DOI: 10.1002/pd.4525
ORIGINAL ARTICLE
Prenatal detection of congenital heart disease in a low risk population undergoing first and second trimester screening Ditte E. S. Jørgensen1*, Niels Vejlstrup2, Connie Jørgensen1, Lisa Leth Maroun3, Jesper Steensberg4, Anette Hessellund5, Finn Stener Jørgensen6,10, Torben Larsen7, Anne-Cathrine Shalmi8, Lillian Skibsted9,10, Helle Zingenberg11, Charlotte Ekelund1 and Ann Tabor1,10 1
Center of Fetal Medicine and Pregnancy, Copenhagen University Hospital Rigshospitalet, Denmark Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Denmark 3 Department of Pathology, Copenhagen University Hospital Rigshospitalet, Denmark 4 Department of Pediatrics, Copenhagen University Hospital Rigshospitalet, Denmark 5 Department of Obstetrics and Gynecology, Næstved Hospital, Denmark 6 Fetal Medicine Unit, Department of Obstetrics and Gynecology, Copenhagen University Hospital Hvidovre Hospital, Denmark 7 Department of Obstetrics and Gynecology, Holbæk Hospital, Denmark 8 Department of Obstetrics and Gynecology, Copenhagen University Hospital North Zealand Hospital, Denmark 9 Department of Obstetrics and Gynecology, Roskilde Hospital, Denmark 10 Faculty of Health Sciences, University of Copenhagen, Denmark 11 Department of Obstetrics and Gynecology, Glostrup/Herlev Hospital, Denmark *Correspondence to: Ditte E. S. Jørgensen. E-mail: [email protected] 2
ABSTRACT Objectives The prenatal detection rate of congenital heart disease (CHD) is low compared with other fetal malformations. Our aim was to evaluate the prenatal detection of CHD in Eastern Denmark. Methods Fetuses and infants diagnosed with CHD in the period 01.01.2008–31.12.2010 were assessed regarding prenatal detection rate and accuracy, as well as correlation with nuchal translucency (NT) thickness. Results Out of 86 121 infants, 831 were born with CHD (0.96%). The prenatal detection rate of ‘all CHD’ was 21.3%, of ‘Major CHD’ 47.4%. Full agreement between prenatal and postnatal/autopsy findings was found in 96% of prenatally detected diagnoses. An NT thickness >95th percentile was found in 15.0% fetuses with ‘Major CHD’. Of ‘Major CHDs’ detected prenatally, 77% were picked up at the time of the malformation scan at weeks 18–21.
Conclusions Nearly half of ‘Major CHDs’ were detected prenatally. The prenatal cardiac diagnoses showed a high degree of accuracy. Increased NT thickness as a screening tool for CHD performed moderately but is an important high risk group for specialist examination. A minority of the prenatally detected CHDs was identified because of extra scans performed in high risk pregnancies. © 2014 John Wiley & Sons, Ltd.
Funding sources: The project was funded by the Danish Council for Independent Research. The organization was not involved in study design, data collection, data analysis, manuscript preparation and/or publication decisions. Conflicts of interest: None declared
INTRODUCTION Congenital heart diseases (CHD) are among the most common congenital malformations. Severe CHD requires major cardiac surgery and can result in neonatal death. Even after radical or palliative surgery, infants with complex CHD have significant co-morbidity and a shorter life expectancy.1–3 The prenatal identification of fetuses with complex CHD is important. If diagnosed prenatally, parents can prepare mentally for the peripartum admission to a neonatal unit and subsequent treatment. Delivery of infants with significant CHD can be planned and referred to hospitals with the relevant expertise and optimal conditions for the child’s treatment. In especially
Prenatal Diagnosis 2015, 35, 325–330
severe cases, the parents can decide to terminate the pregnancy. Prenatal ultrasound screening allows detection of some malformations in the fetal heart. However, the prenatal detection rate of severe CHDs is relatively low (23–57%) compared with other fetal malformations (42–82%).4–10 Improved detection of CHD is desirable, especially because studies have shown that neonatal morbidity and mortality are reduced when severe CHDs are detected prenatally.11,12 Since 1995, pregnant women in Denmark have been offered a malformation scan including a standard fetal heart examination at 18–21 weeks. The standard fetal heart examination in the study period varied between the involved hospitals but
© 2014 John Wiley & Sons, Ltd.
D. E. S. Jørgensen et al.
326
incorporated four-chamber view as a minimum, in some of the hospitals also the three-vessel view and outflow tracts. Since 2006, a nuchal translucency (NT) scan at 11–14 weeks has become part of prenatal screening. The uptake rate of both these screening examinations is over 90%.13,14 In addition, women with a known increased risk of carrying a fetus with CHD are offered a fetal echocardiography performed by a specialist in Fetal Medicine at 14 and/or 21 weeks.15 Since 2006, these supplementary scans have also been performed on fetuses with a NT thickness above the 95th percentile, as international studies have shown a strong correlation between increased NT thickness and the prevalence of CHD.16 The aim of this study was to evaluate the prenatal ultrasound screening program for CHD. This was carried out by determining the prenatal detection rates of CHD in the period 01.01.2008–31.12.2010 and the validity of prenatal cardiac diagnoses. Furthermore, we assessed the correlation between NT and CHD and at which type of scan CHD was diagnosed.
METHODS The study design is a retrospective analysis of prospectively collected data. Infants born with CHD, second trimester terminations due to CHD and second trimester intrauterine demise (miscarriages and stillbirths) with prenatally detected CHD in the period 01.01.2008–31.12.2010 were identified through the National Patient Registry17 and the Medical Birth Registry.18 Supplemental variables were extracted from the Danish Fetal Medicine Database, which contains background characteristics, data on ultrasound examinations in pregnancy and outcome for pregnancies.19 CHD was defined as congenital malformations of the heart chambers, heart valves, great arteries and septal defects, corresponding to diagnosis codes DQ20 to DQ25 in the International Classification of Disease-10 classification system. Patient files of all included cases were reviewed at the involved hospitals. Hence, for practical reasons, all sets of data were limited to Eastern Denmark, that is, the Capital Region and Region Zealand. Exclusion criteria were multiple pregnancies and fetuses or infants with chromosome abnormalities, as these pregnancies are offered a more extended screening program than described earlier and therefore are not representative for the general population that we wanted to examine. We also excluded infants with isolated atrial septum defect and/or isolated patent arterial duct, as these defects, due to the anatomical changes when passing from fetal to newborn circulation, are not detectable prenatally. Furthermore, infants diagnosed with a CHD after 1 year of age and cases, where prenatal scan descrip-tions for unknown reasons were unavailable, were excluded. ‘Major CHD’ was defined according to a predefined list of diagnosis codes (Table 1). Prenatal cardiac diagnoses were validated in all fetuses terminated because of infants born with prenatally detected CHD. This was carried out by looking at the accuracy of prenatal echocardiography descriptions versus postnatal autopsy reports, postnatal echocardiography descriptions and/or surgery descriptions, using the latter three as a gold standard. Nearly all prenatal echocardiography examinations were performed by a cardiologist specialized in fetal cardiology (NV), as most fetuses with a prenatally detected CHD in Eastern Denmark are referred to Prenatal Diagnosis 2015, 35, 325–330
Table 1 Definition of major congenital heart disease (CHD) Major CHD Complete transposition of the great arteries Double outlet right ventricle Atrioventricular septal defect Aortic coarctation Tetralogy of Fallot Congenitally corrected transposition of the great arteries Hypoplastic left heart syndrome Hypoplastic right heart syndrome Common arterial trunk Isomerism with asplenia or polysplenia
this specialist to ascertain the prenatal cardiac diagnosis. The level of agreement between prenatal and postnatal findings was scored using an adapted version of the scoring system described by Hauerberg et al.20 consisting of four groups, A–D, defined as follows: (a) Full agreement between prenatal findings and autopsy findings. (b) Main prenatal findings confirmed and the prognosis correctly predicted (main diagnosis either more specific or different to a minor degree at autopsy, other minor additional anomalies found at autopsy or other minor anomalies found by ultrasound and not confirmed by autopsy). (c) Main prenatal findings not confirmed or autopsy findings substantially different but the prognosis still correctly predicted. (d) Prenatal findings not confirmed, or main autopsy diagnosis was substantially different, and the prognosis was incorrectly predicted (autopsy findings less severe than the prenatal diagnosis, indicating that the information and advice given to the parents was incorrect).
