# Clinical utility of novel biomarkers for prediction of early pregnancy failure

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $671,048

## Abstract

Abstract: The diagnosis and management for women who are at risk for ectopic pregnancy (EP) and
spontaneous abortion (SAB), has not changed substantially in decades. While ultrasound can diagnose a
significant portion of women at presentation, because of its limited accuracy in abnormal and early gestation, a
large number of women need serial tests and procedures to determine the final location and viability of an early
pregnancy. Misdiagnosis and iatrogenic complications during this time are still too common. This conundrum
results in great stress and uncertainty for women undergoing clinical care and their health care teams. To date,
we have demonstrated (and validated) that multiplexed biomarkers from divergent biological pathways can be
used to minimize both false positive and false negative discrimination (rather than balancing the two errors with
lower accuracy). In parallel, we have discovered and screened more than 54 novel biomarkers to obtain 11
candidates that can predict early pregnancy outcome. Using machine learning we have demonstrated that as
few as 3 of these markers can predict the location of an early gestation (IUP vs EP or SAB) with 95%
accuracy. Additionally, an overlapping group of 3 markers can predict the viability of a gestation (IUP vs SAB
or EP) with 94% accuracy. When both tests are used in combination the accuracy is 96.9%. We now plan to
externally validate these companion diagnostic(s) in a separate population-based prospective study and to
determine the optimal conditions of use. We will optimize performance in women presenting with a pregnancy
of unknown location as well as assess predictive values for all women presenting at risk for early pregnancy
loss using an independent population-based prospective study (SA1). We will determine if accuracy can be
improved with the combination of presenting signs, symptoms, and ultrasound findings (SA2). Moreover, we
will validate our biomarker tests in two distinct populations of interest: women with high and low risk for EP: a)
asymptomatic women prior to presentation for care (EAGeR Trial) and b) women diagnosed with a persistent
pregnancy of unknown location (ACTorNOT Trial) (SA3). Developing novel biomarkers that distinguish normal
physiology from the presence of gynecologic disorders is an NICHD research priority area. Our productive and
established team is proposing rigorous cross disciplinary, state of the art, and novel research with great
scientific impact that has the potential to produce a paradigm shift in clinical care models for the diagnosis and
management of women in early pregnancy. Our detailed plan for biomarker development is iterative and
nimble and, importantly, includes validation. Our development plan is informed by methodology from
successful biomarker development, is designed to minimize known pitfalls, and is developed with FDA
guidance.

## Key facts

- **NIH application ID:** 10771208
- **Project number:** 5R01HD110448-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Kurt T Barnhart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $671,048
- **Award type:** 5
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10771208

## Citation

> US National Institutes of Health, RePORTER application 10771208, Clinical utility of novel biomarkers for prediction of early pregnancy failure (5R01HD110448-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10771208. Licensed CC0.

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