Ultrasound Clinics: Antenatal screening with fetal echocardiography:when and how

September 1, 2003



Antenatal screening with fetal echocardiography:
when and how

By Richard M. Benoit, MD, and Joshua A. Copel, MD

Screening for factors known to increase risk of congenital heart disease can help identify cases, but focusing only on at-risk pregnancies will not identify most cardiac malformations.

Heart defects are among the most common congenital abnormalities, occurring in about 0.8% of newborns.1 In half of all cases of congenital heart disease (CHD), the outcome is good. Some such defects are minor and resolve spontaneously, while others that are major—such as tetralogy of Fallot—have an excellent prognosis with surgical correction. Because the remainder of congenital cardiac defects account for a significant proportion of deaths from congenital abnormalities in childhood, improving detection rates for these problems is important.2

Current diagnostic techniques are dependent upon referral of pregnant women who are considered at increased risk for CHD for evaluation by fetal echocardiography, usually at 20 to 22 weeks' gestation. No identifiable risk factor is present, however, in half the pregnancies in which CHD is detected prenatally.3

Properly identifying at-risk pregnancies for referral for fetal echocardiography remains essential to prenatal diagnosis of CHD. Also important is routine ultrasound and anatomical assessment of the fetal heart's four chambers and outflow tracts in the low-risk population. Efforts to determine whether U/S is effective for such screening have revealed a wide range of estimates, depending on a number of study factors, including whether the four-chamber view was used alone or with views of the ventriculoarterial outflow tracts.4-7 The sensitivity of the four-chamber view alone has been estimated at 15% to 35%, and increases to 50% to 70% when views of the outflow tract are included. 3 Fetal echocardiographic evaluation reportedly has a sensitivity in detecting CHD of 30% to 85%, depending on factors such as operator experience, gestational age, maternal weight, and fetal position.4,8

Despite these challenges, careful attention to current clinical guidelines for identifying pregnancies at increased risk for congenital anomalies and CHD, and timely referral for detailed U/S evaluation and fetal echocardiography, continue to be the cornerstones of screening. Women at low risk of carrying affected fetuses can be screened with four-chamber views of the heart (Figure 1). However, these views alone are inappropriate for testing in women with recognized risk factors because of the relatively lower rate of detection of abnormalities, compared with formal fetal echocardiography. Therefore, clinicians must know whom to screen and who should be referred for definitive echocardiographic testing.



This article reviews currently accepted indications for recommending fetal echocardiography. We also provide background information on the usefulness of fetal echocardiography and its potential impact on outcomes, since these factors are the reason behind screening. Finally, the four-chamber and outflow tract views essential in the fetal heart examination will be described and illustrated for review.

Most cases of CHD result from the interaction of various environmental, genetic, and developmental factors.9 Thus, the current indications for obtaining a fetal echocardiogram include a number of familial, maternal, and fetal risk factors (Figure 2).



Familial and genetic risk factors

CHD in a parent or previous sibling, or familial risk factors, are a common indication for referral for fetal echocardiography. The level of recurrence risk depends on the degree of relation between the fetus and affected relative. The absolute relative risk for recurrence in the offspring of an affected parent is approximately 3% to 7%—a significant increase over baseline for low-risk pregnancies (~0.8%).

Familial factors. While a maternal or paternal history of congenital anomaly or CHD is an indication for referral, the risk is higher with a maternal history (Figure 3). Overall, women with CHD have a 4% to 5% risk of having a child with CHD. The degree of risk depends on the type of lesion present in the mother. With atrioventricular septal defects, the recurrence risk for the fetus may be as high as 12%.10 Mothers with left heart obstructive lesions may have a 6% to 10% recurrence rate in their offspring.10



The risk is somewhat less for the offspring of an affected father or if a previous sibling was affected, with the fetus carrying approximately a 2% to 3% risk of CHD.11 When recurrences are found, the cardiac lesion will be the same as the proband in about half of cases.

With a positive family history of congenital anomaly, including previous CHD, genetic counseling is recommended, ideally in the preconception period.

Genetic defects. Awareness of the genetic pathogenesis of CHD has greatly expanded, and numerous single-gene disorders (Mendelian syndromes) have been associated with an increased risk for fetal cardiac malformation (Table 1). Nearly 3% to 5% of CHD is attributed to single-gene disorders.12-14 Our basic understanding of how congenital heart defects occur should continue to increase, based on the outcome of ongoing investigation of the significance of selective gene knockouts important in heart development.