Diagnoses of fetuses terminated because of prenatally detected CHD were validated individually by a cardiologist specialized in fetal cardiology (NV) and a fetal pathologist consultant (LLM). Diagnoses of infants born with prenatally detected CHD were validated individually by a cardiologist specialized in fetal cardiology (NV) and a pediatric cardiologist (JS). When disagreement in the validation occurred, the cases were discussed until agreement was achieved.
Statistical analysis Categorical data were presented as number (%) or proportion with confidence intervals (%, 95% CI).
RESULTS In Eastern Denmark, 86 121 infants were born in the period 01.01.2008–31.12.2010, 831 of them with CHD (0.96%). After exclusion of multiple pregnancies, infants with chromosome abnormalities, isolated atrial septum defect, isolated patent arterial duct and infants diagnosed with CHD more than 1 year after birth, the number of infants born with CHD was 389 (0.45%). Prenatal ultrasound scan descriptions were available in 373 infants. Seven of these were excluded, as the first scan in these pregnancies for unknown reasons was registered after the time for malformation scan. This resulted in a total number © 2014 John Wiley & Sons, Ltd.
Prenatal screening for CHD in a low risk population
of 366 included infants. Additionally, 42 fetuses conceived with CHD in the period were included: 41 terminations due to CHD and one intrauterine demise of a fetus with prenatally detected CHD. No spontaneously miscarried fetuses were diagnosed with CHD. Hence, a total number of 408 included fetuses were conceived with CHD, 135 of them with ‘Major CHD’ (Table 2). The number of prenatally detected CHD was 87 in the ‘all CHD’ group and 64 in the ‘Major CHD’ group, hence a prenatal detection rate at 21.3% (95% CI 17.6–25.6) and 47.4% (95% CI 39.2–55.8) in the two groups, respectively (Table 2). The distribution (infant/termination/intrauterine demise) of the fetuses with prenatally detected CHD is shown in Table 3. For validation of the cardiac malformation diagnoses, we were able to find autopsy reports for 32 out of 41 fetuses terminated because of CHD and postnatal echocardiography or surgery descriptions for 42 out of 45 infants born with prenatally detected CHD. There was full agreement between prenatal and postnatal findings in 64% (group A). Main prenatal findings were confirmed and the prognosis correctly predicted in 33% (group B). Main prenatal findings were not confirmed but the prognosis still correctly predicted in 3% (group C), and main prenatal findings were not confirmed, and the prognosis was incorrectly predicted in 1% (group D). In the two cases classified as group C, the prenatal diagnoses (case 1: tetralogy of Fallot with pulmonary atresia, case 2: complete transposition of the great arteries with ventricular septal defect) were confirmed and the prognosis correctly predicted, but in addition, the autopsies found bilateral vena cava in case 1 and juxta positioning of the atrial appendices in case 2. The one case scored to be in group D was prenatally diagnosed with an outlet ventricular septal defect in combination with a common arterial trunk, while the autopsy
327
report revealed a combination of an outlet ventricular septal defect and transposition of the great arteries. The correlation between NT thickness and CHD in our study population is shown in Table 4. NT thickness measurements were available in 349 out of 408 cases. The mother had chosen not to have a NT scan, had come too late or had a primary CVS in 36 cases, and NT thickness was not available for unknown reasons in 23 cases. Among the 349 cases with available NT values, 120 were in the ‘Major CHD’ group. In this group, 18 (15%) and 5 (4.2%) of the 120 had a NT thickness above the 95th percentile and 99th percentile, respectively. When looking at the type of scan, at which prenatally diagnosed CHD was detected, 2% of the ‘Major’ cases were detected at the NT scan, 14% at the early fetal echocardiography, 77% at the malformation scan, 1% at the late fetal echocardiography and 5% at another scan. Finally, Table 2 also shows that detection rates were more than 85% for four of the 10 ‘Major CHD’ diagnoses (hypoplastic left heart syndrome, hypoplastic right heart syndrome, common arterial trunk and isomerism with asplenia or polysplenia). The detection rates of the last six diagnoses were between 23.5% and 55.6% (complete transposition of the great arteries, double outlet right ventricle, atrioventricular septal defect, aortic coarctation, tetralogy of Fallot and congenitally corrected transposition of the great arteries).
DISCUSSION In this study, the prenatal detection rate for ‘Major CHD’ was 47.4% (95% CI 39.2–55.8). This is comparable with detection rates in other studies, which vary from 23% to 57%.4,5,7–10 The validation of the prenatal cardiac diagnoses showed a high degree of accuracy, as more than 95% of the diagnoses were
Table 2 Detection rates of congenital heart defects in the period 2008–2010 Conceived fetuses with CHD (n) (infants + intrauterine demise + terminations)
CHD detected prenatally (n) (infants + intrauterine demise + termiantions)
Prenatal detection rate (%)
95% CI
All CHD
408
87
21.3
17.6–25.6
Major CHDa
135
64
47.4
39.2–55.8
Individual Major CHDb
165
84
50.3
43.4–58.4
CTGA
31
13
41.9
26.4–59.3
DORV
18
10
55.6
33.7–75.5
AVSD
20
10
50.0
29.9–70.1
AC
34
8
23.5
12.2–40.2
TOF
20
5
25.0
10.8–47.3
ccTGA
2
1
50.0
9.5–90.6
HLHS
27
25
92.6
75.6–99.0
HRHS
7
6
85.7
46.7–99.5
CAT
4
4
100.0
45.4–100.0
IAP
2
2
100.0
29.0–100.0
CTGA, complete transposition of the great arteries; DORV, double outlet right ventricle; AVSD, atrioventricular septal defect; AC, aortic coarctation; TOF, tetralogy of Fallot; ccTGA, congenitally corrected transposition of the great ateries; HLHS, hypoplastic left heart syndrome; HRHS, hypoplastic right heart syndrome; CAT, Common arterial trunk; IAP, isomerism with asplenia or polysplenia. a See Table 1. b Some cases had more than one individual Major CHD diagnose, hence the difference in numbers between this line and the line above.
Prenatal Diagnosis 2015, 35, 325–330
© 2014 John Wiley & Sons, Ltd.
