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Lindsay impacto

  1. 1. Fetal and Maternal Medicine Review 2004; 15:4 327–341 C 2004 Cambridge University Press DOI: 10.1017/S0965539504001330 IMPACT OF PRENATAL DIAGNOSIS ON THE PAEDIATRIC MANAGEMENT OF HEART DEFECTS LINDSEY ALLAN King’s College Hospital, London INTRODUCTION Ultrasound has been used in cardiac diagnosis since the 1960s. The original modality used was M-mode, which recorded the movement of heart structures relative to a single line of sound passed through the heart and was displayed as a paper tracing. During the 1970s, a two-dimensional image became possible, but it was a static image, which had limited value for cardiac evaluation. However, by the end of the 1970s, advances in ultrasound equipment allowed the heart to be displayed in real- time. This technology was applied initially in the adult and subsequently in the child. Echocardiography proved particularly suitable for children, partly because it is non-invasive and repeatable, but also because most heart disease in children is due to malformation of anatomical structure, which ultrasound can ideally display. At the same time, obstetric ultrasound was progressing rapidly and descriptions of the appearances of malformations in most fetal systems began to be published by the end of the 1970s. It was not until real-time equipment became generally available in obstetrics that the fetal heart could be satisfactorily evaluated. This led to descriptions by several authors of normal fetal cardiac anatomy as seen echocardiographically in 1980.1,2,3 The appearances of the echocardiogram in different forms of congenital heart disease (CHD) in children were published in the late 1970’s, setting the stage for diagnosis in fetal life. As a result, by the mid-1980’s, most major forms of CHD had been detected prenatally.4 At this time, detailed fetal cardiac evaluation was confined to specialists in fetal echocardiography and to those patients selected for expert analysis because they fell into a high-risk category for CHD. These high-risk categories included mothers with a family history of CHD, those with maternal diabetes and in fetuses where extracardiac malformations had been identified. However, a novel idea, which had the potential of greatly increasing the impact of fetal echocardiography, was put forward by a French group in 1985. Building on their nationwide network of skilled Address for correspondence: Lindsey Allen, Consultant in Fetal Cardiology, Harris Birthright Centre for Fetal Medicine, King’s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom.
  2. 2. 328 L Allan obstetric ultrasonographers, they suggested teaching them to incorporate a single view of the fetal heart, namely the four chamber view, into routine obstetric scanning. Although this single view of the heart would not detect all major structural heart malformations, theoretically, if systematically applied, it could detect about 60% of them.5 This introduced the concept of screening the normal pregnant population for CHD. At the time, it appeared that about 90% of CHD occurred in low-risk pregnancies, therefore an effective screen of the heart during the obstetric scan enormously expanded the potential for the detection of CHD. The stimulus to detect cardiac abnormalities prenatally is partly driven by the fact that they are still an important cause of mortality in infancy with severe cardiac abnormalities accounting for approximately 20% of neonatal deaths.6 In a significant proportion of these cases the cardiac defect is not recognised during life, but found on post mortem examination.7 As the skill of the obstetric ultrasonographer and the image quality of ultrasound equipment has improved over the years, great artery assessment has been added to the four chamber view during routine examination, such that over 90% of major CHD is potentially detectable in skilled hands. The reality is, however, that success of detection of cardiac anomalies varies8,9,10 widely and tends to be linked to the standard and intensity of more general ultrasound screening. Thus, where a routine fetal anomaly scan, applied to all pregnancies and performed to a high specification, is in place, detection of all anomalies, including heart defects, is high. However, the use of ultrasound during pregnancy varies widely nationally and geographically and even between neighbouring obstetric units, although overall detection of cardiac anomalies of all kinds has shown steady improvement over the 25 years that fetal echocardiography has been possible. As the four-chamber view is technically easier to obtain and analyse, defects which alter the appearance of this view, are preferentially detected prenatally. This was clearly shown in a UK-wide study published in 1999,11 of all cases of CHD found over a 3 year period. In the cases detected in fetal life, diagnoses such as the hypoplastic left heart syndrome, univentricular