British Journal of Obstetrics and Gynaecology March 1992, Vol. 99, pp. 220-225
FETAL A N D N E O N A T A L M E D I C I N E
Screening for congenital heart disease prenatally. Results of a 2%-year study in the South East Thames Region GURLEEN K. SHARLAND L I N D S E Y D. A L L A N Department of Paediatric Cardiology Guv’s HosDital Loidon, UK
ABSTRACT Objective To assess the efficacy of four chamber view examination, during routine obstetric scanning, in the prenatal detection of fetuses with congenital heart disease. Design Prospective observational study. Setting Ten obstetric ultrasound units in the South East Thames Region. Subjects All pregnant women attending for routine obstetric ultrasound examination. Intervention Ultrasonographers performing routine ultrasound examinations were taught to obtain, and correctly interpret, the four chamber view of the fetal heart. When this view could not be achieved adequately, an attempt was made to identify a reason for failure and, if possible, to arrange a repeat scan. All suspected abnormalities were referred to a specialized unit. Main outcome measures Numbers of true abnormalities detected or overlooked, and the number in whom abnormality was suspected incorrectly. Results Over a 2.S-year period, 69% of the known number of cardiac lesions associated with an abnormality of the four chamber view were detected prenatally during the routine obstetric scan, 10% were identified as a result of referal for other high-risk factors and 21% were overlooked. The overall positive predictive value in the 10 obstetric units was 36%. Conclusions Prenatal screening for some forms of major congenital heart disease is possible by including examination of the four chamber view of the fetal heart in routine obstetric scans. However, there are important limiting factors that will influence the success of abnormality detection and must be taken into account if screening is to be effective nationwide.
Congenital malformation is one of the most common causes of mortality in childhood in England and Wales (Forfar 1984). Congenital heart disease is the commonest form of severe congenital abnormality and is associated with over half the deaths from congenital malformations in childhood (OPCS 1986; 1988). Normal cardiac anatomy can be defined in the fetus from 16-18 weeks gestation by ultrasound and an accurate diagnosis of structural cardiac malformations can therefore be predicted from this time (Kleinman et al. 1980; Allan et al. 1984). A detailed complete cardiac scan can usually only be performed in specialised centres with expertise in the diagnosis of congenital heart disease and high risk pregnancies (Sharland & Allan 1990) are referred to such units for fetal echocardiography. However, most children with heart disease are born to mothers who have no known high risk features during pregnancy (Cullen et al. 1990). The concept of prenatal screening for congenital heart disease in this country was therefore introduced, to improve the detection of these cases (Allan ct al. 1986). The method involves teaching ultrasonographers to examine one section of the fetal heart, the four
chamber view, on all routine obstetrics scans. In France, an effective screening programme has already been initiated (Fermont et al. 1985). A recent report from the North Regional fetal abnormality survey, however, suggested that the sensitivity for the antenatal detection of cardiac malformations was poor, as only 3 of 7 1 fetuses with congenital heart disease were detected prenatally (Members of Joint Group on Fetal Abnormalities 1989). This has not been the experience in our unit, where most abnormalities seen are referred after the detection of an abnormal four chamber view on routine scan. Staff in obstetric units all over the country have been taught to examine the four chamber view over the past 4-5 years. However, selection of these units has been arbitrary and determined mainly by the interest shown by the staff. Over the past 2.5 years, 10 obstetric units in the South East Thames Region have been taking part in a more formal screening programme, to assess the efficacy of four chamber view examination, during routine obstetric scanning, in the detection of congenital heart disease.
Correspondence: Dr G. Sharland, Department of Paediatric Cardiology, 11tli Floor, Guy’s Tower, Guy’s Hospital, St. Thomas Street, London SEI 9RT.
Methods
220
The four chamber view is obtained by imaging a transverse
SCREENING FOR CONGENITAL HEART DISEASE
200
single on-site visit to their hospital. The only factor determining hospital selection for a visit was the level of interest shown by the staff. The level of expertise was therefore arbitrary. To assess the impact of four chamber view scanning resulting from this method of teaching, the number of fetuses with cardiac malformations referred to our unit because an abnormality had been suspected on a routine obstetric scan were examined. These were compared with the total number of abnormalities seen per year.
150 u)
n
u)
221
+
5 loo 0 0
z 50
Screening prop-amme in South East Thames Region 1980 81 82
83
84
85 86 Year
87
88
89
90
Fig. 1. The number of fetuses with congenital heart disease (CHD) referred because an abnormality of the four chamber view had been suspected on routine obstetric scanning compared with the total number of fetal cardiac abnormalities seen per annum. 0 total abnormalities; msuspected CHD.
section across the fetal thorax above the level of the diaphragm. The appearance of the four cardiac chambers can vary depending on the orientation of the ultrasound beam to the heart, but ultrasonographers are taught how to identify the different cardiac structures regardless of orientation (Allan et al. 1986) and then to check the following features: ( 1 ) the heart should not occupy more than one third of the fetal thorax; (2) there are two atria (left and right) which are of equal size; (3) there are two ventricles (left and right) which are of equal size and thickness, and also contract equally; (4) there are two atrioventricular valves (mitral valve on the left and tricuspid valve on the right) which meet the atrial and ventricular septa at the crux of the heart in an offset cross-appearance: (5) the foramen ovale defect is present in the atrial septum; (6) the ventricular septum appears intact. Four chuniher view scanriin,q nationwide Over the past 4-5 years, staff involved with obstetric ultrasound, scanning in hospitals throughout the country, have become familiar with the idea of four chamber view scanning, either as a result of hearing Iccturec; on the topic or from a
To examine the efficacy of four chamber view scanning more specifically, a formal screening programme was introduced in 10 obstetric units in the South East Thames Region. The units were selected by contacting both the consultant in charge and the senior radiographer. Those showing a positive response and an interest in taking part in the screening programme were included in the study. All the ultrasonographers involved in routine obstetric scanning were taught to obtain, recognise and interpret, the four chamber view of the fetal heart. When the four chambers were not seen, the ultrasonographers were asked to identify a reason for failure if possible. They were also encouraged to ask pregnant women in whom adequate pictures were not obtained, to return for a repeat scan. Any pregnancy with a suspected abnormality was referred to our unit for further assessment. The paediatricians in each unit were informed that the study was taking place, so that information regarding abnormalities overlooked prenatally could be obtained. The selected units were visited on a regular basis with a time interval between each visit of between 6 weeks and 3 months. Each of these units started the study at a different time, the first starting on April 1st 1988.
