has the greatest potential to improve outcomes and reduce disparities. 1

• Black women face particularly high preeclampsia risk due to higher rates of chronic hypertension, healthcare disparities, and possible genetic factors (e.g., APOL1 gene). 6
• Interventions targeting socioeconomic factors and environmental context are more effective than individual counseling alone. 1
• Remote blood pressure monitoring and mobile health applications can improve access but are not equitably distributed. 1