First‐trimester fetal heart evaluation: time to move forward

Abstract

The importance of the 11–14-week ultrasound exam beyond screening for chromosomal abnormalities is becoming more apparent in the era of non-invasive prenatal testing1, 2. In fact, measurement of nuchal translucency and its establishment in obstetric practice worldwide can be considered the renaissance of prenatal ultrasound. This measurement has fundamentally changed prenatal care by moving the detection of major abnormalities, including cardiac abnormalities, to the early stages of gestation. This allows for earlier and enhanced pregnancy and delivery planning, as well as availability of more reproductive options. Congenital heart defects (CHDs) are the most common congenital anomalies, with an incidence of ∼1% in liveborn babies3. The actual incidence in the fetal period is up to 5-fold higher, given the severity and lethality of many of these complex lesions. The majority of CHDs occur in a low-risk population with no identifiable risk factors4. Typically, the standard evaluation of the fetal heart, including the four-chamber view, outflow tracts and transverse arches, is performed during the routine 18–20-week anatomic assessment. Pregnancies with an abnormality detected on this routine scan are then referred for detailed fetal echocardiography. With improved ultrasound technology and this ‘new window’ of opportunity for assessment at the 11–14-week scan, there is now the potential to evaluate the fetal heart in the first trimester of pregnancy. In the last two decades, several studies have demonstrated the feasibility of first-trimester cardiac evaluation in high-risk populations5, 6, such as those with family history of heart defects, maternal diabetes or teratogen exposure. However, restricting the indications for first-trimester cardiac evaluation to these high-risk categories will detect only a small proportion of cardiac defects. Even expanding first-trimester cardiac evaluation to those with abnormal ultrasound markers, such as thickened nuchal translucency, reversed a-wave in the ductus venosus and tricuspid regurgitation, will still miss almost 50% of major cardiac defects7-9. To date, none of the current first-trimester ultrasound guidelines recommends evaluation of the fetal heart beyond heart rate, position and the four-chamber view10, 11. In light of advancing technology and the ability to detect major chromosomal and structural abnormalities at an earlier gestational age, the time arises to shift our paradigm to routine first-trimester cardiac evaluation and consider including second-trimester standard heart views, such as the four-chamber view, the left and right outflow tract views and the three-vessel view, into our first-trimester evaluation. The criteria for good screening tests have been well-established by the World Health Organization and include six main components: (1) the condition should be of sufficient frequency and severity; (2) the condition should cause a known spectrum of symptoms; (3) the screening test should be simple, reliable and have a low incidence of false-positive and false-negative results; (4) adequate methods of confirmation and follow-up should be available; (5) the condition should be amenable to treatment; and (6) ideally, there should be a cost advantage to society. It is clear that first-trimester fetal heart evaluation meets all of these components. CHDs are the most common anomalies in the fetus and, although the CHD itself does not compromise the fetus due to the parallel nature of the circulation, it can cause severe symptoms postnatally. With proper identification and immediate management, these consequences can potentially be prevented. Current technology has improved the resolution of fetal heart imaging in early gestation, as we describe below. This makes first-trimester screening feasible and reliable. Although the proportion of false positives and false negatives could still be an issue at the beginning of the learning phase in non-experienced hands, this risk has been reported to be very low in experienced centers12, 13. In fact, a systematic review and meta-analysis, published in 2020, demonstrated 75% sensitivity and 99% specificity in the first-trimester detection of CHD, pooling results from 18 centers13. With regard to the fourth criterion, identification of CHD in the first trimester allows sufficient time to monitor the evolution of the severity of the lesion and its impact on the fetus and the mother. Understanding the degree of the defect or the combination of other defects and/or associated genetic abnormalities gives us an opportunity to understand and relay the prognosis of the condition. Additionally, there are some defects that may be amenable to in-utero treatment. With regard to cost, as we already perform an ultrasound examination at this stage of pregnancy (11–14 weeks), adding a couple of additional views to confirm normal four-chamber, great artery and arch views should not add any cost to our existing exam. Well-recognized challenges of first-trimester cardiac scanning include the safety of Doppler application, small fetal size, increased fetal movement and maternal body mass index (BMI). From a safety perspective, all modern ultrasound packages have standardized Doppler settings with dedicated acoustic output limits. These limits are selected and locked to keep the soft-tissue thermal index, bone thermal index and cranial thermal index below 0.7. In a review of first-trimester fetal echocardiography using both high-definition color flow Doppler and pulsed-wave Doppler ultrasound, Nemescu and colleagues demonstrated that the safety indices were remarkably stable and relatively constant for all exams, with all the indices being below the actual recommendations14. With improved grayscale resolution and probe quality, the challenges of small fetal size and increased movement are also now surmountable15. Early evaluation of the fetal heart does not appear