Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe

Authors


Abstract

Objectives

Ultrasound scan in the mid-trimester of pregnancy is now a routine part of prenatal care in most European countries. The objective of this study was to evaluate the prenatal diagnosis of dysmorphic syndromes by fetal ultrasound examination.

Methods

Data from 20 registries of congenital malformations in 12 European countries were included in the study.

Results

There were 2454 cases with congenital heart diseases, 479 of which were recognized syndromes, including 375 chromosomal anomalies and 104 syndromes without chromosomal anomalies. Fifty-one of the 104 were detected prenatally (49.0%). One hundred and ninety-two of 1130 cases with renal anomalies were recognized syndromes, including 128 chromosomal anomalies and 64 syndromes without chromosomal anomalies; 162 of them (84.4%) were diagnosed prenatally, including 109 chromosomal anomalies and 53 non-chromosomal syndromes. Fifty-four of the 250 cases with limb defects were recognized syndromes, including 16 chromosomal syndromes and 38 syndromes without chromosomal anomalies; 21 of these 54 syndromes were diagnosed prenatally (38.9%), including 9 chromosomal syndromes. There were 243 cases of abdominal wall defects including 57 recognizable syndromes, 48 with omphalocele and 9 with gastroschisis; 48 were diagnosed prenatally (84.2%). Twenty-six of the 187 cases with diaphragmatic hernia had recognized syndromes, including 20 chromosomal aberrations and 6 syndromes without chromosomal anomalies. Twenty-two of them (84.6%) were detected prenatally. Sixty-four of 349 cases with intestinal anomalies were recognized syndromes; 24 were diagnosed prenatally (37.5%). There were 553 cases of cleft lip and palate (CL(P)) and 198 of cleft palate (CP) including 74 chromosomal anomalies and 73 recognized non-chromosomal syndromes. Prenatal diagnosis was made in 51 cases of CL(P) (53.7%) and 7 of CP (13.7%). Twenty-two of 188 anencephalic cases were syndromic and all were diagnosed prenatally. Of 290 cases with spina bifida, 18 were recognized syndromes, and of them 17 were diagnosed prenatally. All 11 syndromic encephaloceles were diagnosed prenatally.

Conclusions

Around 50% of the recognized syndromes which are associated with major congenital anomalies (cardiac, renal, intestinal, limb defects, abdominal wall defects and oral clefts) can be detected prenatally by the anomaly scan. However the detection rate varies with the type of syndrome and with the different countries' policies of prenatal screening. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

Introduction

Ultrasound scans for the detection of congenital malformations are now a routine part of prenatal care in most European countries. As technology and skill improve more fetal malformations are recognized1–4. There are many reports of prenatal detection of malformation in high-risk groups but few studies have been reported on the effectiveness of routine anomaly testing in unselected populations5. For example, many cardiac malformations are amenable to prenatal diagnosis but general screening of low-risk populations shows a low detection rate, from 14 to 45%6–9. Some dysmorphic syndromes affecting face or skull and/or hands, feet, ears, and external genitalia can be diagnosed prenatally by ultrasound examination, for example, trisomy 13, trisomy 18 and thanatophoric dwarfism, but others with milder features are more difficult to detect prenatally, for example, 22q11 deletion (Di George syndrome)10 and Crouzon syndrome.

The objective of this study was to evaluate the prenatal diagnosis of dysmorphic syndromes across Europe by routine fetal ultrasound examination.

Material and methods

Data were provided by 20 congenital malformation registries, 18 of which are population-based, from 12 European countries (Table 1). Sixteen of them collaborate in the EUROCAT program, use the same epidemiological methodologies, and their general characteristics have been previously described11. The remaining registries used the same coding system with multiple sources of ascertainment and active case finding11. Included in this study were all live births, still births and terminations of pregnancy with a major malformation, defined as a structural abnormality detectable by ultrasound, diagnosed prenatally or within 7 days of birth. Routine prenatal ultrasound screening for congenital malformations was performed in all registry areas except in Denmark and in The Netherlands. In countries with more than one ultrasound screening offered (Table 2), the additional scan performed in the first and/or third trimesters of pregnancy was mainly for biometric purposes. The sonography was performed by trained operators. Cases with prenatally suspected malformations detected in a district hospital were referred for confirmation to a specialist center.

Table 1. Details of registries participating in the study
RegistryStudy period (months)Births (n)Malformed (n)Prenatal detection rate (n (%))
  1. N, Northern; SW, South-west; NE, North-east.