heart and atrioventricular septal defect predominated, in contrast to the postnatal series where arch anomalies, tetralogy of Fallot and ventricular septal defects predominated. The detection of a possible cardiac abnormality during the routine scan allows the patient to be referred to the fetal cardiologist for more detailed diagnosis and counselling. The ideal fetal cardiologist has skill in obstetric imaging, a thorough understanding of the fetal spectrum of CHD, coupled with up-to-date knowledge of local and international results of the management of different types of CHD, both immediate and long-term, in order to offer the detailed counselling which the parents need when a cardiac malformation is found in the fetus. The advent in the mid-1990s of screening for nuchal translucency (NT) at 12 weeks gestation was a further significant advance in the fetal echocardiographic field.12,13 Nuchal translucency detected a significant group of pregnancies at high- risk of CHD, which had not been identified as such before. It was shown that if the NT measurement was above the 95th centile, there was an association not only with chromosomal defects, which was the primary aim of nuchal translucency
  3. 3. Impact of prenatal diagnosis on the paediatric management of heart defects 329 Table 1 Incidence of CHD per 1000, with increasing NT 0 20 40 60 80 100 120 140 160 180 200 2.5-3.5 3.5-4.5 4.5-5.5 5.5-6.5 >6.5 measurement, but also with CHD. The incidence of CHD increases with increased levels of NT. In a recent analysis of our own data, there was a rate of CHD at twice normal if the NT was between the 95–99th centile (about 2.6–3.5 mm) increasing to twenty-six times the normal rate if the NT was over 6.5 mm (Table 1). The group of patients with NT > 95th centile is probably the most useful high-risk group for selection for detailed fetal echocardiography. Interestingly, increased NT is not associated with any particular form of CHD. Table 2 shows a recent analysis of the type of CHD seen in 123 cases with increased NT and normal chromosomes, where a similar scatter of CHD was seen to the spectrum which might be expected in infants. Coarctation was slightly over-represented in the fetus but some of these cases are likely to have progressed to the hypoplastic left heart syndrome by birth. There has been some debate about the incidence of increased NT in those with CHD, with rates of 17% and 56% found in different studies.14,15 The real figure is probably around 25%. The incidence of CHD is about 8/1000 livebirths. About 4–5 of these 8 children have ventricular septal defects, secundum atrial septal defects, mild pulmonary stenosis or persistent arterial ducts. With the exception of moderate to large ventricular septal defects, none of these lesions are detectable in the fetus. However, all these lesions can be readily treated surgically or by catheter techniques, or even may not require intervention at all, and are compatible with a normal quality of life and life-span. In contrast, about 3/8 cases of CHD per 1000 are major forms of CHD, which nearly all require surgical treatment, and sometimes repeated intervention, at a varying risk of mortality and morbidity, depending on the type of defect. These forms of CHD can
  4. 4. 330 L Allan Table 2 Types of CHD seen in a series of 123 cases with increased NT and normal chromosomes. DIV = double inlet ventricle, HLH = hypoplastic left heart syndrome, DORV = double outlet right ventricle, VSD = ventricular septal defect, TOF = tetralogy of Fallot, AVSD = atrioventricular septal defect. 0 5 10 15 20 25 Pulmonary atresia Mitral atresia Ebsteins Isomerism Aortic stenosis Tricuspid atresia DIV HLH DORV Transposition VSD TOF AVSD Coarctation severely impact the child’s life and, even if successfully treated, will nearly all impair the quality of life and/or shorten the lifespan. It is this severe spectrum of disease that is typically detected in fetal life. TERMINATION OF PREGNANCY The detection of CHD during pregnancy offers the patient the possibility of termination of pregnancy. In the UK, prior to 24 weeks gestation, this course of action may be chosen legally for fetal anomalies. However, in the setting of CHD, termination is more likely to be chosen by the parents when there are associated extracardiac anomalies and/or chromosomal anomalies, or where the complexity of the heart malformation is such that a poor outlook is anticipated. In addition, in general, the earlier the diagnosis is made of fetal abnormality, the more likely termination is to be chosen. Thus, the more widespread application of nuchal translucency screening has led to earlier diagnosis of CHD, even as early as 12 weeks gestation, which in turn is likely to lead to a higher rate of pregnancy interruption for CHD in the future. Termination of pregnancy after 24 weeks gestation is confined to the most severe forms of CHD or those with multiple malformations and is uncommon.
