Efficacy of Routine Fetal Ultrasound Screening for Congenital Heart Disease in Normal Pregnancy
Background Second trimester routine ultrasound evaluation of the fetal heart by means of the four-chamber view has been proposed for prenatal detection of cardiac anomalies. The aim of this study was to evaluate the efficacy of this procedure.
Methods and Results A prospective follow-up study on 6922 scanned fetuses was performed. Pregnant women without known risk factors who were scheduled for a routine fetal ultrasound examination between 16 and 24 weeks gestation were invited to participate. Follow-up until 6 months postpartum was available for 5660 subjects (81.8%), of whom 5319 fulfilled all eligibility criteria. By comparing the prenatal diagnosis to the postnatal diagnosis, we obtained sensitivity, specificity, and predictive value (positive and negative). A total of 80 cases of congenital malformations were diagnosed during the study: 44 cases of congenital heart disease, 40 cases of noncardiac malformations, and a combination of the two in 4 cases. The fetal four chamber–view examination was considered abnormal in 7 women who were subsequently referred for extensive fetal ultrasound examination. Two proved to be carrying an affected fetus. Similarly, prenatal referral of 14 women because of suspected noncardiac malformations yielded 12 such cases. The fetal four chamber–view examination had a sensitivity of 4.5% (95% CI, 0.6% to 15%). Sensitivity for noncardiac anomalies was 30% (95% CI, 16.6% to 46.5%). Overall sensitivity of ultrasound examination was 16.3% (95% CI, 2.09% to 48.8%). Specificity and negative predictive value were high (>98%). The positive predictive value was low with wide CIs.
Conclusions These results suggest that the current mode of routine prenatal ultrasound screening for congenital malformations is inefficient, particularly for cardiac anomalies.
Congenital heart disease constitutes an important proportion of all major congenital malformations, which are present in 2% to 3% of neonates.1 2 The estimated birth prevalence of cardiac malformations is 8 per 1000.3 Approximately half of the cases of congenital heart disease have only minor consequences or can be corrected easily with surgery, yet 35% of infant deaths due to congenital malformations are related to cardiovascular anomalies.4 5 Hence, congenital heart disease remains an important issue in infant health. In addition, cardiovascular anomalies are strongly associated with other anomalies or chromosomal aberrations.6 7 8
Because the etiology of congenital malformations of the cardiovascular system is still largely unknown,7 9 10 primary prevention is not yet possible. The main options available as methods of secondary prevention are prenatal detection and subsequent adjustment of the obstetric policy or termination of the pregnancy if a fatal anomaly is detected. Ultrasound visualization and interpretation of the fetal four-chamber view at 16 to 24 weeks’ gestational age have been advocated as an efficient and accurate screening test for prenatal detection of the majority of cardiac malformations.11 12 Accordingly, assessment of the four-chamber view has been incorporated into routine fetal ultrasound in many countries, including the Netherlands.13 Despite its popularity, there has been no formal evaluation of a single routine ultrasound examination of the fetal heart at a gestational age of ≈20 weeks by means of the fetal four-chamber view in a low-risk population. Therefore, the aim of the present study was to examine the performance of this screening test in normal pregnancies and the current, typical clinical setting.
Pregnant women referred for routine fetal ultrasound and who fulfilled the eligibility criteria were invited to participate in the study by the sonographers, ie, ultrasound technicians, midwives, or physicians. Altogether, 15 referring ultrasound units in the Rotterdam metropolitan area participated after approval of their local ethical committees. All participating women gave verbal consent and resided in the southwestern part of the Netherlands. From March 1991 until January 1993, 6922 fetuses were scanned and included in the study. Maternal age was 28.9±4.6 years (mean±SD; range, 14 to 47 years).
Women were considered eligible if they were scheduled for routine fetal ultrasound examination between weeks 16 and 24 of pregnancy. Women referred for determination of gestational age or growth discrepancy, reassurance because of a preceding miscarriage, lack of fetal movement, inability to detect a fetal heartbeat, or other miscellaneous reasons were also considered eligible. All women with known risk factors for congenital heart disease in their offspring (eg, a previous child, their partner, or themselves affected with congenital heart disease), maternal juvenile diabetes, maternal lupus erythematosus, maternal phenylketonuria, maternal rubella, or maternal drug or teratogen exposure (for example, use of anticonvulsants, retinoic acid, or morphine mimetics such as heroin and methadone) were excluded because these characteristics currently constitute an acknowledged indication for extensive fetal echocardiography.14
Personnel and Equipment
In each of the participating ultrasound centers, the majority of examinations were performed by specific experienced personnel. Of 6922 examinations, 3747 (54%) were performed by technicians, 776 (11%) by midwives, 1391 (20%) by trainees in obstetrics and gynecology, and 1008 (15%) by consultants. The majority of sonographers involved in the present study had an ample background in fetal ultrasound examination, and all had taken an intensive, 2-day ultrasound training course on the evaluation of the fetal four-chamber view, including a hands-on tutorial, before participating in the study. During the study, the ultrasound units were visited frequently. Also, the sonographers were motivated and supported by the project supervisor and were informed about the progress of the study without being told of the findings. Various brands and types of ultrasound equipment—all state-of-the-art, two-dimensional appliances (see “Appendix”)—were used in the participating ultrasound units depending on local preference. The aim was to investigate a setting that resembled current routine practice as closely as possible with regard to experience and expertise of the sonographers as well as quality of equipment.
