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

TL;DR

This study explores how clock proteins like ADA12 in maternal serum could help predict term delivery dates more accurately than current methods.

Contribution

The study identifies 15 serum proteins, including ADA12, associated with time to birth, with 11 being newly linked to gestational age.

Findings

High levels of ADA12 in maternal serum were associated with earlier term births compared to low levels.

Fifteen serum proteins, including ADA12, showed statistically significant associations with time to birth.

Eleven of the identified proteins had not previously been linked to gestational age.

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 390/7 weeks vs. 393/7 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.

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