Echocardiographic Studies of the Human Fetus: Prenatal Diagnosis of Congenital Heart Disease and Cardiac Dysrhythmias

VOLUME 65 . JUNE 1980 O NUMBER 6

Pediatrics

Echocardiographic

Studies

of the Human

Fetus:

Prenatal

Diagnosis

of Congenital

Heart

Disease

and Cardiac

Dysrhythmias

Charles

S. Kleinman,

MD, John

C. Hobbins,

MD,

C. Carl

Jaffe,

MD,

Diana C. Lynch, RN, and Norman S. Talner, MD

From the Departments of Pediatrics, Diagnostic Radiology, and Obstetrics and

Gynecology, Yale University School of Medicine and Yale-New Haven Hospital, New

Haven, Connecticut

ABSTRACT. During obstetrical ultrasound examinations, 200 M-mode and 35 real-time two-dimensional

echocar-diographic studies were performed on 180 fetuses of high-risk pregnancies. Fetal gestational ages ranged from 18 to

41 weeks. M-mode “sweeps” demonstrating mitral- and

septal-aortic fibrous continuity were obtained in 1 15

stud-ies. Paradoxic septal motion in 50 fetuses suggested

rela-tive right ventricular volume loading. Congenital cardiac

malformations were accurately diagnosed in a 34-week

fetus with pulmonary atresia and hypoplastic right

yen-tricle and in a 28-week fetus with a univentricular heart.

Congenital complete atrioventricular block was diagnosed

in a 28-week fetus and atrial flutter with variable

atrio-ventricular block was diagnosed in a 38-week fetus. The

use of echocardiographic studies to evaluate cardiac

structure and rhythm in utero assists in counseling

pro-spective parents and in planning postnatal management

for their offspring. Pediatrics 65:1059-1067, 1980;

ultra-sound echocardiography, prenatal diagnosis, fetal

heart, fetal echocardiography.

the assessment of fetal growth patterns and in the

diagnosis of congenital malformations such as limb

abnormalities, hydrocephaly, and

anencephaly.’

Little

possibility of diagnosing disorders of congenital

car-diac structure and function prenatally.2’3

We have applied M-mode and real-time

two-di-mensional echocardiographic imaging techniques to

assess the structure and rhythm of the developing

human heart. With this approach, major cardiac

malformations have been diagnosed in two fetuses

and cardiac rhythm disturbances recognized in two

other fetuses and form the basis of this report.

Advance knowledge prior to delivery of the

pres-ence or absence of certain congenital cardiac defects

can permit better counseling of prospective parents

who are at risk for offspring with heart disease, and

may aid management ofthe remainder of pregnancy

and delivery.

Ultrasonic examinations of the developing

hu-man fetus have been performed extensively during

the past several years and are of considerable aid in

Received for publication June 13, 1979; accepted Sept 14, 1979.

Presented in part to the Section on Developmental Biology of

the Society for Pediatric Research, New York, April 28, 1978.

Reprint requests to (C.S.K.) Department of Pediatrics, Yale

University School of Medicine, 333 Cedar St, New Haven, CT

06510.

PEDIATRICS (ISSN 0031 4005). Copyright © 1980 by the

American Academy of Pediatrics.

METHODS

There were 200 M-mode and 35 real-time

two-dimensional echocardiographic studies performed

on 180 fetuses between 18 and 41 weeks gestation.

The patient population surveyed consisted of

preg-nant women who were referred to our high-risk

obstetrical clinic (Table).

The orientation of the fetus within the uterus and

the position of the fetal heart with relation to the

TABLE. Profile of Obstetrical Risk Factors

No. of Patients

33 9 1 19 15 9 3 8 3 19 18 8 7 27 1

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Fig 1. M-mode echocardiogram at midventricular level

in a 33-week fetus. ARVW, anterior right ventricular wall;

IvS, interventricular septum; LV, left ventricular cavity;

MV, mitral valve; RV, right ventricular cavity; TV,

tn-cuspid valve.

Fetal risk factors

Intrauterine growth retardation

Fetal cardiac arrhythmia Fetal bradycardia Maternal risk factors

Heart disease Congenital Acquired Drug mgestions Alcohol Amphetamines Anticonvulsants Lithium Rh sensitization Diabetes mellitus Preeclampsia

Collagen vascular disease Familial risk factors

Congenital heart disease

Previous offspring

Paternal

Total 180

routine ultrasound examination with either a

B-mode scanner (Picker Echoview 80L) or a linear

array real-time scanner (Air Shields or ADR). Fetal

cardiac M-mode studies were performed by using

an ultrasonograph (Smith-Kline Instruments

Eko-line 20) interfaced with a strip-chart recorder and

a 3.5 MHz nonfocused transducer (Aerotech).

