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.

Objective: In fetal diagnosis the myriad and diversity of heart rate variability (HRV) indices prevents a comparable routine evaluation of disturbances in fetal development and well-being. The work aims at the extraction of a small set of HRV key indices that could help to establish a universal, overarching tool to screen for any disturbance. Approach: HRV indices were organized in categories of short-term (prefix s) and long-term (prefix l) amplitude fluctuations (AMP), complexity (COMP), and patterns (PATTERN) and common representatives for each category were extracted. This procedure was done with respect to the diagnostic value in the evaluation of the maturation age throughout the second and complete third trimester of pregnancy as well as to potential differences associated with maternal life-style factors (physical exercise, smoking), nutrient intervention (docosahexaenoic acid (DHA) supplementation), and complications of pregnancy (gestational diabetes mellitus (GDM), intra-uterine growth restriction (IUGR)). Main results: We found a comprehensive minimal set that includes [lAMP: short term variation (STV), initially introduced in cardiotocography, sAMP: heart rate increase across one interbeat interval of phase rectified averaged signal - acceleration capacity (ACst1), lCOMP: scale 4 multi-scale entropy (MSE4), PATTERN: skewness] for the maturation age prediction, and partly overlapping [lAMP: STV, sAMP: ACst1, sCOMP: Lempel Ziv complexity (LZC)] for the discrimination of the deviations. Significance: The minimal set of category-based HRV representatives allows for a screening of fetal development and well-being. These results are an important step towards a universal and comparable diagnostic tool for the early identification of developmental disturbances. Novelty & Significance Fetal development and its disturbances have been reported to be associated with a multiplicity of HRV indices. Furthermore, these HRV indices change with maturation. We propose the abstraction of HRV categories defined by short- and long-term fluctuation amplitude, complexity, and pattern indices that cover all relevant aspects of maturational age, behavioral influences and a series of pathological disturbances. The study data are provided by multiple centers. Our approach is an important step towards the goal of a standardized diagnostic tool for early identification of fetal developmental disturbances with respect to the reduction of serious complications in the later life.

Pre-eclampsia (PE) is a gestational disease featured by hypertension, arterial systemic vasculopathy, multiple organ failure and fetal compromise. The aim of the investigation was to determine the role of maternal respiratory sinus arrhythmia (RSA) in regulation of the fetal circulatory system in case of healthy pregnancy and in PE. The investigation of maternal and fetal HRV and fetal CTG variables in 106 patients at 34–40 weeks of gestation was performed. 30 of them had healthy pregnancy and were involved in the Group I. In Group II 44 pregnant women with mild-moderate PE were observed. 32 patients with severe PE were monitored in Group III. The maternal sympathetic overactivity modulated HRV in PE by suppressing total power (TP) and parasympathetic tone. The lack of RSA was explored in preeclamptic patients. The centralization of hemodynamics was a result of the hypersympatheticotonia in severe PE. Fetal circulatory response to PE featured by an increased sympathetic tone. The modulated fetal CTG variables captured the suppression of fetal biophysical activity and the development of fetal distress in severe PE. Strong relationship between maternal and fetal TPs, maternal and fetal RMSSDs was found in healthy pregnancy. The correlations between the maternal and fetal TPs, the maternal and fetal RMSSDs in the patients with severe PE were disturbed. The maternal RSA propagated its influence on the fetal autonomic nervous regulation in normal gestation. The maternal and fetal hemodynamic coupling was reduced in PE.

Objective. Fetal arrhythmias are a life-threatening disorder occurring in up to 2% of pregnancies. If identified, many fetal arrhythmias can be effectively treated using anti-arrhythmic therapies. In this paper, we present a novel method of detecting fetal arrhythmias in short length non-invasive fetal electrocardiography (NI-FECG) recordings. Approach. Our method consists of extracting a fetal heart rate time series from each NI-FECG recording and computing an entropy profile using a data-driven range of the entropy tolerance parameter r . To validate our approach, we apply our entropy profiling method to a large clinical data set of 318 NI-FECG recordings. Main Results. We demonstrate that our method ( TotalSampEn ) provides strong performance for classifying arrhythmic fetuses (AUC of 0.83) and outperforms entropy measures such as SampEn (AUC of 0.68) and FuzzyEn (AUC of 0.72). We also find that NI-FECG recordings incorrectly classified using the investigated entropy measures have significantly lower signal quality, and that excluding recordings of low signal quality (13.5% of recordings) increases the classification performance of TotalSampEn (AUC of 0.90). Significance. The superior performance of our approach enables automated detection of fetal arrhythmias and warrants further investigation in a prospective clinical trial.

Complete atrioventricular block in fetuses is known to be mostly associated with autoimmune disease and can be irreversible if no steroids treatment is provided. Conventional methods used in clinical practice for diagnosing fetal arrhythmia are limited since they do not reflect the primary electrophysiological conduction processes that take place in the myocardium. The non-invasive fetal electrocardiogram has the potential to better support fetal arrhythmias diagnosis through the continuous analysis of the beat to beat variation of the fetal heart rate and morphological analysis of the PQRST complex. We present two retrospective case reports on which atrioventricular block diagnosis could have been supported by the non-invasive fetal electrocardiogram. The two cases comprised a 22-year-old pregnant woman with the gestational age of 31 weeks and a 25-year-old pregnant woman with the gestational age of 41 weeks. Both women were admitted to the Department of Maternal and Fetal Medicine at the Kyiv and Kharkiv municipal perinatal clinics. Patients were observed using standard fetal monitoring methods as well as the non-invasive fetal electrocardiogram. The non-invasive fetal electrocardiographic recordings were analyzed retrospectively, where it is possible to identify the presence of the atrioventricular block. This study demonstrates, for the first time, the feasibility of the non-invasive fetal electrocardiogram as a supplementary method to diagnose of the fetal atrioventricular block. Combined with current fetal monitoring techniques, non-invasive fetal electrocardiography could support clinical decisions.