The ultrasound examinations were performed according to the guidelines issued by the Dutch Society of Obstetrics and Gynecology,13 which correspond to guidelines issued by the American Institute for Ultrasound in Medicine. The examinations of the fetal four-chamber view were evaluated and coded as normal, abnormal, or impossible to assess, according to standard criteria. The fetal heart should be located in the middle of the thorax and should occupy approximately one third of the thorax, display atria and ventricles of equal size, have an intact ventricular septum, have a foramen ovale flap demonstrated in the left atrium, and have offset atrioventricular valves, that is, a more apical insertion of the tricuspid valve and, potentially, visualization of the “moderator band” in the right ventricle11 12 (Fig 1⇓). In addition, data on gestational age, as determined by biometry, and suspected presence of other congenital malformation(s) were recorded. Fetal biparietal distance, femur length, and abdominal circumference were measured. In addition, the cerebral ventricles, spine, stomach, urinary bladder, kidneys, and umbilical cord insertion were inspected. Generally, four to five fetal ultrasound examinations per hour were performed, which took 10 to 15 minutes per patient. Finally, a code for the category of referring obstetrician (midwife, general practitioner, or gynecologist), the indication for an ultrasound scan (routine, determination of gestational age, or other), and whether or not the pregnant woman was subsequently referred for extended fetal ultrasound examination were noted. Follow-up data on all women and their children were collected until 6 months postnatally. In collaboration with local Child Health Clinics, the required data (date of birth, sex, and presence of congenital anomalies) were obtained by means of coded business reply cards for most women. In the Netherlands, Child Health Clinics routinely offer physical examination of infants and an interview with their parents within a month after birth and subsequently at monthly intervals until the infant has reached the age of 6 months. If no data or incomplete data were available, the woman’s general practitioner was approached for additional information. Finally, if an anomaly was suspected and the infant had been referred for expert examination, hospital records, findings on additional ultrasound examination, and autopsy records, if applicable, were retrieved and coded.
By comparing the prenatal diagnosis (presence or absence of anomalies) with the postnatal diagnosis, the latter being taken as a gold standard, we categorized all ultrasound examinations as true positive in cases when a suspected anomaly was confirmed, false positive when a suspected anomaly could not be confirmed, false negative when an anomaly was missed by ultrasound examination, or true negative when no anomalies were present. Because no consequences were attached to a four chamber–view examination that was indeterminable, such cases were considered to have a normal screening test. Data were subdivided according to the presence of congenital heart disease and noncardiac congenital anomalies. In addition, by means of expert consensus, all anomalies were categorized as major (definitely considered detectable prenatally, eg, disrupting four-chamber view anatomy), minor (possibility of prenatal detection is debatable due to size, location, or nature of the anomaly), or undetectable (excluded from analysis). The last category consists of anomalies such as patent ductus arteriosus, which sometimes occurs in combination with secundum-type atrial septal defect, cryptorchism, and syndactyly. Because there is general consensus that these anomalies may be considered part of normal fetal development or cannot be recognized on prenatal ultrasound examination, such cases were subsequently omitted from analysis.15 The sensitivity, specificity, positive predictive value, and negative predictive value were calculated with corresponding exact 95% binomial CIs.16 In addition, the prevalence of congenital malformations (the proportion of infants affected) was calculated.
Subjects and Ultrasound Examinations
Of the 6922 fetuses that were screened, 6571 (95%) underwent a routine ultrasound examination between 16 and 24 weeks’ gestational age. Fig 2⇓ shows the distribution of the duration of pregnancy at which the ultrasound examinations were performed. In 501 (7.2%) of the fetuses, an adequate four-chamber view could not be obtained. Fig 2⇓ also demonstrates how visualization of the four-chamber view related to gestational age.
