Can fetal heart rate variability obtained from cardiotocography provide the same diagnostic value like from electrophysiological interbeat intervals?

OBJECTIVE: Fetal heart rate variability (HRV) is widely used for monitoring fetal developmental disturbances. Only expensive fetal magnetocardiography (fMCG) allows the precise recording of the individual fetal heart beat intervals uncovering also highly frequent vagal modulation. In contrast, transabdominal fetal electrocardiography (fECG) suffers from noise overlaying the fetal cardiac signal. Cardiotocography (CTG) is the clinical method of choice, however, based on Doppler ultrasound, improper to resolve single beats concisely. The present work addresses the transferability of established electrophysiological HRV indices to CTG recordings during the fetal maturation period of 20-40 weeks of gestation (WGA). APPROACH: We compared (a) HRV indices obtained from fMCG, CTG and fECG of short-term amplitude fluctuations (sAMPs) and long-term amplitude fluctuations (lAMPs) and complexity, and (b) their diagnostic value for identifying maturational age, fetal growth restriction (FGR) and small for gestational age (SGA). We used the functional brain age score (fABAS) and categories of long- and short-term regulation and complexity. MAIN RESULTS: Integrating all substudies, we found: (a) indices related to long-term regulation, and with modified meaning and values of short-term regulation and sympathovagal balance (SVB) according to electrophysiological HRV standards can be obtained from CTG. (b) Models using HRV indices calculated from CTG allow the identification of maturational age and discriminate FGR from controls with almost similar precision as electrophysiological means. (c) A modified set of HRV parameters containing short- and long-term regulation and long-term/short-term ratio appeared to be most suitable to describe autonomic developmental state when CTG data is used. SIGNIFICANCE: Whereas the predominantly vagally modulated beat-to-beat precise high frequencies of HRV are not assessable from CTG, we identified relevant related HRV indices and categories for CTG recordings with diagnostic potential. They require further evaluation and confirmation with respect to any issues of fetal developmental and perinatal problems in subsequent studies. This methodology significantly extends the measures of established CTG devices. Novelty and significance HRV indices provide predestinated diagnostic markers of autonomic control in fetuses. However, the established CTG does not provide the temporal precision of electrophysiological recordings. Beat-to-beat related, mainly vagally modulated behavior is not exactly represented in CTG. However, a set of CTG-specific HRV indices that are mainly comparable to established electrophysiological HRV parameters obtained by magnetocardiography or electrocardiography provided almost similar predictive value for fetal maturational age and were helpful in characterizing FGR. These results require validation in the monitoring of further fetal developmental disturbances. We recommend a corresponding extension of CTG methodology.

Universal characteristics of evolution and development are inherent in fetal autonomic brain maturation.

Adverse prenatal environmental influences to the developing fetus are associated with mental and cardiovascular disease in later life. Universal developmental characteristics such as self-organization, pattern formation, and adaptation in the growing information processing system have not yet been sufficiently analyzed with respect to description of normal fetal development and identification of developmental disturbances. Fetal heart rate patterns are the only non-invasive order parameter of the developing autonomic brain available with respect to the developing complex organ system. The objective of the present study was to investigate whether universal indices, known from evolution and phylogeny, describe the ontogenetic fetal development from 20 weeks of gestation onwards. By means of a 10-fold cross-validated data-driven multivariate regression modeling procedure, relevant indices of heart rate variability (HRV) were explored using 552 fetal heart rate recordings, each lasting over 30 min. We found that models which included HRV indices of increasing fluctuation amplitude, complexity and fractal long-range dependencies largely estimated the maturation age (coefficients of determination 0.61-0.66). Consideration of these characteristics in prenatal care may not only have implications for early identification of developmental disturbances, but also for the development of system-theory-based therapeutic strategies.

Monitoring fetal maturation-objectives, techniques and indices of autonomic function.

Monitoring the fetal behavior does not only have implications for acute care but also for identifying developmental disturbances that burden the entire later life. The concept, of 'fetal programming', also known as 'developmental origins of adult disease hypothesis', e.g. applies for cardiovascular, metabolic, hyperkinetic, cognitive disorders. Since the autonomic nervous system is involved in all of those systems, cardiac autonomic control may provide relevant functional diagnostic and prognostic information. The fetal heart rate patterns (HRP) are one of the few functional signals in the prenatal period that relate to autonomic control and, therefore, is predestinated for its evaluation. The development of sensitive markers of fetal maturation and its disturbances requires the consideration of physiological fundamentals, recording technology and HRP parameters of autonomic control. Based on the ESGCO2016 special session on monitoring the fetal maturation we herein report the most recent results on: (i) functional fetal autonomic brain age score (fABAS), Recurrence Quantitative Analysis and Binary Symbolic Dynamics of complex HRP resolve specific maturation periods, (ii) magnetocardiography (MCG) based fABAS was validated for cardiotocography (CTG), (iii) 30 min recordings are sufficient for obtaining episodes of high variability, important for intrauterine growth restriction (IUGR) detection in handheld Doppler, (iv) novel parameters from PRSA to identify Intra IUGR fetuses, (v) evaluation of fetal electrocardiographic (ECG) recordings, (vi) correlation between maternal and fetal HRV is disturbed in pre-eclampsia. The reported novel developments significantly extend the possibilities for the established CTG methodology. Novel HRP indices improve the accuracy of assessment due to their more appropriate consideration of complex autonomic processes across the recording technologies (CTG, handheld Doppler, MCG, ECG). The ultimate objective is their dissemination into routine practice and studies of fetal developmental disturbances with implications for programming of adult diseases.