Common Findings in Late Gestation Fetal Echocardiography

Abstract

Objective

Fetal echocardiography (FE) provides detailed information about cardiac structure and function in-utero. Limited information is available regarding normal findings late in pregnancy. We therefore sought to identify and describe common cardiac findings in late gestation.

Methods

Fetuses with structurally normal hearts were identified in mid-gestation within a subset of pregnant women in a prospective study. Atrioventricular valves (AV), right and left atrium (RA/LA), aortic isthmus (AoI) and ductus arteriosus (DA) dimensions and flow abnormalities, aneurysm of septum primum, and presence/grade of tricuspid regurgitation (TR) were assessed throughout pregnancy. Linear and logistic regression analyses were used to characterize change in quantitative and qualitative FE parameters by gestational age.

Results

40 fetuses between 24 and 38 weeks gestational age (GA) were studied. Each had a FE study completed before and after 34 weeks gestation that were compared. Tricuspid/mitral valve and RA/LA ratios increased with GA (p<0.001). More frequently noted after 34 weeks GA were tapering of the DA (2.5% vs. 32%), prominent AoI diastolic flow (5% vs. 67%), prominent DA diastolic flow (2.5% vs. 25%), trivial/mild TR (35% vs. 80%), and aneurysm of septum primum (37% vs 80%). These findings all increased linearly with GA (p<0.001).

Conclusion

AV valve and RA/LA disproportion, mild DA tapering, prominent AoI and DA diastolic flow, trivial/mild TR, and aneurysm of septum primum are frequently identified after 34 weeks GA. This suggests that these FE findings in isolation are likely normal and are a result of the physiologic alterations that occur late in the third trimester.

Introduction

Fetal echocardiography (FE) has been established as the standard tool for diagnosing congenital heart disease in prenatal life.^1,2 Expanding indications for screening fetal echocardiography have resulted in increased utilization of this highly sensitive diagnostic test. Current guidelines suggest that fetal echocardiography be performed between 18 and 22 weeks gestation.³ Nevertheless, screening fetal echocardiography is frequently performed for a variety of indications late in pregnancy, well into the third trimester.

Improved ultrasound technology, sonographer technique, and published guidelines have resulted in a marked increase in the ability to identify relatively subtle findings. This increase in diagnostic capabilities improves recognition of congenital heart disease, but it also affords the opportunity to characterize with greater nuance the anatomic and physiologic alterations that occur throughout pregnancy. The changes that occur in the last weeks of pregnancy are particularly dynamic.^4-6 Accordingly, we sought to describe common fetal echocardiographic findings in third trimester FE in a group of healthy normal fetuses.

Materials and Methods

Study population

This was a prospective study design based on historical data from FE evaluations of patients referred to the Fetal Heart Program at Children's National Medical Center from March 2014 to November 2015. Fetuses with structurally normal hearts as identified by mid-gestation FE were identified as part of an ongoing prospective study. All fetuses then underwent additional standardized FE, with at least one study after 34 weeks gestation. GA ranged from 24 to 38 weeks. Any fetus with a structurally normal heart without studies before and after 34 weeks GA and fetuses diagnosed with congenital heart disease were excluded from the study. Only fetuses with structurally normal hearts in mid-gestation were included.

Fetal echocardiography

FE was performed according to the Children's National Medical Center protocol on a GE Vivid 7 or Philips iE33 ultrasound machine. All studies were performed by a single experienced FE technologist (AF). Each mid-gestation FE was reviewed by a cardiologist (MTD or DNS) and identified as a structurally and functionally normal heart. Subsequently, a second observer reviewed all images to complete data collection (LT and DNS).

The fetal heart was imaged in multiple planes and measurements were made according to guidelines published by the American Society of Echocardiography.¹ Qualitative assessments of RA size were made and corroborated by measurements performed in two dimensions: posterior atrial wall to AV annulus and free wall to mid atrial septum (Figure 1). All atrial measurements were performed in the four-chamber view at end diastole.

Figure 1.

4 chamber view at 37 weeks gestation. Atria were measured from posterior wall to AV annulus and free wall to mid atrial septum at end diastole. RA=right atrium, RV=right ventricle, LA=left atrium, LV=left ventricle, *= FO

The qualitative presence of ductus arteriosus (DA) tapering, defined as aortic insertion smaller than pulmonary insertion into the descending aorta, was noted. Ductus arteriosus (DA) and aortic isthmus (AoI) diameters were also measured in systole in the three vessel and trachea view. Prominent AoI and DA diastolic flow, defined as antegrade diastolic flow without the presence of aliasing, was identified qualitatively by color Doppler.

Color and pulsed-wave Doppler were used to assess the presence of atrioventricular valve regurgitation. Pulsed Doppler velocity-time waveforms were obtained to assess flow across all valves and major blood vessels. Trivial or mild tricuspid regurgitation was defined as the presence of regurgitation seen with color Dopper, but when interrogated with pulsed-wave Doppler the jet was not detectable (trivial) or not holosystolic (mild). Aneurysm of septum primum, defined as the septum projecting at least halfway into the LA, was also identified (Figure 2).⁷

Figure 2.

