Methods

This investigation represented a prospective cross-sectional cohort study performed from February 2009 through December 2012. To increase the number of fetuses assessed at the earliest gestations, we included additional consecutive pregnancies encountered at <9 ⁺⁶ weeks’ GA through December 2013. Women were referred for early FE who were identified as being at increased risk for fetal CHD. Additionally, healthy pregnant women with no increased risk were also recruited. Multiple-gestation pregnancies were included in the study in the setting of known increased risk for CHD (monochorionic twins) and/or pregnancies conceived with assisted reproduction and healthy volunteers. Institutional ethical approval was obtained before commencement of the study.

To be included for review, the first fetal echocardiographic examination needed to be performed before 14 ⁺⁰ weeks, and written informed consent was obtained from all participants. Consent included discussion regarding the limitations of early FE as well as a discussion regarding theoretical risks of the procedure. FE was performed in the fetal cardiology clinic at a single tertiary referral center. TA and TV ultrasound was performed by either a physician or a sonographer trained specifically in FE. FE was performed using either the Siemens S2000 (Siemens Healthcare, Erlangen, Germany) or the GE Voluson E8 (GE Healthcare, Little Chalfont, United Kingdom). For TA imaging, either a 9-MHz linear transducer or a 7-MHz wide-band convex transducer was used on the Siemens S2000, and for TV imaging a 9- to 12-MHz endocavity probe was used on the Voluson E8.

Crown-rump length (CRL) was obtained in all cases. GA was calculated using the patient’s last known menstrual period or early ultrasound if available. For consistency, we defined all pregnancies into “GA” (week of gestation) from 6 weeks’ GA, defining further the days of that gestational week from +0 to +6 days. This allowed the same terminology from 6 to 13 weeks’ GA. Using established guidelines, before 12 ⁺⁰ weeks GA, CRL was used to define GA if there was a >5-day discrepancy between last menstrual period and CRL. Between 12 ⁺⁰ and 13 ⁺⁶ weeks, GA was based on CRL if there was a >7-day difference between CRL and last menstrual period. If the pregnancy was conceived using assisted insemination techniques, the date of insemination was used to calculate GA, and if in vitro fertilization was used, the date of implantation was used to calculate GA. For all pregnancies, irrespective of GA, we described findings in the “fetus” and did not differentiate between embryonic and fetal stages, given the continuum of ages examined.

Early Fetal Echocardiographic Technique

For TA imaging, especially for the earliest gestations with the fetus typically positioned very low within the maternal pelvis, the transducer was positioned immediately above the maternal symphysis pubis, with orientation of the plane of imaging behind the pubic bones. Images were optimized to gain the highest possible frame rates, aiming for ≥50 Hz but usually >80 Hz. The highest frequency transducer was always attempted first, with change to the lower frequency probe if image resolution was insufficient. In many cases, both low- and high-frequency probes were used at different times in the examination, depending on fetal position. Optimization for image acquisition included reducing depth to a minimum, narrowing the sector width to as small as practical, and aligning the area of focus appropriately. TA imaging was attempted in all patients after 8 ⁺⁰ weeks’ GA, with TV ultrasound performed only if TA imaging resulted in an inability to sufficiently visualize the fetal cardiac anatomy (minimum sought: four chambers, great arteries, and arches) and the distance between the fetal chest and cervix was shorter than the distance between the fetal chest and maternal abdominal wall ( Figure 1 ). We have previously published a description of the procedure for TV FE.

Two-dimensional image that demonstrates assessment of distance between the fetal chest and maternal cervix and abdomen in (A) 10 ⁺³ -week and (B) 13 ⁺³ -week GA pregnancies. To assess this, the transducer is oriented longitudinally over the middle of the maternal pelvis. Particularly at earlier GAs, and as is shown in (A) , the fetal chest is often in closer proximity to the cervix, thus resulting in better image resolution of cardiac anatomy by TV imaging. In contrast, by 13 weeks, the distances may be similar or the fetal chest may be closer to the maternal abdominal wall.