Results The number of abnormalities identified by four chamber view screening as a proportion of the total number detected in our unit over the last 10 years is shown in Fig. 1 . The overall numbers referred as a suspected abnormality have increased steadily since the introduction of four chamber view scanning and, over the past 3 years, the proportion of abnormal fetuses
Table 1. The results of four chamber view screening in the 10 selected obstetric units in the South East Thames Region*
Unit
1 2 3 4 5 6 7 8 9 10 Total
Months in study
Deliveries per year
32 29 27 25 19 14 12
2269 1820 244 I 2889 1802 2439 3300 3067 1956 1878
11
9 9
Expected number
Nos. detected
12
12 6 8 S 5 4 4 3 3 3 S3
191
12 6 7 7 6 3 3
*Additional eight fetal cardiac anomalies were detected in pregnancies referred for other reasons N/K = none known.
Nos. missed
False positives
1
32
3 I 2 1
16 8
2 3 2 N/K I 16
9 5 6 6 7 4 3 96
222
G . K . S H A R L A N D & L . D. A L L A N
Table 2. Breakdown of the cardiac diagnosis in 53 fetuses with congenital heart disease detected by screening Diagnosis Hypoplastic left heart syndrome Atrioventricular septal defect Critical aortic stenosis Coarctationflnterrupted aortic arch Mitral atresia Ventricular septal defect, double outlet right ventricle Ventricular septal defect Pulmonary atresia, intact ventricular septum Pulmonary atresia, ventricular septal defect Double inlet ventricle Tricuspid atresia Aortic atresia, Ebstein's anomaly Absent pulmonary valve with tetralogy of Fallot Ebstein variant, ventricular septal defect Cardiac tumour
Number 10 10 5 4 4 4 4 2 2 2 2 1 1
who were referred for this reason has been 80-85% of'the total number of cardiac defects detected. These referrals have been obtained from over 100 different hospitals throughout the country. Assessment of the numbers of cardiac abnormalities overlooked during this period was not possible, due to the number of units involved and the large geographical area covered.
Missed abnormalities during study period During the study period, there were 16 cardiac abnormalities, that were considered likely to be associated with an abnormal four chamber view in early pregnancy, but which were overlooked prenatally in the screening units. These are listed in Table 3 and the numbers missed in the individual units in Table 1. Abnormalities of the great arteries that were missed, since these are sometimes associated with a normal four chamber view, are excluded here. It is possible that there are some false negatives we have not identified, as not all cases of congenital heart disease present in the first few weeks of life, and babies may have been transferred to other hospitals without the knowledge of local paediatricians, but this is unlikely. Table 4 shows a list of abnormalities that were considered to be detectable on a four chamber view and Table 5 lists conditions that may be associated with a normal view. The scan records of the 16 fetuses where congenital heart disease was not detected prenatally were examined retrospectively. In four, gross maternal obesity did not allow an adequate view of the fetal heart. In a further four, the gestational age was < 18 weeks at the time of the scan and in three, the four chamber view had not been seen adequately because of an unsuitable fetal lie. In the remaining five, no specific difficulty had been reported and four chambers were apparently seen. In two of these five, the scan had been performed by a junior, relatively inexperienced, member of staff.
Abnormalities detected from screening programme
Sensitivity and specificity
Between 1980 and 1988 the 10 units selected for this study had referred only eight fetuses with cardiac abnormality suspected during routine scan for fetal echocardiography. In contrast, during the study period of 32 months, 53 fetuses with congenital heart disease were detected by four chamber view screening. The number of abnormalities detected in the 10 individual units are shown in Table 1. The expected number of abnormalities in Table 1 was calculated on the prediction that severe fetal cardiac malformation should be detectable on four chamber view examination only in 2/1000 pregnancies. The number of deliveries annually and the time since the start of the study have been taken into account here. A breakdown of the cardiac diagnoses is shown in Table 2. There were an additional eight fetal cardiac abnormalities detected prenatally in women booked at these units, but who were referred for other reasons: six because there was an extracardiac fetal abnormality, one with a family history of congenital heart disease and one because of maternal diabetes.
Of the total number of known abnormalities detectable, 69% were identified as a result of screening, 10% were identified as a result of referral for other high-risk factors and only 21% were overlooked. The sensitivity of four chamber view screening for detecting cardiac lesions associated with an abnormal four chamber view during the study period was thus 77% (true positives/true positives + false negatives). During the study period there were 96 fetuses in whom a cardiac abnormality was suspected but the cardiac structure was found to be normal on a subsequent scan in our unit. The numbers in the individual lOOr A
-
s?
800) 0 )
-
In c1
2
60-
.-2
2
40-
0)
Table 3. Breakdown of the cardiac diagnosis in the 16 fetuses with congenital heart disease that were overlooked during the screening study Diagnosis Hypoplastic left heart syndrome Atrioventricular septal defect Coarctation Interrupted aortic arch Critical aortic stenosis Critical pulmonary stenosis
Number
n E
-
{
20-
d
-
0
1
I--I--.-----.I 1
I
3
I
I
1
6 Months in study
I
9
I
I
12
Fig. 2. The percentage of fetuses in whom the four chamber view of the fetal heart could not be seen at before or after 18 weeks gestation. The scans were performed by the same staff, in the same unit, using the same ultrasound imaging system. The results shown are from approximately 1360 pregnant women screened in Unit 2 during the < 18 weeks; > 18 weeks, first 9 months in the study. -U-
-.-
SCREE:NING FOR C O N G E N I T A L H E A R T D I S E A S E
223
Table 4. Cardiac anomalies usually associated with an abnormal four chamber view of the fetal heart Mitral atresia Tricuspid atresia Aortic atresia Pulmonary atresia Atrioventricular septal defect Critical aortic stenosis
Critical pulmonary stenosis Severe coarctation Double inlet ventricle Severe Ebstein’s anomaly/tricuspid valve dysplasia Large ventricular septal defect Unobstructed total anomalous pulmonary venous connection
units is shown in Table 1. These, therefore, represent false positives in terms of the initial screening. Since the total number of women with a normal fetus scanned during the study period was over 30 000, the specificity for screening in this study was over 99%. The positive predictive value of four chamber view screening in the 10 units combined was 36%. However, as indicated in Table 1, this varied in the individual units, and was 50% in three of the units. The number of false positives was related to the confidence and experience of the staff, rather than to the equipment being used. Reasons for not ohtuining jbur- chamber ljieu
The main factors recorded for not obtaining a four chamber view were maternal obesity, difficult fetal lie, a gestational age of less than 18 weeks, and equipment giving poor resolution. The influence of gestational age on depicting the four chambers was demonstrated by Unit 2. Pregnant women in this unit had their routine scans at 16 weeks gestation at the start of the study, although some scans were performed after this time. The four chambers could not be seen adequately in most fetuses examined before 18 weeks gestation, whereas scanning after this time improved identification considerably (Fig. 2). Two of the abnormalities missed by this unit were during examinations before 16 weeks gestation. As a result, 10 months after the start of the study, the timing of the routine scan was changed to 18 weeks. The equipment was different in each of the units and the resolution available affected the percentage of fetuses in whom the four chambers could be seen. In Unit 3, the same staff were using two machines which provided images of different quality. Machine 1 (Picker LSC 7000-2) had both a 5 MHz and 3.5 MHz transducer and provided higher resolution images compared to machine 2 (Picker LS 5000), which only had a 3.5 MHz transducer. The percentage of fetuses in whom the four chambers could not be identified for the two machines is shown in Fig. 3. It can be seen that the four chamber view could be identified in a larger proportion using machine 1 than machine 2. Recall raw
The percentage of fetuses in whom a four chamber view could not be seen varied greatly in the different units at the start of the study. However, this improved with time, as is illustrated by
the first four units, all of whom have been in the study for over 2 years (Fig. 4). During the 2-year period, the percentage in whom four chambers could not be seen on the first attempt gradually fell. This trend was also observed in the other six units, so that by the end of the study, all I0 units reported identification of the four chamber view in at least 85-90% of fetuses on the first attempt, the percentage being higher in the units that had been in the study longer. The rate of recalling pregnant women in whom four chambers had not been seen in the fetus, thus also changed with time. As the proportion in whom an adequate view was achieved increased, the total number needing to be recalled decreased so that it became increasingly feasible to recall those in whom the four chamber view had been inadequately seen. Thus, the final percentage in whom four chambers could not be seen was less than 5% in most units. Outcome
The outcome of the 53 fetuses with cardiac abnormality detected as a result of the screening programme is shown in Table 6. Overall 45 were detected at a gestation at which termnation of pregnancy was an option, and 36 of the 45 pregnant women (80%) chose this course. Of the remaining fetuses, spontaneous intrauterine death occurred in four and nine babies died postnatally. There are four survivors, all with major heart disease.