Two-dimensional (real-time) cardiac scans were

per-formed by using a cardiac imager (Picker 80 CI)

with a 3.5 MHz transducer (Aerotech).

Efforts were made to obtain M-mode cardiac

sweeps from apex to aortic root, through the fetal

left hemithorax (in a manner simulating a postnatal

cardiac examination). The fetal echocardiographic

studies, in general, added no more than 20 to 25

minutes to the patient examination. Difficulties in

imaging were encountered if the fetus was

posi-tioned with limbs or vertebral column between the

abdominal wall and the heart. Inadequate studies

resulted when the fetuses were very active and in

three cases in which massive maternal obesity

pre-cluded adequate ultrasonic penetration.

Reposi-tioning the mother into a decubitus position or

allowing her to walk about the laboratory for 10 to

15 minutes repositioned the fetus sufficiently to

allow echocardiographic study in nine of 21 fetuses

in whom unsatisfactory studies were initially

ob-tamed. Six of 14 fetuses at first inadequately

scanned underwent successful study at a later date,

one to three weeks following the initial examination

attempt.

Real-time sector scans were obtained with

ex-amination performed along the ventricular

“long-axis,” “short-axis,” and along oblique planes which

resulted in “four-chamber” views of the heart.4

The atrioventricular and semilunar valves and

cardiac chambers were identified in systematic

fashion by their relative positions and by their

characteristic patterns of motion.5

Interventricular septal motion was recorded at

the level of the mitral valve leaflets-the position

recommended for ventricular measurements in

ex-aminations of small hearts by the Committee on

M-mode Standardization of the American Society of

Echocardiography.6 In the absence of an

accom-panying electrocardiographic signal, systole and

diastole were identified by the apex and nadir,

respectively, of left ventricular posterior wall

mo-tion.

RESULTS

A satisfactory echocardiographic study of the

fetus requires demonstration of atnoventricular

valve anatomy within the ventricular chambers and

atrioventricular and semilunar valve relationships

as established on a continuous sweep from

ventric-ular chamber to cardiac root. Such M-mode scans

were obtained on 130 of the 180 (72%) fetuses

ex-amined. A representative M-mode echocardiogram

at midventricular level in a 34-week fetus is

dem-onstrated in Fig 1, permitting identification of

yen-tricular chambers and the mitral and tricuspid

ventric---

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ular chambers and great arteries were obtained in

30 of the 35 (86%) fetuses studied.

Interventricular septal motion could be assessed

in 90 (50%) of our 180 patients. Forty fetuses (44%)

had normal interventricular septal motion (ie,

pos-tenor systolic motion of the septum toward the

anteriorly-contracting left ventricular posterior

F, .

-wall). Fifty (55%) of these 90 fetuses manifested

paradoxic interventricular septal motion. Thirteen

had type A septal motion (ie, anterior septal motion,

away from the posterior wall in systole) and 37

fetuses had type B septal motion (ie, little or no

systolic excursion of the septum).7

Complex congenital heart disease was diagnosed

Fig 2. Top, M-mode echocardiogram at midventnicular level in a 34-week fetus with

intrauterine growth retardation. Only one atrioventnicular valve could be identified, within

a large (18 to 22 mm) ventricular chamber. The anterior ventricular cavity is hypoplastic

(6 mm diameter). Bottom, M-mode echocardiogram at midventnicular level on the same

patient. Study performed at 1 hour of age. Note the similarity between studies. IVS,

interventricular septum; LV, left ventricular cavity; MV, mitral valve; RV, right ventricular

prenatally in two cases. A “muscle-bound”

hypo-plastic (6 mm) right ventricular chamber was

dem-onstrated in a 34-week gestational fetus who was

referred for evaluation of intrauterine growth

retar-dation. The left ventricular cavity was enlarged (18

to 22 mm), and contained a readily definable mitral

valve (Fig 2, top). This infant was cyanotic at birth.

Postnatal echocardiography (Fig 2, bottom)

con-firmed the prenatal findings. Cardiac

catheteriza-tion and cineangiography established the diagnosis

of pulmonary atresia with intact interventricular

septum and hypoplastic right ventricle.

