Preeclampsia (PE) is a pregnancy-specific life-threatening disorder and one of the leading causes of maternal and fetal morbidity and mortality. It is responsible for approximately 16% of maternal deaths in the US and is the leading cause of intensive care unit admissions in the 6 weeks following delivery. Rates of severe PE have tripled since 1980. The diagnosis of PE is complicated by heterogeneity in the clinical presentation and symptom overlap with other medical conditions seen during pregnancy. Maternal and perinatal outcomes for women with PE can be significantly improved if the condition is identified early and intervention and treatment strategies can be accessed quickly. The current gold standard in clinical practice is to screen women at risk for PE based on clinical history and risk factors. While this strategy is well accepted, it remains a broadband screening with limited specificity and a high rate (64%) of false positives. Recent studies have shown that measurement of PlGF and sFlt-1 in the blood permit tracking the disease onset in patients at high-risk for developing PE. There is an urgent need for the development of an innovative device for a rapid, portable, and cost-effective testing of PE that leverages these biomarkers and can be used in a wide variety of health care environments, namely centralized laboratories, physician's offices, and at home. The objective of this Phase I proposal is to develop a novel reader-free point-of-care (PoC) device, PreeMo, for the monitoring and management of PE. PreeMo is an elegantly simple, inexpensive, rapid, accurate and easy to use device to measure quantitatively both PlGF and sFlt-1 in a single test, in less than two minutes, from finger prick blood sample. Importantly, the PreeMo device will feature all of the characteristics required for successful use in low resource settings with an ultimate goal of becoming FDA cleared for home use. The development plan will follow a Phase I for the identification and optimization of affinity reagents, and a Phase II to pre-clinically validate the PreeMo assay with clinical samples from women with a confirmed diagnosis of PE. Specifically, this Phase I efforts will focus on comprehensive development of the multiplex assay format and extended pre-clinical validation. Aim 1. PreeMo Development and Optimization: We will develop a multiplex assay prototype capable of performing bioassays for sFlt-1 and PlGF in parallel from a single blood sample. Aim 2. PreeMo Pre-clinical validation vs. benchmark lab-based device: PreeMo prototype test cards will be challenged with serum collected from pregnant women with confirmed PE along with sample specific de-identified medical history. Benchmarking will be performed against laboratory values. The successful development of this technology could significantly reduce hospitalization times and help prevent maternal and fetal morbidity arising from PE.
Public Health Relevance Statement: Project Narrative Preeclampsia (PE) is a life-threatening multi-system disorder of pregnancy characterized by hypertension and a leading cause of maternal and fetal morbidity and mortality, affecting 5% to 10% of pregnant women worldwide. In this Phase I application we will develop the first point-of-care blood test for the monitoring and early diagnosis of the onset of PE during pregnancy. The development of this novel PE test (PreeMo) addresses an unmet clinical need. The implantation of PreeMo in the clinical setting is expected to provide an immediate health benefit for millions of women and their at-risk infants, and will substantially reduce the economic burden associated with this disorder.
Project Terms: Address; Admission activity; Affect; Affinity; American; Angiogenesis Inhibitors; Antibodies; Antigens; base; Bedside Testings; Benchmarking; Biological Assay; Biological Markers; Blood; Blood specimen; Blood Tests; Characteristics; Clinical; clinical Diagnosis; clinical practice; Congresses; cost effective; Data; design; Detection; Development; Development Plans; Devices; Diagnosis; Disease; Disease Management; Early Diagnosis; Early Intervention; early onset; Economic Burden; Environment; Evolution; fetal; Fingers; Fostering; Funding; Future; Goals; Gold; Gynecologist; Health Benefit; Healthcare; Healthcare Systems; Heterogeneity; high risk; High-Risk Pregnancy; Home environment; Hospitalization; Hypertension; implantation; improved; Infant; innovation; Institutes; Intensive Care Units; Intervention; Intuition; Investments; Kidney; Laboratories; Lesion; Life; Maternal Mortality; Measurement; Measures; Medical; Medical History; Methods; microfluidic technology; mobile application; Monitor; monitoring device; Morbidity - disease rate; mortality; Multi-Institutional Clinical Trial; novel; Onset of illness; Patients; perinatal outcomes; Phase; Physicians' Offices; Placental Growth Factor; point of care; portability; pre-clinical; Pre-Eclampsia; Predictive Value; Pregnancy; pregnancy disorder; Pregnant Women; Premature Birth; prevent; Privatization; prototype; Reader; Reagent; Recommendation; Recording of previous events; Research; Resources; Risk; Risk Factors; Sampling; screening; screening guidelines; Serum; specific biomarkers; Specificity; standard of care; success; symptomatology; Symptoms; Technology; technology development; Test Result; Testing; Time; treatment strategy; Underinsured; urgent care; Validation; Vascular Endothelial Growth Factor Receptor-1; Woman