D. E. S. Jørgensen et al.
328
Table 3 Distribution (infant/termination/intrauterine demise) of conceived fetuses with congenital heart disease (CHD) prenatally detected Intrauterine demise of fetuses with CHD detected prenatally
Terminations due to CHD
Infants born with CHD detected prenatally
CHD detected prenatally (infants + intrauterine demise + terminations)
All CHD
1
41
45
87
Major CHDa
1
40
23
64
Individual Major CHDb
1
51
32
84
CTGA
0
7
6
13
DORV
0
7
3
10
AVSD
0
6
4
10
AC
0
0
8
8
TOF
0
1
4
5
ccTGA
1
0
0
1
HLHS
0
20
5
25
HRHS
0
4
2
6
CAT
0
4
0
4
IAP
0
2
0
2
CTGA, complete transposition of the great arteries; DORV, double outlet right ventricle; AVSD, atrioventricular septal defect; AC, aortic coarctation; TOF, tetralogy of Fallot; ccTGA, congenitally corrected transposition of the great arteries; HLHS, hypoplastic left heart syndrome; HRHS, hypoplastic right heart syndrome; CAT, Common arterial trunk; IAP, isomerism with asplenia or polysplenia. a See Table 1. b Some cases had more than 1 individual Major CHD diagnose, hence the difference in numbers between this line and the line above.
scored to be group A or B. It may be discussed whether the two cases in group C were correctly classified or should have been in group B, but the persons validating the diagnoses assessed them to be in group C as they would not categorize the additional findings as ‘minor’. The case in group D is instructive: Because the great vessels run in parallel, transposition of the great arteries may be interpreted as common arterial trunk, if the echocardiography is difficult and the separation is not seen. The surgical outcome is less favorable for common arterial trunk compared with arterial switch of transposition of the great arteries, because the common arterial trunk will need a homograft. The differentiation between the two diagnoses is important, as many families will consider abortion if a child is expected to have repeated surgeries instead of one radical operation. The validation results are in accordance with Khoo et al., a retrospective study of the efficiency of fetal echocardiography, which also found fetal echocardiography to be an accurate tool for prenatal diagnosis of CHD.21 The benefits of accurate prenatal diagnosis are multiple, in that it gives healthcare personnel and parents a reliable basis for decision making. In pregnancies that are not terminated, it gives optimal conditions for the newborn, its family
Table 4 Correlation between nuchal translucency thickness and congenital heart disease (CHD) All CHD Fetuses/infants with CHD
408
Nuchal translucency value available
349
Major CHDa 135 120
th
27 (7.7%)
18 (15.0%)
th
10 (2.9%)
5 (4.2%)
Nuchal translucency thickness >95 percentile Nuchal translucency thickness >99 percentile a
See Table 1 for definition.
Prenatal Diagnosis 2015, 35, 325–330
and the healthcare personnel regarding planning and treatment. Among the fetuses with a ‘Major CHD’, 15% (95% CI 9.6–22.6) had a NT thickness above the 95th percentile. These results indicate a modest effect of NT thickness as a screening tool for major cardiac defects. Increased NT is still though an important reason for high risk referral even though it results in a large number of patients referred for specialized fetal echocardiography. The marker is an essential complement to a screening strategy based on maternal history, where, for example, family history of CHD, maternal diabetes mellitus and intake of teratogenic medications will place 2–5% of women in a ‘high risk’ group but only detect 5–10% of all major cardiac defects.22 Our findings are in accordance with recent studies.22–26 It is, however, difficult to compare the results of these studies, because of varying definitions of ‘all CHD’, ‘Major CHD’, inclusion and exclusion criteria, background risk in the populations, methods for data collection, follow-up length, and different NT cut-offs. Nevertheless, it seems as though that the high detection rates found in earlier studies has declined to around 15–20%,16,22–29 although one study recently published a detection rate of 34%.30 If NT is combined with ductus venosus and tricuspid flow, it may be possible to increase the detection rate to more than 50%.31,32 Further investigation of this screening method would be interesting. We found that the majority of prenatally detected CHDs are identified at the malformation scan at 18–21 weeks, which in Denmark is performed by a sonographer. A minority of the prenatally detected CHDs was identified by a specialist echocardiography at 14 or 21 weeks offered in high risk pregnancies. This correlates with other studies showing that 10% of infants born with CHD have identifiable risk factors and that the majority of CHDs are found in unselected pregnancies.9,11 © 2014 John Wiley & Sons, Ltd.
Prenatal screening for CHD in a low risk population
We furthermore examined the detection rate according to the type of CHD and found that diagnoses mostly detected by the four-chamber view (hypoplastic left heart syndrome and hypoplastic right heart syndrome) had detection rates of more than 85%, while diagnoses mostly detected by the three-vessel view or outflow tracts (double outlet right ventricle, complete transposition of the great arteries and tetralogy of Fallot) all had lower detection rates. This tendency probably reflects the experience of the examiners, as the four-chamber view is the most basic scanning plane of the fetal heart, whereas the three-vessel view and outflow tracts are more advanced scanning planes not yet fully implemented at all hospitals as part of the routine scan. This study was partly based on registries and has limitations typical for this kind of studies. The three registries (the National Patient Registry, Medical Birth Registry and Danish Fetal Medicine Database) are, however, considered to be of high quality,33 and the files of all included cases were reviewed. We believe that all datasets in our study are reliable and complete. Another limitation of our study is that one (NV) of the three persons validating the diagnoses performed most of the prenatal echocardiographies. All validations were, however, performed by two persons, and therefore, we consider this a minor limitation. For practical reasons, the study was limited to Eastern Denmark. We have no reason to believe that rates would be different in the Western part of the country, as the prenatal screening program is the same throughout Denmark. In view of the results earlier, it is imperative to continue to improve the quality of CHD scans in the low risk population. The improvement of this offer in the Capital Region and Region Zealand has been – and still is – a continuum, and effort should be made to ensure an equal quality of fetal heart examinations across hospitals. The tendency of a high detection level in malformations detected by the four-chamber view and a lower detection level in malformations detected by the three-vessel view and outflow tracts indicates that the expertise of the sonographers has reached a certain level and that efforts must be made to take that expertise to the next level. Studies have shown that clinical experience has a significant impact on the examination of the fetal heart and
329
prenatal detection.8 We plan to optimize the detection of CHD through our education and supervision program for sonographers, as their routine scanning of the large low risk population is very important in identifying detectable CHDs. The objective is that all sonographers shall be certified in the second trimester scan, including performance of three-vessel view and outflow tracts, by the Fetal Medicine Foundation. In conclusion, nearly half of ‘Major CHDs’ were detected in this large unselected population. In experienced hands, the prenatal cardiac diagnoses showed a high degree of accuracy. We found the performance of increased NT thickness as a screening tool for CHD to be moderate, but it is an important high risk group for specialist examination. It may be improved by addition of ductus venosus and tricuspid flow measurements, and further investigation of this area is needed. The majority of prenatally detected CHDs were identified in the low risk population at the 18–21 weeks’ malformation scan performed by a sonographer and a minority detected because of extra scans performed by a doctor in high risk pregnancies. This indicates that it may not be possible to achieve a welldefined high risk population. A future optimization of the detection of CHD may have this aspect in mind, and continuous education and supervision of the sonographers should be prioritized. WHAT’S ALREADY KNOWN ABOUT THIS TOPIC? • The prenatal detection rate of congenital heart disease (CHD) is low compared with other fetal malformations.