Funen County, Odense, Denmark18  8788  8925 (28.1)
Groningen, N Netherlands30 34 085 438100 (22.8)
Rotterdam, SW Netherlands18 47 895 18650 (26.9)
Paris, France 9 27 550 592399 (67.4)
Strasbourg, France30 33 155 648335 (51.7)
Lausanne, Switzerland30 18 907 351202 (57.5)
Croatia30 10 718 11522 (19.1)
Basque Country, Spain24 32 429 405220 (54.3)
Barcelona, Spain18 19 357 206135 (65.5)
El Valles, Spain30  5737 10868 (63.0)
Styria, Austria30 29 026 246129 (52.4)
Lithuania30 95 469 807193 (23.9)
SW Ukraine30 44 761 342115 (33.6)
NE Italy, Italy30111 719 818305 (37.3)
Sicily, Italy30 25 339 280100 (35.7)
Tuscany, Italy30 67 1201044332 (31.8)
Mainz, Germany30  9535 274141 (51.5)
Leipzig, Germany30  8745  7161 (85.9)
Wessex, UK30 65 559 859482 (56.1)
Oxford, UK30 13 136 247187 (75.7)
Total 709 03081263601 (44.3)
Table 2. Current practice in the participating registries
PracticeRegistry
  1. TOP, termination of pregnancy; E, early i.e. around 10 weeks of gestation, for biometric purposes; L, late i.e. around 30 weeks of gestation, for biometric purposes; SW, South-west; NE, North-east.

Number of ultrasound examinations
 One examination
  18–22 weeksOxford, Wessex (UK)
 Two examinations
  E + 20–22 weeksLausanne (Switzerland)
  L + 16–20 weeksStyria (Austria), SW Ukraine
  E + 16–18 weeksLithuania
 Three examinations
  E + L + 18–22 weeksSicily, Tuscany, NE Italy (Italy), Mainz, Leipzig (Germany)
  E + L + 18–20 weeksBasque Country, Barcelona, El Valles (Spain), Croatia
  E + L + 18–24 weeksStrasbourg, Paris (France)
 Not routineFunen County (Denmark), Groningen, Rotterdam (The Netherlands)
TOP: upper gestational age limit
 NoneFrance, Germany, UK
 22–24 weeksSpain, Lithuania, Croatia, Italy, Denmark, The Netherlands, Switzerland, Austria
 28 weeksUkraine

Termination of pregnancy after prenatal diagnosis of major congenital malformation has no upper gestational age limit in France, Germany and the UK. In the other countries it was allowed in the second trimester of pregnancy in all registry areas, with upper gestational age limits ranging between 22 and 28 weeks.

The ICD/BPA 9 coding system12 was used by all participating registries for diagnosis. For the purpose of this study all forms coded 74 000 to 75 999 were included in the analysis. Validation was performed at local and at central database levels11. Protection of privacy was assured, so confidentiality is preserved.

The malformations were classified as isolated when only one malformation was present and as non-isolated when one or more additional malformations were diagnosed. Non-isolated anomalies were subdivided into chromosomal if associated with a chromosomal anomaly, syndromic if the malformation was part of a non-chromosomal malformation syndrome, or multiple if at least one other major malformation was present in non-syndromic cases.

The study period was 1 July 1996 to 31 December 1998 but not all registries covered the whole time period. The total number of births in the registry areas was 709 030, including 8126 malformed children (Table 1).

Results

We report the dysmorphic syndromes in categories of congenital anomalies.

Congenital heart diseases

There were 2454 cases with congenital heart diseases and 479 of them had recognized syndromes; 375 of these had chromosomal anomalies including 345 common anomalies (Table 3) and 104 had normal chromosomes. These included 28 22q11 deletions (42.9% were prenatally detected); 17 situs inversus (64.7% were prenatally detected); 15 VATER association (46.7% were prenatally diagnosed); 4 Noonan syndrome, 4 fetal alcohol syndrome, 3 CHARGE association, and 33 others (47.7% (21/44) of these were detected prenatally) (Table 4).

Table 3. Chromosomal anomalies with congenital heart defects (CHD)
CHDTrisomy 21Trisomy 18Trisomy 13Turner syndrome
  1. AVSD, atrioventricular septal defect; VSD, ventricular septal defect; ASD, atrial septal defect; COA, coarctation of aorta; Complex, association of two or more CHD. Other includes hypoplastic left heart, double outlet right ventricle, pulmonary atresia, aortic atresia, aortic stenosis and unspecified CHD.

AVSD 76 4 2 
VSD 6838 6 
ASD 51 4 1 
Single ventricle  1 2  
Tetralogy of Fallot  4  4 
COA   3 7
Complex cardiopathy  3 3 5 1
Other 36 813 5
Total239593413
Table 4. Non-chromosomal recognized syndromes with congenital heart defects (CHD)
nSyndromeCHDPNDTOP (n)
n(%)
  1. PND, prenatal diagnosis; TOP, termination of pregnancy; VSD, ventricular septal defect; HLH, hypoplasia left heart; ASD, atrial septal defect; AVSD, atrioventricular septal defect; Complex, association of two or more CHD; TGA, transposition of great arteries; PS, pulmonary stenosis; Fallot, tetralogy of Fallot.

