Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study

Dufford, Max T.; Fleischer, Tracey C.; Sommerville, Laura J.; Badsha, Md. Bahadur; Polpitiya, Ashoka D.; Logan, Jennifer; Fox, Angela C.; Rust, Sharon R.; Cox, Charles B.; Garite, Thomas J.; Boniface, J. Jay; Kearney, Paul E.

doi:10.3390/life15020224

Open AccessArticle

Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study

by

Max T. Dufford

,

Tracey C. Fleischer

,

Laura J. Sommerville

,

Md. Bahadur Badsha

,

Ashoka D. Polpitiya

,

Jennifer Logan

,

Angela C. Fox

,

Sharon R. Rust

,

Charles B. Cox

,

Thomas J. Garite

,

J. Jay Boniface

and

Paul E. Kearney

^*

Sera Prognostics, Inc., Salt Lake City, UT 84109, USA

^*

Author to whom correspondence should be addressed.

Life 2025, 15(2), 224; https://doi.org/10.3390/life15020224

Submission received: 20 December 2024 / Revised: 23 January 2025 / Accepted: 31 January 2025 / Published: 3 February 2025

(This article belongs to the Special Issue Obstetrics and Gynecology Medicine: Go From Bench to Bedside)

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Abstract

Our ability to accurately predict the delivery date of term pregnancies is limited by shortcomings of modern-day clinical tools and due date estimation methods. The pregnancy clock is a series of coordinated and harmonized signals between mother, fetus, and placenta that regulate the length of gestation. Clock proteins are thought to be important mediators of these signals, yet few studies have investigated their potential utility as predictors of term delivery date. In this study, we performed a cross-sectional proteome analysis of 2648 serum samples collected between 18 and 28 weeks of gestation from mothers who delivered at term. The cohort included pregnancies both with and without complications. A total of 15 proteins of diverse functionalities were shown to have a direct association with time to birth (TTB), 11 of which have not been previously linked to gestational age. The protein A Distintegrin and Metalloproteinase 12 (ADA12) was one of the 15 proteins shown to have an association with TTB. Mothers who expressed the highest levels of ADA12 in the cohort (90th percentile) gave birth earlier than mothers who expressed the lowest levels of ADA12 (10th percentile) at a statistically significant rate (median gestational age at birth 39^0/7 weeks vs. 39^3/7 weeks, p < 0.001). Altogether, these findings suggest that ADA12, as well as potentially other clock proteins, have the potential to serve as clinical predictors of term delivery date in uncomplicated pregnancies and represent an important step towards characterizing the role(s) of clock proteins in mediating pregnancy length.

Keywords: clock proteins; term delivery date; time to birth; prediction; gestational age; a distintegrin and metalloproteinase 12

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MDPI and ACS Style

Dufford, M.T.; Fleischer, T.C.; Sommerville, L.J.; Badsha, M.B.; Polpitiya, A.D.; Logan, J.; Fox, A.C.; Rust, S.R.; Cox, C.B.; Garite, T.J.; et al. Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study. Life 2025, 15, 224. https://doi.org/10.3390/life15020224

AMA Style

Dufford MT, Fleischer TC, Sommerville LJ, Badsha MB, Polpitiya AD, Logan J, Fox AC, Rust SR, Cox CB, Garite TJ, et al. Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study. Life. 2025; 15(2):224. https://doi.org/10.3390/life15020224

Chicago/Turabian Style

Dufford, Max T., Tracey C. Fleischer, Laura J. Sommerville, Md. Bahadur Badsha, Ashoka D. Polpitiya, Jennifer Logan, Angela C. Fox, Sharon R. Rust, Charles B. Cox, Thomas J. Garite, and et al. 2025. "Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study" Life 15, no. 2: 224. https://doi.org/10.3390/life15020224

APA Style

Dufford, M. T., Fleischer, T. C., Sommerville, L. J., Badsha, M. B., Polpitiya, A. D., Logan, J., Fox, A. C., Rust, S. R., Cox, C. B., Garite, T. J., Boniface, J. J., & Kearney, P. E. (2025). Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study. Life, 15(2), 224. https://doi.org/10.3390/life15020224

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Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study

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