WHAT DOES THIS STUDY ADD? • Nearly half of ‘Major CHDs’ were detected prenatally. The prenatal cardiac diagnoses showed a high degree of accuracy. NT thickness performed moderately as screening tool for CHD.
Ethics approval The Danish Data Protection Agency, the Danish National Board of Health and the Research Committee of the DFMD approved this study.
REFERENCES 1. Karsdorp PA, Everaerd W, Kindt M, Mulder BJ. Psychological and cognitive functioning in children and adolescents with congenital heart disease: a meta-analysis. J Pediatr Psychol 2007;32(5):527–41. 2. Makrydimas G, Sotiriadis A, Ioannidis JP. Screening performance of first-trimester nuchal translucency for major cardiac defects: a metaanalysis. Am J Obstet Gynecol 2003;189(5):1330–5. 3. Zomer AC, Vaartjes I, Grobbee DE, Mulder BJ. Adult congenital heart disease: new challenges. Int J Cardiol 2013;163(2):105–7. 4. Crane JP, LeFevre ML, Winborn RC, et al. A randomized trial of prenatal ultrasonographic screening: impact on the detection, management, and outcome of anomalous fetuses. The RADIUS Study Group. Am J Obstet Gynecol 1994;171(2):392–9. 5. Grandjean H, Larroque D, Levi S. The performance of routine ultrasonographic screening of pregnancies in the Eurofetus Study. Am J Obstet Gynecol 1999;181(2):446–54.
Prenatal Diagnosis 2015, 35, 325–330
6. Pinto NM, Keenan HT, Minich LL, et al. Barriers to prenatal detection of congenital heart disease: a population-based study. Ultrasound Obstet Gynecol 2012;40(4):418–25. 7. Stefos T, Plachouras N, Sotiriadis A, et al. Routine obstetrical ultrasound at 18– 22 weeks: our experience on 7,236 fetuses. J Matern Fetal Med 1999;8(2):64–9. 8. Tegnander E, Eik-Nes SH. The examiner’s ultrasound experience has a significant impact on the detection rate of congenital heart defects at the second-trimester fetal examination. Ultrasound Obstet Gynecol 2006;28(1):8–14. 9. Tegnander E, Williams W, Johansen OJ, et al. Prenatal detection of heart defects in a non-selected population of 30,149 fetuses – detection rates and outcome. Ultrasound Obstet Gynecol 2006;27(3):252–65. 10. Vial Y, Tran C, Addor MC, Hohlfeld P. Screening for foetal malformations: performance of routine ultrasonography in the population of the Swiss Canton of Vaud. Swiss Med Wkly 2001;131(33–34):490–4.
© 2014 John Wiley & Sons, Ltd.
330
11. Bonnet D, Coltri A, Butera G, et al. Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality. Circulation 1999;99(7):916–18. 12. Tworetzky W, McElhinney DB, Reddy VM, et al. Improved surgical outcome after fetal diagnosis of hypoplastic left heart syndrome. Circulation 2001;103(9):1269–73. 13. Ekelund CK, Jorgensen FS, Petersen OB, et al. Impact of a new national screening policy for Down’s syndrome in Denmark: population based cohort study. BMJ 2008;337:a2547. 14. Ekelund CK, Andersen HJ, Christensen J, et al. Down’s syndrome risk assessment in Denmark – secondary publication. Ugeskr Laeger 2010;172(23):1759–61. 15. ISOUG Education Committee. Cardiac screening examination of the fetus: guidelines for performing the ‘basic’ and ‘extended basic’ cardiac scan. Ultrasound Obstet Gynecol 200627(1):107–13. 16. Souka AP, Von Kaisenberg CS, Hyett JA, et al. Increased nuchal translucency with normal karyotype. Am J Obstet Gynecol 2005;192(4):1005–21. 17. Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health 2011;39(7 Suppl):30–3. 18. Knudsen LB, Olsen J. The Danish Medical Birth Registry. Dan Med Bull 1998;45(3):320–3. 19. Ekelund CK, Skovbo P, Holmskov A, et al. Development and establishment of a national Danish fetal medicine database for quality surveillance and research. 2014 [WWW document]. URL http://onlinelibrary.wiley.com/doi/ 10.1002/uog.7151/full [accessed on 5 april 2014] 20. Hauerberg L, Skibsted L, Graem N, Maroun LL. Correlation between prenatal diagnosis by ultrasound and fetal autopsy findings in secondtrimester abortions. Acta Obstet Gynecol Scand 2012;91(3):386–90. 21. Khoo NS, Van EP, Richardson M, Robertson T. Effectiveness of prenatal diagnosis of congenital heart defects in South Australia: a population analysis 1999–2003. Aust N Z J Obstet Gynaecol 2008;48(6):559–63. 22. Mogra R, Alabbad N, Hyett J. Increased nuchal translucency and congenital heart disease. Early Hum Dev 2012;88(5):261–7.
Prenatal Diagnosis 2015, 35, 325–330
D. E. S. Jørgensen et al.
23. Clur SA, Ottenkamp J, Bilardo CM. The nuchal translucency and the fetal heart: a literature review. Prenat Diagn 2009;29(8):739–48. 24. Muller MA, Clur SA, Timmerman E, Bilardo CM. Nuchal translucency measurement and congenital heart defects: modest association in lowrisk pregnancies. Prenat Diagn 2007;27(2):164–9. 25. Simpson LL, Malone FD, Bianchi DW, et al. Nuchal translucency and the risk of congenital heart disease. Obstet Gynecol 2007; 109(2 Pt 1):376–83. 26. Westin M, Saltvedt S, Bergman G, et al. Is measurement of nuchal translucency thickness a useful screening tool for heart defects? A study of 16,383 fetuses. Ultrasound Obstet Gynecol 2006;27(6):632–9. 27. Hafner E, Schuller T, Metzenbauer M, et al. Increased nuchal translucency and congenital heart defects in a low-risk population. Prenat Diagn 2003;23(12):985–9. 28. Hyett J, Perdu M, Sharland G, et al. Using fetal nuchal translucency to screen for major congenital cardiac defects at 10–14 weeks of gestation: population based cohort study. BMJ 19999;318(7176):81–5. 29. Mavrides E, Cobian-Sanchez F, Tekay A, et al. Limitations of using first-trimester nuchal translucency measurement in routine screening for major congenital heart defects. Ultrasound Obstet Gynecol 2001;17(2):106–10. 30. Syngelaki A, Chelemen T, Dagklis T, et al. Challenges in the diagnosis of fetal non-chromosomal abnormalities at 11–13 weeks. Prenat Diagn 2011;31(1):90–102. 31. Chelemen T, Syngelaki A, Maiz N, et al. Contribution of ductus venosus Doppler in first-trimester screening for major cardiac defects. Fetal Diagn Ther 2011;29(2):127–34. 32. Pereira S, Ganapathy R, Syngelaki A, et al. Contribution of fetal tricuspid regurgitation in first-trimester screening for major cardiac defects. Obstet Gynecol 2011;117(6):1384–91. 33. Klemmensen AK, Olsen SF, Osterdal ML, Tabor A. Validity of preeclampsiarelated diagnoses recorded in a national hospital registry and in a postpartum interview of the women. Am J Epidemiol 2007;166(2):117–24.
© 2014 John Wiley & Sons, Ltd.
