Keywords congenital heart disease - CHD - fetal anatomy ultrasound - fetal echocardiography
Cardiac anomalies are the most common congenital malformation, with an estimated incidence
of 4 to 13 per 1,000 live births.[1 ]
[2 ]
[3 ] Consequently, congenital heart disease (CHD) is an important cause of neonatal morbidity
and mortality.[4 ]
[5 ]
[6 ] Advances in prenatal ultrasound have allowed for more frequent antenatal detection
of CHD, facilitating the care of affected infants at birth.[7 ] Though the majority of these pregnancies occur in women without known risk factors,
certain conditions, such as diabetes mellitus and family history of CHD, have been
associated with increased risk of CHD.[8 ]
[9 ]
[10 ] In pregnancies complicated by preexisting diabetes mellitus, rates of CHD have been
reported to be as high as 21 to 46 per 1,000 live births.[11 ] The recurrence rate for mothers who have previously given birth to an infant with
CHD is ∼19 per 1,000 live births.[8 ]
Recommendations by the American College of Obstetrics and Gynecology, the American
Institute of Ultrasound in Medicine (AIUM), and the International Society of Ultrasound
in Obstetrics and Gynecology are for women with known risk factors for CHD to undergo
two screening tests, a detailed fetal anatomy ultrasound and a fetal echocardiogram,
as opposed to anatomic survey alone.[2 ]
[12 ]
[13 ]
[14 ] The utility of fetal echocardiography in diagnosing CHD after normal cardiac imaging
on detailed anatomic survey has been questioned in previous work.[6 ]
[11 ]
[15 ]
[16 ] Despite this, recommendations have not changed. Thus, we aimed to reassess the rate
of abnormal fetal echocardiography after normal detailed anatomy ultrasound if interpreted
by maternal–fetal medicine specialists in a large, contemporary cohort of women meeting
referral criteria for both exams.
Materials and Methods
After Institutional Review Board approval, we performed a retrospective review of
women undergoing both detailed anatomy ultrasound and fetal echocardiography at the
same regional prenatal diagnosis center between 2010 and 2014. Both anatomic survey
and fetal echocardiography were performed between 16 and 26 weeks of gestation, and
were interpreted by maternal–fetal medicine specialists. We chose this gestational
age range to reflect routine referral patterns, while allowing some flexibility for
those women presenting later to care. Women included had at least one indication for
fetal echocardiography as recommended by the AIUM and normal cardiac anatomy on the
initial detailed anatomic survey. We excluded women with previous abnormal ultrasound
(e.g., thickened nuchal translucency, ≥ 3 mm, or cystic hygroma), and those with abnormal
or incomplete cardiac images on the initial anatomic survey. Echogenic intracardiac
foci, choroid plexus cysts, and two-vessel umbilical cords were considered normal
variants and were not excluded.
All detailed fetal anatomy ultrasounds were performed by Registered Diagnostic Medical
Sonographers (RDMS) credentialed with an Obstetrics/Gynecology specialty at an AIUM
accredited prenatal diagnosis center. Following RDMS certification, these sonographers
were proctored by a senior board-certified maternal–fetal medicine specialist in the
performance of the detailed anatomic survey. Exams were read and interpreted by maternal–fetal
medicine specialists. During the study period, detailed anatomy ultrasounds assessed
the four-chamber heart, and left and right ventricular outflow tract views only; additional
views, such as the three-vessel trachea view, were not routinely performed. Fetal
echocardiography was performed in real-time by select maternal–fetal medicine physicians
according to published guidelines.[2 ]
We collected maternal demographic information, body mass index (BMI), diabetic status,
pregnancy characteristics including plurality, gestational age at the time of each
ultrasound, as well as indications for and results of fetal echocardiography. When
a cardiac abnormality was suspected prenatally, neonatal medical records were reviewed
for any postnatal cardiac imaging results or special care (e.g., neonatal intensive
care unit admission). Postnatal imaging to confirm normal fetal echocardiographic
findings was not routinely performed. The primary outcome was abnormal fetal echocardiogram,
defined as a structural cardiac abnormality. Cardiac abnormalities were considered
major if likely to require surgery within the first 6 months of life, and minor if
unlikely to require such intervention. Based on past work, we expected a detection
rate of CHD by fetal echocardiogram after a normal anatomic survey of 3% or less.[6 ]
[11 ]
[15 ]
[16 ] We chose an a priori sample size of 1,000 pregnancies to achieve a reasonably narrow
95% confidence interval (CI) around an estimated primary outcome rate of 3% (95% CI:
2.0–4.3%). Data analysis was performed with Stata/SE 13.1.