4 chamber view at 35 weeks gestation. Note the aneurysm of septum primum. RA=right atrium, RV=right ventricle, LA=left atrium, LV=left ventricle, *= FO

Biometric assessments, including biparietal diameter, head circumference, abdominal circumference, and femur length, were performed. Estimated fetal weight was calculated. Middle cerebral artery, umbilical artery, umbilical vein, and ductus venosus flow patterns were assessed by pulsed-wave Doppler. Pulsatility index was calculated for the middle cerebral and umbilical arteries.

Statistical analysis

Results obtained from FE, before and after 34 weeks for each fetus, were compiled and compared. Longitudinal, linear and logistic regression analyses were conducted to characterize change in quantitative and qualitative FE parameters and to adjust variance estimates for the correlation between repeated assessments of the same person. A matched pairs analysis based on McNemar's test was conducted to compare pre (<34 weeks GA) to post (≥ 34 weeks GA) change. In cases of zero cells 1 unit was added to all cells to permit a conservative test of difference.

Institutional review

The Institutional Review Board at Children's National Medical Center approved the protocol for this study.

Results

Ninety-one FE studies were performed in a population of forty-nine pregnant women. Nine women did not have studies completed both before and after 34 weeks and were excluded from this study. A total of 40 fetuses were studied, each having a FE study completed before and after 34 weeks GA. The range of GA was between 24 and 38 weeks. Studies less than 34 weeks GA were then compared to those studies that were greater than or equal to 34 weeks GA.

Using World Health Organization fetal growth charts, all fetuses were noted to have normal growth as suggested by the abdominal circumference, head circumference and weight (>10^th percentile) for gestational age.⁸ The umbilical artery and vein were assessed in all but one fetus. Umbilical artery pulsatility indices were normal, with values between the 5^th and 95^th percentile for gestational age.⁹ Umbilical vein Doppler patterns were also normal, with continuous flow and an absence of pulsations with atrial systole.

Doppler assessment of the middle cerebral artery was completed on 75 of the 80 FE studies. The pulsatility index was calculated for each study and was noted to be normal, between 5^th and 95^th percentiles for gestational age.¹⁰

Mean TV annulus prior to 34 weeks GA measured 0.88 cm (range 0.66-1.2 cm), whereas it measured 1.28 cm (range 0.95-1.5 cm) after 34 weeks GA. Mean MV annulus prior to 34 weeks GA measured 0.8 cm (range 0.63-1.0 cm), whereas after 34 weeks GA the mean was 1.09 cm (range 0.92-1.3 cm). TV/MV ratio throughout gestation increased significantly with GA (p<0.001) (Figure 3).

Figure 3.

TV/MV ratio throughout gestation increased significantly with GA (p<0.001).

Atrial sizes were qualitatively and quantitatively assessed. Before 34 weeks GA, all fetuses had qualitatively similar RA and LA size. Among fetuses with GA ≥34 weeks, 28 of 40 were noted to have a qualitatively enlarged right atrium (p<0.001). This was corroborated by quantitative analyses. The ratio of the dimensions of the RA/LA, from the posterior wall to a closed atrioventricular valve at end diastole, was noted to be 0.97 before 34 weeks GA and 1.05 after 34 weeks GA (p<0.01) (Figure 4). The ratio of the dimensions of the RA/LA, from the free wall to the atrial septum, before 34 weeks GA was 1.03 and the ratio after 34 weeks GA was 1.28 (p<0.01) (Figure 4).

Figure 4.

Quantitative assessment of RA size with measurements from the posterior atrial wall to AV annulus and free wall to mid atrial septum in the 4 chamber view.

DA and AoI at their insertion into the descending aorta were also measured and compared before and after 34 weeks gestation. The DA/AoI ratio was noted to decline with GA, 1.11 at 24 weeks and 1.04 by 36 weeks. However, the rate of change was not statistically significantly significant (p=0.24) (Figure 5).

Figure 5.

The DA/AoI ratio was noted to decline with GA. However, the rate of change was not statistically significantly different from zero (p=0.24).

Prominent DA and AoI diastolic flow increased with gestational age (p < 0.0001). Prominent DA diastolic flow was noted in 1/40 (2.5%) before 34 weeks GA and in 21/40 (52.5%) after 34 weeks GA (p<0.001; OR 21, CI 3.4-868.5). Among the late gestation studies, this was accompanied by DA narrowing in 10/40 (25%) (Figure 6). Prominent AoI diastolic flow was noted in 2/40 (5%) and 27/40 (67%) before and after 34 weeks gestation, respectively (p<0.001; OR 26, CI 4.3-1065.9).

Figure 6.