ORIGINAL ARTICLE
Prenatal detection of congenital heart disease in a low risk population undergoing first and second trimester screening Ditte E. S. Jørgensen1*, Niels Vejlstrup2, Connie Jørgensen1, Lisa Leth Maroun3, Jesper Steensberg4, Anette Hessellund5, Finn Stener Jørgensen6,10, Torben Larsen7, Anne-Cathrine Shalmi8, Lillian Skibsted9,10, Helle Zingenberg11, Charlotte Ekelund1 and Ann Tabor1,10 1
Center of Fetal Medicine and Pregnancy, Copenhagen University Hospital Rigshospitalet, Denmark Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Denmark 3 Department of Pathology, Copenhagen University Hospital Rigshospitalet, Denmark 4 Department of Pediatrics, Copenhagen University Hospital Rigshospitalet, Denmark 5 Department of Obstetrics and Gynecology, Næstved Hospital, Denmark 6 Fetal Medicine Unit, Department of Obstetrics and Gynecology, Copenhagen University Hospital Hvidovre Hospital, Denmark 7 Department of Obstetrics and Gynecology, Holbæk Hospital, Denmark 8 Department of Obstetrics and Gynecology, Copenhagen University Hospital North Zealand Hospital, Denmark 9 Department of Obstetrics and Gynecology, Roskilde Hospital, Denmark 10 Faculty of Health Sciences, University of Copenhagen, Denmark 11 Department of Obstetrics and Gynecology, Glostrup/Herlev Hospital, Denmark *Correspondence to: Ditte E. S. Jørgensen. E-mail: [email protected] 2
ABSTRACT Objectives The prenatal detection rate of congenital heart disease (CHD) is low compared with other fetal malformations. Our aim was to evaluate the prenatal detection of CHD in Eastern Denmark. Methods Fetuses and infants diagnosed with CHD in the period 01.01.2008–31.12.2010 were assessed regarding prenatal detection rate and accuracy, as well as correlation with nuchal translucency (NT) thickness. Results Out of 86 121 infants, 831 were born with CHD (0.96%). The prenatal detection rate of ‘all CHD’ was 21.3%, of ‘Major CHD’ 47.4%. Full agreement between prenatal and postnatal/autopsy findings was found in 96% of prenatally detected diagnoses. An NT thickness >95th percentile was found in 15.0% fetuses with ‘Major CHD’. Of ‘Major CHDs’ detected prenatally, 77% were picked up at the time of the malformation scan at weeks 18–21.
Conclusions Nearly half of ‘Major CHDs’ were detected prenatally. The prenatal cardiac diagnoses showed a high degree of accuracy. Increased NT thickness as a screening tool for CHD performed moderately but is an important high risk group for specialist examination. A minority of the prenatally detected CHDs was identified because of extra scans performed in high risk pregnancies. © 2014 John Wiley & Sons, Ltd.
Funding sources: The project was funded by the Danish Council for Independent Research. The organization was not involved in study design, data collection, data analysis, manuscript preparation and/or publication decisions. Conflicts of interest: None declared
INTRODUCTION Congenital heart diseases (CHD) are among the most common congenital malformations. Severe CHD requires major cardiac surgery and can result in neonatal death. Even after radical or palliative surgery, infants with complex CHD have significant co-morbidity and a shorter life expectancy.1–3 The prenatal identification of fetuses with complex CHD is important. If diagnosed prenatally, parents can prepare mentally for the peripartum admission to a neonatal unit and subsequent treatment. Delivery of infants with significant CHD can be planned and referred to hospitals with the relevant expertise and optimal conditions for the child’s treatment. In especially
Prenatal Diagnosis 2015, 35, 325–330
severe cases, the parents can decide to terminate the pregnancy. Prenatal ultrasound screening allows detection of some malformations in the fetal heart. However, the prenatal detection rate of severe CHDs is relatively low (23–57%) compared with other fetal malformations (42–82%).4–10 Improved detection of CHD is desirable, especially because studies have shown that neonatal morbidity and mortality are reduced when severe CHDs are detected prenatally.11,12 Since 1995, pregnant women in Denmark have been offered a malformation scan including a standard fetal heart examination at 18–21 weeks. The standard fetal heart examination in the study period varied between the involved hospitals but
© 2014 John Wiley & Sons, Ltd.
D. E. S. Jørgensen et al.
326
incorporated four-chamber view as a minimum, in some of the hospitals also the three-vessel view and outflow tracts. Since 2006, a nuchal translucency (NT) scan at 11–14 weeks has become part of prenatal screening. The uptake rate of both these screening examinations is over 90%.13,14 In addition, women with a known increased risk of carrying a fetus with CHD are offered a fetal echocardiography performed by a specialist in Fetal Medicine at 14 and/or 21 weeks.15 Since 2006, these supplementary scans have also been performed on fetuses with a NT thickness above the 95th percentile, as international studies have shown a strong correlation between increased NT thickness and the prevalence of CHD.16 The aim of this study was to evaluate the prenatal ultrasound screening program for CHD. This was carried out by determining the prenatal detection rates of CHD in the period 01.01.2008–31.12.2010 and the validity of prenatal cardiac diagnoses. Furthermore, we assessed the correlation between NT and CHD and at which type of scan CHD was diagnosed.
METHODS The study design is a retrospective analysis of prospectively collected data. Infants born with CHD, second trimester terminations due to CHD and second trimester intrauterine demise (miscarriages and stillbirths) with prenatally detected CHD in the period 01.01.2008–31.12.2010 were identified through the National Patient Registry17 and the Medical Birth Registry.18 Supplemental variables were extracted from the Danish Fetal Medicine Database, which contains background characteristics, data on ultrasound examinations in pregnancy and outcome for pregnancies.19 CHD was defined as congenital malformations of the heart chambers, heart valves, great arteries and septal defects, corresponding to diagnosis codes DQ20 to DQ25 in the International Classification of Disease-10 classification system. Patient files of all included cases were reviewed at the involved hospitals. Hence, for practical reasons, all sets of data were limited to Eastern Denmark, that is, the Capital Region and Region Zealand. Exclusion criteria were multiple pregnancies and fetuses or infants with chromosome abnormalities, as these pregnancies are offered a more extended screening program than described earlier and therefore are not representative for the general population that we wanted to examine. We also excluded infants with isolated atrial septum defect and/or isolated patent arterial duct, as these defects, due to the anatomical changes when passing from fetal to newborn circulation, are not detectable prenatally. Furthermore, infants diagnosed with a CHD after 1 year of age and cases, where prenatal scan descrip-tions for unknown reasons were unavailable, were excluded. ‘Major CHD’ was defined according to a predefined list of diagnosis codes (Table 1). Prenatal cardiac diagnoses were validated in all fetuses terminated because of infants born with prenatally detected CHD. This was carried out by looking at the accuracy of prenatal echocardiography descriptions versus postnatal autopsy reports, postnatal echocardiography descriptions and/or surgery descriptions, using the latter three as a gold standard. Nearly all prenatal echocardiography examinations were performed by a cardiologist specialized in fetal cardiology (NV), as most fetuses with a prenatally detected CHD in Eastern Denmark are referred to Prenatal Diagnosis 2015, 35, 325–330
Table 1 Definition of major congenital heart disease (CHD) Major CHD Complete transposition of the great arteries Double outlet right ventricle Atrioventricular septal defect Aortic coarctation Tetralogy of Fallot Congenitally corrected transposition of the great arteries Hypoplastic left heart syndrome Hypoplastic right heart syndrome Common arterial trunk Isomerism with asplenia or polysplenia
this specialist to ascertain the prenatal cardiac diagnosis. The level of agreement between prenatal and postnatal findings was scored using an adapted version of the scoring system described by Hauerberg et al.20 consisting of four groups, A–D, defined as follows: (a) Full agreement between prenatal findings and autopsy findings. (b) Main prenatal findings confirmed and the prognosis correctly predicted (main diagnosis either more specific or different to a minor degree at autopsy, other minor additional anomalies found at autopsy or other minor anomalies found by ultrasound and not confirmed by autopsy). (c) Main prenatal findings not confirmed or autopsy findings substantially different but the prognosis still correctly predicted. (d) Prenatal findings not confirmed, or main autopsy diagnosis was substantially different, and the prognosis was incorrectly predicted (autopsy findings less severe than the prenatal diagnosis, indicating that the information and advice given to the parents was incorrect).
