Kits and methods to distinguish false labor and true labor
Inventors
TARCA, Adi L. • Chaemsaithong, Piya • Chaiworapongsa, Tinnakorn • Hassan, Sonia S. • Romero, Roberto
Assignees
Wayne State University • US Department of Health and Human Services
Publication Number
US-11204354-B2
Publication Date
2021-12-21
Expiration Date
2036-11-07
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Abstract
Kits and methods to distinguish between false and true labor are provided. The kits and methods can utilize differences in abundance and/or differences in the rate of change in abundance of B7-H2, SORC2, TF, C1-Esterase Inhibitor, Ran, IMD-H1 and/or PGAM1, as markers of true labor.
Core Innovation
The invention provides kits and methods to distinguish between false labor and true labor by utilizing differences in abundance and/or differences in the rate of change in abundance of specific protein markers including B7-H2, SORC2, TF, C1-Esterase Inhibitor, Ran, IMDH1, and PGAM1 found in maternal blood plasma. Two models have been developed for predicting true labor: one model uses the rate of change in abundance of four markers (B7-H2, SORC2, TF, and C1-Esterase Inhibitor) across at least two measurements during pregnancy, and another model uses changes in abundance of four markers (TF, Ran, IMDH1, and PGAM1) at patient admission.
The problem being solved is the challenge in obstetrical care to accurately diagnose true labor as opposed to false labor. Current clinical criteria, such as symptoms and cervical examination (e.g., Bishop Score), are poor predictors and labor diagnosis is retrospective. Overdiagnosis of labor leads to unnecessary hospitalization, psychological stress, increased medical costs, and potentially harmful interventions such as analgesia and labor induction, especially problematic in preterm labor. No prior diagnostic tests are available to definitively differentiate true labor from false labor.
This invention addresses the unmet need for a robust and novel diagnostic tool by providing methods that detect labor-specific changes in maternal plasma proteins with high specificity, as high as 94%. These biomarkers serve as molecular indicators that true labor is occurring or imminent. The kits and methods can reduce unnecessary hospital admissions and medical interventions by accurately identifying patients unlikely to deliver. The use of protein abundance changes, including rates of change over time, allows personalized assessment using samples taken at multiple time points during pregnancy or at admission with suspected labor symptoms.
Claims Coverage
The patent includes two independent claims covering kits for measuring specific labor biomarkers using arrays and instructions for analysis.
Kit comprising an array measuring seven labor biomarkers
A kit that includes an array capable of measuring tissue factor (TF), ICOS Ligand (B7-H2), VPS10 Domain Containing Receptor SorCS2 (SORC2), Plasma Protease C1 Inhibitor (C1-Esterase Inhibitor), Ras-related Nuclear protein (Ran), Inosine-5′-monophosphate dehydrogenase (IMDH1), and Phosphoglycerate mutase 1 (PGAM1) from a biological sample obtained from a pregnant female.
Instructions for calculating rate of change of abundance to diagnose labor
The kit includes instructions directing calculation of the rate of change of abundance for TF, B7-H2, SORC2, and C1-Esterase Inhibitor between two samples taken at different times from the same pregnant female, including a formula using gestational age to calculate a true labor score. The instructions define thresholds for the score to classify false labor or true labor.
Instructions for calculating change in abundance compared to reference levels
The kit includes instructions to calculate changes in abundance of TF, Ran, IMDH1, and PGAM1 compared to reference levels derived from a population not in true labor, and to calculate a true labor score using a Linear Discriminant Analysis model. Thresholds for classification into false labor or true labor are provided.
The independent claims collectively cover a diagnostic kit with arrays for measuring seven specific protein biomarkers and instructions for interpreting their absolute levels, change over time, or rate of change to accurately distinguish true labor from false labor in pregnant females.
Stated Advantages
High specificity (up to 94%) in distinguishing true labor from false labor, enabling reduction of unnecessary hospital admissions and medical interventions.
Ability to predict the onset of true labor using molecular markers in maternal blood plasma, improving diagnostic accuracy over current clinical methods.
Use of longitudinal measurements and rate of change in protein abundance reduces variability and enhances discrimination between true and false labor.
Tests can be applied at multiple time points during pregnancy or at hospital admission when labor symptoms are present.
Documented Applications
Diagnosing true labor in pregnant females experiencing symptoms such as cramps, back pain, cervical dilation, or contractions to distinguish true labor from false labor.
Use of maternal blood plasma samples taken at multiple time points during pregnancy or upon hospital admission to calculate labor likelihood scores.
Clinical decision-making tool to reduce unnecessary hospital admissions, medical interventions such as analgesia and labor induction, and associated costs by identifying patients unlikely to deliver imminently.
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