Follow-up until 6 months postpartum has been completed for 5660 fetuses (81.8%). Of these, 119 appeared to have been included despite known risk factors for congenital heart disease, and 222 were screened outside the 16- to 24-week gestational age range. Consequently, the analysis presented pertains to 5319 routine fetal ultrasound examinations in the gestational age range of 16 to 24 weeks (mean, 19 weeks 5 days), with complete information available on the outcome of pregnancy until 6 months postpartum.
Outcome of Ultrasound
Of all women who were screened prenatally, 7 (0.10%) were subsequently referred for extended fetal echocardiography because of the abnormal appearance of the fetal four-chamber view. Another 14 (0.20%) were referred because of other suspected congenital anomalies. Two suspected cases of congenital heart disease that were referred for further examination were confirmed on subsequent evaluation. Noncardiac anomalies were detected more accurately; of the 14 cases referred, 12 proved to be affected.
Outcome of Pregnancy
Eventually, congenital anomalies were recognized in 118 cases (2.2%; 95% CI, 1.8% to 2.7%). There were 62 cases (1.2%; 95% CI, 0.9% to 1.5%) with congenital heart disease (6 of whom also had other congenital anomalies). Noncardiac anomalies were detected in 62 cases (1.2%; 95% CI, 0.9% to 1.5%). Furthermore, 5 cases of congenital heart disease occurred in combination with chromosomal anomalies. When evaluated according to category (major, minor, or unrecognizable) of anomalies, 80 major and minor cases (1.5%; 95% CI, 1.2% to 1.9%) remained for secondary analysis. These included 44 cases of congenital heart disease (4 in combination with other malformations) and 40 cases of noncardiac anomalies. The types of congenital anomalies (categorized according to total anomalies, ie, minor and major combined, and major anomalies only) encountered in these 80 cases are listed in Table 1⇓. Because any one fetus may have had several anomalies, the sum of anomalies in the “total” row is >80.
Performance of Ultrasound
In the categories of cardiac anomalies, noncardiac anomalies, and all anomalies combined, a distinction has been made between the number of major and minor anomalies combined and the subsample of major anomalies likely to have generated an abnormal image at 20 weeks’ gestational age. This is reflected in separate analyses according to case severity. Table 2⇓ shows the findings of routine prenatal screening for congenital anomalies of the heart. Sensitivity for cases of congenital heart disease was low (4.5%; 95% CI, 0.6% to 15%) even if only major anomalies are considered (16.7%; 95% CI, 2.1% to 48.4%). Sensitivity was somewhat higher for noncardiac anomalies (30%; 95% CI, 17% to 47%) and higher still for major anomalies (40%; 95% CI, 23% to 60%). Sensitivity for all anomalies combined was intermediate (overall: 16%, 95% CI of 9.0% to 26%; major: 33%, 95% CI of 19% to 50%). As expected, specificity was high (>99%) for both categories of anomalies. Also, the negative predictive value was high (99%). The positive predictive value varied considerably over the categories of anomalies and could not be established accurately, as illustrated by the wide CIs. Test characteristics and prevalence values are summarized in Table 3⇓.
Because we were concerned about the possibility of selective participation of mothers with children who either have no anomalies or represent a population with a relatively high number of anomalies, a random sample of 1500 ultrasound examinations (100 from each of the participating ultrasound units) was evaluated with regard to data on gestational age, referring obstetrician, indication for ultrasound, suspected presence of congenital malformations, and referral for further evaluation. Because this random sample could not be selected on the basis of gestational age, a wider gestational age range was represented. Furthermore, it appeared that slightly more examinations in the sample were requested by consultants. However, the small proportion of women referred because of suspected fetal anomalies was equal to that in the study population. In addition, we were able to study the database of the Division of Prenatal Diagnosis of the Department of Obstetrics and Gynaecology of Dijkzigt University Hospital, which serves the Rotterdam metropolitan area as a tertiary referral center, and check it for women not included in the present study who otherwise would have qualified as participants. Only one woman with a suspected anomaly on the fetal four-chamber view had been referred during the period of enrollment in the current study who was not included.
The objective of the present study was to evaluate the efficacy of the fetal four-chamber view in routine screening of normal pregnancies to detect congenital heart disease. Our findings indicate that the fetal four-chamber view, as evaluated during routine fetal ultrasound in the second trimester of pregnancy, does not provide an accurate screening test. Even major anomalies that are likely to create an abnormal fetal four-chamber view were not detected prenatally to a satisfactory degree.