Discussion Congenital malformations remain one of the major causes of perinatal and infant mortality in developed countries. The Helsinki Ultrasound Trial recently examined the effect of screening all pregnant women with ultrasound in a population where the perinatal mortality is already very low (Saari-Kemppainen et al. 1990). The main cause of perinatal mortality in this population is major congenital malformation. This study showed that the perinatal mortality in a screened group was significantly lower than in a control group, the difference being due to the detection of major fetal anomalies by ultrasound screening and subsequent termination of pregnancy. The results of our study show that screening for some of the major forms of congenital heart disease can be implemented prenatally by those performing the routine obstetric scan if the four chamber view of the fetal heart is examined correctly. This
Table 5. Cardiac anomalies usually associated with a normal four chamber view of the fetal heart Transposition of the great arteries Tetralogy of Fallot Double outlet right ventricle
Mild/moderate coarctation Mild/moderate pulmonary and aortic stenosis Small ventricular septal defect
224
G . K . S H A R L A N D & L. D. A L L A N
-
50L
-8 40 C
Q Q ln c
0 C
2 0)
n
E,
r V d
0
4
8
12 16 20 Months in study
24
28
Fig. 3. Percentage of fetuses in whom the four chamber view of the fetal heart was not seen, using two different ultrasound machines. Machine 1 had both a 5 MHz and 3.5 MHz tranducer and provided images of much higher resolution than machine 2, which only had a 3.5 MHz transducer. Both types of imaging system were operated by the same staff, in the same unit. The results shown are from Unit 3, where approximately 4880 pregnant women were screened for congenital heart disease during 24 months of the study period. -0machine 1; -.-machine 2. I
is inconsistent with the conclusions of the Northern Regional abnormality survey which stated that the sensitivity of antenatal diagnosis for cardiac malformations remains poor (Members of the Joint Study Group on Fetal Abnormalities 1989). In a recent study from a referral centre for paediatric cardiology in a different region (Cullen et al. 1990), it was estimated that of 431 newborn infants presenting with congenital heart disease, 222 were potentially detectable by examining the four chamber view. In 81 of the 431 the study was prospective so that the prenatal history could be obtained. It was estimated that 55 of the 81 could have been detected by four chamber view screening but only five had been diagnosed prenatally. In 54 of the 81 (67%), the routine scan was performed before I 8 weeks gestation. The authors concluded that mid-trimester detection of cardiac malformation was poor and that training at
primary scan level, together with modification of the timing of the routine scan, was required. We think that this can be done. The World Health Organisation criteria for screening are as follows: (1) The condition should be of sufficient frequency and severity; (2) The condition should cause a known spectrum of symptoms; (3) The screening test should be simple, reliable, and have a low incidence of false positive and false negative results; (4) Adequate methods of confirmation and follow-up must be available; (5) The condition should be amenable to treatment; and (6) Ideally there should be a cost advantage to society. Screening for congenital heart disease by examination of the four chamber view on routine obstetric scans fulfils most of the above criteria. Congenital heart disease is a common congenital abnormality, the reported incidence varying betwen 4- 10 per 1000 live births (Hoffman 1990). The forms of congenital heart disease detectable on four chamber examination alone will be present in 1 in 500 pregnancies and are usually at the severe end of the spectrum of cardiac malformation (Allan et al. 1985). Examination of the four chamber view is a simple and reliable means of screening, provided the operator has learnt to obtain and interpret the view correctly. The proportion of false positive and false negatives could still be improved in the units performing the primary screening scan, but is low in the specialist unit to which the pregnancies are referred (Allan et al. 1989). With increasing experience and improving technology it is very likely that this will improve in the screening units so that the number of abnormalities missed is minimal and the majority of referrals to a specialised unit are true positives. Of the 53 abnormalities detected on screening, 45 were detected and referred at a gestation at which termination of pregnancy was an option and 36 pregnant women chose this course. The diagnosis of heart disease was confirmed at postmortem study in all except two of the fetuses following a termination or a spontaneous intrauterine death. Permission for autopsy was refused in these two fetuses. In all of the fetuses with predicted heart disease born alive, the diagnosis of heart disease was confirmed postnatally either by echocardiography, cardiac catheterization, or at operation or postmortem. Although it is difficult to estimate the exact cost effectiveness of this type of screening programme because of the number of pregnancies terminated, there were 36 fewer babies born who would have presented to a paediatric cardiology unit or would have needed a neonatal cot. It is possible that some of these might have died in-utero, but the majority would probably have reached term. If screening is implemented effectively in all the obstetric units in this country and if the proportion of parents electing to end the pregnancy, when there is major disease in the fetus, stays the same as that experienced Table 6. The outcome for 53 fetuscs with congenital heart disease detected by screening
Months in study
Fig. 4. The changes in the percentage of fetuses in whom the four chamber view of the fetal heart could not be adequately achieved on the first attempt, in Units 1 , 2 , 3 and 4 in the study, over a 2 year period. The numbers of pregnant women screened in each unit, during the 24 month period shown, were approximately 4530,3640,4880, and 5780 Unit 1; -0- Unit 2; -0Unit 3; respectivcly. -0Unit 4.
