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

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 gesta...

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Main Authors: 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, Paul E. Kearney
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Language:English
Published: MDPI AG 2025-02-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/2/224
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author 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
Paul E. Kearney
author_facet 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
Paul E. Kearney
author_sort Max T. Dufford
collection DOAJ
description 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<sup>0/7</sup> weeks vs. 39<sup>3/7</sup> weeks, <i>p</i> < 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.
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spelling doaj-art-97c8d9186cc046f99ed3525b4a62c2d92025-08-20T03:12:22ZengMDPI AGLife2075-17292025-02-0115222410.3390/life15020224Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept StudyMax T. Dufford0Tracey C. Fleischer1Laura J. Sommerville2Md. Bahadur Badsha3Ashoka D. Polpitiya4Jennifer Logan5Angela C. Fox6Sharon R. Rust7Charles B. Cox8Thomas J. Garite9J. Jay Boniface10Paul E. Kearney11Sera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USASera Prognostics, Inc., Salt Lake City, UT 84109, USAOur 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<sup>0/7</sup> weeks vs. 39<sup>3/7</sup> weeks, <i>p</i> < 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.https://www.mdpi.com/2075-1729/15/2/224clock proteinsterm delivery datetime to birthpredictiongestational agea distintegrin and metalloproteinase 12
spellingShingle 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
Paul E. Kearney
Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study
Life
clock proteins
term delivery date
time to birth
prediction
gestational age
a distintegrin and metalloproteinase 12
title Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study
title_full Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study
title_fullStr Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study
title_full_unstemmed Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study
title_short Clock Proteins Have the Potential to Improve Term Delivery Date Prediction: A Proof-of-Concept Study
title_sort clock proteins have the potential to improve term delivery date prediction a proof of concept study
topic clock proteins
term delivery date
time to birth
prediction
gestational age
a distintegrin and metalloproteinase 12
url https://www.mdpi.com/2075-1729/15/2/224
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