Several factors may explain these results. The size of fetal structures is related to gestational age. Hence, visualization early in the second trimester, when the fetus is small, will be limited by the resolution of the ultrasound equipment. However, as is apparent from Fig 2⇑, the majority of scans were performed beyond 17 weeks’ gestational age, a time generally deemed appropriate for structural ultrasound examination. In addition, the proportion of fetal hearts that could not be assessed remained stable after 17 weeks of gestation; therefore, the scans appear to have been performed at an appropriate moment. Furthermore, all participating ultrasound units had state-of-the-art equipment at their disposal. The scans were performed by specialized technicians, midwives, or consultants trained in ultrasound examination in 80% of the women and by sonographers (trainees) with varying degrees of experience in the remainder. We feel that this mix adequately reflects the current ultrasound practice of routine screening and, if anything, the quality of the procedures was greater than usually encountered. In addition, because we were aware that trainees who performed ultrasound examinations tended to be rotated to other locations rather frequently, all participating ultrasound units were visited regularly. During these visits, the progress of the study and the demand for additional training of junior sonographers were assessed. The effect of increasing experience of the sonographers could be judged by evaluation of the number of inadequate four-chamber view visualizations during the study. However, the proportion of adequate ultrasound evaluations of the fetal heart did not materially fluctuate nor was there any indication of a particular trend during the period of participation. Interestingly, the proportion of fetal four-chamber views judged as indeterminable did not differ among the categories of sonographers. Also, all sonographers had taken similar additional training in the fetal four-chamber view examination before they participated in the study. A comparison of the sensitivities accomplished by each category of sonographers could have yielded important practical information on the expertise required. However, in view of the few anomalies actually detected prenatally, it is not feasible to analyze the data separately. In summary, it appears unlikely that variations in experience and skills had a major impact on the efficacy of the screening procedure.
Rather poor performance was observed for noncardiac congenital anomalies also, with a 30% sensitivity; this resulted in a sensitivity of 16% for all anomalies combined. A discussion analogous to that on the fetal four-chamber view applies to other congenital anomalies as well. Again, the results cannot be readily explained by any of the variables discussed thus far.
The nature of the anomalies encountered in routine screening explains part of the low sensitivity of prenatal detection observed in the present study. Some malformations—for instance, a small ventricular septal defect or an atrial septal defect—may not be visible with current ultrasound equipment or may not be visible by means of the four-chamber view alone. The proportional distribution of congenital anomalies encountered at birth may clarify this argument. Approximately 30% of the cases had ventricular septal defects, 10% had a patent ductus arteriosus, 10% had atrial septal defects, 10% had pulmonary stenosis, and another 25% were cases of tetralogy of Fallot, coarctation of the aorta, aortic stenosis, and transposition of the great arteries.17 As also alluded to by Nelson et al,18 a major proportion of these anomalies is not likely to be diagnosed by means of the fetal four-chamber view, especially in a nonreferral setting. Furthermore, a congenital anomaly may not remain in a steady state. A duodenal or urinary tract obstruction, for instance, may only become visible late in the second trimester. The anatomic substrate may be present already but may not yet have functional (recognizable) consequences at 20 weeks’ gestation. This may even apply in some severe cardiac anomalies like hypoplastic left heart.19 Specific conditions of the ultrasound examination may add another explanation for the failure to recognize even gross cardiac pathology. Severe maternal obesity or unfavorable fetal position may considerably hamper possibilities to assess the fetal structures. However, the stable and limited proportion of cases with an indeterminable four-chamber view does not support a major effect of scanning conditions. Apparently, the sensitivity is determined in part by the (im)possibilities of detection by means of prenatal ultrasound and in part by the natural history of the specific anomalies. Nevertheless, even if anomalies for which the possibility for prenatal detection is uncertain were left out of the analysis, low sensitivities were found. The exclusion of “minor” anomalies from evaluation could suggest that one considers these cases irrelevant from an obstetric and pediatric point of view. Yet, minor variants of congenital malformations may have the same cause as major defects and may be associated similarly with other anomalies. In view of this, it would seem irrational to consider such cases irrelevant.