Outcome
-.-
Termination Intrauterine death Neonatal death Alive
Numbers
Percentage (%)
36 4 9 4
68 8 17 8
S C R E E N I N G FOR C O N G E N I T A L HEART D I S E A S E
in our unit, the number of newborn infants presenting to paediatric cardiology units will be significantly altered. An important benefit of prenatal diagnosis of congenital heart disease is to allow planning of delivery in a unit with paediatric cardiology facilities available, so that postnatal care can be optimal and the transfer of a sick baby avoided. There are several factors that seemed to be important in influencing the results obtained in the units selected for study. The enthusiasm and attitude of the staff were often reflected in the results. There were two units that were initially reluctant to join in the study. The inclusion of the four chamber view was initially thought to be time consuming and the ultrasonographers were reluctant to recall pregnant women in whom the four chamber view had not been seen, as they thought this would take up too much scan time. However, the realization that congenital heart disease is more common than many of the other types of structural anomalies sought for on a routine scan, and that severe forms can be fatal, helped to change such an attitude, particularly after a major cardiac abnormality had been missed. Thus, with increasing enthusiasm as the study progressed, ultrasonographers became more familiar with the normal features of the four chamber view, found it easier to incorporate it into the routine scan, and came to regard examination of the four chambers of the heart as an essential part of the scan. As a result, the percentage of fetuses in whom four chambers were seen at the first attempt improved and the number recalled when the four chambers had not been seen also increased, so that there was only a small percentage in whom the four chambers were not seen finally. The number of staff involved in scanning in each unit varied and often there were new junior staff rotating into the department. Some of the new staff were not familiar with the correct interpretation of the four chamber view and a few abnormalities were overlooked for this reason. It was, therefore, important to keep in close contact with the units on a regular basis and continue with teaching, particularly for any new recruits. The most commonly reported reasons for not obtaining a four chamber view of the fetal heart were maternal obesity, awkward fetal lie particularly with the spine anterior, poor resolution equipment and a gestational age of less than 18 weeks. The gestational age at which the routine scans are performed is an important factor in the detection of most structural anomalies, the ideal time for examining the fetal heart being between 18-20 weeks gestation. At the start of the study, 4 of the 10 units were performing routine scans before 18 weeks which meant that there were a significant number of fetuses in whom the four chamber view could not be seen. Recalling a large number of pregnant women was not practical in terms of scanning time. However, during the course of the study, and partly as a result of it, all the units now scan at 18 weeks or later and nearly all those seen before this time are recalled. Success in obtaining a satisfactory view of the heart was greatly influenced by the equipment being used. This varied widely from unit to unit both in quality, numbers of machines and types of transducer available for use. Since the start of the study, three units have acquired new equipment. Again, this has occurred as a result of the screening programme, as ultrasonographers have become more aware of what is missed with poor resolution equipment. Unfortunately, however, there are still units that are working with equipment which does not
225
allow staff to detect all the malformations of which they are potentially capable. There are many factors that will affect the efficacy of four chamber view screening but these can be changed with time and effort. Screening for congenital heart disease is already taking place in many centres in the United Kingdom. Increasing experience of ultrasonographers performing routine scans at 18-20 weeks gestation using high resolution equipment will improve the results significantly. This would have a major impact on the numbers and types of malformations presenting to paediatric cardiology units in the future.
Acknowledgments The authors are supported by the British Heart Foundation and G.K.S. partly by the SETRHA.
References Allan L. D., Chita S. K., Sharland G. K., Fagg N.L., Anderson R. H. & Crawford D. C. (1989) The accuracy of fetal echocardiography in the diagnosis of congenital heart disease. I n t J Cardiol 25, 279-288. Allan L. D., Crawford D. C., Anderson R. H. & Tynan M. J. (1984) Echocardiographicand anatomical correlations in fetal congenital heart disease. Br Heart J 52, 542-548. Allan L. D., Crawford D. C., Anderson R. H. & Tynan M. J. (19x5) Spectrum of congenital heart disease detected echocardigraphically in prenatal life. Br Heart J 54, 523-536. Allan L. D., Crawford D. C., Chita S. K. & Tynan M. J. (1986) Prenatal screening for congenital heart disease. Rr M d J 292, 1717-1719. Cullen S., Franklin R., Sharland G., Allan L. & Sullivan I. (1990) Potential impact of population screening for prenatal diagnosis of congenital heart disease. (Abstr.) Proceedings of British Cardiac Society. Br Heart .I 64( I), YO. Fermont L., De Geeter B., Aubry M. C., Kachener J. & Sidi D. (19x5) A close collaboration between obstetricians and cardiologists allows antenatal detection of severe cardiac malformations by 2D echocardiography. (Abstr.) Proceedings 2nd World Congress of Paediatric Cardiology. New York, p. 10. Forfar J. 0. (1984) Demography, vital statistics and the pattern of disease in childhood. In Textbook ofPaediatrics. (Forfar J. 0. & Arneil G. C., eds), Churchill Livingstone, p. I I . Hoffman J. I. E. (1 990) Congenital heart disease: Incidence and inheritance. Pediat Clin North A m 37( I), 25-43. Kleinman C. S., Hobbins J. C., Lynch D. C. & Talner N. S. (1980) Echocardiographic studies of the human fetus: prenatal diagnosis of congenital heart disease and cardiac dysrhythmias. Pediafrics 65, 1059-1068. Members of the Joint Study Group on Fetal Abnormalities (1989) Recognition and management of fetal abnormalities. Arch Dis Child 64, 971-976. OPCS (1986) Mortality Statistics, Perinatal and infant: social and biological factors. Series DH3, no. 20, pp. 28, 42, 48. OPCS (1988) Congenital malformation statistics: notifications. Series MB3, no. 4, ix. Saari-Kemppainen A., Karjalainen O., Ylostalo P. & Heinonen 0. P. (1 990) Ultrasound screening and perinatal mortality: controlled trial of systemic one-stage screening in pregnancy. Lancet 336, 389-391. Sharland G. & Allan L. (1990) Detection of congenital abnormalities of the cardiovascular system by ultrasound. In Modern Antenatal Care ofthe Fetus (ChamberlainG., ed.) Blackwell Scientific Publications, Oxford, p. 356. Received 23 May 1991 Accepted 20 September 1991
FETAL A N D N E O N A T A L M E D I C I N E
Screening for congenital heart disease prenatally. Results of a 2%-year study in the South East Thames Region GURLEEN K. SHARLAND L I N D S E Y D. A L L A N Department of Paediatric Cardiology Guv’s HosDital Loidon, UK
ABSTRACT Objective To assess the efficacy of four chamber view examination, during routine obstetric scanning, in the prenatal detection of fetuses with congenital heart disease. Design Prospective observational study. Setting Ten obstetric ultrasound units in the South East Thames Region. Subjects All pregnant women attending for routine obstetric ultrasound examination. Intervention Ultrasonographers performing routine ultrasound examinations were taught to obtain, and correctly interpret, the four chamber view of the fetal heart. When this view could not be achieved adequately, an attempt was made to identify a reason for failure and, if possible, to arrange a repeat scan. All suspected abnormalities were referred to a specialized unit. Main outcome measures Numbers of true abnormalities detected or overlooked, and the number in whom abnormality was suspected incorrectly. Results Over a 2.S-year period, 69% of the known number of cardiac lesions associated with an abnormality of the four chamber view were detected prenatally during the routine obstetric scan, 10% were identified as a result of referal for other high-risk factors and 21% were overlooked. The overall positive predictive value in the 10 obstetric units was 36%. Conclusions Prenatal screening for some forms of major congenital heart disease is possible by including examination of the four chamber view of the fetal heart in routine obstetric scans. However, there are important limiting factors that will influence the success of abnormality detection and must be taken into account if screening is to be effective nationwide.
