Background & Significance: Each year, out of 4 million pregnancies in North America, approximately 800,000 are classified as high risk. A striking 20% of these pregnancies develop critical perinatal disorders. The notable gap in early-stage diagnostic tools underscores a pressing need in perinatal medicine. Objective & Innovation: We propose a pioneering approach to delineate the clinical relevance of placental biomarkers, detectable in the cervical canal during the first trimester. Utilizing these biomarkers, we aim to offer clinicians a cutting-edge diagnostic solution, paving the way for earlier interventions and enhancing the negative predictive value of current measures. Approach: · Milestone 1: Systematic collection and archival of cervical and blood specimens from 200 high-risk pregnancies between 10-12 weeks of gestation. Specialized collection kits ensure efficiency, while informed consent facilitates a secure and comprehensive data collation. · Milestone 2: Quantitative assessment of biomarker concentrations by ELISA in archived samples. Targeting five pivotal placenta proteins, we aim to highlight those indicative of pregnancies prone to fetal growth restriction, miscarriage, or preeclampsia. · Milestone 3: Establish rigorous correlations between cervical specimen biomarker levels and clinical outcomes. Advanced regression analysis will determine the relationship between biomarkers and birthweight. Comprehensive digital records on perinatal pathologies will support correlation analyses, ROC evaluations, and model-fitting techniques. Projections indicate approximately 18% (or 25) of this high-risk cohort will experience perinatal complications—evident distinctly in cervical biomarker levels. Team & Commercialization: Led by a distinguished team with a track record of groundbreaking research in reproductive health, and supported by experts in clinical perinatology, biomarker detection and data analysis, we are uniquely positioned to tackle this challenge. Our clear roadmap includes patenting all IP and aspires to launch a diagnostic kit that will benefit the vast number of high-risk pregnancies, initially with potential for a point-of-care solution in the clinic and subsequently at home, signaling strong commercial promise. Feasibility & Impact: With pilot data and a structured methodology, the proposed study is on track to validate the diagnostic platform, laying groundwork for a more comprehensive Phase II clinical utility validation study. Early identification of at-risk patients promises a significant reduction in adverse outcomes, offering immense benefits to both mothers and infants and generating considerable healthcare savings. Conclusion: Merging in-depth research with tangible clinical benefits, our initiative represents a transformative shift in early-stage perinatal intervention, with vast implications for a significant portion of pregnancies.

Narrative version We aim to introduce a first-trimester testing platform to detect early pregnancy complications, allowing timely interventions for high-risk pregnancies. Using a non-intrusive method akin to a pap test, we will quantify protein biomarkers indicative of the risk level for pregnancy disorders. This approach will offer insights comparable to ultrasound but much earlier in the pregnancy, facilitating personalized care plans. Our goal is to launch a point- of-care perinatal test, revolutionizing care for mothers and their babies.