Fig 3. Top, M-mode echocardiographic study at ventricular level in a 28-week fetus with

intrauterine growth retardation. The anterior mitral valve leaflet traverses the plane of

the remnant of interventricular septum. Bottom, Mitral valve is displaced into the

ventricular outflow tract at the level of the cardiac base. Ao, aorta; IVS, interventnicular

Fig 4. Left, Single frame of videotape recording of

real-time two-dimensional study ofthe same fetus represented

in Fig 3. Frame is four-chamber view in early diastole.

Right, Diagram representing frame on left. Atnal septum

separates the two atrial chambers (A). The common

anterior valve leaflet (arrow) bridges the large

atrioven-tricular canal-type ventricular defect and opens into the

large single ventricular chamber (V).

ARTICLES 1063

Fig 5. Autopsy specimen of heart from fetus represented in Figs 3 and 4. Right atrium

and ventricular inflow tract into large single ventricular chamber are exposed. Note the

fenestrated membrane covering the fossa ovalis. The atrial septum primum is intact. FO,

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Fig 6. Mitral valve echocardiogram from a 28-week fetus. The A waves of the anterior

mitral leaflet lack a fixed relationship with the E points of mitral valve motion. a, A points;

e, E points; IVS, interventncular septum; MV, mitral valve; PLVW, posterior left

ventric-ular wall.

M-mode study of a 28-week gestational fetus

referred for evaluation of intrauterine growth

retar-dation suggested an atnoventricular canal defect,

with a rudimentary rim of interventncular septum

through which the anterior mitral leaflet appeared

to move during diastole (Fig 3, top). The anterior

atrioventricular valve leaflet was displaced into the

left ventricular outflow tract during diastole (Fig 3,

bottom) and total diastolic excursion of the

atrio-ventricular valve was large (30 mm). The

four-chamber real-time two-dimensional study in this

fetus demonstrated an intact atrial septum pnmum

with a large posterior ventricular defect resulting in

a common ventricular chamber (Fig 4). The

refer-ring physician was informed of these findings and

the strong possibility of Down’s syndrome was

dis-cussed. The fetus was stifiborn at 30 weeks gestation

and was found at autopsy to have a univentncular

heart with a rudiment of conal septum and an intact

atrial septum pnmum with a fenestrated membrane

overlying the foramen ovale (Fig 5). Clinical

stig-mata of Down’s syndrome were noted, although

karyotyping was not successfully performed.

Severe cardiac rhythm disturbances were found

in two additional fetuses by using M-mode studies.

One 28-week gestation was diagnosed to have

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Fig 7. Lead 2 of electrocardiogram taken at 10 minutes

of age from newborn whose fetal echocardiographic study

is presented in Fig 6. Note how the P waves appear to

“march through” the QRS complexes.

plete atrioventricular block on the basis of an

ab-normality of mitral valve and left ventricular

pos-tenor wall motion. Mitral valve “A” points

ap-peared to “march through” the mitral “E” points

(Fig 6) in a manner similar to the “march” of the

electrocardiographic P waves through the QRS

complexes of the postnatal electrocardiogram (Fig

7) and thus confirmed the presence of complete

atrioventricular block. After further questioning of

this patient’s mother, a history of arthralgias and

transient skin rashes was uncovered and the

sero-logic diagnosis of systemic lupus erythematosis was

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Fig 8. Top, M-mode echocardiogram at the level of the cardiac base in a 38-week fetus

referred for evaluation of a fetal arrhythmia. Note the regular, rapid undulation of the left

atnal wall (rate 300/minute). Bottom, Rapid but irregular response is noted in the

echocardiogram at the ventricular level in the same fetus. Ao, aorta; IVS, interventricular

septum; LA, left atrium; LV, left ventricular cavity; MV, mitral valve.

A second fetus, referred at 38 weeks gestation for ventricular septal motion (Fig 8, bottom). It was

evaluation of an irregular heart rhythm, was found elected to deliver this child by cesarean section

to have rapid movement of the left atrial wall, at a after an unsuccessful attempt to induce labor. The

rate of approximately 300 beats per minute (Fig 8, infant was mature at birth but was in mild

conges-top). The ventricular response rate was rapid but tive cardiac failure due to atnal flutter with a rapid

1066 PRENATAL DIAGNOSIS OF CONGENITAL HEART DISEASE

IIJ’

Fig 9. Lead 2 of electrocardiogram at 5 minutes of age

in newborn whose fetal echocardiogram is presented in

Fig 8. Note atrial flutter at approximately 310 beats!

minute with variable ventricular response.

block (Fig 9). The child was electrically

cardio-verted at birth and maintained in sinus rhythm

thereafter on digoxin therapy.