The authors of early reports on routine fetal echocardiography, ie, the four-chamber view, advocated this technique as a useful tool to detect congenital heart disease prenatally.11 12 Our data are not consistent with this view. However, as discussed in a previous review of routine fetal echocardiography,20 it is quite likely that many of the early studies suffered from substantial limitations in design and may have led to overly enthusiastic views. Authors commonly were experts in the field of fetal ultrasound who worked in referral or teaching centers. Accordingly, the study population as well as the ultrasound technique may not have been representative of what is encountered in a general routine ultrasound clinic, where sonographers may be less skilled, face crowded office hours, and have a nonselected population with a low prevalence of anomalies. In addition, case ascertainment has not always been sufficiently complete, eg, retrospective with a short period of follow-up of cases suspected of anomalies. Stillborn fetuses or affected infants may not reach a tertiary hospital or may not be examined routinely. All this may have caused serious bias and overestimated sensitivities. The present prospective cohort study has complete follow-up on the fetuses. The gold standard method of postnatal examination applied in the present study, however, may require some additional comment. Routine physical examination and an interview until 6 months postnatally may have left some minor anomalies undetected. Yet, a prevalence of congenital heart disease in excess of that usually reported was observed.1 2 3 Accordingly, it is likely that ascertainment was virtually complete. Moreover, any cases not detected postnatally would have led to an even lower sensitivity without altering the overall study results. Similarly, any anomalies detected in the 1262 cases for whom follow-up could not be ascertained would not have altered the inference. Assuming a prevalence of congenital heart disease of 0.8%, another 10 cases might have occurred, lowering the estimated sensitivity slightly. Recent reports on ultrasound in second trimester pregnancy that originated from ultrasound units that employ regular personnel and scanning time show an efficacy of routine fetal ultrasound examination for detection of congenital anomalies that is comparable to our findings.21 22 23 24 25 26 27 The recent RADIUS study21 actually demonstrated completely similar reports with regard to scans performed before 24 weeks’ gestation.
As discussed, the level of expertise and skills of the sonographers in the present study represent the level of quality in ultrasound examination currently observed in routine screening practice. Suggestions for additional training of the sonographers as well as additional scanning projections have been submitted.28 29 Great effort and substantial resources may be required to establish a level of ultrasound examination skills sufficient to have a major impact on detection rates. Even if achieved, a sizable proportion of cases may remain technically undetectable within the period of gestational age considered optimal for screening. Despite the obvious advantages of prenatal detection in individual cases, we feel that an overall net benefit of routine ultrasound screening has not been established. False-negative and false-positive diagnoses will always occur and have to be taken into account. In addition, it may well be that in a major proportion of the cases that are potentially detectable, prognosis will not improve significantly with early detection.30 31
In conclusion, the findings in the present prospective study indicate that in the setting we have described, routine fetal echocardiography at 20 weeks’ gestational age by means of the fetal four-chamber view does not suffice as a prenatal screening test for congenital heart disease.
The following is a list of hospitals or ultrasound clinics that participated in the study as well as the brand and type of the ultrasound equipment applied locally and its carrier frequency.
Ikazia, Rotterdam: Aloka SSD 620 (3.5 MHz).
St Franciscus Gasthuis, Rotterdam (2 clinics): Hitachi EUB 415 (3.5 MHz). Stichting Trombosedienst & Artsenlaboratorium Rotterdam, Rotterdam: Aloka SSD 650 (3.5 MHz).
University Hospital Rotterdam Dijkzigt, Rotterdam: Hitachi EUB 450 (3.5 MHz).
Zuiderziekenhuis Rotterdam: Toshiba SSA 240A (3.75 MHz).
Westeinde Ziekenhuis, Den Haag: Toshiba SSA 250A (3.5 MHz).
Merwede Ziekenhuis, Dordrecht: Toshiba SSA 240A (3.75 MHz).
Drechtsteden Ziekenhuis Jacobus, Zwijndrecht: Toshiba SSA 90 (3.75 MHz).
Drechtsteden Ziekenhuis Refaja, Dordrecht: Aloka SSD 620 (3.5 MHz).
Reinier de Graaf Gasthuis, Delft: Toshiba SSA 250A (3.75 MHz).
’t Lange Land Ziekenhuis, Zoetermeer: Siemens Sonoline SLI (3.5 MHz).
Holy Ziekenhuis, Vlaardingen: Toshiba SSA 250A (3.75 MHz).
IJsselland Ziekenhuis, Capelle a.d. IJssel: Aloka SSD 650CL (3.5 MHz).
Schieland Ziekenhuis, Schiedam: Toshiba SSA 250A (3.75 MHz).
This study was supported by the Netherlands Heart Foundation (grant No. 89.053). We are very much indebted to all the pregnant women, sonographers, obstetricians, child health clinics, general practitioners, pediatricians, and pediatric cardiologists who participated in the study for their willingness to cooperate and provide us with the necessary data. In addition, we thank Andrina Cleveringa, Sharmila Bhikha, and Agnes van der Voorn for their enthusiastic and skillful contribution to the data collection and management and Marcel Eijgermans for his continuous support regarding database handling.
- Received September 12, 1995.
- Revision received December 28, 1995.
- Accepted January 2, 1996.
- Copyright © 1996 by American Heart Association
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