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J Ultrasound Med. Author manuscript; available in PMC 2018 December 01.
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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.
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.
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Keywords
Echocardiography (Fetal); Echocardiography (Pediatric); Pediatrics
Address for the authors and correspondence: Lauren Tague, Children's National Medical Center, Department of Cardiology, 111
Michigan Avenue NW, Suite WW3-200, Washington, DC, 20010, USA, Phone: (202) 476-2020, Fax: (202) 476-5700,
Lauren.Tague@childrensnational.org.
Tague et al. Page 2
Introduction
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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.
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
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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
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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
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.
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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.
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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 (>10th
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 5th and 95th
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 5th
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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).
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
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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).
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).
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
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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).
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.
Trivial/mild TR was more often identified after 34 weeks gestation, 14/40 (35%) versus
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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 some16-18, and this study adds to the existing literature by quantifying atrial
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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
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
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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.
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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
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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.
Acknowledgments
Research reported in this publication was supported by the National Institutes of Health under award number
RO1HL116585 IDDRC grant P30HD40677.
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The content is solely the responsibility of the authors and does not necessarily represent the official views of the
National Institutes of Health.
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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
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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
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Figure 3.
TV/MV ratio throughout gestation increased significantly with GA (p<0.001).
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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.
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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).
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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
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Table 1
Finding <34 weeks n=40 ≥34 weeks n=40 Odds Ratio P value 95% Confidence Interval
Tague et al.
*
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