  5. 5. Impact of prenatal diagnosis on the paediatric management of heart defects 331 As a result of increasing detection of major CHD prenatally, the prevalence of some major forms of heart malformation has been shown to have fallen as a result of termination.16 In a study of all cases of pulmonary atresia with intact ventricular septum seen in the UK between 1991 and 1995, the prevalence in postnatal life was shown to have fallen from 5.6 to 4.1 in England because of prenatal detection and termination of pregnancy. It is likely that this effect may increase in the future as prenatal detection of CHD improves, reducing the number of the most complex cases of CHD coming to the paediatric cardiologist. However, counterbalancing this is the fact that as the prognosis for surgical repair of many heart defects continues to improve, the counsellor is able to be more optimistic about the results and termination may be chosen less often. PROGRESSION OF CHD One of the most interesting observations in fetal cardiology has been that some forms of CHD progress in fetal life. This has been seen in both aortic and pulmonary stenosis where the valve appeared echocardiographically normal in early pregnancy but became stenosed later, or where the degree of stenosis has progressed from mild to severe or even to atresia during gestation. In pulmonary stenosis, this can occur in isolated valve disease or in more complex CHD where pulmonary stenosis is a component. Thus, for example, in tetralogy of Fallot, transposition with ventricular septal defect or double outlet right ventricle, the pulmonary valve obstruction can increase during pregnancy to pulmonary atresia and thus duct dependency after birth.17 In some cases of critical aortic stenosis, the left ventricle is usually dilated in early pregnancy but it fails to keep pace with normal growth resulting in a small left ventricle by term, with quite different implications for surgical management.18 In coarctation, poor growth of the aortic arch can occur, such that an extended arch repair through a sternotomy is necessary after birth, with a higher morbidity and mortality, rather than the simpler surgical approach of a lateral thoractomy. Valvar incompetence can also progress in utero, particularly in the tricuspid valve, leading to hydrops and even intrauterine death. In addition, there are some cardiac lesions which are not usually evident early in pregnancy but which evolve towards term. Examples include cardiac tumours and cardiomyopathies. Thus, although a normal fetal cardiac scan in competent hands at 20 weeks can exclude most major heart disease, there are forms of major disease which progress from milder disease or may develop in later pregnancy. However, such examples are rare. FETAL THERAPY There are some fetal conditions where prenatal treatment is appropriate. In fetal tachycardias, the fetus can be treated by maternal anti-arrhythmic drugs which cross the placenta. Treatment can prevent the development of cardiac failure, if the tachycardia is detected soon after its initiation. Once the fetus is in cardiac failure
  6. 6. 332 L Allan RV LV spine Figure 1 The left ventricle is dilated, globular in shape and poorly contracting in the moving image. This appearance is typically seen associated with a critically obstructed aortic valve, which is amenable to prenatal balloon valvoplasty. LV = left ventricle, RV = right ventricle. due to a tachycardia, the fetus is at considerable risk of mortality and treatment can be life-saving.19 Although these cases are uncommon, treatment is well-established in this context. Prenatal balloon valvoplasty was first suggested at the end of the 1980s for conditions where an isolated obstructive lesion was present, such as aortic stenosis (Figure 1). It was observed that as pregnancy advanced in a fetus with a critically obstructed aortic valve, the left ventricle either failed to grow sufficiently or became irreparably damaged by endocardial fibroelastosis. At this time, there was no surgical treatment available for a hypoplastic or inadequate left ventricle, and thus these cases were associated with a high mortality after birth. The rationale for prenatal treatment was to relieve valvar obstruction sufficiently early in pregnancy to avoid the secondary effects of the obstructed valve on the left ventricle and give it “recovery time” prior to birth, while the circulation was also supported by the right ventricle. The left ventricular apex was punctured directly using a needle through which a guide wire