Risk for congenital heart disease with Mendelian syndromes

Autosomal dominant conditionsRisk of CHD
Autosomal recessive conditionsRisk of CHD
Ellis-van Creveld50%
Thrombocytopenia-absent radius33%
Short rib-polydactylycommon


Chromosomal abnormalities also greatly increase the risk of congenital heart malformations (Table 2).15 Up to 40% of fetuses diagnosed with a congenital heart defect on fetal echocardiography have chromosomal anomalies.15 However, pregnancy loss due to aneuploidy leads to only about a 5% observed rate of chromosomal anomaly among liveborns with CHD.12 The low postnatal rate may be due, in part, to pregnancy terminations resulting from prenatal diagnosis of fetuses with aneuploidy and CHD.16


Risk for congenital heart disease with chromosomal anomalies

Chromosomal anomalyRisk of CHD
Trisomy 13~80%
Trisomy 18~100%
Trisomy 21~40%–50%
Turner’s syndrome~20%–40%


In any case where CHD is diagnosed prenatally, genetic counseling should be offered, and amniocentesis considered. Proper testing includes fluorescent in situ hybridization (FISH) analysis when an identified microdeletion syndrome is suspected (such as 22q11), or when rapid results are needed for standard aneuploidies. The 22q11 deletion syndrome, identified with DiGeorge syndrome, refers to a clinical spectrum that can include various abnormalities, such as cardiac disease (conotruncal abnormalities), abnormal facies, thymic hypoplasia, cleft palate, developmental delay, and hypocalcemia.17 Although Marfan syndrome and idiopathic hypertrophic subaortic stenosis do not appear prenatally, genetic counseling for prospective parents should still include a discussion of the potential risks of CHD in offspring.

Maternal risk factors

Maternal factors that increase the risk of CHD in offspring include maternal CHD, as described above, exposure to cardiac teratogens, metabolic diseases, and autoantibodies (Ro and/or La). All are indications for referral for genetic counseling, detailed U/S, and fetal echocardiography.

Exposure to cardiac teratogens. Exposure to drugs and infection during the first 8 weeks of pregnancy increases the risk of CHD. Several of the potential teratogens listed in Table 3 are considered folic acid antagonists, compounds that may increase the risk of cardiovascular defects, neural tube defects (NTDs), oral clefts, and urinary tract defects. There are two general types of folic acid antagonists: dihydrofolate reductase inhibitors and antiepileptic drugs. Dihydrofolate reductase inhibitors, which block conversion of folate to its more active metabolites, include aminopterin, methotrexate, sulfasalazine, pyrimethamine, triamterene, and trimethoprim. Antiepileptic drugs (such as carbamazepine, phenytoin, primidone, and phenobarbital) can affect various other enzymes in folate metabolism, impair folate absorption, or increase folate degradation. Folic acid supplementation may reduce the risks of these defects.18


Maternal risk factors for congenital heart disease


Maternal diseases. Fetal echocardiography should be offered to all women who have diabetes at the time of conception because the incidence of CHD is fivefold higher in this population.19 Typical defects include ventricular septal defects and transposition of the great arteries. First-trimester elevated HgbA1C increases the risk of structural defects, and preconception care reduces the risk of congenital anomalies.20,21 With an HgbA1C of less than 7%, the risk of CHD is low, whereas a value greater than 8.5% can increase risk of a structural defect to as high as 22%.20 The thickness of the interventricular septum is increased among fetuses of diabetic mothers, even when diabetic control is good and estimated fetal weights are comparable.22 Increased thickness of the interventricular septum typically involves some degree of diastolic dysfunction, although there is usually no change in systolic function.23 Fortunately, the majority of infants affected by this hypertrophic cardiomyopathy are asymptomatic at birth and free of residual disease by 2 years of age.24

Maternal phenylketonuria requires careful management and control of phenylalanine levels. Poor control has been shown to increase the risk of fetal cardiac disease, with maternal phenylalanine levels greater than 600 mmol/L in the first 8 weeks of pregnancy associated with a 14% incidence of structural heart malformations.25

The emergence of thrombophilia as an important pregnancy risk factor has led to an increased awareness of the potential risks associated with mutations of the methylenetetrahydrofolate reductase (MTHFR) enzyme. The observation that periconceptional folic acid supplementation may not only reduce risks of NTDs but also reduce the risk of congenital heart defects spurred interest in further examining this association.26 In addition, the homozygous C677T mutation in MTHFR has been isolated with increased frequency among infants with NTDs, oral clefts, and structural heart malformations.27 Thus, the presence of maternal mutations in the MTHFR gene should prompt clinicians to recommend folic acid supplementation and genetic sonography. Referral for fetal echocardiography also should be considered, particularly if both parents are known to carry MTHFR mutations. However, routine screening for MTHFR is not yet recommended, and we do not yet know whether increased frequency of MTHFR mutation is associated with or causes congenital heart malformations.27