Diagnoses of fetuses terminated because of prenatally detected CHD were validated individually by a cardiologist specialized in fetal cardiology (NV) and a fetal pathologist consultant (LLM). Diagnoses of infants born with prenatally detected CHD were validated individually by a cardiologist specialized in fetal cardiology (NV) and a pediatric cardiologist (JS). When disagreement in the validation occurred, the cases were discussed until agreement was achieved.
Statistical analysis Categorical data were presented as number (%) or proportion with confidence intervals (%, 95% CI).
RESULTS In Eastern Denmark, 86 121 infants were born in the period 01.01.2008–31.12.2010, 831 of them with CHD (0.96%). After exclusion of multiple pregnancies, infants with chromosome abnormalities, isolated atrial septum defect, isolated patent arterial duct and infants diagnosed with CHD more than 1 year after birth, the number of infants born with CHD was 389 (0.45%). Prenatal ultrasound scan descriptions were available in 373 infants. Seven of these were excluded, as the first scan in these pregnancies for unknown reasons was registered after the time for malformation scan. This resulted in a total number © 2014 John Wiley & Sons, Ltd.
Prenatal screening for CHD in a low risk population
of 366 included infants. Additionally, 42 fetuses conceived with CHD in the period were included: 41 terminations due to CHD and one intrauterine demise of a fetus with prenatally detected CHD. No spontaneously miscarried fetuses were diagnosed with CHD. Hence, a total number of 408 included fetuses were conceived with CHD, 135 of them with ‘Major CHD’ (Table 2). The number of prenatally detected CHD was 87 in the ‘all CHD’ group and 64 in the ‘Major CHD’ group, hence a prenatal detection rate at 21.3% (95% CI 17.6–25.6) and 47.4% (95% CI 39.2–55.8) in the two groups, respectively (Table 2). The distribution (infant/termination/intrauterine demise) of the fetuses with prenatally detected CHD is shown in Table 3. For validation of the cardiac malformation diagnoses, we were able to find autopsy reports for 32 out of 41 fetuses terminated because of CHD and postnatal echocardiography or surgery descriptions for 42 out of 45 infants born with prenatally detected CHD. There was full agreement between prenatal and postnatal findings in 64% (group A). Main prenatal findings were confirmed and the prognosis correctly predicted in 33% (group B). Main prenatal findings were not confirmed but the prognosis still correctly predicted in 3% (group C), and main prenatal findings were not confirmed, and the prognosis was incorrectly predicted in 1% (group D). In the two cases classified as group C, the prenatal diagnoses (case 1: tetralogy of Fallot with pulmonary atresia, case 2: complete transposition of the great arteries with ventricular septal defect) were confirmed and the prognosis correctly predicted, but in addition, the autopsies found bilateral vena cava in case 1 and juxta positioning of the atrial appendices in case 2. The one case scored to be in group D was prenatally diagnosed with an outlet ventricular septal defect in combination with a common arterial trunk, while the autopsy
327
report revealed a combination of an outlet ventricular septal defect and transposition of the great arteries. The correlation between NT thickness and CHD in our study population is shown in Table 4. NT thickness measurements were available in 349 out of 408 cases. The mother had chosen not to have a NT scan, had come too late or had a primary CVS in 36 cases, and NT thickness was not available for unknown reasons in 23 cases. Among the 349 cases with available NT values, 120 were in the ‘Major CHD’ group. In this group, 18 (15%) and 5 (4.2%) of the 120 had a NT thickness above the 95th percentile and 99th percentile, respectively. When looking at the type of scan, at which prenatally diagnosed CHD was detected, 2% of the ‘Major’ cases were detected at the NT scan, 14% at the early fetal echocardiography, 77% at the malformation scan, 1% at the late fetal echocardiography and 5% at another scan. Finally, Table 2 also shows that detection rates were more than 85% for four of the 10 ‘Major CHD’ diagnoses (hypoplastic left heart syndrome, hypoplastic right heart syndrome, common arterial trunk and isomerism with asplenia or polysplenia). The detection rates of the last six diagnoses were between 23.5% and 55.6% (complete transposition of the great arteries, double outlet right ventricle, atrioventricular septal defect, aortic coarctation, tetralogy of Fallot and congenitally corrected transposition of the great arteries).
DISCUSSION In this study, the prenatal detection rate for ‘Major CHD’ was 47.4% (95% CI 39.2–55.8). This is comparable with detection rates in other studies, which vary from 23% to 57%.4,5,7–10 The validation of the prenatal cardiac diagnoses showed a high degree of accuracy, as more than 95% of the diagnoses were
Table 2 Detection rates of congenital heart defects in the period 2008–2010 Conceived fetuses with CHD (n) (infants + intrauterine demise + terminations)
CHD detected prenatally (n) (infants + intrauterine demise + termiantions)
Prenatal detection rate (%)
95% CI
All CHD
408
87
21.3
17.6–25.6
Major CHDa
135
64
47.4
39.2–55.8
Individual Major CHDb
165
84
50.3
43.4–58.4
CTGA
31
13
41.9
26.4–59.3
DORV
18
10
55.6
33.7–75.5
AVSD
20
10
50.0
29.9–70.1
AC
34
8
23.5
12.2–40.2
TOF
20
5
25.0
10.8–47.3
ccTGA
2
1
50.0
9.5–90.6
HLHS
27
25
92.6
75.6–99.0
HRHS
7
6
85.7
46.7–99.5
CAT
4
4
100.0
45.4–100.0
IAP
2
2
100.0
29.0–100.0
CTGA, complete transposition of the great arteries; DORV, double outlet right ventricle; AVSD, atrioventricular septal defect; AC, aortic coarctation; TOF, tetralogy of Fallot; ccTGA, congenitally corrected transposition of the great ateries; HLHS, hypoplastic left heart syndrome; HRHS, hypoplastic right heart syndrome; CAT, Common arterial trunk; IAP, isomerism with asplenia or polysplenia. a See Table 1. b Some cases had more than one individual Major CHD diagnose, hence the difference in numbers between this line and the line above.
Prenatal Diagnosis 2015, 35, 325–330
© 2014 John Wiley & Sons, Ltd.
