Issued by: EndPreeclampsia, Inc
Perspective: Patient Advocacy Organization
Position Statement
EndPreeclampsia strongly supports the urgent and equitable development, validation, regulatory approval, payer coverage, reimbursement, and equitable clinical adoption of biomarkers and biomarker-based testing for hypertensive disorders of pregnancy (HDP). Robust biomarkers offer a transformative opportunity to enable better risk stratification, targeted surveillance, early risk prediction, earlier diagnosis, and timely intervention, improving outcomes for pregnant people and infants while reducing health system costs and inequities.3-7
Background and Problem Statement
HDP, including preeclampsia, eclampsia, HELLP Syndrome, mirror syndrome, gestational hypertension, and chronic hypertension with superimposed preeclampsia, remains a leading and increasing cause of maternal and perinatal morbidity and mortality.1,8 Despite decades of clinical advances, care for HDP still relies heavily on late-manifesting clinical signs (i.e., blood pressure elevations, proteinuria, end-stage organ failure, and fetal decompensation) rather than early, disease-specific indicators.2,3 There has not been significant advancement in these criteria in over 50 years.
Preeclampsia affects approximately 1 in 12 pregnancies in the U.S. and disproportionately impacts Black, Indigenous, and rural communities. Historical approaches to diagnosis have centered on the presentation of symptoms that, by their very nature, reflect advancement in disease progression. Further, the diagnostic criteria currently used in the United States were developed over 60 years ago and reflect an antiquated understanding of disease causation. As a result:
● Disease is frequently diagnosed late, when placental and vascular injury is already established.
● Clinicians lack objective tools to distinguish true preeclampsia physiology from mimicking conditions such as an exacerbation of chronic hypertension.
● Risk prediction is imprecise, leading to both under- and over-surveillance.
● Opportunities for prevention, efficient selection for therapeutic trials, and personalized care are missed.
From a public policy, clinical, and patient health outcomes standpoint, the historical
diagnostic paradigm is outdated and misaligned with modern precision medicine capabilities.
The Case for Biomarkers in HDP
Extensive basic science, translational, and clinical research demonstrates that preeclampsia is driven by placental dysfunction and angiogenic imbalance, processes not captured by blood pressure measurement alone.3,7 The disease has several subtypes that can be distinguished by different biomarker patterns.7 As such, biomarkers reflecting these pathways provide objective, disease-specific insight that can meaningfully improve care.
1. Earlier Detection and Risk Stratification
Validated biomarkers can identify biologic risk before overt clinical symptoms, enabling earlier detection and refined risk stratification, and targeted interventions.4–7Prospective studies show that biomarkers can predict progression to preeclampsia and adverse outcomes within clinically actionable timeframes.4,5,7
This supports a shift from reactive management to anticipatory, precision-based surveillance and proactive intervention.
2. Improved Diagnostic Accuracy
Validated biomarkers, particularly those reflecting placental dysfunction and angiogenic imbalance, can improve diagnostic precision in suspected HDP.3–7Studies evaluating placental growth factor (PlGF) and the soluble fms-like tyrosine kinase-1 to PlGF (sFlt-1:PlGF) ratio demonstrate high negative predictive value for ruling out preeclampsia with severe features and improved differentiation from mimicking conditions. 4–6
Objective biomarker data support clearer clinical decision-making, reduce unnecessary hospitalizations, and minimize delays in appropriate escalation of care.4,5
3. Reduction in Maternal and Neonatal Morbidity
Earlier and more precise screening and diagnosis support:
● Prevention of severe maternal complications (e.g., stroke, HELLP syndrome, renal failure).
● Reduction in medically indicated preterm birth – and subsequent neonatal intensive care unit (NICU) stays – driven by diagnostic uncertainty.
● Improved neonatal outcomes through optimized timing of delivery.
Public policy evidence consistently shows that upstream detection and prevention yield the greatest return on investment in maternal health.
