D. Casati

Parameters influence on acceleration and deceleration capacity based on trans-abdominal ECG in early fetal growth restriction at different gestational age epochs

OBJECTIVE Intrauterine growth restriction (IUGR) is characterized by chronic nutrient deprivation and hypoxemia that alters the autonomous nervous system regulation of fetal heart rate variability (fHRV). Phase-rectified signal averaging (PRSA) is a new algorithm capable to identify periodic and quasi-periodic patterns of HR, and which is used to quantify the average acceleration and deceleration capacity (AC/DC) of the heart. The computation of AC/DC depends on the parameters T and s, which we set so that s=T. T and s determine the periodicities that can be detected (the larger T the smaller the frequency of oscillations for which the method is most sensitive). The aim of the study was to evaluate the influence of the parameter T on PRSA computation, based on trans-abdominally acquired fetal ECG (ta-fECG), in early IUGR (<34 weeks of gestation) at two different gestational age epochs. STUDY DESIGN AC/DC were calculated for different T values (1÷45) on fetal RR intervals derived from ta-fECG in 22 IUGR and in 37 appropriate for gestational age (AGA) fetuses matched for gestational age, in two gestational age epochs: very preterm group (≥26÷<30 weeks), and preterm group (≥30÷<34 weeks), respectively. RESULTS AC/DC were significantly lower in IUGR than in AGA fetuses for all T≥5 values (p<0.05). The best area under the receiver operating characteristic curve (AUC) in identifying IUGR at time of recording was observed for T9 [AUC AC-T9 0.87, 95% confidence interval (CI) 0.77-0.96; and AUC DC-T9 0.89, 95% CI 0.81-0.98), and in range of T 7÷15. In the same T interval, AC/DC were significantly lower in very preterm than in preterm IUGR group (p<0.05), while there were no differences in AGA fetuses at two gestational age epochs (p>0.05), respectively. The AUCs of AC-T9 and DC-T9 significantly outperformed that obtained by short-term variation (AUC 0.77, 95% CI 0.65-0.90; p=0.009 and p=0.003, respectively). CONCLUSIONS Our study shows that within the range of T parameter 1÷45, T=9 proved to be the best value to discriminate the AC and DC of the fetal heart rate of IUGR from AGA fetuses prior to 34 weeks of gestation. These significant differences are emphasized in very preterm gestational age epochs.

Acceleration and Deceleration Capacity of Fetal Heart Rate in an In-Vivo Sheep Model

Background Fetal heart rate (FHR) variability is an indirect index of fetal autonomic nervous system (ANS) integrity. FHR variability analysis in labor fails to detect early hypoxia and acidemia. Phase-rectified signal averaging (PRSA) is a new method of complex biological signals analysis that is more resistant to non-stationarities, signal loss and artifacts. It quantifies the average cardiac acceleration and deceleration (AC/DC) capacity. Objective The aims of the study were: (1) to investigate AC/DC in ovine fetuses exposed to acute hypoxic-acidemic insult; (2) to explore the relation between AC/DC and acid-base balance; and (3) to evaluate the influence of FHR decelerations and specific PRSA parameters on AC/DC computation. Methods Repetitive umbilical cord occlusions (UCOs) were applied in 9 pregnant near-term sheep to obtain three phases of MILD, MODERATE, and SEVERE hypoxic-acidemic insult. Acid-base balance was sampled and fetal ECGs continuously recorded. AC/DC were calculated: (1) for a spectrum of T values (T = 1÷50 beats; the parameter limits the range of oscillations detected by PRSA); (2) on entire series of fetal RR intervals or on “stable” series that excluded FHR decelerations caused by UCOs. Results AC and DC progressively increased with UCOs phases (MILD vs. MODERATE and MODERATE vs. SEVERE, p<0.05 for DC  = 2–5, and AC  = 1–3). The time evolution of AC/DC correlated to acid-base balance (0.4<<0.9, p<0.05) with the highest for . PRSA was not independent from FHR decelerations caused by UCOs. Conclusions This is the first in-vivo evaluation of PRSA on FHR analysis. In the presence of acute hypoxic-acidemia we found increasing values of AC/DC suggesting an activation of ANS. This correlation was strongest on time scale dominated by parasympathetic modulations. We identified the best performing parameters (), and found that AC/DC computation is not independent from FHR decelerations. These findings establish the basis for future clinical studies.

Fetal and maternal heart rate confusion during intra-partum monitoring: comparison of trans-abdominal fetal electrocardiogram and Doppler telemetry

Objective: To compare intra-partum performance of trans-abdominal electrocardiogram with Doppler telemetry. Methods: In this prospective longitudinal study, simultaneous monitoring with trans-abdominal ECG and Doppler telemetry was performed in 41 uncomplicated term singleton pregnancies during labour. Results: The overall success rate for FHR monitoring was similar between trans-abdominal ECG and Doppler telemetry (88.5 ± 16.7% vs 89.4 ± 7.6%), except for the second stage of labour. A significantly higher rate of confusion (p < 0.001) between fetal and maternal heart was found for Doppler telemetry (4.5 ± 4.5%) compared with trans-abdominal ECG (1.3 ± 1.9%), especially in the second stage and during maternal movements. Conclusions: Trans-abdominal ECG monitoring is feasible, with comparable success rate to traditional Doppler telemetry, without interfering with maternal mobility or requiring midwife intervention. The reduction in maternal\fetal heart rate confusion from trans-abdominal ECG could reduce incorrect obstetric interpretation.