Results
We screened 1,883 ultrasound reports of women who underwent both detailed fetal anatomic
survey and fetal echocardiography at our center between 2010 and 2014, of which we
excluded 883 ([Fig. 1 ]). After exclusions, the echocardiography results and medical records of 1,000 women
carrying 1,052 fetuses were reviewed. The majority of women were Caucasian and multiparous
([Table 1 ]). There were 937 live births (including 45 twins and 1 set of triplets) at the hospital
primarily affiliated with the prenatal diagnosis center, and 7 confirmed pregnancy
losses or terminations. The majority of women had only one fetal echocardiogram during
the studied pregnancy (956/1,000), whereas 43 had two, and one woman had three, yielding
a total of 1,045 fetal echocardiograms performed during the study period. The mean
time between first detailed anatomic survey and fetal echocardiography was 10.3 days
(standard deviation 12.1 days).
Table 1
Baseline characteristics of women undergoing fetal echocardiography
Variable
N = 1,000 women
Maternal age (y)
30.0 (26.0–34.0)
Nulliparous
364 (36.4)
Twins
50 (5.0)
Monochorionic/monoamniotic
0 (0)
Monochorionic /diamniotic
26 (2.6)
Dichorionic/diamniotic
24 (2.4)
Triplets
1 (0.10)
Ethnicity/race
White
665 (66.5)
African American
73 (7.3)
Hispanic
161 (16.1)
Asian
42 (4.2)
Other
59 (5.9)
BMI (kg/m2 ) at first prenatal visit
n = 641
26.7 (23.4–32.2)
Diabetes
n = 924
Type 1
65 (7.0)
Type 2
137 (14.8)
Gestational
137 (14.8)
First trimester Hgb A1c (%)
Type 1
n = 55
7.5 (7.0–8.3)
Type 2
n = 96
6.7 (6.1–8.1)
IVF
50 (5.0)
Gestational age at first anatomy US (wk)
20.0 (18.6–21.1)
Gestational age at first fetal echo (wk)
21.1 (20.6–22.1)
Abbreviations: BMI, body mass index; IVF, in vitro fertilization; US, ultrasound.
Note: Data presented as n (%) or median (interquartile range).
Fig. 1 Derivation of study population. NT, nuchal translucency; TTTS, twin–twin transfusion
syndrome. * Twins (n = 50) and triplets (n = 1).
The most common indication for echocardiography was family history of CHD, followed
by preexisting diabetes mellitus ([Table 2 ]). There were 71 women referred for fetal echocardiography due to suspected preexisting
diabetes mellitus, of which 67.6% had an abnormal diagnostic test for gestational
diabetes at ≤ 136/7 weeks' gestation. Of the nine women referred due to abnormal genetic testing (increased
risk of aneuploidy or Smith–Lemli–Opitz syndrome by cell-free fetal deoxyribonucleic
acid testing or integrated screening), seven underwent amniocentesis, identifying
three abnormalities (trisomy 21, a balanced translocation involving chromosomes 2
and 16, and a 45, X/46, XY mosaic).
Table 2
Indications for fetal echocardiography
Indication
N = 1,000 women
Family history of CHD
426 (42.6)
First degree relative
268 (62.9)
Other or unspecified
158 (37.1)
Preexisting diabetes mellitus
190 (19)
Other[a ]
118 (11.8)
Drug exposure
95 (9.5)
Fetal arrhythmia
65 (6.5)
Multiple indications
50 (5.0)
Monochorionic twins
23 (2.3)
Assisted reproductive technology
19 (1.9)
+SSA or +SSB antibodies
7 (0.7)
Inherited disorder
7 (0.7)
Abbreviation: CHD, congenital heart disease.
Note: Data presented as n (%).
a Suspected preexisting diabetes mellitus (n = 71), abnormal genetic testing (n = 9), two-vessel umbilical cord (n = 15), and others.