DISCUSSION

M-mode and real-time two-dimensional imaging

of the developing fetal heart has been demonstrated

in previous studies during the late second and third

tnmesters of pregnancy.2’3’9’2 The present study

has established the feasibility of using

echocardio-graphic imaging techniques to accurately diagnose

congenital cardiac malformations and rhythm

dis-turbances in utero. Cases of the correct diagnosis of

a hypoplastic right ventricle at 34 weeks gestation,

univentricular heart at 28 weeks gestation, and

complex rhythm disturbances at 28 and 38 weeks

gestation illustrate this approach. To date,

postna-tal evaluations of all of the patients who were

successfully scanned have uncovered no false

neg-ative or false positive results.

While it is unlikely that small atrial or ventricular

septal communications could be detected in utero,

it is possible to detect atrioventricular canal defects

and atrioventncular valve atresia and ventricular

cavity hypoplasia. Visualization of two well-formed

semilunar valves rules out valve atresia and the

ability to ascertain the presence of mitral- and

septal-aortic fibrous continuity is important in

eval-uating conotruncal abnormalities such as tetralogy

of Fallot and persistent truncus arteriosus.5

Observation of paradoxic interventncular septal

motion in the majority of fetuses suggests the

pres-ence of relative right ventricular volume loading in

utero7”315 and correlates with fetal lamb blood flow

studies of Heymann and Rudolph which have

shown that 67% of combined ventricular output is

ejected by the right ventricle.’6 Concern that

eval-uation of septal motion in M-mode studies could be

influenced by transducer position relative to the

“pivot-point” of the septum appears to be

unwar-ranted, because initial studies using

two-dimen-sional sector scanning that permitted visualization

of the entire septum support the impression of

paradoxic septal motion found in 18 of 30 patients

(56%).

We have, to date, been unable to obtain verifiable

data concerning left ventricular stroke output, due

to the presence of paradoxic septal motion, which

interferes with these calculations. Further use of

real-time two-dimensional imaging of the entire left

ventricle may permit future estimates of ventricular

volumes and outputs.’7 Serial assessment of growth

patterns of cardiac wall thickness and cavity

dimen-sions in utero may allow diagnosis of relative cavity

hypoplasia or dilation and diagnosis of hypertrophic

cardiomyopathy should be possible antenatally.

While the use of these techniques for routine

screening would be inefficient and costly, the

ex-amination of a population at high risk for structural

or functional heart disease can potentially be

valu-able. Included in this group would be the offspring

of parents who either have congenital heart disease

or cardiomyopathy or who have had children with

congenital heart disease or genetically determined

cardiomyopathies as well as in situations where the

risk of congenital heart disease is enhanced such as

maternal diabetes, collagen vascular disease, and

drug ingestion (alcohol, amphetamines,

anticonvul-santa, or lithium).’8

SUMMARY

Echocardiography provides a method for

estab-lishing the prenatal diagnosis of certain structural

or rhythm abnormalities of the heart in the

devel-oping human fetus. Information obtained from such

studies is of value to the pediatrician and

obstetri-cian in formulating plans for management of

preg-nancy, delivery, and the immediate postnatal period

as well as providing the capability to counsel

pro-spective parents who are at high risk for bearing

children with heart disease.

ACKNOWLEDGMENT

This work was supported by the National Institutes of

Health, National Institute of Child Health and Human

Development, Public Health Service grant HD 10138,

and by The National Foundation.

REFERENCES

1. Hobbins JC, Winsberg F: Ultrasonography in Obstetrics

and Gynecology. Baltimore, Williams & Wilkins Co, 1977

2. Winsberg F: Echocardiography of the fetal and newborn heart. Invest Radiol 3:152, 1972

3. Sahn DJ, Lange L, Allen HD, et a!: A quantitative

nonin-vasive study of normal fetal cardiac growth using real-time cross-sectional echocardiography, abstracted. Pediatr Res

13:351, 1979

4. Tajik AJ, Seward JB, Hagler DJ, et al: Two-dimensional real-time ultrasonic imaging of the heart and great vessels: Technique, image orientation, structure identification, and validation. Mayo Clin Proc 53:271, 1978

analysis in infants with congenital heart disease. Circulation

50:1072, 1974

6. Sahn DJ, DeMaria A, Kisslo, J, et al: Recommendations

regarding quantitation in M-mode echocardiography:

Re-suits of a survey of echocardiographic measurements.