4. Advancing Health Equity
Preeclampsia-related morbidity and mortality disparities are exacerbated by inconsistent access to specialty care and delayed diagnosis. Biomarker testing can be implemented equitably to:
● Standardize assessment across care settings, including both rural and urban under-resourced clinics.
● Reduce provider bias by anchoring decisions in objective biologic data.
● Support consistent thresholds for escalation of care.
Equitable access to biomarker testing must be a core implementation principle, not an afterthought. Additionally, biomarkers must be developed and validated in diverse populations, and their performance metrics demonstrated to be independent of race and ethnicity.
5. Enabling Research, Therapeutics, and Innovation
Biomarkers are essential infrastructure for:
● Clinical trials of targeted therapies for preeclampsia.
● Drug development focused on placental and endothelial pathways.
● Longitudinal research linking pregnancy complications to lifelong cardiovascular health.
Without validated biomarkers and urgent implementation, innovation in preeclampsia treatment will remain stalled.
Patient-Centered Evidence Supporting Biomarker Adoption: Findings from EndPreeclampsia’s Funded Work
EndPreeclampsia’s strong support for biomarkers is grounded not only in clinical and policy evidence, but also in patient-prioritized research identified through a funded initiative to build patient-centered research capacity for hypertensive disorders of pregnancy (HDPs).
To facilitate meaningful patient and stakeholder engagement in research prioritization, EndPreeclampsia convened two complementary stakeholder groups:
● Patient-Centered Research Ambassadors, comprised of individuals with lived experience of HDPs (patients and family members), trained in both patient-centered research principles and foundational HDP science; and
● ASPIRE (Alliance for Stakeholders of Preeclampsia to Inform Research Efforts), a multidisciplinary advisory board of patients, clinicians, researchers, and policy-relevant experts.
Lived Experience Identifies Screening and Diagnosis as the Top Priority
Convening focus groups representing a wide range of HDP experience, pregnancy outcomes, and identities, and using thematic analysis, the project team identified five overarching patient-centered research topics. The highest-priority topic, ranked most important by patients with lived experience, was HDP screening, risk factors, prevention, and treatment.
Patients consistently reported:
● Delayed or missed diagnosis of HDPs;
● Late referral to Maternal–Fetal Medicine or high-risk obstetric care;
● Limited management options once diagnosed; and
● Structural barriers to postpartum hypertension care.
These findings underscore that the clinical shortcomings addressed by biomarkers are not theoretical; they are experienced directly by patients and families.
From a public health perspective, these findings are critical: they demonstrate that biomarker-based approaches directly respond to patient-defined gaps in care and align with the goals of patient-centered comparative effectiveness research.
Policy-Relevant Implications
This funded work reinforces the point that biomarker development and implementation are not solely clinician-driven innovations; they are explicitly demanded by patients to improve the timeliness, accuracy, and equity of HDP care. Incorporating biomarkers into research agendas, clinical guidelines, and coverage policies is therefore essential to meeting federal standards for patient-centeredness and stakeholder-informed evidence generation.
Evidence Base: Key Biomarker Trials in Hypertensive Disorders of Pregnancy
| Study / Guideline | Biomarker(s) Evaluated | Population | Key Findings | Clinical Implications |
| PELICAN Study (Chappell et al.)6 | PlGF | Suspected preeclampsia | High accuracy for ruling out preeclampsia within 14 days | Supports early exclusion and outpatient management |
| PROGNOSIS (Zeisler et al.)4 | sFlt-1:PlGF ratio | Suspected preeclampsia | High negative predictive value for short-term disease progression | Improves triage and reduces unnecessary admissions |
| PROGNOSIS Asia / Validation Studies5 Levine et al.6 | sFlt-1:PlGF ratio sFlt-1, soluble endoglin | Diverse international cohorts Established preeclampsia | Consistent diagnostic and prognostic performance Identified angiogenic imbalance as core pathology | Demonstrates generalizability Foundation for biomarker-driven approaches |
| ACOG Practice Bulletin No. 2221 Elovitz et al.7 | Clinical criteria; emerging biomarkers Cell-free RNA | U.S. clinical guidance North America | Acknowledges evolving role of biomarkers Subtypes of preeclampsia can be distinguished by and predicted by molecular phenotypes | Supports guideline integration as evidence matures Predictive stratification of patients at risk of preeclampsia |
Policy and System-Level Recommendations
EndPreeclampsia calls for coordinated federal, state, and private-sector action to accelerate progress:
1. Federal Research Investment
● Increased NIH and NICHD funding dedicated to further biomarker discovery and validation.
