Fetal Cardiovascular Decompensation During Labor Predicted From the Individual Heart Rate Tracing: A Machine Learning Approach in Near-Term Fetal Sheep Model

Abstract

Background: When exposed to repetitive umbilical cord occlusions (UCO) with worsening acidemia, fetuses eventually develop cardiovascular decompensation manifesting as pathological hypotensive arterial blood pressure (ABP) responses to fetal heart rate (FHR) decelerations. Failure to maintain cardiac output during labor is a key event leading up to brain injury. We reported that the timing of the event when a fetus begins to exhibit this cardiovascular phenotype is highly individual and was impossible to predict.Objective: We hypothesized that this phenotype would be reflected in the individual behavior of heart rate variability (HRV) as measured by root mean square of successive differences of R-R intervals (RMSSD), a measure of vagal modulation of HRV, which is known to increase with worsening acidemia. This is clinically relevant because HRV can be computed in real-time intrapartum. Consequently, we aimed to predict the individual timing of the event when a hypotensive ABP pattern would emerge in a fetus from a series of continuous RMSSD data.Study Design: Fourteen near-term fetal sheep were chronically instrumented with vascular catheters to record fetal arterial blood pressure, umbilical cord occluder to mimic uterine contractions occurring during human labor and ECG electrodes to compute the ECG-derived HRV measure RMSSD. All animals were studied over a ~6 h period. After a 1–2 h baseline control period, the animals underwent mild, moderate, and severe series of repetitive UCO. We applied the recently developed machine learning algorithm to detect physiologically meaningful changes in RMSSD dynamics with worsening acidemia and hypotensive responses to FHR decelerations. To mimic clinical scenarios using an ultrasound-based 4 Hz FHR sampling rate, we recomputed RMSSD from FHR sampled at 4 Hz and compared the performance of our algorithm under both conditions (1,000 Hz vs. 4 Hz).Results: The RMSSD values were highly non-stationary, with four different regimes and three regime changes, corresponding to a baseline period followed by mild, moderate, and severe UCO series. Each time series was characterized by seemingly randomly occurring (in terms of timing of the individual onset) increase in RMSSD values at different time points during the moderate UCO series and at the start of the severe UCO series. This event manifested as an increasing trend in RMSSD values, which counter-intuitively emerged as a period of relative stationarity for the time series. Our algorithm identified these change points as the individual time points of cardiovascular decompensation with 92% sensitivity, 86% accuracy and 92% precision which corresponded to 14 ± 21 min before the visual identification. In the 4 Hz RMSSD time series, the algorithm detected the event with 3 times earlier detection times than at 1,000 Hz, i.e., producing false positive alarms with 50% sensitivity, 21% accuracy, and 27% precision. We identified the overestimation of baseline FHR variability by RMSSD at a 4 Hz sampling rate to be the cause of this phenomenon.Conclusions: The key finding is demonstration of FHR monitoring to detect fetal cardiovascular decompensation during labor. This validates the hypothesis that our HRV-based algorithm identifies individual time points of ABP responses to UCO with worsening acidemia by extracting change point information from the physiologically related fluctuations in the RMSSD signal. This performance depends on the acquisition accuracy of beat to beat fluctuations achieved in trans-abdominal ECG devices and fails at the sampling rate used clinically in ultrasound-based systems. This has implications for implementing such an approach in clinical practice.