At the start of all fetal echocardiographic examinations, the fetal left and right sides were clearly established by orienting the fetus in the longitudinal plane, fetal head to the left of the screen with the transducer dot leftward, and then rotating 90° clockwise onto the four-chamber cardiac view. This approach resulted in the fetus’s being oriented “head up, feet down,” allowing determination of fetal left and right both in real time and on review of images offline. Normal visceral situs was then established by showing leftward cardiac apex, a left-sided stomach, and an inferior vena cava (IVC) draining to the right-sided atrium. This technique could not be used for TV imaging, because of difficulty in establishing fetal orientation reliably using this approach, and thus as much as possible, situs was determined using the TA approach before TV imaging.

Imaging of the four-chamber view, including the mitral and tricuspid valves, both great arteries with demonstration of great artery crossing, aortic and ductal arches, and systemic (IVC) and pulmonary veins, was attempted in all fetuses. Visualization of the IVC directly entering the right atrium was used as a marker of normal systemic venous drainage. Assessment of pulmonary venous drainage was determined to be successful if at least two pulmonary veins were seen entering the left atrium, one from the left and one from the right side. Aortic and ductal arches were assessed sweeping up from the four-chamber view to the three-vessel tracheal view. The three-vessel view allowed assessment of arch position, size, and patency as well as relationship to the trachea. The appearance of the V shape as the arches came together from anterior to posterior was essential in assessing their course and position in the fetal chest. Assessment of the arches in the sagittal plane was attempted in all cases and gave additional information on arch size and flow.

Fetal echocardiograms were reviewed online (L.K.H.) and independently offline by two physicians (L.K.H. and D.H.). Each echocardiogram was reviewed as to whether specific features of the cardiac anatomy were visible ( Table 1 ), along with the defined biometry measures and fetal heart rate. Both 2D and color Doppler imaging was performed in all cases. Duration of imaging and use of color and spectral Doppler was kept to a minimum. As is recommended, both thermal index (TI) and mechanical index (MI) were displayed on the screen and monitored with their values at ≤1.0 throughout the examination at all times possible. Study duration per fetus and highest MI and TI were recorded. If particularly limited views of the fetal heart were obtained before 11 weeks’ GA, often because of a very difficult fetal position, a repeat fetal echocardiographic examination was offered before 14 weeks. However, serial or repeat first trimester FE was not routinely offered if only minor details could not be ascertained. A second-trimester (after 18 weeks) fetal echocardiographic study was organized for all participants, and postnatal echocardiography was also offered to all.

Table 1

Features assessed on early FE

Cardiac axis

Atrial and visceral situs

Four-chamber view

Mitral and tricuspid valves (2D and color Doppler)

Aortic outflow tract (2D and color Doppler)

Pulmonary outflow tract (2D and color Doppler)

Crossing of great arteries (2D and color Doppler)

Aortic arch (2D and color Doppler)

Ductal arch (2D and color Doppler)

IVC (2D and color Doppler)

Cardiac inflow pulsed-wave Doppler (left and/or right)

Pulmonary veins (2D and color Doppler) ∗

Fetal heart rate

 

∗ Included at least one left and one right pulmonary vein.