Of the 1,052 fetuses, 5 had an abnormal echocardiogram, 0.5%, 95% CI: 0.2–1.1% ([Table 3 ]). Only one major cardiac anomaly was identified, which led to pregnancy termination
(a complex defect involving a stenotic pulmonary valve and severe tricuspid regurgitation);
neither invasive genetic testing nor fetal autopsy was performed. Four fetuses were
diagnosed with minor abnormalities (all ventricular septal defects), of which three
had postnatal cardiac imaging that was normal. None of the four live-born infants
with an abnormal fetal echocardiogram required special care in the immediate neonatal
period.
Table 3
Distribution of abnormal fetal echocardiograms and outcomes
Participant
Suspected cardiac anomaly
Indication for fetal echocardiogram
Pregnancy outcome
Postnatal imaging or autopsy result
1
VSD
Family history of CHD
Live birth
Normal
2
VSD
Family history of CHD
Live birth
Normal
3
VSD
ART
Live birth
None available
4
VSD
Trisomy 21 on amniocentesis
Live birth
Normal
5
Complex structural heart defect[a ]
Family history of CHD
Termination
None available
Abbreviations: ART, artificial reproductive technology; CHD, congenital heart disease;
VSD, ventricular septal defect.
a Involved a stenotic pulmonary valve and severe tricuspid regurgitation.
Discussion
In this contemporary, well-characterized cohort of women meeting screening criteria
for both detailed anatomy ultrasound and fetal echocardiography, the rate of abnormal
fetal echocardiogram after a normal detailed anatomy ultrasound interpreted by maternal–fetal
medicine specialists was low. The course of only 1 of 1,000 pregnancies (0.1%) was
altered on the basis of an abnormal echocardiogram following a normal detailed anatomy
ultrasound. These findings suggest that when the detailed anatomy ultrasound is performed
by a specialized physician, there may be limited utility to an additional fetal echocardiogram.
We cannot comment on the utility of the fetal echocardiogram in other practice settings.
In background investigation, we conducted a search of the electronic databases Medline,
PubMed, and the Cochrane Database of Systematic Reviews through November 2016 using
the phrases or keywords “fetal echocardiography utility”; “fetal echocardiography”
and (1) “normal anatomic survey,” (2) “normal anatomy ultrasound,” or (3) “level II
ultrasound”; and “fetal echocardiography and CHD.” We also reviewed the reference
lists of each article identified in our electronic search for relevant studies. We
were able to identify four studies that previously evaluated fetal echocardiography
in women with normal cardiac imaging on anatomy ultrasound (results summarized along
with our work in [Table 4 ]).[6 ]
[11 ]
[15 ]
[16 ] Though their methodologies were somewhat varied, all authors concluded that the
utility of echocardiography in this setting is limited. Summing the data from these
reports yields an abnormality rate of 0.1% (95% CI: 0.03–0.29%) for major or severe
CHD, and 2.0% (95% CI: 1.5–2.5%) for minor or mild CHD by fetal echocardiography after
normal cardiac imaging on anatomic survey. Our findings reinforce the conclusions
made by these authors, and again raise important questions regarding the usefulness
of fetal echocardiography as a second screening test after a normal detailed anatomy
ultrasound.
Table 4
Summary of the current and prior studies
Study
Inclusions
Cardiac images in anatomy US
Most common indications for fetal echo
Major[a ] or severe[b ] CHD
Minor[c ] or mild[d ] CHD
Muller et al[16 ] (2005)
Anatomy US and fetal echo at same facility
Fetal echo at 17–30 wk
4CH
LVOT
Preexisting DM
Fetal anomaly
Family history of CHD
2/578 (0.4%)
4/578[e ] (0.7%)
Starikov et al[11 ] (2009)
Anatomy US at 16–20 wk with normal cardiac images
Fetal echo at same facility
4CH
LVOT
RVOT
AMA
US marker of aneuploidy
Family history of CHD
0/481 (0.0%)
1/481[f ] (0.2%)
Sekhavat et al[15 ] (2010)
Anatomy US and fetal echo at same facility
Maternal DM
Excluded suspected CHD and GA > 29 wk
Not specified
Maternal DM
0/584 (0.0%)
19/584 (3.3%)
Friedman et al[6 ] (2011)[g ]
Anatomy US and fetal echo at same facility
Normal anatomy US
4CH
LVOT
RVOT
Aortic arch
Ductal arch
Family history of CHD
DM
0/371 (0.0%)
31/371 (9.8%)
Froehlich et al (2016)[g ]
Anatomy US and fetal echo at same facility at 16–26 wk
Normal anatomy US
4CH
LVOT
RVOT
Preexisting DM
Family history of CHD
1/1,000 (0.1%)
4/1,000 (0.4%)
Total (%) (95% CI)
3/3,014 (0.1) (0.03–0.29)
59/3,014 (2.0)
(1.5–2.5)
Abbreviations: 4CH, four-chamber heart; AMA, advanced maternal age; CHD, congenital
heart disease; CI, confidence interval; DM, diabetes mellitus; GA, gestational age;
LVOT, left ventricular outflow tract; RVOT, right ventricular outflow tract; US, ultrasound.