Three vessel view at 35 weeks gestation. Note the ductus arteriosus tapering at its insertion into the descending aorta. DA= ductus arteriosus Ao= aorta

Of the 40 fetuses less than 34 weeks GA, 15 were noted to have aneurysm of septum primum. Aneurysm of septum primum was noted in 32 out of 40 fetuses after 34 weeks GA (p<0.001, OR 18; CI=32.8-750.0) (Table 1). Only GA was a statistically significant predictor of aneurysm of septum primum (p<0.001); however, the RA/LA ratio of the measurements from the atrial free wall to atrial septum increase tended to predict septum primum aneurysm (OR=3.56, p=0.17), although this did not reach statistical significance.

Table 1.

Finding	Frequency by Group		McNemar's Test Comparison of Discordant Pairs**
	<34 weeks n=40	≥34 weeks n=40	Odds Ratio	P value	95% Confidence Interval
Qualitative RA enlargement	0	28	**29	< 0.001	4.8-1184.4
Ductus arteriosus narrowing	1	13	**14	< 0.001	2.1-592.0
Prominent Aol diastolic flow	2	27	**26	< 0.001	4.3-1065.9
Prominent DA diastolic flow	1	21	**21	< 0.001	3.4-868.5
Tricuspid valve regurgitation†	14	32	19	< 0.001	3.0-789.5
Septum primum aneurysm	15	32	**18	< 0.001	32.8-750.0

^*Discordant Pairs [> 34 wks(cond+), <34kws(cond−)] vs. [>34wks (Cond−), <34wks (cond+)]

^**OR and 95% CI estimated by adding one to each cell

^†Trivial or mild

Trivial/mild TR was more often identified after 34 weeks gestation, 14/40 (35%) versus 32/40 (80%) fetuses before and after 34 weeks gestation, respectively (p<0.001; OR 19, CI 3.0-789.5) (Table 1). All FE, before and after 34 weeks GA, had normal right to left foramen ovale and DA flow, and qualitatively normal right and left ventricular systolic function.

Discussion

There is abundant literature detailing quantitative and qualitative assessments of many aspects of the fetal heart.^11-15 Late gestation fetal cardiac assessment has also been described by some^16-18, and this study adds to the existing literature by quantifying atrial and atrioventricular valve disproportion and their associations with other findings, including aneurysm of septum primum, tricuspid valve insufficiency, and mild flow aberrations in the ductal and aortic arches in late gestation. Importantly, all fetuses were identified as “normal” in mid-gestation. Care was taken to evaluate the fetal growth and well-being on all studies using standard biometric measurements, and MCA and UA flow assessment. All fetuses in this study exhibited normal growth, normal cerebral blood flow patterns, and no evidence of placental insufficiency. This is of particular importance as these findings may also be associated with IUGR.¹⁹

We identified that in the third trimester, TV/MV disproportion, RA/LA disproportion, DA tapering, prominent DA and AoI diastolic flow, trivial/mild TR, and aneurysm of septum primum were frequently identified. We propose that these findings in the absence of any other systemic findings are benign and represent changes in in-utero physiology that occur late in pregnancy. Of note, although several fetuses exhibited mild right/left heart size discrepancy and prominent diastolic flow in the aorta, no fetus had signs concerning for aortic arch obstruction based on contemporary literature.^20-21

It is well known that the response of the DA to increased oxygen content is ductal closure, which then results in a shift in atrial pressure and functional closure of the foramen ovale.^22-23 Less is known, however, about changes that occur in utero prior to this postnatal event. This study suggests that certain structural and physiologic adaptations may begin weeks before birth and may result in the discrepancies often noted when comparing mid- to late-gestation fetal cardiac assessments. Conceivably, late gestation alterations including ductus arteriosus narrowing and increased pulmonary blood flow result in greater pulmonary venous return. The resultant changes in atrial pressures may produce shifts in the systemic venous return such that more flow is directed through right-sided heart structures, resulting in the relative enlargement observed in this study. Similarly, atrial pressure shifts may result in early adherence and tethering of septum primum, further limiting right-to-left atrial flow and thereby increasing right-sided enlargement. Finally, this tethering effect with billowing of the mid-portion of septum primum into the LA may be responsible for the aneurysmal appearance of septum primum on many FEs in our study.

Given the increasing utilization of late gestation FE, characterization of common and likely normal findings becomes important. Enhanced understanding of normal fetal cardiac changes late in gestation may ultimately have implications for referral patterns, initial or follow-up fetal cardiology evaluations, and even reducing psychological stress on families concerned about potential congenital heart disease.

Limitations

There are several important limitations to this study. Given the study design, no postnatal echocardiographic data were available, however all patients were seen postnatally and no cardiovascular symptoms or need for cardiology follow up were identified. Additionally, the study was performed in a single center and sample size was limited to the research sample available for analysis. From a technical perspective, late-gestation FE poses challenges, including difficult fetal position, maternal habitus, and otherwise difficult windows.

Conclusion

This study identified several findings which appear to be common in late gestation fetal echocardiography. These changes likely represent normal physiologic adaptations that occur late in the third trimester. Additional studies of term fetuses or even during the labor process may yield additional insight and information into the transition from fetal to postnatal life. At a minimum, accurately identifying common normal findings studying fetuses may prove useful in influencing referral patterns and alleviating family anxiety regarding potential heart disease.