Artificial Intelligence-derived Cardiotocography Age as a Digital Biomarker for Predicting Future Adverse Pregnancy Outcomes

Cardiotocography (CTG) is a low-cost, non-invasive fetal health assessment technique used globally, especially in underdeveloped countries. However, it is currently mainly used to identify the fetus's current status (e.g., fetal acidosis or hypoxia), and the potential of CTG in predicting future adverse pregnancy outcomes has not been fully explored. We aim to develop an AI-based model that predicts biological age from CTG time series (named CTGage), then calculate the age gap between CTGage and actual age (named CTGage-gap), and use this gap as a new digital biomarker for future adverse pregnancy outcomes. The CTGage model is developed using 61,140 records from 11,385 pregnant women, collected at Peking University People's Hospital between 2018 and 2022. For model training, a structurally designed 1D convolutional neural network is used, incorporating distribution-aligned augmented regression technology. The CTGage-gap is categorized into five groups: < -21 days (underestimation group), -21 to -7 days, -7 to 7 days (normal group), 7 to 21 days, and > 21 days (overestimation group). We further defined the underestimation group and overestimation group together as the high-risk group. We then compare the incidence of adverse outcomes and maternal diseases across these groups. The average absolute error of the CTGage model is 10.91 days. When comparing the overestimation group with the normal group, premature infants incidence is 5.33% vs. 1.42% (p < 0.05) and gestational diabetes mellitus (GDM) incidence is 31.93% vs. 20.86% (p < 0.05). When comparing the underestimation group with the normal group, low birth weight incidence is 0.17% vs. 0.15% (p < 0.05) and anaemia incidence is 37.51% vs. 34.74% (p < 0.05). Artificial intelligence-derived CTGage can predict the future risk of adverse pregnancy outcomes and hold potential as a novel, non-invasive, and easily accessible digital biomarker.