  7. 7. Impact of prenatal diagnosis on the paediatric management of heart defects 333 and subsequent balloon catheter could be passed. It was then positioned and inflated in the valve orifice. There was limited success in the early cases and some difficulties with balloon technology,20 while at the same time, treatment strategies in the form of the Norwood operation for the hypoplastic left heart syndrome began to achieve better results21 and thus the technique fell out of use. Interest has been rekindled more recently, partly because of improved technology, and partly in an attempt to avoid one ventricle repair on either the right or left sides of the heart.22,23 It remains to be seen whether this technique will find an established role in Fetal/Paediatric Cardiology practise. DELIVERY OF A FETUS WITH CHD Depending on the type of defect, presentation in CHD varies from acute decompensation soon after birth to gradual deterioration over the first months of life, with all stages in between. Examples of conditions which can cause symptoms immediately after birth include severe Ebstein’s malformation and tricuspid dysplasia, transposition of the great arteries and total anomalous pulmonary venous drainage. Ebstein’s malformation is an anomaly of the tricuspid valve in which the orifice of the tricuspid valve is displaced into the right ventricle. With a mild degree of displacement, the neonate is likely to be asymptomatic but with more severe degrees, especially if there is severe tricuspid regurgitation, postnatal ventilation can be difficult due to lung hypoplasia. This, in turn, is due to compression of the fetal lung fields by cardiomegaly. If the neonate can be supported through the early period and there is sufficient lung volume, tricuspid regurgitation tends to lessen as the pulmonary pressure falls in the first weeks of life. However, some extreme examples do not survive this early period despite maximum support. In the majority of cases of transposition of the great arteries (Figure 2), the neonate is noticed to be cyanosed in the first days of life but about 20% present more acutely, becoming hypoxic and acidotic within even an hour of birth. This subgroup of cases have a restrictive or intact atrial septum, preventing oxygenated blood reaching the systemic circulation, resulting in rapid deterioration and even death before the neonate can reach a cardiology centre. These infants can be successfully treated by ultrasound-guided tearing of the atrial septum by a balloon catheter, if they reach help in time. In total anomalous pulmonary venous drainage, if the pulmonary veins drain to an obstructed confluence, which can occur with both supra and infracardiac drainage, the neonate can become severely cyanosed and require urgent surgical relief. In transposition and total anomalous pulmonary venous drainage, maintaining ductal patency is not usually of much benefit. However, there is a group of patients who are termed “duct-dependent” and who do benefit from maintaining the duct open using prostaglandins. In these cases, depending on the cardiac defect, either the pulmonary or systemic circulation is dependent on the patency of the arterial duct. The arterial duct naturally starts to close some hours or days after birth but can do so acutely, either causing severe cyanosis (if the pulmonary blood flow is affected) or systemic collapse
  8. 8. 334 L Allan RV Ao LV PA Figure 2 The great arteries do not show their usual spiral relationship but arise in parallel orientation. This is characteristic of transposition of the great arteries. In this condition, delivery where immediate cardiological care can be instituted can improve the outcome. LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery. (if the aortic blood flow is affected). Conditions where the pulmonary circulation is duct dependent include severe pulmonary stenosis or atresia, which can be isolated or be a component of different forms of intracardiac malformation such as tetralogy of Fallot (Figure 3), or double outlet right ventricle. Conditions where the systemic circulation is duct dependent include aortic stenosis or atresia (Figure 4), and interruption or coarctation of the aortic arch. In contrast, many conditions, such as an atrioventricular septal defect, for example, are associated with the gradual devel- opment of cardiac failure over the first 2–4 months of life and do not present urgently (Figure 5). From the time of the earliest reports of fetal cardiac diagnosis, it has been clear that the outcome for the fetus with CHD is less good than would be expected in postnatal life.24,25 This is because of the bias towards detecting the most severe CHD prenatally, due to the way patients are selected for fetal echocardiography.