a Major CHD requires medical or surgical intervention within first 6 months or year
of life.
b Severe CHD requires surgical intervention or mandatory cardiac follow-up.
c Minor CHD unlikely to require surgery within first 6 months of life.
d Mild CHD not likely to be hemodynamically significant but might require postnatal
follow-up.
e Number of women with normal cardiac images on anatomy ultrasound.
f Ventricular septal defect categorized as “minor” for purposes of this table.
g Excludes fetuses with extracardiac malformations.
The main strength of our study is its size; this is the largest evaluation of this
question to date. We intentionally chose a sample size of 1,000, whereas other studies
were smaller and did not include a priori sample size calculations. Using strict inclusion
and exclusion criteria, we studied a select cohort of women meeting screening criteria
for fetal echocardiography, but who lacked first or second trimester ultrasonographic
features that may have placed their fetuses at even higher risk of CHD. Thus, we were
able to identify a specific group of women in whom detailed anatomic survey alone
is likely a sufficient screening strategy for CHD. This is especially important in
an era where medical care dollars are becoming increasingly constrained. Pinto et
al estimated the cost of one fetal echocardiogram to be $358 (2015 USD).[17 ] In our cohort, 1,045 fetal echocardiograms were performed to identify one clinically
significant abnormality. Using their cost estimate means we expended $374,110 to identify
one clinically significant fetal cardiac abnormality.
It is important to note that the purpose of this study was not to define the performance
(i.e., sensitivity and specificity) of fetal echocardiography as a screening test,
which would have required postnatal echocardiography of all neonates included in the
study. Rather, our aim was to determine how often echocardiography will be deemed
abnormal after a normal detailed anatomy ultrasound, and the subsequent effect the
results may have on prenatal management or immediate neonatal care. We must also note
that in the years following the study period, the cardiac views routinely included
in the detailed anatomy ultrasound at our center have been expanded in accordance
with updated guidelines.[18 ] In addition to the four-chamber heart, and left and right ventricular outflow tract
views, we now routinely assess the aortic arch, three-vessel and three-vessel trachea,
and superior and inferior vena cavae views. Repeating this study in light of these
expanded views would likely yield an even lower rate of abnormal echocardiogram after
a normal detailed anatomy ultrasound.
We acknowledge several study limitations. This study was performed in a population
in which all detailed anatomy ultrasounds and fetal echocardiograms are interpreted
by maternal–fetal medicine specialists. Our findings may not be reproducible in settings
with other screening practices, especially when performed by physicians other than
maternal–fetal medicine specialists, or those with lower CHD prenatal detection rates.
In addition, as a referral center, some women present for ultrasonography but deliver
elsewhere. Consequently, we did not have access to complete prenatal records or outcome
data for all women included in the study. This led to some missing maternal demographic
data, such as BMI, and may also have limited our ability to assign the true indication(s)
for fetal echocardiography. Similar to Starikov et al, we excluded women with incomplete
cardiac views at the time of the anatomy ultrasound. Consequently, this analysis cannot
be used to comment on the most appropriate next screening step for these women. Finally,
we did not correct for correlation among the minority of women who had more than one
fetal echocardiogram. However, doing so, given the infrequency of detected cardiac
abnormalities, could not have materially affected our conclusions.
Fetal echocardiography is routinely performed for women at increased risk of CHD in
addition to detailed anatomic survey without clear evidence of benefit. In a high-resource
setting, where all exams are interpreted by maternal–fetal medicine specialists, the
addition of fetal echocardiography after a normal detailed anatomy ultrasound is unlikely
to change clinical management or to be cost-effective. As we strive to maximize health
care efficiency and minimize costs, it may be most effective to encourage detailed
anatomy ultrasounds performed by specialists, reducing the need for additional imaging
in some patients.