Cir-culation 58:1072, 1978

7. Meyer RA, Schwartz DC, Bearing G, et al: Ventricular septum in right ventricular volume overload: An echocardio-graphic study. Am J Cardiol 30:349, 1972

8. McCue CM, Mantakas ME, Tingelstad JB, et al: Congenital heart block in newborns of mothers with connective tissue disease. Circulation 56:82, 1977

9. Baars AM, Merkus JMWM: Fetal echocardiography: A new

approach to the study of the dynamics of the fetal heart and

its component parts. Eur J Obstet Gynec Reprod Biol 72:91,

1977

10. Egeblad H, Bang J, Northeved A: Ultrasonic identification and examination of fetal heart structures. J Clin Ultrasound

3:95, 1975

11. Lee FYL, Batson HWK, Alleman N, et al: Fetal cardiac structure: Identification and recognition. Am J Obstet Gyn.

ecol129:503, 1977

12. Suzuki I, Minei U, Schnitzer LE: Ultrasonographic mea-surement offetal heart volume for estimation of birthweight.

Obstet Gynecol 43:867, 1974

13. Hagan AD, Francis GS, Sahn DJ, et al: Ultrasound

evaiua-tion of systolic anterior septal motion in patients with and

without right ventricular volume overload. Circulation 50:

248, 1974

14. Pearlman AS, Clark CE, Henry WL, et al: Determinants of

ventricular septal motion: Influence of relative right and left ventricular size. Circulation 54:83, 1976

15. Weyman AE, Wann 5, Feigenbaum H, et al: Mechanism of

abnormal septal motion in patients with right ventricular volume overload: A cross-sectional echocardiographic study.

Circulation 54:179, 1976

16. Rudolph AM: Congenital Diseases of the Heart. Chicago,

Year Book Medical Publishers, 1974

17. Carr KW, Engler RL, Forsythe JR, et al: Measurement of

left ventricular ejection fraction by mechanical

cross-sec-tional echocardiography. Circulation 59:1196, 1979

18. Nora JJ, Nora AH: The evolution of specific genetic and

environmental counseling in congenital heart diseases.

Cir-culation 57:205, 1978

INSTRUCTIONS OF AN EIGHTEENTH CENTURY ENGLISH FATHER TO

HIS DAUGHTER ON HOW TO RAISE HER SON

John Taylor (1694-1761), the editor of the first Hebrew Concordance of the

English Bible, offered his daughter in his pamphlet entitled The Value of a

Child (1752) the following advice on raising her son.’

Let him be well established in liberty (liberty to use and improve his understanding)

and the rights of conscience; but for others as well as himself. Address his understanding;

encourage his enquiries, and use him betimes to think and reason. Represent vice in the

most odious, virtue in the most amiable colours. Especially give him a deep sense of

truth and integrity, and an abhorrence of all manner of falsehood, fraud, craft, subterfuge

and dissimulation, as base and dishonourable, and highly displeasing to God. You cannot

cherish veracity too much. Never be severe for any fault he ingenuously acknowledges.

But while you are convincing him of the wrong he has done, honour and commend him

for the truth he has spoken. Make him sensible [that] bodily appetites and passions are

very dangerous, if not duly restrained. Give him a low, opinion of splendor and show, and

deceive him not into wrong thoughts of himself by gaudy ornaments. Teach him to

reverence the human nature even in the poorest and suffer him not to treat any with

contempt. Cherish modesty and check a forward, bold behaviour; it may grow into an

unruly dissolute insolence. Suffer him not to be a man, but as years and understanding

allow. Boys are by no means fit to govern themselves, or to direct others. Inure him to

diligence and close application, (properly intermixed with play and diversion) when he is

strong enough to apply to learning; and let him want no advantage of increasing in

knowledge and wisdom you can procure, or he can improve. And rest persuaded that

your sincere and pious endeavours will not be in vain. The nature of things, and the

promise of God insure success.

REFERENCE

Noted by T.E.C., Jr, MD

1. Taylor J: The Value ofa Child; or, Motives to the Good Education of Children. London, James