Results

A total of 261 early fetal echocardiographic examinations were performed in 202 individual pregnancies, including 166 singletons, 33 sets of twins, and three sets of triplets. In 15 pregnancies (including 11 singletons, three sets of twins, and one triplet gestation, totaling 20 fetuses), insufficient resolution of the fetal heart at <11 weeks’ GA and maternal request for repeat early assessment prompted repeat FE within 2 to 3 weeks, with sufficient views achieved in all. All but 15 of the pregnancies were referred for FE because they were considered at risk for CHD on the basis of American Heart Association guidelines. Fourteen women (13 singletons, one set of dichorionic, diamniotic twins) volunteered to participate in the study without known risk factors for fetal CHD; informed consent was obtained. Most fetuses (221 of 241 [92%]) underwent follow-up second-trimester ( n = 217, all ≥18 weeks) or third-trimester ( n = 4) FE. Twenty fetuses (8%) did not undergo second- or third-trimester FE: in seven fetuses (3%), the mothers withdrew from the study after the initial first-trimester FE; in nine singleton pregnancies, there was spontaneous fetal demise; three singleton pregnancies had termination of pregnancy (two with trisomy 21, one with cystic hygroma); and one pregnancy underwent selective reduction for a twin with a large cystic hygroma. After unremarkable findings on second-trimester FE, two singleton pregnancies underwent elective termination for noncardiac pathology (one each with cytomegalovirus infection and cerebral anomaly). No autopsies were performed among terminated pregnancies. One infant was found to have a small muscular ventricular septal defect on postnatal examination and echocardiography, which was not identified prenatally. All remaining fetuses had postnatal confirmation of no significant cardiac pathology on examination through contact with their primary care providers. Sixty-eight (28%) had agreed to postnatal echocardiography that confirmed first-trimester findings.

Figure 2 demonstrates the number of fetuses studied at the different GA time points as well as the use of TV imaging in each group. TV imaging was required in addition to TA imaging in 88% of patients ( n = 103 of 117) before 11 ⁺⁰ weeks and in only 12% ( n = 10 of 86) between 12 ⁺⁰ and 13 ⁺⁶ weeks. TV imaging resulted in a shorter distance between the fetal chest and the transducer in almost all studies before 12 weeks (average distance on TA imaging, 5.5 cm [range, 2.4–10.3 cm]; average distance on TV imaging, 3.2 cm [range, 2.9–11.0 cm]).There was an increase in the distance with GA by TV imaging and a progressive decrease by TA imaging such that in 13th week, the distance by TA imaging was either the same or shorter in many (average distance on TA imaging, 4.8 cm [range, 2.8–7.1 cm]; average distance on TV imaging, 4.3 cm [range, 4.2–4.5 cm]). TV imaging provided a more limited range of motion than TA imaging and, as such, depended even more so on optimal fetal position and maternal uterine and placental anatomy for sufficient image resolution. A retroverted uterus, for instance, did not permit imaging of fetal cardiac anatomy given lack of an imaging plane from the cervix, and either a low-lying placenta or uterine fibroids often increased the fetal distance from the transducer, which importantly affected image resolution, especially at earlier GAs. When the fetus was in a cephalic or transverse presentation with the spine toward the cervix, acquisition of cardiac views was also difficult. Use of the highest frequency transducers available, reducing the depth and narrowing the scanning sector, and the use of active zoom features were critical for providing sufficient resolution of the cardiac anatomy using either TA or TV approaches at all GAs examined. Slow left-to-right movement, rotation, and angling of the TA or TV transducer permitted sweeping through the fetus usually in longitudinal and cross-sectional planes. With respect to fetal position, for most examinations, the fetus was very mobile, and thus, when a suboptimal position was present at the start of the examination, the fetus often moved to a position that was more effective for imaging. Gentle shaking of the maternal lower abdomen or having the mother move about usually resulted in fetal movement and frequently optimized images.

Graph showing the number of fetuses scanned at the different GAs, with the number assessed using the TA approach demonstrated in blue and the number with both TV and TA scanning in green .

Mean (±2 SDs) scanning time per fetus, as calculated by documenting the start and end time of each study, was 24 ± 17 min per fetus. Study duration increased with advancing gestation of assessment up to 11 weeks ( Table 2 ). With earlier gestation studies, assessment times were kept to a minimum, particularly when image resolution was insufficient to delineate cardiac anatomy on TA and TV examination, and to reduce ultrasound exposure. In later gestation, longer studies occurred, often as a more comprehensive cardiac assessment was possible including assessment of pulmonary veins.