  9. 9. Impact of prenatal diagnosis on the paediatric management of heart defects 335 LV RV <Ao RV PA> <Ao spine Figure 3 In the left panel, there is a ventricular septal defect with the aorta overriding the crest of the ventricular septum. The scan plane immediately above this level is shown in the right hand panel, where the pulmonary artery is seen crossing over the aortic origin in a normal fashion. However, the pulmonary artery is smaller than the aorta, which is the reverse of normal. This finding in association with aortic override, indicates a diagnosis of tetralogy of Fallot. Some cases of tetralogy of Fallot are duct dependent and should benefit from prenatal diagnosis. Those fetuses with gross cardiac abnormalities detected on screening and those with extracardiac anomalies or hydrops are preferentially referred. There is a higher incidence of chromosomal anomalies in fetal series than in live-births.25 There is a small but fairly consistent incidence of spontaneous intrauterine death of between 5–10% in fetal series, partly due to the presence of associated chromosomal anomalies but not entirely. Some fetuses with CHD die in utero for no apparent reason. The outcome after the diagnosis of CHD in a recent series of 956 cases is shown in Table 3. A high rate of termination reflects our high incidence of chromosomal anomalies, as many of our cases of CHD come from the NT screening programme, but there is also an incidence of spontaneous intrauterine death and neonatal loss despite maximal treatment. In a series of cases of the hypoplastic left heart syndrome diagnosed in fetal life, the mortality in the fetally diagnosed cases was almost twice that of those submitted to first stage Norwood surgery in the same institution.26 This could be accounted for by chromosomal anomalies, other extracadiac malformations or extreme prematurity in the fetal “intention-to-treat” group, all of which were less common in the postnatal group, or such postnatal patients were not submitted for surgery and therefore not counted in the surgical series. In addition, there were some cases of a restrictive atrial septum in the fetal series who decompensated so acutely after birth, that they would have died before reaching the surgical centre, had they not been prenatally diagnosed. There is no evidence that early or operative delivery in CHD will improve outcome, although both might be considered in the rare cases where cardiac function deteriorates in late gestation. Early delivery might be considered in the setting of
  10. 10. 336 L Allan RA RV LA Figure 4 In this four chamber view, the mitral valve is atretic and the left ventricle hypoplastic. This was a case of the hypoplastic left heart syndrome. In such a fetus the systemic perfusion is dependent on the patency of the arterial duct which naturally closes within hours or days of birth, sometimes acutely. If the neonate is not treated urgently with prostaglandins, irreparable damage can occur to the kidneys and liver. Thus, this cardiac condition would be expected to benefit from prenatal detection and delivery in a specialised centre. increasing hydrops in CHD or in a fetal tachycardia resistant to therapy but the disadvantages of prematurity, and lung immaturity in particular, must be weighed against any possible advantage. However, it seems intuitively obvious that those cases where early or urgent cardiological treatment is required must benefit from prenatal diagnosis, by being delivered at, or close to, the site of cardiological care. This is particularly relevant in settings where the specialised cardiac centre is geographically remote, as intrauterine transfer is much more stable than the transfer of a sick