Brain sparing effect in growth-restricted fetuses is associated with decreased cardiac acceleration and deceleration capacities: a case-control study.

Phase rectified signal averaging (PRSA) is a new method of fetal heart rate variability (fHRV) analysis that quantifies the average acceleration (AC) and deceleration capacity (DC) of the heart. The aim of this study was to evaluate AC and DC of fHR [recorded by trans‐abdominal fetal electrocardiogram (ta‐fECG)] in relation to Doppler velocimetry characteristics of intrauterine growth restriction (IUGR).

Analysis of fetal heart rate variability in frequency domain: methodical considerations

Koome et al. (2014) investigated the possibility of inferring the status of fetal autonomic nervous system activity from heart rate (FHR) variability (fHRV) analysis in frequency domain. The authors provide evidence that this is not possible. However, a number of crucial methodological issues need to be resolved before this conclusion can be drawn. First, information on the fetal ECG sampling rate is not provided, but it is crucial for a correct estimation and analysis of HRV (1996; Karin et al. 1993). The time scale of subtle fHRV events requires the temporal resolution of R peak detection in the QRS complex to be within <1 ms (Karin et al. 1993). Second, the low-frequency to high-frequency ratio (LF/HF) of fHRV spectral power is presented and used as the measure of autonomic balance. This mathematical approach has been challenged because it does not reflect the underlying autonomic nervous system physiology (Eckberg, 1997). The authors themselves discuss this as an explanation for why the measure failed. Low-frequency spectral power reflects both sympathetic and parasympathetic influences, while HF spectral power reflects parasympathetic influences; consequently, changes in the ratio do not purely reflect the balance between sympathetic and parasympathetic activity. To assess autonomic balance, one would need to use direct measurements of sympathetic activity, such as muscle or renal sympathetic nerve activity, and relate these to changes in the HF power spectrum. Lastly, there are a number of concerns with the authors’ approach to frequency domain analysis, as follows. First, the adult HF band range was taken (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996) rather than the fetal one (Karin et al. 1993, 1996; Van Leeuwen et al. 2003). Thus, the conclusion that no developmental change in HF frequency band was present is premature, as it was probably low-pass filtered above the 0.4 Hz cut-off chosen by the authors. Second, the fHRV intervals of 120 s may not have captured well the intermittent respiratory activity contributing to the higher frequency spectral power of fHRV and the LF and very LF band contributions (Karin et al. 1993, 1996). It is not clear how the authors validated these stationarity and physiological aspects. Third, while Van Leeuwen et al. (2003) likewise defined HF as <0.4 Hz, they did look at higher frequencies and reported a developmental increase of spectral power in those frequencies. Fourth, were the frequency domain measures normalized in relationship to the integration band width prior to statistical analysis? This is crucial for the assessment of developmental effects when the overall variability and spectral power change (Karin et al. 1993, 1996). Fifth, David et al. (2007) have shown in human fetuses that if mean FHR drops below 130 beats min−1, aliasing of the respiratory frequency contained in the FHR signal will occur; breathing faster than 50% of mean FHR will exceed the Nyquist critical value of 1.2 Hz and result in aliasing when estimating the HF component of fHRV. To rule this out, the authors need to assess the fetal respiratory frequency spectrum and FHR range in 0.8 gestation group. The above critique demonstrates why fHRV analysis in the frequency domain has a low appeal for animal model-based or human fHRV monitoring. The expertise required to dissect modulatory contributions of the parasympathetic branch of the autonomic nervous system to fHRV versus the sympathetic modulatory contributions restricts the physiological applicability and dissemination of this approach. For these reasons, the time domain fHRV measures should be preferred, because they have been widely validated for detection of physiological and pathophysiological phenomena and are safer to use (Garzoni et al. 2013). Adherence to a fetal equivalent of the adult HRV Task Force is needed (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996) to promote and maintain a gold standard in validation of fHRV methodology at the fetal stage of development in animal and human studies. This is a conditio sine qua non to foster the development of objective and reliable fetal monitoring technologies relying on estimation of sympathetic and parasympathetic modulation of fHRV.