Congenital malformation is one of the most common causes of mortality in childhood in England and Wales (Forfar 1984). Congenital heart disease is the commonest form of severe congenital abnormality and is associated with over half the deaths from congenital malformations in childhood (OPCS 1986; 1988). Normal cardiac anatomy can be defined in the fetus from 16-18 weeks gestation by ultrasound and an accurate diagnosis of structural cardiac malformations can therefore be predicted from this time (Kleinman et al. 1980; Allan et al. 1984). A detailed complete cardiac scan can usually only be performed in specialised centres with expertise in the diagnosis of congenital heart disease and high risk pregnancies (Sharland & Allan 1990) are referred to such units for fetal echocardiography. However, most children with heart disease are born to mothers who have no known high risk features during pregnancy (Cullen et al. 1990). The concept of prenatal screening for congenital heart disease in this country was therefore introduced, to improve the detection of these cases (Allan ct al. 1986). The method involves teaching ultrasonographers to examine one section of the fetal heart, the four
chamber view, on all routine obstetrics scans. In France, an effective screening programme has already been initiated (Fermont et al. 1985). A recent report from the North Regional fetal abnormality survey, however, suggested that the sensitivity for the antenatal detection of cardiac malformations was poor, as only 3 of 7 1 fetuses with congenital heart disease were detected prenatally (Members of Joint Group on Fetal Abnormalities 1989). This has not been the experience in our unit, where most abnormalities seen are referred after the detection of an abnormal four chamber view on routine scan. Staff in obstetric units all over the country have been taught to examine the four chamber view over the past 4-5 years. However, selection of these units has been arbitrary and determined mainly by the interest shown by the staff. Over the past 2.5 years, 10 obstetric units in the South East Thames Region have been taking part in a more formal screening programme, to assess the efficacy of four chamber view examination, during routine obstetric scanning, in the detection of congenital heart disease.
Correspondence: Dr G. Sharland, Department of Paediatric Cardiology, 11tli Floor, Guy’s Tower, Guy’s Hospital, St. Thomas Street, London SEI 9RT.
Methods
220
The four chamber view is obtained by imaging a transverse
SCREENING FOR CONGENITAL HEART DISEASE
200
single on-site visit to their hospital. The only factor determining hospital selection for a visit was the level of interest shown by the staff. The level of expertise was therefore arbitrary. To assess the impact of four chamber view scanning resulting from this method of teaching, the number of fetuses with cardiac malformations referred to our unit because an abnormality had been suspected on a routine obstetric scan were examined. These were compared with the total number of abnormalities seen per year.
150 u)
n
u)
221
+
5 loo 0 0
z 50
Screening prop-amme in South East Thames Region 1980 81 82
83
84
85 86 Year
87
88
89
90
Fig. 1. The number of fetuses with congenital heart disease (CHD) referred because an abnormality of the four chamber view had been suspected on routine obstetric scanning compared with the total number of fetal cardiac abnormalities seen per annum. 0 total abnormalities; msuspected CHD.
section across the fetal thorax above the level of the diaphragm. The appearance of the four cardiac chambers can vary depending on the orientation of the ultrasound beam to the heart, but ultrasonographers are taught how to identify the different cardiac structures regardless of orientation (Allan et al. 1986) and then to check the following features: ( 1 ) the heart should not occupy more than one third of the fetal thorax; (2) there are two atria (left and right) which are of equal size; (3) there are two ventricles (left and right) which are of equal size and thickness, and also contract equally; (4) there are two atrioventricular valves (mitral valve on the left and tricuspid valve on the right) which meet the atrial and ventricular septa at the crux of the heart in an offset cross-appearance: (5) the foramen ovale defect is present in the atrial septum; (6) the ventricular septum appears intact. Four chuniher view scanriin,q nationwide Over the past 4-5 years, staff involved with obstetric ultrasound, scanning in hospitals throughout the country, have become familiar with the idea of four chamber view scanning, either as a result of hearing Iccturec; on the topic or from a
To examine the efficacy of four chamber view scanning more specifically, a formal screening programme was introduced in 10 obstetric units in the South East Thames Region. The units were selected by contacting both the consultant in charge and the senior radiographer. Those showing a positive response and an interest in taking part in the screening programme were included in the study. All the ultrasonographers involved in routine obstetric scanning were taught to obtain, recognise and interpret, the four chamber view of the fetal heart. When the four chambers were not seen, the ultrasonographers were asked to identify a reason for failure if possible. They were also encouraged to ask pregnant women in whom adequate pictures were not obtained, to return for a repeat scan. Any pregnancy with a suspected abnormality was referred to our unit for further assessment. The paediatricians in each unit were informed that the study was taking place, so that information regarding abnormalities overlooked prenatally could be obtained. The selected units were visited on a regular basis with a time interval between each visit of between 6 weeks and 3 months. Each of these units started the study at a different time, the first starting on April 1st 1988.