D. E. S. Jørgensen et al.
328
Table 3 Distribution (infant/termination/intrauterine demise) of conceived fetuses with congenital heart disease (CHD) prenatally detected Intrauterine demise of fetuses with CHD detected prenatally
Terminations due to CHD
Infants born with CHD detected prenatally
CHD detected prenatally (infants + intrauterine demise + terminations)
All CHD
1
41
45
87
Major CHDa
1
40
23
64
Individual Major CHDb
1
51
32
84
CTGA
0
7
6
13
DORV
0
7
3
10
AVSD
0
6
4
10
AC
0
0
8
8
TOF
0
1
4
5
ccTGA
1
0
0
1
HLHS
0
20
5
25
HRHS
0
4
2
6
CAT
0
4
0
4
IAP
0
2
0
2
CTGA, complete transposition of the great arteries; DORV, double outlet right ventricle; AVSD, atrioventricular septal defect; AC, aortic coarctation; TOF, tetralogy of Fallot; ccTGA, congenitally corrected transposition of the great arteries; HLHS, hypoplastic left heart syndrome; HRHS, hypoplastic right heart syndrome; CAT, Common arterial trunk; IAP, isomerism with asplenia or polysplenia. a See Table 1. b Some cases had more than 1 individual Major CHD diagnose, hence the difference in numbers between this line and the line above.
scored to be group A or B. It may be discussed whether the two cases in group C were correctly classified or should have been in group B, but the persons validating the diagnoses assessed them to be in group C as they would not categorize the additional findings as ‘minor’. The case in group D is instructive: Because the great vessels run in parallel, transposition of the great arteries may be interpreted as common arterial trunk, if the echocardiography is difficult and the separation is not seen. The surgical outcome is less favorable for common arterial trunk compared with arterial switch of transposition of the great arteries, because the common arterial trunk will need a homograft. The differentiation between the two diagnoses is important, as many families will consider abortion if a child is expected to have repeated surgeries instead of one radical operation. The validation results are in accordance with Khoo et al., a retrospective study of the efficiency of fetal echocardiography, which also found fetal echocardiography to be an accurate tool for prenatal diagnosis of CHD.21 The benefits of accurate prenatal diagnosis are multiple, in that it gives healthcare personnel and parents a reliable basis for decision making. In pregnancies that are not terminated, it gives optimal conditions for the newborn, its family
Table 4 Correlation between nuchal translucency thickness and congenital heart disease (CHD) All CHD Fetuses/infants with CHD
408
Nuchal translucency value available
349
Major CHDa 135 120
th
27 (7.7%)
18 (15.0%)
th
10 (2.9%)
5 (4.2%)
Nuchal translucency thickness >95 percentile Nuchal translucency thickness >99 percentile a
See Table 1 for definition.
Prenatal Diagnosis 2015, 35, 325–330
and the healthcare personnel regarding planning and treatment. Among the fetuses with a ‘Major CHD’, 15% (95% CI 9.6–22.6) had a NT thickness above the 95th percentile. These results indicate a modest effect of NT thickness as a screening tool for major cardiac defects. Increased NT is still though an important reason for high risk referral even though it results in a large number of patients referred for specialized fetal echocardiography. The marker is an essential complement to a screening strategy based on maternal history, where, for example, family history of CHD, maternal diabetes mellitus and intake of teratogenic medications will place 2–5% of women in a ‘high risk’ group but only detect 5–10% of all major cardiac defects.22 Our findings are in accordance with recent studies.22–26 It is, however, difficult to compare the results of these studies, because of varying definitions of ‘all CHD’, ‘Major CHD’, inclusion and exclusion criteria, background risk in the populations, methods for data collection, follow-up length, and different NT cut-offs. Nevertheless, it seems as though that the high detection rates found in earlier studies has declined to around 15–20%,16,22–29 although one study recently published a detection rate of 34%.30 If NT is combined with ductus venosus and tricuspid flow, it may be possible to increase the detection rate to more than 50%.31,32 Further investigation of this screening method would be interesting. We found that the majority of prenatally detected CHDs are identified at the malformation scan at 18–21 weeks, which in Denmark is performed by a sonographer. A minority of the prenatally detected CHDs was identified by a specialist echocardiography at 14 or 21 weeks offered in high risk pregnancies. This correlates with other studies showing that 10% of infants born with CHD have identifiable risk factors and that the majority of CHDs are found in unselected pregnancies.9,11 © 2014 John Wiley & Sons, Ltd.
Prenatal screening for CHD in a low risk population
We furthermore examined the detection rate according to the type of CHD and found that diagnoses mostly detected by the four-chamber view (hypoplastic left heart syndrome and hypoplastic right heart syndrome) had detection rates of more than 85%, while diagnoses mostly detected by the three-vessel view or outflow tracts (double outlet right ventricle, complete transposition of the great arteries and tetralogy of Fallot) all had lower detection rates. This tendency probably reflects the experience of the examiners, as the four-chamber view is the most basic scanning plane of the fetal heart, whereas the three-vessel view and outflow tracts are more advanced scanning planes not yet fully implemented at all hospitals as part of the routine scan. This study was partly based on registries and has limitations typical for this kind of studies. The three registries (the National Patient Registry, Medical Birth Registry and Danish Fetal Medicine Database) are, however, considered to be of high quality,33 and the files of all included cases were reviewed. We believe that all datasets in our study are reliable and complete. Another limitation of our study is that one (NV) of the three persons validating the diagnoses performed most of the prenatal echocardiographies. All validations were, however, performed by two persons, and therefore, we consider this a minor limitation. For practical reasons, the study was limited to Eastern Denmark. We have no reason to believe that rates would be different in the Western part of the country, as the prenatal screening program is the same throughout Denmark. In view of the results earlier, it is imperative to continue to improve the quality of CHD scans in the low risk population. The improvement of this offer in the Capital Region and Region Zealand has been – and still is – a continuum, and effort should be made to ensure an equal quality of fetal heart examinations across hospitals. The tendency of a high detection level in malformations detected by the four-chamber view and a lower detection level in malformations detected by the three-vessel view and outflow tracts indicates that the expertise of the sonographers has reached a certain level and that efforts must be made to take that expertise to the next level. Studies have shown that clinical experience has a significant impact on the examination of the fetal heart and
329
prenatal detection.8 We plan to optimize the detection of CHD through our education and supervision program for sonographers, as their routine scanning of the large low risk population is very important in identifying detectable CHDs. The objective is that all sonographers shall be certified in the second trimester scan, including performance of three-vessel view and outflow tracts, by the Fetal Medicine Foundation. In conclusion, nearly half of ‘Major CHDs’ were detected in this large unselected population. In experienced hands, the prenatal cardiac diagnoses showed a high degree of accuracy. We found the performance of increased NT thickness as a screening tool for CHD to be moderate, but it is an important high risk group for specialist examination. It may be improved by addition of ductus venosus and tricuspid flow measurements, and further investigation of this area is needed. The majority of prenatally detected CHDs were identified in the low risk population at the 18–21 weeks’ malformation scan performed by a sonographer and a minority detected because of extra scans performed by a doctor in high risk pregnancies. This indicates that it may not be possible to achieve a welldefined high risk population. A future optimization of the detection of CHD may have this aspect in mind, and continuous education and supervision of the sonographers should be prioritized. WHAT’S ALREADY KNOWN ABOUT THIS TOPIC? • The prenatal detection rate of congenital heart disease (CHD) is low compared with other fetal malformations.