to be impacted by maternal obesity. In our center, we compared early assessment of fetal heart landmarks using two-dimensional (2D) sonography with color/power Doppler in obese vs non-obese women16. We found that there was no significant difference between the groups in the ability of experienced sonographers to evaluate the four-chamber view, outflow tract relationships and transverse arches. Approximately 6% of obese women required additional imaging with transvaginal sonography at the time of the 11–14-week scan. The chance of needing transvaginal ultrasound rose as BMI rose. Despite this, the median scan time was only 5 min longer in the obese group16. We believe that obesity should not be a contraindication to evaluating the fetal heart in the first trimester. In fact, it is imperative that we perform early fetal heart evaluations in obese women, given that their risk for fetal CHD appears to be increased. In these women, early gestation may give us a ‘window’ to evaluate the fetal heart, given that it is located within the depth of penetration of the transvaginal probe. Demonstrating the four-chamber view at the time of nuchal translucency measurement, as well as obtaining the tricuspid valve waveform, has become routine in many centers as part of first-trimester screening programs. Given the embryology of the fetal heart, the outflow tracts and arches should also be complete in development by this time. Therefore, adding these views to demonstrate normal cardiac development has become very feasible in the first trimester using 2D ultrasound with advanced conventional color and high-definition power Doppler application (Figure 1a–c). One step beyond 2D ultrasound is four-dimensional fetal echocardiographic technique utilizing spatiotemporal image correlation and tomographic ultrasound imaging display. This technique is effective in displaying examination planes that constitute the extended cardiac examination. It has been used previously in high-risk populations and showed a sensitivity of 91%, specificity of 100%, positive predictive value of 100% and negative predictive value of 99% in the detection of major cardiac defects. This technique also avoids the challenge of fetal movement since the cardiac sweep starting from the four-chamber to the three-vessel view can be performed in 7.5–15 s (Figure 1d–f)17. As a new modality, SlowflowHD™ (GE Healthcare, Zipf, Austria) is a type of power Doppler which is optimized for sensitivity to the microvasculature18. This application can depict the slow flow of smaller vessels in the branching vascular bed of the fetus. Its unique characteristics are a high-display frame rate, high-line density (high resolution) and good sensitivity. SlowflowHD uses dedicated and sophisticated wall filters and operates in a typical pulse-repetition frequency range of 180–300 Hz, making it robust against tissue and motion artifacts. This technology allows detection of flow speeds to only a few cm/s, demonstrates atrial and ventricular filling and shows the precise morphological appearance of the atria and ventricles in the first trimester. In addition, radiant flow can be added to SlowflowHD. To date, this new modality has been used to evaluate fetal abdominal blood vessels and organ microvasculature; however, there are no current published studies assessing its utility in the first-trimester evaluation of the fetal heart. In our practice, we have been using SlowflowHD in our first-trimester assessment to complement cardiac assessment and demonstrate fetal circulation and details of the fetal heart structure. As a Doppler technology, it appears to be very useful in the small first-trimester heart and has the potential to expand the spectrum of cardiac anomalies detected beyond four-chamber and outflow-tract abnormalities. In particular, the addition of radiant flow enables one to demonstrate the different levels of crux insertions. To date, identifying the different levels of crux insertions has been a challenge in the first-trimester heart. If the 2D conventional Doppler images are not clear, it is difficult to demonstrate this detail by color Doppler imaging. We have observed that SlowflowHD with enabled radiant flow improves the image quality of the crux. We speculate that this effect can be explained by clutter suppression that may reduce the power in cases of moving tissue. The other application of SlowflowHD to first-trimester heart assessment is demonstration of the pulmonary veins and inferior and superior vena cava drainage into the left and right atria, respectively (Figure 2). In addition, due to the same mechanism as mentioned above, assessment of atrioventricular discordance and the morphological details of the ventricles is also impressive using this evaluation. This can be very helpful in the diagnosis of heterotaxy syndromes (Figure 2). Clinically, first-trimester fetal heart assessment and early detection of CHD has numerous advantages. It enables early genetic testing, early decision-making about pregnancy continuation and earlier planning for appropriate management during and after pregnancy. Parents are then given additional time to educate themselves, set expectations and seek adequate resources. A normal first-trimester cardiac assessment may also provide reassurance to high-risk patients who might have a prior child with CHD. We certainly do not suggest that first-trimester cardiac evaluation should replace standard second-trimester screening, as there are many defects that evolve over time and will be best assessed later in gestation. However, we do suggest that we start taking advantage of technology and the development of new imaging modalities and applications which make early and accurate identification of CHDs possible in the first trimester. Maybe the time has come to shift the paradigm and revise our guidelines to include routine evaluation of basic fetal heart views in the first trimester.

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