Assessment of Fetal Development Using Cardiac Valve Intervals

Abstract

An automated method to assess the fetal physiological development is introduced which uses the component intervals between fetal cardiac valve timings and the Q-wave of fetal electrocardiogram (fECG). These intervals were estimated automatically from one-dimensional Doppler Ultrasound and noninvasive fECG. We hypothesize that the fetal growth can be estimated by the cardiac valve intervals. This hypothesis was evaluated by modeling the fetal development using the cardiac intervals and validating against the gold standard gestational age identified by Crown-Rump Length (CRL). Among the intervals, electromechanical delay time, isovolumic contraction time, ventricular filling time and their interactions were selected in a stepwise regression process that used gestational age as the target in a cohort of 57 fetuses. Compared with the gold standard age, the newly proposed regression model resulted in a mean absolute error of 3.8 weeks for all recordings and 2.7 weeks after excluding the low quality recordings. Since Fetal Heart Rate Variability (FHRV) has been proposed in the literature for assessing the fetal development, we compared the performance of gestational age estimation by our new valve-interval based method, vs. FHRV, while assuming the CRL as the gold standard. The valve interval-based method outperformed both the model based on FHRV. Results of evaluation for 30 abnormal cases showed that the new method is less affected by arrhythmias such as tachycardia and bradycardia compared to FHRV, however certain types of heart anomalies cause large errors (more than 10 weeks) with respect to the CRL-based gold standard age. Therefore, discrepancies between the regression based estimation and CRL age estimation could indicate the abnormalities. The cardiac valve intervals have been known to reflect the autonomic function. Therefore the new method potentially provides a novel approach for assessing the development of fetal autonomic nervous system, which may be growth curve independent.

Keywords: 1D Doppler ultrasound; autonomic nervous system (ANS); cardiotocography (CTG); fetal development; fetal electrocardiography (fECG); fetal monitoring; gestational age; systolic and diastolic time intervals.

Figure 1

An illustrative example of fetal cardiac intervals. STI, Systolic Time Interval; EDT, Electromechanical Delay Time; ICT, Isovolumic Contraction Time; PEP, Pre-Ejection Period; VET, Ventricular Ejection Time; IRT, Isovolumic Relaxation Time; VFT, Ventricular Filling Time.

Figure 2

Block diagram of the training and testing processes of the method used for automated identification of opening and closing of the valves (Marzbanrad et al., 2014a).

Figure 3

Applying threshold for acceptable DUS and fECG signal quality, the absolute error for GA estimation is reduced. The absolute error (weeks) is plotted vs. the thresholds for fECG and DUS signal quality scores. The number of excluded cases for different choices of the quality thresholds are shown on the grid knots.

Figure 4

(A) The estimated GA using cardiac valve timings and the GA based on CRL as a gold standard were compared for 22 healthy fetuses with fECG quality score > 0.4 and DUS quality score > 0.3. r, Pearson correlation r-value; r2, Pearson r-value squared; SSE, sum of squared error; n, number of fetuses. (B) Bland-Altman plot (bias and 95% limits of agreement: 1.96 SD) for the estimated and CRL-based GA. RPC(%): reproducibility coefficient and % of mean values, CV: coefficient of variation (SD of mean values in %).

Figure 5

The estimated GA using cardiac valve timings vs. the GA based on CRL as a gold standard are shown for 30 abnormal cases. The 95% Confidence Interval (CI) for healthy cases (as shown in Figure 4) and y = x line are also shown for comparison. The abnormality types are specified for the cases with estimated GA being outside the 95% CI. More details can be found in Table 4. (WPW, Wolff-Parkinson-White syndrome; VSD, Ventricular Septal Defect; PA, Pulmonary Atresia; ASD, Atrial Septal Defect; CDH, Congenital Diaphragmatic Hernia; CA, Chromosomal Aberration; AV block, Atrioventricular block; SA, Single Atrium; CAV, Cardiac Allograft Vasculopathy; CAVC, Common Atrioventricular Canal; PS, Polysplenia Syndrome; CHD, Congenital Heart Disease; NIHF, Nonimmune Hydrops Fetalis).