WHAT DOES THIS STUDY ADD? • Nearly half of ‘Major CHDs’ were detected prenatally. The prenatal cardiac diagnoses showed a high degree of accuracy. NT thickness performed moderately as screening tool for CHD.
Ethics approval The Danish Data Protection Agency, the Danish National Board of Health and the Research Committee of the DFMD approved this study.
REFERENCES 1. Karsdorp PA, Everaerd W, Kindt M, Mulder BJ. Psychological and cognitive functioning in children and adolescents with congenital heart disease: a meta-analysis. J Pediatr Psychol 2007;32(5):527–41. 2. Makrydimas G, Sotiriadis A, Ioannidis JP. Screening performance of first-trimester nuchal translucency for major cardiac defects: a metaanalysis. Am J Obstet Gynecol 2003;189(5):1330–5. 3. Zomer AC, Vaartjes I, Grobbee DE, Mulder BJ. Adult congenital heart disease: new challenges. Int J Cardiol 2013;163(2):105–7. 4. Crane JP, LeFevre ML, Winborn RC, et al. A randomized trial of prenatal ultrasonographic screening: impact on the detection, management, and outcome of anomalous fetuses. The RADIUS Study Group. Am J Obstet Gynecol 1994;171(2):392–9. 5. Grandjean H, Larroque D, Levi S. The performance of routine ultrasonographic screening of pregnancies in the Eurofetus Study. Am J Obstet Gynecol 1999;181(2):446–54.
Prenatal Diagnosis 2015, 35, 325–330
6. Pinto NM, Keenan HT, Minich LL, et al. Barriers to prenatal detection of congenital heart disease: a population-based study. Ultrasound Obstet Gynecol 2012;40(4):418–25. 7. Stefos T, Plachouras N, Sotiriadis A, et al. Routine obstetrical ultrasound at 18– 22 weeks: our experience on 7,236 fetuses. J Matern Fetal Med 1999;8(2):64–9. 8. Tegnander E, Eik-Nes SH. The examiner’s ultrasound experience has a significant impact on the detection rate of congenital heart defects at the second-trimester fetal examination. Ultrasound Obstet Gynecol 2006;28(1):8–14. 9. Tegnander E, Williams W, Johansen OJ, et al. Prenatal detection of heart defects in a non-selected population of 30,149 fetuses – detection rates and outcome. Ultrasound Obstet Gynecol 2006;27(3):252–65. 10. Vial Y, Tran C, Addor MC, Hohlfeld P. Screening for foetal malformations: performance of routine ultrasonography in the population of the Swiss Canton of Vaud. Swiss Med Wkly 2001;131(33–34):490–4.
© 2014 John Wiley & Sons, Ltd.
330
11. Bonnet D, Coltri A, Butera G, et al. Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality. Circulation 1999;99(7):916–18. 12. Tworetzky W, McElhinney DB, Reddy VM, et al. Improved surgical outcome after fetal diagnosis of hypoplastic left heart syndrome. Circulation 2001;103(9):1269–73. 13. Ekelund CK, Jorgensen FS, Petersen OB, et al. Impact of a new national screening policy for Down’s syndrome in Denmark: population based cohort study. BMJ 2008;337:a2547. 14. Ekelund CK, Andersen HJ, Christensen J, et al. Down’s syndrome risk assessment in Denmark – secondary publication. Ugeskr Laeger 2010;172(23):1759–61. 15. ISOUG Education Committee. Cardiac screening examination of the fetus: guidelines for performing the ‘basic’ and ‘extended basic’ cardiac scan. Ultrasound Obstet Gynecol 200627(1):107–13. 16. Souka AP, Von Kaisenberg CS, Hyett JA, et al. Increased nuchal translucency with normal karyotype. Am J Obstet Gynecol 2005;192(4):1005–21. 17. Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health 2011;39(7 Suppl):30–3. 18. Knudsen LB, Olsen J. The Danish Medical Birth Registry. Dan Med Bull 1998;45(3):320–3. 19. Ekelund CK, Skovbo P, Holmskov A, et al. Development and establishment of a national Danish fetal medicine database for quality surveillance and research. 2014 [WWW document]. URL http://onlinelibrary.wiley.com/doi/ 10.1002/uog.7151/full [accessed on 5 april 2014] 20. Hauerberg L, Skibsted L, Graem N, Maroun LL. Correlation between prenatal diagnosis by ultrasound and fetal autopsy findings in secondtrimester abortions. Acta Obstet Gynecol Scand 2012;91(3):386–90. 21. Khoo NS, Van EP, Richardson M, Robertson T. Effectiveness of prenatal diagnosis of congenital heart defects in South Australia: a population analysis 1999–2003. Aust N Z J Obstet Gynaecol 2008;48(6):559–63. 22. Mogra R, Alabbad N, Hyett J. Increased nuchal translucency and congenital heart disease. Early Hum Dev 2012;88(5):261–7.
Prenatal Diagnosis 2015, 35, 325–330
D. E. S. Jørgensen et al.
23. Clur SA, Ottenkamp J, Bilardo CM. The nuchal translucency and the fetal heart: a literature review. Prenat Diagn 2009;29(8):739–48. 24. Muller MA, Clur SA, Timmerman E, Bilardo CM. Nuchal translucency measurement and congenital heart defects: modest association in lowrisk pregnancies. Prenat Diagn 2007;27(2):164–9. 25. Simpson LL, Malone FD, Bianchi DW, et al. Nuchal translucency and the risk of congenital heart disease. Obstet Gynecol 2007; 109(2 Pt 1):376–83. 26. Westin M, Saltvedt S, Bergman G, et al. Is measurement of nuchal translucency thickness a useful screening tool for heart defects? A study of 16,383 fetuses. Ultrasound Obstet Gynecol 2006;27(6):632–9. 27. Hafner E, Schuller T, Metzenbauer M, et al. Increased nuchal translucency and congenital heart defects in a low-risk population. Prenat Diagn 2003;23(12):985–9. 28. Hyett J, Perdu M, Sharland G, et al. Using fetal nuchal translucency to screen for major congenital cardiac defects at 10–14 weeks of gestation: population based cohort study. BMJ 19999;318(7176):81–5. 29. Mavrides E, Cobian-Sanchez F, Tekay A, et al. Limitations of using first-trimester nuchal translucency measurement in routine screening for major congenital heart defects. Ultrasound Obstet Gynecol 2001;17(2):106–10. 30. Syngelaki A, Chelemen T, Dagklis T, et al. Challenges in the diagnosis of fetal non-chromosomal abnormalities at 11–13 weeks. Prenat Diagn 2011;31(1):90–102. 31. Chelemen T, Syngelaki A, Maiz N, et al. Contribution of ductus venosus Doppler in first-trimester screening for major cardiac defects. Fetal Diagn Ther 2011;29(2):127–34. 32. Pereira S, Ganapathy R, Syngelaki A, et al. Contribution of fetal tricuspid regurgitation in first-trimester screening for major cardiac defects. Obstet Gynecol 2011;117(6):1384–91. 33. Klemmensen AK, Olsen SF, Osterdal ML, Tabor A. Validity of preeclampsiarelated diagnoses recorded in a national hospital registry and in a postpartum interview of the women. Am J Epidemiol 2007;166(2):117–24.
© 2014 John Wiley & Sons, Ltd.
![[Prenatal screening of congenital heart defects in population at low risk of congenital defects. A reality today].](/assets/img/hold.png)