  11. 11. Impact of prenatal diagnosis on the paediatric management of heart defects 337 RV LV < < Figure 5 This four-chamber view shows a defect at the crux of the heart, an atrioventricular septal defect. Such a malformation will not cause immediate symptoms in the newborn, so can be safely delivered locally. neonate. Although many authors have tried to prove the benefit of planned delivery after prenatal diagnosis, it has been difficult to show for various reasons. In many cases, this is because the numbers of prenatally diagnosed cases are not sufficient for statistical analysis.27,28 Some authors have looked at mixed diagnostic groups, with the more severe lesions predominating in the fetal series.29 Also, in general, this question cannot be addressed by a tertiary referral centre, as they do not usually have a method to ascertain cases who have died in the periphery prior to referral. Had they been included, such cases would have had the effect of increasing the mortality in the postnatally diagnosed cases, but they are not usually recognised. Deaths from unrecognised CHD occurred in up to 15% of cases of the hypoplastic left heart syndrome in one reported series.7 Subsets of cases of the hypoplastic left heart syndrome which are at especially high risk of early death, such as those with a restrictive atrial septum are over-represented in the fetal series, supporting the concept that these cases would not have reached the referral centre had they not been detected prenatally. The only series which was sufficiently large to analyse and was population based and therefore ascertained all cases in a geographical area, whether
  12. 12. 338 L Allan Table 3 Outcome of 956 cases of fetal CHD evaluated between 1998 and 2004. TOP = termination of pregnancy, IUD = intrauterine death, NND = neonatal death, InfD = infant death, uk = unknown or presently continuing pregnancies 0 100 200 300 400 500 600 TOP IUD Alive NND InfD uk they reached the referral centre or not, was that of Bonnet et al.30 This was a ten year study of a single diagnostic category, transposition of the great arteries, and was based in the Paris area of France. This showed a clear advantage for the cases prenatally diagnosed with no mortality in this group, as compared to an 8% mortality prior to surgery, plus an 8% mortality after surgery in the postnatally diagnosed group. More recently, similar results were reported in a study of neonates with coarctation of the aorta, demonstrating that the risk of postnatal death was decreased in the prenatally diagnosed group and that they were more haemodynamically stable preoperatively.31 Clearly, mortality is rather a crude outcome measure and long-term morbidity in infants with CHD should be explored in more detail. In all the studies which have looked at prenatal versus postnatal diagnosis in terms of outcome, the prenatally diagnosed cases have been haemodynamically more stable in the immediate postnatal period than those postnatally diagnosed.32 This would be expected to translate into a better neurological result in the long-term for those prenatally diagnosed. A number of studies have shown that after staged surgical reconstruction for hypoplastic left heart there is a major risk of long-term neurodisability.33,34,35 This risk appears to be improving with advancing era36 but such data still gives cause for concern. There is clear evidence to show a correlation between length of stay in the intensive care unit and IQ.37 In a significant number of neonates requiring intervention, prenatal diagnosis reduces the time in the intensive care unit and this in turn may influence long-term morbidity and neurological outcome. Only large studies, evaluating neurological development in children 5–15 years after treatment for CHD will prove this point and these are notoriously hard to perform.