Results The number of abnormalities identified by four chamber view screening as a proportion of the total number detected in our unit over the last 10 years is shown in Fig. 1 . The overall numbers referred as a suspected abnormality have increased steadily since the introduction of four chamber view scanning and, over the past 3 years, the proportion of abnormal fetuses
Table 1. The results of four chamber view screening in the 10 selected obstetric units in the South East Thames Region*
Unit
1 2 3 4 5 6 7 8 9 10 Total
Months in study
Deliveries per year
32 29 27 25 19 14 12
2269 1820 244 I 2889 1802 2439 3300 3067 1956 1878
11
9 9
Expected number
Nos. detected
12
12 6 8 S 5 4 4 3 3 3 S3
191
12 6 7 7 6 3 3
*Additional eight fetal cardiac anomalies were detected in pregnancies referred for other reasons N/K = none known.
Nos. missed
False positives
1
32
3 I 2 1
16 8
2 3 2 N/K I 16
9 5 6 6 7 4 3 96
222
G . K . S H A R L A N D & L . D. A L L A N
Table 2. Breakdown of the cardiac diagnosis in 53 fetuses with congenital heart disease detected by screening Diagnosis Hypoplastic left heart syndrome Atrioventricular septal defect Critical aortic stenosis Coarctationflnterrupted aortic arch Mitral atresia Ventricular septal defect, double outlet right ventricle Ventricular septal defect Pulmonary atresia, intact ventricular septum Pulmonary atresia, ventricular septal defect Double inlet ventricle Tricuspid atresia Aortic atresia, Ebstein's anomaly Absent pulmonary valve with tetralogy of Fallot Ebstein variant, ventricular septal defect Cardiac tumour
Number 10 10 5 4 4 4 4 2 2 2 2 1 1
who were referred for this reason has been 80-85% of'the total number of cardiac defects detected. These referrals have been obtained from over 100 different hospitals throughout the country. Assessment of the numbers of cardiac abnormalities overlooked during this period was not possible, due to the number of units involved and the large geographical area covered.
Missed abnormalities during study period During the study period, there were 16 cardiac abnormalities, that were considered likely to be associated with an abnormal four chamber view in early pregnancy, but which were overlooked prenatally in the screening units. These are listed in Table 3 and the numbers missed in the individual units in Table 1. Abnormalities of the great arteries that were missed, since these are sometimes associated with a normal four chamber view, are excluded here. It is possible that there are some false negatives we have not identified, as not all cases of congenital heart disease present in the first few weeks of life, and babies may have been transferred to other hospitals without the knowledge of local paediatricians, but this is unlikely. Table 4 shows a list of abnormalities that were considered to be detectable on a four chamber view and Table 5 lists conditions that may be associated with a normal view. The scan records of the 16 fetuses where congenital heart disease was not detected prenatally were examined retrospectively. In four, gross maternal obesity did not allow an adequate view of the fetal heart. In a further four, the gestational age was < 18 weeks at the time of the scan and in three, the four chamber view had not been seen adequately because of an unsuitable fetal lie. In the remaining five, no specific difficulty had been reported and four chambers were apparently seen. In two of these five, the scan had been performed by a junior, relatively inexperienced, member of staff.
Abnormalities detected from screening programme
Sensitivity and specificity
Between 1980 and 1988 the 10 units selected for this study had referred only eight fetuses with cardiac abnormality suspected during routine scan for fetal echocardiography. In contrast, during the study period of 32 months, 53 fetuses with congenital heart disease were detected by four chamber view screening. The number of abnormalities detected in the 10 individual units are shown in Table 1. The expected number of abnormalities in Table 1 was calculated on the prediction that severe fetal cardiac malformation should be detectable on four chamber view examination only in 2/1000 pregnancies. The number of deliveries annually and the time since the start of the study have been taken into account here. A breakdown of the cardiac diagnoses is shown in Table 2. There were an additional eight fetal cardiac abnormalities detected prenatally in women booked at these units, but who were referred for other reasons: six because there was an extracardiac fetal abnormality, one with a family history of congenital heart disease and one because of maternal diabetes.
Of the total number of known abnormalities detectable, 69% were identified as a result of screening, 10% were identified as a result of referral for other high-risk factors and only 21% were overlooked. The sensitivity of four chamber view screening for detecting cardiac lesions associated with an abnormal four chamber view during the study period was thus 77% (true positives/true positives + false negatives). During the study period there were 96 fetuses in whom a cardiac abnormality was suspected but the cardiac structure was found to be normal on a subsequent scan in our unit. The numbers in the individual lOOr A
-
s?
800) 0 )
-
In c1
2
60-
.-2
2
40-
0)
Table 3. Breakdown of the cardiac diagnosis in the 16 fetuses with congenital heart disease that were overlooked during the screening study Diagnosis Hypoplastic left heart syndrome Atrioventricular septal defect Coarctation Interrupted aortic arch Critical aortic stenosis Critical pulmonary stenosis
Number
n E
-
{
20-
d
-
0
1
I--I--.-----.I 1
I
3
I
I
1
6 Months in study
I
9
I
I
12
Fig. 2. The percentage of fetuses in whom the four chamber view of the fetal heart could not be seen at before or after 18 weeks gestation. The scans were performed by the same staff, in the same unit, using the same ultrasound imaging system. The results shown are from approximately 1360 pregnant women screened in Unit 2 during the < 18 weeks; > 18 weeks, first 9 months in the study. -U-
-.-
SCREE:NING FOR C O N G E N I T A L H E A R T D I S E A S E
223
Table 4. Cardiac anomalies usually associated with an abnormal four chamber view of the fetal heart Mitral atresia Tricuspid atresia Aortic atresia Pulmonary atresia Atrioventricular septal defect Critical aortic stenosis
Critical pulmonary stenosis Severe coarctation Double inlet ventricle Severe Ebstein’s anomaly/tricuspid valve dysplasia Large ventricular septal defect Unobstructed total anomalous pulmonary venous connection
units is shown in Table 1. These, therefore, represent false positives in terms of the initial screening. Since the total number of women with a normal fetus scanned during the study period was over 30 000, the specificity for screening in this study was over 99%. The positive predictive value of four chamber view screening in the 10 units combined was 36%. However, as indicated in Table 1, this varied in the individual units, and was 50% in three of the units. The number of false positives was related to the confidence and experience of the staff, rather than to the equipment being used. Reasons for not ohtuining jbur- chamber ljieu
The main factors recorded for not obtaining a four chamber view were maternal obesity, difficult fetal lie, a gestational age of less than 18 weeks, and equipment giving poor resolution. The influence of gestational age on depicting the four chambers was demonstrated by Unit 2. Pregnant women in this unit had their routine scans at 16 weeks gestation at the start of the study, although some scans were performed after this time. The four chambers could not be seen adequately in most fetuses examined before 18 weeks gestation, whereas scanning after this time improved identification considerably (Fig. 2). Two of the abnormalities missed by this unit were during examinations before 16 weeks gestation. As a result, 10 months after the start of the study, the timing of the routine scan was changed to 18 weeks. The equipment was different in each of the units and the resolution available affected the percentage of fetuses in whom the four chambers could be seen. In Unit 3, the same staff were using two machines which provided images of different quality. Machine 1 (Picker LSC 7000-2) had both a 5 MHz and 3.5 MHz transducer and provided higher resolution images compared to machine 2 (Picker LS 5000), which only had a 3.5 MHz transducer. The percentage of fetuses in whom the four chambers could not be identified for the two machines is shown in Fig. 3. It can be seen that the four chamber view could be identified in a larger proportion using machine 1 than machine 2. Recall raw
The percentage of fetuses in whom a four chamber view could not be seen varied greatly in the different units at the start of the study. However, this improved with time, as is illustrated by
the first four units, all of whom have been in the study for over 2 years (Fig. 4). During the 2-year period, the percentage in whom four chambers could not be seen on the first attempt gradually fell. This trend was also observed in the other six units, so that by the end of the study, all I0 units reported identification of the four chamber view in at least 85-90% of fetuses on the first attempt, the percentage being higher in the units that had been in the study longer. The rate of recalling pregnant women in whom four chambers had not been seen in the fetus, thus also changed with time. As the proportion in whom an adequate view was achieved increased, the total number needing to be recalled decreased so that it became increasingly feasible to recall those in whom the four chamber view had been inadequately seen. Thus, the final percentage in whom four chambers could not be seen was less than 5% in most units. Outcome
The outcome of the 53 fetuses with cardiac abnormality detected as a result of the screening programme is shown in Table 6. Overall 45 were detected at a gestation at which termnation of pregnancy was an option, and 36 of the 45 pregnant women (80%) chose this course. Of the remaining fetuses, spontaneous intrauterine death occurred in four and nine babies died postnatally. There are four survivors, all with major heart disease.