The maximum recorded TI or MI was documented for each study. TI values remained <0.5 (mean ± 2 SDs, 0.27 ± 0.1), and MI values remained ≤1.2 (mean ± 2 SDs, 0.96 ± 0.3) throughout all studies performed ( Table 2 ). The highest MI values (1.1–1.2) occurred only with use of wider sector widths when briefly evaluating fetal position and CRL, decreasing as sector width and depth were reduced and with the use of zoom features. An MI of 1.0 to 1.2 was observed only in one to three recorded still frames or clips for any study.

Cardiac Anatomic Assessment

Cardiac activity with confirmation of heart rate could be demonstrated between 6 ⁺⁰ and 7 ⁺⁶ weeks, but it was not possible to discern detailed features of the fetal cardiac anatomy at this early age. However, at least one outflow tract could be identified using color Doppler in 83% ( n = 5 of 6) between 7 ⁺⁰ and 7 ⁺⁶ weeks, and at least one cardiac inflow color Doppler signal was obtained in 88% ( n = 7 of 8) from 6 ⁺⁰ and 7 ⁺⁶ .

A four-chambered heart could be imaged in 52% ( n = 12 of 23) between 8 ⁺⁰ and 8 ⁺⁶ weeks by 2D imaging, increasing to 98% from 11 ⁺⁰ weeks onward ( Table 2 ). In the eighth and early ninth weeks of gestation, the four-chamber view demonstrated generous atrial cavities relative to the ventricular cavities, and the atria were very thin walled. A degree of pericardial effusion was usually evident, and the heart was large relative to the thorax. Imaging of mitral and tricuspid valve leaflets in the four-chamber view was not possible before 10 weeks’ gestation, as the image resolution was not sufficient to demonstrate the thin leaflets. Furthermore, although the four chambers could be clearly seen in the majority from 8 weeks’ GA, the offset of the AV valves and assessment of the anterior mitral valve leaflet in short-axis views was generally not resolved by imaging until after 12 weeks.

The cardiac axis could be assessed in the majority at the ninth week (59% [ n = 24 of 41]) and in almost all from 11 ⁺⁰ weeks onward (98% [ n = 142 of 144]). The cardiac axis was usually more midline at the earlier GAs and rotated leftward through the latter half of the first trimester, as we have previously reported and as demonstrated in Figure 3 . Situs could be determined in the eighth week in only 13% ( n = 3 of 25) but could be shown in the majority from 11 ⁺⁰ weeks onward (59% [ n = 34 of 58]). Lack of success in defining situs in the earlier gestations was due to an inability to fully define the fetal anatomy, including the heart, stomach, and IVC via the TA approach.

Appearance of the four chambers at 8, 9, 11, and 13 weeks of gestation by FE. Note the more midline appearance of the cardiac axis at 8 and 9 weeks and a more leftward position of the ventricular septum relative to the midline at 11 and 13 weeks. At 8 weeks, the larger atrial relative to the ventricular cavities can be appreciated. The heart at earlier gestations is also relatively large relative to the fetal thorax. LV , Left ventricle; RV , right ventricle; Sp , spine.

The IVC was first visualized on 2D imaging from 7 ⁺⁰ weeks. With the use of color Doppler, visualization of the IVC at 7 ⁺⁰ to 7 ⁺⁶ weeks was possible in 33% ( n = 2 of 6; Table 2 , Figure 4 ). The addition of color Doppler, typically using significantly lower Nyquist settings than for arterial structures, improved visualization of systemic veins compared with 2D imaging alone from 9 ⁺⁰ to 12 ⁺⁶ weeks ( P < .0001). Pulmonary veins were first imaged, using color Doppler, between 11 ⁺⁰ and 11 ⁺⁶ weeks (2% [ n = 1 of 58]), and this improved to 23% ( n = 7 of 31) on 2D imaging or 42% ( n = 13 of 31) using color Doppler between 13 ⁺⁰ and 13 ⁺⁶ weeks.

Graph demonstrating the frequency with which the IVC and pulmonary veins could be demonstrated by 2D imaging and by color Doppler imaging at the different GAs. Note that each week of gestation along the x axis includes +0 to +6 days. ^∗ P = .0001 for 2D versus Color Doppler imaging.

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