  13. 13. Impact of prenatal diagnosis on the paediatric management of heart defects 339 SUMMARY Prenatal diagnosis of CHD disease has influenced the practise of Paediatric Cardiology in a variety of ways and is likely to have an increasing effect in the future. Fetal echocardiography now constitutes a significant proportion of the work of a specialised Paediatric Cardiology unit. Early diagnosis and termination of pregnancy may reduce the prevalence of complex disease in postnatal series. At the present time, at least a third of neonates presenting to most units will have been identified in fetal life and this figure is likely to increase as routine screening continues to improve, and nuchal translucency screening becomes more widely adopted. Planning the delivery where skilled and experienced cardiac support can be initiated immediately, and intervention performed where appropriate, will potentially salvage those with urgently presenting or duct dependent lesions. Long-term morbidity associated with the repair of CHD in infancy is likely to improve as a result of ideal perinatal management. REFERENCES 1 Lange LW, Sahn DJ, Allen HD, Goldberg SJ, Anderson C, Giles H. Qualitative real-time cross-sectional echocardiographic imaging of the human fetus during the second half of pregnancy. Circulation 1980; 62: 799–806. 2 Kleinman CS, Hobbins JC, Jaffe CC, Lynch DC, Talner NS. Echocardiographic studies of the human fetus: prenatal diagnosis of congenital heart disease and cardiac dysrhythmias. Pediatrics 1980; 65: 1059–67. 3 Allan LD, Tynan MJ, Campbell S, Wilkinson J, Anderson RH. Echocardiographic and anatomical correlates in the fetus. Br Heart J 1980; 44: 444–51. 4 Allan LD, Crawford DC, Anderson RH, Tynan MJ. Echocardiographic and anatomical correlations in fetal congenital heart disease. Br Heart J 1984; 52: 542–48. 5 Allan LD, Crawford DC, Chita SK, Tynan MJ. Prenatal screening for congenital heart disease. Br Med J 1986; 292: 1717–719. 6 Young ID, Clarke M. Lethal malformations and perinatal mortality: A ten year review with comparison of ethnic differences. Br Med J 1987; 295: 88–91. 7 Abu-Harb M, Hey E, Wren C. Death in infancy from unrecognised congenital heart disease. Arch Dis Child 1994; 71: 3–7. 8 Sharland GK, Allan LD. Screening for congenital heart disease prenatally. Results of a 2 1/2-year study in the South East Thames Region. Br J Obstet Gynaecol 1992; 99: 220–25. 9 Tegnander E, Eik-Nes SH, Linker DT. Incorporating the four-chamber view of the fetal heart into the second-trimester routine fetal examination. Ultrasound Obstet Gynecol 1994; 4: 24–28. 10 Garne E, Stoll C, Clementi M. Euroscan Group. Evaluation of prenatal diagnosis of congenital heart diseases by ultrasound: experience from 20 European registries. Ultrasound Obstet Gynecol 2001; 17: 386–91. 11 Bull C. On behalf of the British Paediatric Cardiac Association. Current and potential impact of fetal diagnosis on the prevalence and spectrum of serious congenital heart disease at term. Lancet 1999; 354: 1242–247. 12 Snijders RJ, Johnson S, Sebire NJ, Noble PL, Nicolaides KH. First-trimester ultrasound screening for chromosomal defects. Ultrasound Obstet Gynecol 1996; 7: 216–26. 13 Hyett JA, Perdu M, Sharland GK, Snijders RS, Nicolaides KH. Increased nuchal translucency at 10–14 weeks of gestation as a marker for major cardiac defects. Ultrasound Obstet Gynecol 1997; 10: 242–46.
  14. 14. 340 L Allan 14 Mavrides E, Cobian-Sanchez F, Tekay A, Moscoso G, Campbell S, Thilaganathan B, Carvalho JS. Limitations of using first-trimester nuchal translucency measurement in routine screening for major congenital heart defects. Ultrasound Obstet Gynecol 2001; 17: 106–10. 15 Hyett J, Perdu M, Sharland G, Snijders R, Nicolaides KH. Using fetal nuchal translucency to screen for major congenital cardiac defects at 10–14 weeks of gestation: population based cohort study. Br Med J 1999; 318: 81–85. 16 Daubeney PE, Sharland GK, Cook AC, Keeton BR, Anderson RH, Webber SA. Pulmonary atresia with intact ventricular septum: impact of fetal echocardiography on incidence at birth and postnatal outcome. UK and Eire collaborative study of pulmonary atresia with intact ventricular septum. Circulation 1998; 98: 562–66. 17 Allan LD, Sharland GS, Tynan M. Natural history of hypoplastic left heart syndrome. Int J Cardiol 1989; 25: 341–43. 