Discussion Congenital malformations remain one of the major causes of perinatal and infant mortality in developed countries. The Helsinki Ultrasound Trial recently examined the effect of screening all pregnant women with ultrasound in a population where the perinatal mortality is already very low (Saari-Kemppainen et al. 1990). The main cause of perinatal mortality in this population is major congenital malformation. This study showed that the perinatal mortality in a screened group was significantly lower than in a control group, the difference being due to the detection of major fetal anomalies by ultrasound screening and subsequent termination of pregnancy. The results of our study show that screening for some of the major forms of congenital heart disease can be implemented prenatally by those performing the routine obstetric scan if the four chamber view of the fetal heart is examined correctly. This
Table 5. Cardiac anomalies usually associated with a normal four chamber view of the fetal heart Transposition of the great arteries Tetralogy of Fallot Double outlet right ventricle
Mild/moderate coarctation Mild/moderate pulmonary and aortic stenosis Small ventricular septal defect
224
G . K . S H A R L A N D & L. D. A L L A N
-
50L
-8 40 C
Q Q ln c
0 C
2 0)
n
E,
r V d
0
4
8
12 16 20 Months in study
24
28
Fig. 3. Percentage of fetuses in whom the four chamber view of the fetal heart was not seen, using two different ultrasound machines. Machine 1 had both a 5 MHz and 3.5 MHz tranducer and provided images of much higher resolution than machine 2, which only had a 3.5 MHz transducer. Both types of imaging system were operated by the same staff, in the same unit. The results shown are from Unit 3, where approximately 4880 pregnant women were screened for congenital heart disease during 24 months of the study period. -0machine 1; -.-machine 2. I
is inconsistent with the conclusions of the Northern Regional abnormality survey which stated that the sensitivity of antenatal diagnosis for cardiac malformations remains poor (Members of the Joint Study Group on Fetal Abnormalities 1989). In a recent study from a referral centre for paediatric cardiology in a different region (Cullen et al. 1990), it was estimated that of 431 newborn infants presenting with congenital heart disease, 222 were potentially detectable by examining the four chamber view. In 81 of the 431 the study was prospective so that the prenatal history could be obtained. It was estimated that 55 of the 81 could have been detected by four chamber view screening but only five had been diagnosed prenatally. In 54 of the 81 (67%), the routine scan was performed before I 8 weeks gestation. The authors concluded that mid-trimester detection of cardiac malformation was poor and that training at
primary scan level, together with modification of the timing of the routine scan, was required. We think that this can be done. The World Health Organisation criteria for screening are as follows: (1) The condition should be of sufficient frequency and severity; (2) The condition should cause a known spectrum of symptoms; (3) The screening test should be simple, reliable, and have a low incidence of false positive and false negative results; (4) Adequate methods of confirmation and follow-up must be available; (5) The condition should be amenable to treatment; and (6) Ideally there should be a cost advantage to society. Screening for congenital heart disease by examination of the four chamber view on routine obstetric scans fulfils most of the above criteria. Congenital heart disease is a common congenital abnormality, the reported incidence varying betwen 4- 10 per 1000 live births (Hoffman 1990). The forms of congenital heart disease detectable on four chamber examination alone will be present in 1 in 500 pregnancies and are usually at the severe end of the spectrum of cardiac malformation (Allan et al. 1985). Examination of the four chamber view is a simple and reliable means of screening, provided the operator has learnt to obtain and interpret the view correctly. The proportion of false positive and false negatives could still be improved in the units performing the primary screening scan, but is low in the specialist unit to which the pregnancies are referred (Allan et al. 1989). With increasing experience and improving technology it is very likely that this will improve in the screening units so that the number of abnormalities missed is minimal and the majority of referrals to a specialised unit are true positives. Of the 53 abnormalities detected on screening, 45 were detected and referred at a gestation at which termination of pregnancy was an option and 36 pregnant women chose this course. The diagnosis of heart disease was confirmed at postmortem study in all except two of the fetuses following a termination or a spontaneous intrauterine death. Permission for autopsy was refused in these two fetuses. In all of the fetuses with predicted heart disease born alive, the diagnosis of heart disease was confirmed postnatally either by echocardiography, cardiac catheterization, or at operation or postmortem. Although it is difficult to estimate the exact cost effectiveness of this type of screening programme because of the number of pregnancies terminated, there were 36 fewer babies born who would have presented to a paediatric cardiology unit or would have needed a neonatal cot. It is possible that some of these might have died in-utero, but the majority would probably have reached term. If screening is implemented effectively in all the obstetric units in this country and if the proportion of parents electing to end the pregnancy, when there is major disease in the fetus, stays the same as that experienced Table 6. The outcome for 53 fetuscs with congenital heart disease detected by screening
Months in study
Fig. 4. The changes in the percentage of fetuses in whom the four chamber view of the fetal heart could not be adequately achieved on the first attempt, in Units 1 , 2 , 3 and 4 in the study, over a 2 year period. The numbers of pregnant women screened in each unit, during the 24 month period shown, were approximately 4530,3640,4880, and 5780 Unit 1; -0- Unit 2; -0Unit 3; respectivcly. -0Unit 4.