Assessment of coupling between trans-abdominally acquired fetal ECG and uterine activity by bivariate phase-rectified signal averaging analysis

Couplings between uterine contractions (UC) and fetal heart rate (fHR) provide important information on fetal condition during labor. At present, couplings between UC and fHR are assessed by visual analysis and interpretation of cardiotocography. The application of computerized approaches is restricted due to the non-stationarity of the signal, missing data and noise, typical for fHR. Herein, we propose a novel approach to assess couplings between UC and fHR, based on a signal-processing algorithm termed bivariate phase-rectified signal averaging (BPRSA). Methods Electrohysterogram (EHG) and fetal electrocardiogram (fECG) were recorded non-invasively by a trans-abdominal device in 73 women at term with uneventful singleton pregnancy during the first stage of labor. Coupling between UC and fHR was analyzed by BPRSA and by conventional cross power spectral density analysis (CPSD). For both methods, degree of coupling was assessed by the maximum coefficient of coherence (CPRSA and CRAW, respectively) in the UC frequency domain. Coherence values greater than 0.50 were consider significant. CPRSA and CRAW were compared by Wilcoxon test. Results At visual inspection BPRSA analysis identified coupled periodicities in 86.3% (63/73) of the cases. 11/73 (15%) cases were excluded from further analysis because no 30 minutes of fECG recording without signal loss was available for spectral analysis. Significant coupling was found in 90.3% (56/62) of the cases analyzed by BPRSA, and in 24.2% (15/62) of the cases analyzed by CPSD, respectively. The difference between median value of CPRSA and CRAW was highly significant (0.79 [IQR 0.69–0.90] and 0.29 [IQR 0.17–0.47], respectively; p<0.0001). Conclusion BPRSA is a novel computer-based approach that can be reliably applied to trans-abdominally acquired EHG-fECG. It allows the assessment of correlations between UC and fHR patterns in the majority of labors, overcoming the limitations of non-stationarity and artifacts. Compared to standard techniques of cross-correlations, such as CPSD, BPRSA is significantly superior.

The association of first trimester uterine arteries Doppler velocimetry with different clinical phenotypes of hypertensive disorders of pregnancy: a longitudinal study

Abstract Introduction: Current classification of hypertensive disorders of pregnancy (HDP) is mostly based on temporal classification differentiating HDP according to early and late onset of the disease. However, epidemiological and clinical data suggest that there are two different clinical phenotypes of HDP that coexist at any gestational age: HDP associated to intrauterine growth restriction (HDP-IUGR) and HDP associated to appropriate for gestational age fetal growth (HDP-AGAf). The aim of the study was to evaluate the association of first trimester uterine arteries (UtA) by Doppler velocimetry, and maternal risk factors with HDP according to two different classifications: one based on gestational age at delivery (early- and late-HDP), and one based on longitudinal ultrasound evaluation of fetal growth (HDP-IUGR and HDP-AGAf), independently of the gestational age. Methods: Maternal characteristics and mean pulsatility index (PI) of UtA were collected at 11–13 gestational weeks. A longitudinal ultrasound follow-up of fetal growth in each trimester and clinical outcome were obtained in 4290 singleton pregnancies. Results: UtA-PI was significantly higher in women who developed HDP-IUGR (n = 22) and the odds ratio (OR) to develop HDP-IUGR from 25 to 39 weeks was 8.6 (p < .0001). HDP-AGAf (n = 112) was significantly associated with a higher BMI, multiparity, and maternal age, but not with UtA-PI (OR 1.3; p = .2). In women with an abnormal UtA-PI, the odds of developing early (n = 15) and late-HDP (n = 119) were 3.0 (p = .03) and 1.7 (p = .002), respectively. The AUCs for HDP-IUGR and early-HDP were 0.84 and 0.71, respectively. Discussion: UtA Doppler velocimetry in the first trimester was strongly associated with HDP-IUGR all along gestation, as a proxy of placental insufficiency, and showed no association with HDP-AGAf. Our findings suggest an efficacy of first trimester UtA Doppler velocimetry to identify HDP-IUGR independently of the gestational age, and a limited value for HDP not associated with intrauterine growth restriction (IUGR).

Correlation between average acceleration and deceleration capacity of fetal heart rate and biomarkers of acid-base status in a vivo sheep model

Jelmer R Prins, Leigh R Guerin, Bihong Zhang, John E Schjenken, Simon C Barry, Sarah A Robertson

Analysis of fetal ECG in fetal growth restriction

Jelmer R Prins, Leigh R Guerin, Bihong Zhang, John E Schjenken, Simon C Barry, Sarah A Robertson

OP09.01: First trimester uterine artery Doppler velocimetry and arterial tonometry

antral follicles. After the year of observation the ovary volume reduced (6.7 ± 1.2/5.1 ± 1.2 ml) with no significant difference from initial data noted in both groups. At the same period the follicular size was normal in the 1st group, in the 2nd group the maximal size of the follicles exceeded 9 mm (significant difference from the initial data P < 0.05). Initially the hormone level in both groups was normal. In 6 months the level of AMH in both groups reduced, but the difference was insignificant with no changes in FSH and E2 levels. By the end of the observation the hormone level didn’t change in the 1st group, in the 2nd group was registered a reduction of AMH level remaining in the range of age norm, but significantly lower than initial (1.98 ± 0.57/1.02 ± 0.30 ng/ml P < 0.05). Conclusions: The influence of UAE on ovary function of fertile patients cannot be ruled out, the risk of reduction of ovarian reserve increases in the older age group.