18 Hornberger LK, Sanders SP, Sahn DJ, Rice MJ, Spevak PJ, Benacerraf BR et al. In utero pulmonary artery and aortic growth and potential for progression of pulmonary outflow tract obstruction in tetralogy of Fallot. J Am Coll Cardiol 1995; 25: 739–45. 19 Maxwell DJ, Crawford DC, Curry PVM, Tynan MJ, Allan LD. Obstetric importance, diagnosis and management of fetal tachycardias. Br Med J 1988; 297: 107–10. 20 Maxwell DJ, Allan LD, Tynan MJ. Balloon dilatation of the aortic valve in the fetus. Br Heart J 1991; 65: 256–58. 21 Bu’Lock FA, Stumper O, Jagtap R, Silove ED, DeGiovanni JW, Wright JG et al. Surgery for infants with a hypoplastic systemic ventricle and severe outflow tract obstruction: early results form a modified Norwood procedure. Br Heart J 1995; 73: 456–61. 22 Tulzer G, Arzt W, Franklin RCG, Loughna PV, Mair R, Gardiner HM. Fetal pulmonary valvuloplasty for critical pulmonary stenosis or atresia with intact septum. Lancet 2002; 360: 1567–568. 23 Tworetzky W, Marshall AC. Balloon valvuloplasty for congenital heart disease in the fetus. Clin Perinatol 2003; 30: 541–50. 24 Paladini D, Russo M, Teodoro A, Pacileo G, Capozzi G, Martinelli P et al. Prenatal diagnosis of congenital heart disease in the Naples area during the years 1994–1999 – the experience of a joint fetal-pediatric cardiology unit. Prenat Diagn 2002; 22: 545–52. 25 Allan LD, Sharland GK, Milburn A, Lockhart SM, Groves AM, Anderson RH et al. Prospective diagnosis of 1006 consecutive cases of congenital heart disease in the fetus. J Am Coll Cardiol 1994; 23: 1452–458. 26 Allan LD, Apfel HD, Printz BF. Outcome after prenatal diagnosis of hypoplastic left heart syndrome. Heart 1998; 79: 371–73. 27 Chang AC, Huhta JC, Yoon GC, Wood DG, Tulzer G, Cohen et al. Diagnosis, transport and outcome in fetuses with left ventricular outflow tract obstruction. J Thoac Cardovasc Surg 1991; 102: 841–48. 28 Kumar RK, Newburger JW, Gauvreau K, Kamenir SA, Hamberger LK. Comparison of outcome when hypoplastic left heart syndrome and transposition of the great arteries are diagnosed prenatally versus when diagnosis of these two conditions is only made postnatally. Am J Cardiol 1999; 83: 1649–653. 29 Copel JA, Tan AS, Kleinmann CS. Does prenatal diagnosis of congenital heart disease alter short term outcome?Ultrasound Obstet Gynaecol 1997; 10: 237–41. 30 Bonnet D, Coltri A, Butera G, Fermont L, Bidois J, Kachaner J, Sidi D. Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality. Circulation 1999; 99: 916–18. 31 Franklin O, Burch M, Manning N, Sleeman K, Gould S, Archer N. Prenatal diagnosis of coarctation of the aorta improves survival and reduces morbidity. Heart 2002; 87: 67–69. 32 Verheijen PM, Lisowski LA, Stoutenbeek P, Hitchcock JF, Bennink GB, Meijboom EJ. Lactacidosis in the neonate is minimized by prenatal detection of congenital heart disease. Ultrasound Obstet Gynecol 2002; 19: 552–55. 33 Rogers BT, Msall ME, Buck GM, Lyon NR, Norris MK, Roland JM et al. Neurodevelopmental outcome in infants with hypoplastic left heart syndrome. J Pediatr 1995; 126: 496–98. 34 Kern JH, Hayes CJ, Michler RE, Gersony WM, Quaegebeur JM. Survival and risk factor analysis for the Norwood procedure for the hypoplastic left heart syndrome. Am J Cardiol 1997; 80: 170–74.
  15. 15. Impact of prenatal diagnosis on the paediatric management of heart defects 341 35 Mahle WT, Clancy RR, McGaurn SP, Goin JE, Clark BJ. Impact of prenatal diagnosis on survival and early neurological morbidity in neonates with the hypoplastic left heart syndrome. Pediatrics 2001; 107: 1277–282. 36 Goldberg CS, Schwartz EM, Brunberg JA, Mosca RS, Bove EL, Schork MA et al. Neurodevelopmental outcome of patients after the Fontan operation: a comparison between children with hypoplastic left heart syndrome and other single functional ventricle lesions. J Pediatrics 2000; 137: 646–52. 37 Newburger JW, Wypij D, Bellinger DC, du Plessi AJ, Kuban KC, Rappaport LA et al. Length of stay after infant heart surgery is related to cognitive outcome at age 8 years. J Pediatr 2003; 143: 67–73.