The presence of maternal autoantibodies, particularly anti-Ro and anti-La, has been associated with an increased risk of congenital heart block and cardiomyopathy. Approximately 60% of mothers who deliver a child with congenital heart block have antibodies to soluble tissue ribonucleotide protein antigen (anti-Ro and anti-La antibodies), with a recurrence risk of up to 30%.28 Echocardiography is indicated to assess cardiac structures, as well as to look for AV dissociation and determine heart rate. Pulsed Doppler assessment of the "mechanical PR interval" has been shown to be an important tool in describing the fetal conduction system and identifying variations in fetal heart block.29 Administration of steroids to the mother is the most common form of treatment for heart block.30-32 Serial fetal echocardiography to monitor PR interval in at-risk fetuses is currently under investigation in a multicenter trial.

Fetal factors

Increased first-trimester nuchal translucency. Nuchal translucency (NT) refers to the fluid-filled space at the back of the fetal neck. Increased fetal NT at 10 to 14 weeks' gestation is a nonspecific marker for genetic syndromes and structural anomalies, including heart disease.33 The increased risk for CHD, even with a normal karyotype, warrants referral for fetal echocardiography.34 This association has raised interest in possible application of the NT technique as a screening tool for CHD. The sensitivity of NT measurement for detection of CHD in a low-risk population ranges from 15% to 40%, depending on cut-off criteria and prevalence in the population being studied.35,36 Thus, an abnormal NT test indicates an increased risk for aneuploidy and structural abnormality. Depending on the extent of the NT, associated biochemical marker results, and maternal age, genetic counseling and chorionic villous sampling (CVS) or amniocentesis may be offered, along with a detailed anatomic U/S survey at 16 to 18 weeks' gestation, and fetal echocardiography at 20 to 22 weeks.

Fetal extracardiac abnormality. A major risk factor for CHD is identification of an extra-cardiac anomaly in the fetus. Abnormalities in more than one organ system significantly increase the risk of CHD.37 Table 4 lists some of the noncardiac anomalies most commonly reported in conjunction with CHD. Complete cardiac evaluation is required when any of these anomalies are noted. Ten percent to 20% of fetuses with nonimmune hydrops typically are found to have abnormal cardiac anatomy. Up to 30% of cases of omphalocele may be associated with CHD, which may affect the outcome of surgical repair.37


Fetal risk factors for congenital heart disease


In 40% to 50% of cases, suspected cardiac anomaly on routine second-trimester screening U/S is later confirmed.38 Fetal cardiac arrhythmia also is often considered a risk factor, since irregular fetal heart rhythms are commonly identified in clinical practice. However, when we reviewed 595 referrals for fetal echocardiography due to irregular fetal heart rhythm, we found only two fetuses with structural disease, no different than in the general population.39

Of the 595 referrals, 255 had an irregularity of rhythm, 330 had normal sinus rhythm, and 10 were found to have other arrhythmias (five with SVT, two with atrial flutter, and one with ventricular tachycardia).39 Although a large majority of fetal cardiac arrhythmias are isolated extrasystoles, with no increased risk of structural malformation, congenital heart block is associated with a structural defect about 50% of the time.40


CHD is a common cause of neonatal and infant morbidity and mortality. Prenatal diagnosis remains an important goal. Screening for familial, maternal, and fetal factors known to increase the risk of CHD can help identify cases, but screening only at-risk pregnancies will not identify the majority of cases of cardiac malformations. Therefore, routine screening of the fetal heart's four chambers and outflow tract in low-risk pregnancy remains important for the detection of CHD.

Visit http:/www.contemporaryobgyn.net for an overview by Dr. Benoit on how to perform basic antenatal screening with fetal echocardiography.


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Dr. Benoit is Assistant Clinical Professor, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Brown University School of Medicine, Women and Infants' Hospital, Providence, R.I. Dr. Copel is Professor, Department of Obstetrics and Gynecology, Section Head, Maternal-Fetal Medicine, and Director of Obstetrics, Yale-New Haven Hospital, New Haven, Conn.
Department editors are Joshua A. Copel, MD, and Ilan E. Timor-Tritsch, MD, Professor of Obstetrics and Gynecology, and Director of the Obstetrical and Gynecological Ultrasound Unit, New York University School of Medicine, New York, N.Y.