Outcome
-.-
Termination Intrauterine death Neonatal death Alive
Numbers
Percentage (%)
36 4 9 4
68 8 17 8
S C R E E N I N G FOR C O N G E N I T A L HEART D I S E A S E
in our unit, the number of newborn infants presenting to paediatric cardiology units will be significantly altered. An important benefit of prenatal diagnosis of congenital heart disease is to allow planning of delivery in a unit with paediatric cardiology facilities available, so that postnatal care can be optimal and the transfer of a sick baby avoided. There are several factors that seemed to be important in influencing the results obtained in the units selected for study. The enthusiasm and attitude of the staff were often reflected in the results. There were two units that were initially reluctant to join in the study. The inclusion of the four chamber view was initially thought to be time consuming and the ultrasonographers were reluctant to recall pregnant women in whom the four chamber view had not been seen, as they thought this would take up too much scan time. However, the realization that congenital heart disease is more common than many of the other types of structural anomalies sought for on a routine scan, and that severe forms can be fatal, helped to change such an attitude, particularly after a major cardiac abnormality had been missed. Thus, with increasing enthusiasm as the study progressed, ultrasonographers became more familiar with the normal features of the four chamber view, found it easier to incorporate it into the routine scan, and came to regard examination of the four chambers of the heart as an essential part of the scan. As a result, the percentage of fetuses in whom four chambers were seen at the first attempt improved and the number recalled when the four chambers had not been seen also increased, so that there was only a small percentage in whom the four chambers were not seen finally. The number of staff involved in scanning in each unit varied and often there were new junior staff rotating into the department. Some of the new staff were not familiar with the correct interpretation of the four chamber view and a few abnormalities were overlooked for this reason. It was, therefore, important to keep in close contact with the units on a regular basis and continue with teaching, particularly for any new recruits. The most commonly reported reasons for not obtaining a four chamber view of the fetal heart were maternal obesity, awkward fetal lie particularly with the spine anterior, poor resolution equipment and a gestational age of less than 18 weeks. The gestational age at which the routine scans are performed is an important factor in the detection of most structural anomalies, the ideal time for examining the fetal heart being between 18-20 weeks gestation. At the start of the study, 4 of the 10 units were performing routine scans before 18 weeks which meant that there were a significant number of fetuses in whom the four chamber view could not be seen. Recalling a large number of pregnant women was not practical in terms of scanning time. However, during the course of the study, and partly as a result of it, all the units now scan at 18 weeks or later and nearly all those seen before this time are recalled. Success in obtaining a satisfactory view of the heart was greatly influenced by the equipment being used. This varied widely from unit to unit both in quality, numbers of machines and types of transducer available for use. Since the start of the study, three units have acquired new equipment. Again, this has occurred as a result of the screening programme, as ultrasonographers have become more aware of what is missed with poor resolution equipment. Unfortunately, however, there are still units that are working with equipment which does not
225
allow staff to detect all the malformations of which they are potentially capable. There are many factors that will affect the efficacy of four chamber view screening but these can be changed with time and effort. Screening for congenital heart disease is already taking place in many centres in the United Kingdom. Increasing experience of ultrasonographers performing routine scans at 18-20 weeks gestation using high resolution equipment will improve the results significantly. This would have a major impact on the numbers and types of malformations presenting to paediatric cardiology units in the future.
Acknowledgments The authors are supported by the British Heart Foundation and G.K.S. partly by the SETRHA.
References Allan L. D., Chita S. K., Sharland G. K., Fagg N.L., Anderson R. H. & Crawford D. C. (1989) The accuracy of fetal echocardiography in the diagnosis of congenital heart disease. I n t J Cardiol 25, 279-288. Allan L. D., Crawford D. C., Anderson R. H. & Tynan M. J. (1984) Echocardiographicand anatomical correlations in fetal congenital heart disease. Br Heart J 52, 542-548. Allan L. D., Crawford D. C., Anderson R. H. & Tynan M. J. (19x5) Spectrum of congenital heart disease detected echocardigraphically in prenatal life. Br Heart J 54, 523-536. Allan L. D., Crawford D. C., Chita S. K. & Tynan M. J. (1986) Prenatal screening for congenital heart disease. Rr M d J 292, 1717-1719. Cullen S., Franklin R., Sharland G., Allan L. & Sullivan I. (1990) Potential impact of population screening for prenatal diagnosis of congenital heart disease. (Abstr.) Proceedings of British Cardiac Society. Br Heart .I 64( I), YO. Fermont L., De Geeter B., Aubry M. C., Kachener J. & Sidi D. (19x5) A close collaboration between obstetricians and cardiologists allows antenatal detection of severe cardiac malformations by 2D echocardiography. (Abstr.) Proceedings 2nd World Congress of Paediatric Cardiology. New York, p. 10. Forfar J. 0. (1984) Demography, vital statistics and the pattern of disease in childhood. In Textbook ofPaediatrics. (Forfar J. 0. & Arneil G. C., eds), Churchill Livingstone, p. I I . Hoffman J. I. E. (1 990) Congenital heart disease: Incidence and inheritance. Pediat Clin North A m 37( I), 25-43. Kleinman C. S., Hobbins J. C., Lynch D. C. & Talner N. S. (1980) Echocardiographic studies of the human fetus: prenatal diagnosis of congenital heart disease and cardiac dysrhythmias. Pediafrics 65, 1059-1068. Members of the Joint Study Group on Fetal Abnormalities (1989) Recognition and management of fetal abnormalities. Arch Dis Child 64, 971-976. OPCS (1986) Mortality Statistics, Perinatal and infant: social and biological factors. Series DH3, no. 20, pp. 28, 42, 48. OPCS (1988) Congenital malformation statistics: notifications. Series MB3, no. 4, ix. Saari-Kemppainen A., Karjalainen O., Ylostalo P. & Heinonen 0. P. (1 990) Ultrasound screening and perinatal mortality: controlled trial of systemic one-stage screening in pregnancy. Lancet 336, 389-391. Sharland G. & Allan L. (1990) Detection of congenital abnormalities of the cardiovascular system by ultrasound. In Modern Antenatal Care ofthe Fetus (ChamberlainG., ed.) Blackwell Scientific Publications, Oxford, p. 356. Received 23 May 1991 Accepted 20 September 1991
