Measuring the time-scale-dependent information flow between maternal and fetal heartbeats during the third trimester

TL;DR

This study addresses how prenatal maternal stress shapes time-scale–dependent information flow between maternal and fetal heartbeats. By applying an information-theoretic framework (ER, SE, TE) within a multi-layer conditioning scheme, it reveals dual coupling modes: a stress-invariant, state-dependent synchronization and a stress-sensitive temporal information transfer, with TE showing sex-dependent modulation. The strongest, universal coupling occurs when maternal decelerations constrain fetal HR complexity by about 60%, indicating a robust interdependence, while TE captures stress-modulated directional information flow and potential cortisol-related effects—though many neurodevelopmental associations require replication due to limited power. The findings extend the Fetal Stress Index concept, offering mechanistic insight into maternal–fetal communication and highlighting methodological considerations, including sampling rate, conditioning, and the need for larger, preregistered studies to validate sex-specific and developmental implications.

Abstract

Prenatal maternal stress alters maternal-fetal heart rate coupling, as demonstrated by the Fetal Stress Index derived from bivariate phase-rectified signal averaging. Here, we extend this framework using information-theoretical measures to elucidate underlying mechanisms. In 120 third-trimester pregnancies (58 stressed, 62 control), we computed transfer entropy (TE), entropy rate (ER), and sample entropy (SE) under multiple conditioning paradigms, employing mixed linear models for repeated measures. We identify dual coupling mechanisms at the short-term (0.5 - 2.5 s), but not long-term (2.5 - 5 s) time scales: (1) stress-invariant state-dependent synchronization, with maternal decelerations exerting approximately 60% coupling strength on fetal heart rate complexity - a fundamental coordination conserved across demographics; and (2) stress-sensitive temporal information transfer (TE), showing exploratory associations with maternal cortisol that require replication. A robust sex-by-stress interaction emerged in TE from mixed models, with exploratory female-specific coupling patterns absent in males. Universal acceleration predominance was observed in both maternal and fetal heart rates, stronger in fetuses and independent of sex or stress. We provide insight into the dependence of these findings on the sampling rate of the underlying data, identifying 4 Hz, commonly used for ultrasound-derived fetal heart rate recordings, as the necessary and sufficient sampling rate regime to capture the information flow. Information-theoretical analysis reveals that maternal-fetal coupling operates through complementary pathways with differential stress sensitivity, extending the Fetal Stress Index by elucidating causal foundations. Future studies should explore additional information-theoretical conditional approaches to resolve stress-specific and time-scale-specific differences in information flow.

Figures (13)

• Figure 1: Recruitment flow chart for the FELICITy dataset.
• Figure 2: Example of mother HR (mHR) data. The raw mHR sampled at 1kHz is a stepwise function of time (black). We low-pass filter the raw mHR signal using a low-pass cutoff frequency $1/\tau$, where the time-scale $\tau$ represents the scale at which we will further analyze the information contents of the heart rates. Low-pass-filtered signal are then downsampled at $f_s$=20Hz. Two examples are represented: one for $\tau$=0.5s (blue) and one for $\tau$=2s (magenta). Larger circles indicate times when the filtered mHR signal is increasing, which we define as accelerations. Conversely, little dots correspond to decelerations.
• Figure 3: Statistics of decelerations/accelerations ratios computed at timescale $\tau=2.5$s. The upper and lower parts correspond to the mother's HR and the fetus's HR, respectively. In each case, the first line presents the fraction of time points that are decelerations or accelerations. In contrast, the second line presents the ratio of decelerations to accelerations.
• Figure 4: Group dependencies of statistics of decelerations/accelerations ratios computed at timescale $\tau=2.5$s, for female () and male (♂) fetuses, in both the stressed and control group.
• Figure 5: Entropy rate $h$ as a measure of information or complexity in the conditioned signals. (a) results when conditioning is performed on the maternal HR signal, and (b) when it is performed on the fetal HR signal. Dotted lines pertain to fetal HR and continuous lines to maternal HR. Blue (resp. orange) curves are obtained by conditioning on mHR accelerations (resp. mHR decelerations). Green (resp. red) curves are obtained by conditioning on fHR accelerations (resp. fHR decelerations). For reference, we have plotted the entropy rate measured in fHR (dotted black line) and mHR (continuous black line) without any conditioning. For each curve, a shaded area represents the dispersion of the values over the cohort.