● Inclusion of diverse populations in biomarker research cohorts.
2. Regulatory and Coverage Pathways
● Clear regulatory pathways for approval of HDP biomarker tests.
● CMS and private payer coverage for evidence-based biomarker testing.
● Avoidance of prior authorization and cost-sharing barriers that limit access.
3. Clinical Integration and Guidelines
● Support of validated biomarkers in national clinical guidelines.
● Provider education and training on interpretation and appropriate use.
● Integration into prenatal care workflows and electronic health records.
4. Equity-Focused Implementation
● Monitoring for disparities in test performance, access, and utilization.
● Support for safety-net providers and rural health systems.
● Community engagement to build trust and understanding.
Addressing Concerns and Misconceptions
EndPreeclampsia acknowledges concerns regarding overtesting, cost, and clinical uncertainty. These risks are best addressed through:
● Rigorous validation and evidence-based thresholds.
● Clear clinical protocols tied to test results.
● Ongoing outcomes research and real-world data collection.
Avoiding biomarker adoption due to imperfect implementation risks perpetuates a status quo that fails pregnant patients.
Conclusion
The evidence is clear: biomarkers represent a critical next step in modernizing care for hypertensive disorders of pregnancy. They offer better risk stratification in asymptomatic individuals, earlier detection, more precise prognosis, improved outcomes, and a pathway toward equity and innovation.
EndPreeclampsia urges policymakers, maternal health societies, researchers, laboratories, clinicians, investors, employers, and payers to act decisively to support biomarker development and testing, not as an optional
add-on, but as an essential component of high-quality, standardized evidence-based maternity care. Healthy pregnancies depend on detecting disease sooner.
References
1. American College of Obstetricians and Gynecologists (ACOG). Gestational Hypertension and Preeclampsia. Practice Bulletin No. 222. Obstetrics & Gynecology. 2020.
2. American College of Obstetricians and Gynecologists (ACOG). Emerging Diagnostic and Prognostic Biomarkers in Preeclampsia. Committee Opinion. ACOG; reaffirmed 2023.
3. Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: Pathophysiology, Challenges, and Perspectives. Circulation Research. 2019;124(7):1094–1112.
4. Zeisler H, Llurba E, Chantraine F, et al. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. New England Journal of Medicine. 2016;374:13–22.
5. Zeisler H, Llurba E, Verlohren S, et al. Validation of the sFlt-1:PlGF Ratio in the Diagnosis of Preeclampsia. Hypertension. 2019;74(2): 353–360.
6. Chappell LC, Duckworth S, Seed PT, et al. Diagnostic Accuracy of Placental Growth Factor in Women with Suspected Preeclampsia (PELICAN Study). Circulation. 2013;128(19):2121–2131. 7. Levine RJ, Lam C, Qian C, et al. Soluble Endoglin and Other Circulating Antiangiogenic Factors in Preeclampsia. New England Journal of Medicine. 2006;355:992–1005.
7. Elovitz, M.A, Gee, E.P.S., Delaney-Busch, N. et al. Molecular subtyping of hypertensive disorders of pregnancy. Nature Communications 16, 2948 (2025)
8. World Health Organization (WHO). WHO Recommendations for Prevention and Treatment of Pre-eclampsia and Eclampsia. WHO; updated guidance 2022.
9. U.S. Preventive Services Task Force (USPSTF). Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality. JAMA. 2021;326(12):1186–1191. 10. Patient-Centered Outcomes Research Institute (PCORI). PCORI Methodology Standards. Updated Methodology Report. PCORI; 2019.