Detailed quantification of cardiac morphology
The use of centiles for critical determination of the size and growth of fetal organs is well established. Traditionally, available studies have examined absolute values of normal structures across gestation. However, as the size of the fetus may vary markedly throughout gestation, the use of z-scores (expressed as the number of SDs a measurement departs from the population mean) has been advocated. There is a general consensus that cardiac measurements are not routinely required during echocardiographic assessment of the fetus. Calculation of z-scores normalizes cardiac structures to body size7. In 2005, Schneider and colleagues published formulae for regression equations and nomograms allowing z -scores to be calculated for 17 cardiac structures in normal fetuses in relation to noncardiac biometric parameters (femur length, biparietal diameter and gestation age)8. Recently, novel nomograms for cardiac (bi-)ventricular widths and their corresponding ratios have been published (increase in the RV/LV ratio with GA)9. Krishnan et al. examined 13 cardiac dimensions and concluded that predictive models based on GA provided the best fit for determining normal measurements of fetal cardiac structures10. In fact, these normative data differ from those of prior reports11. In a recent commentary on potential causal variables, Cantinotti and colleagues highlighted multiple methodological and numerical limitations of the available studies including the sample size, data size, measurement methods, normalization, and expression of data12. Moreover, the resultant nomograms were not tested on affected fetuses with CHD nor were correlations quantified to determine the clinical significance of abnormal measures13. A number of left- and right-sided lesions may antenatally present with abnormal ventricular proportions and growth exceeding normal values. Precise quantification of these echocardiographic parameters may act as a proxy to estimate the need for neonatal intervention and single-ventricle palliation in fetuses with suspected obstructive cardiac lesions14. In this regard, fetuses with left ventricular length z-scores that are 2–4 standard deviations below normal have an increased risk of developing a hypoplastic left heart syndrome (HLHS) variant. The initial echocardiographic examination at 18–22 weeks is unable to distinguish cases of fetal cardiac asymmetry that are destined to develop into HLHS variants from the eventually normal cases, underscoring the need for serial exams in cases suspicious for LVOT obstructions15. In addition to the recommended biometric cardiac parameters recommended by national and international guidelines, a number of measurements have been introduced into the literature16,17. Gagnon et al. published the results of 57 cardiac measurements and found nonlinear relationships with GA for most parameters investigated18. Particularly, identification of subtle changes in cardiac morphology (e.g., aortic arch anomalies) might be challenging. The fetal left common carotid-to-left subclavian artery distance (LCSA) and ascending aorta (AAo)-descending aorta (DAo) and transverse aorta (Tao)-DAo angles are novel measures that can differentiate between subjects with and without aortic coarctation (CoA)19. However, for reliable quantification of an abnormal aortic angulation in cases suspicious for CoA, a true sagittal anatomic plane is warranted. Similarly, as stated above, proper assessment of abnormal ventricular or vascular size is directly related to the ability to generate exact diagnostic sections of the fetal heart. In general, to preclude off-axis images of the 4-chamber view, alignment is needed to visualize the entire boarders of each cardiac chamber within the fetal thorax. Departing (oblique) cutting planes may consecutively result in abnormal values for cardiac dimensions. In 4D echocardiography, a specific cardiac phase can by identified and analyzed by observing the global contractility of the myocardium and the response and integrity of the cardiac valves within an entire heart cycle (frame-by-frame)20,21. This volumetric approach constitutes a reliable and accurate method for obtaining true fetal cardiac dimension measurements in second and third trimester fetuses22,23. The same applies for objective evaluation of fetal cardiac function to provide important information on hemodynamic status, which will be discussed later.
A major limiting factor is that detailed offline analysis and navigation within a volume data set is useful when performed by skilled examiners with expertise in (volume) echocardiography. Recent data show that a semiautomatic workflow-based approach using FINE could reliably reconstruct standard diagnostic planes even in unexperienced hands24. This technology now allows calculation of quantitative cardiac biometry measurements (e.g., ventricular and atrial size, diameter of outflow tracts, valvular hinges)21.