28Deletion 22q1125 conotruncal, 3 VSD1242.9 7
1Aarskog syndromeVSD 0  
1Acardia-anencephaly  1  1
1Amniotic band syndromeHLH 1  1
2Pentalogy of Cantrell2 exstrophy of heart   2
1Cerebro-costo-mandibular syndromeVSD 1  
3CHARGE association2 VSD, ASD 0  
2Chondrodysplasia punctata (rhizomelic)2 VSD 1  
2Ellis–Van Creveld syndromeVSD, AVSD 2  1
4Fetal alcohol syndrome3 VSD, 1 ASD 2  1
1Franceschetti syndromeVSD 0  
2Fryns syndrome2 VSD 2  1
1Goldenhar syndromeVSD 0  
1Greig syndromeASD 1  
2Holt–Oram syndromeASD, complex CHD 0  
17Situs inversus5 dextrocardia, AVSD, 2 TGA, 2 ASD, 5 complex, HLH, VSD1164.7 9
1Multiple pterygium syndromeASD 0  
1Neonatal marfan syndromeComplex 0  
4Noonan syndrome3 PS, 1 complex 2  
2Orofaciodigital syndrome1 complex, 1 VSD 2  1
2Pierre Robin sequence1 ASD, 1 VSD 0  
1Prader–Willi syndromeVSD 0  
1Roberts syndromeComplex 1  1
1Robinow syndromeVSD 0  
1Simson–Golabi–Behmel syndromeASD 1  
4Skeletal dysplasia1 complex, 2 VSD, 1 ASD 3  2
1Smith-Lemli–Opitz syndrome type 21 complex 1  
15VATER association3 Fallot, 5 complex, 2 tricuspid atresia, 3 ASD, 2 VSD 746.7 5
1Zellweger syndromeVSD 0  
Total 104  5149.032

Eighty-six of the 375 cases with chromosomal anomalies were terminated (22.9%).

Renal malformations

There were 1130 cases with renal anomalies and 192 of them had recognized syndromes; 128 of these were chromosomal aberrations and 64 had normal chromosomes. Of the 192 with recognized syndromes, 162 (84.4%) were diagnosed prenatally, including 109 with chromosomal aberrations and 53 with normal chromosomes (Table 5).

Table 5. Chromosomal anomalies and non-chromosomal recognized syndromes associated with renal malformations
MalformationnPND (n)TOP (n)
  1. PND, prenatal diagnosis; TOP, termination of pregnancy.

Chromosomal anomalies
 Numeric aberrations
  Trisomy 18 31 2421
  Trisomy 21 28 2120
  Trisomy 13 21 1814
  Monosomy X 17 158
  Triploidy 15 1513
  Trisomy 22  2  2 1
  Tetraploidy  1  1 1
  Trisomy 16  1  1 1
 Structural aberrations
  Translocations  4  4 1
  Deletions  3  3 1
  Duplications  1  1 0
  Others  4  4 2
Total12810983
Non-chromosomal syndromes
 VA(C)TER(L) 15 11 7
 Meckel–Gruber 13 1312
 Osteochondrodysplasias 12  8 4
 Caudal regression  5  4 4
 Megacystis-microcolon  3  3 0
 Di George  2  2 1
 Fetal alcohol  2  0 0
 Others 12 12 3
Total 64 5331

Limb reduction defects

There were 250 cases with limb reduction defects and 54 of them had recognized syndromes; 16 of these were chromosomal syndromes (Table 6) and 38 had normal chromosomes (Table 7). Of the 54 with recognized syndromes, 21 (38.9%) were diagnosed prenatally, including 9 chromosomal syndromes and 12 with normal chromosomes. Of the 16 recognized chromosomal syndromes (Table 6), 5 had terminal transverse limb reduction defects and 7 were longitudinal deficiencies including 5 radial aplasias. Nine were detected prenatally (75%) and 8 pregnancies were terminated. All 12 of the prenatally diagnosed cases with normal chromosomes were terminated.

Table 6. Chromosomal anomalies with limb reduction defects (LRD)
LRDChromosomal anomaly (n)
Trisomy 18Trisomy 21KlinefelterTriple XDeletion 3qDeletion 7qTranslocation t(5;14) (p13;q13)Isochromosome 12p
Terminal1 11 11 
Intercalary        
Longitudinal7       
Split    1   
Short limbs       1
Short femur 2      
Table 7. Non-chromosomal recognized syndromes with associated limb reduction defects (LRD)
nSyndromeLRDPND (n)TOP (n)
  1. PND, prenatal detection; TOP, termination of pregnancy; FFU, femur–fibula–ulna; TAR, radial aplasia–thrombocytopenia syndrome.

7Amniotic band7 terminal 1 1
6VATER1 intercalary, 3 terminal, 1 phocomelia, 1 amelia 2 2
3Caudal regression3 terminal 2 2
1Adams OliverTerminal 0 0
1AarskogShort limbs 0 0
1AcardiacAmelia 1 1
1Ulnar-mammaryLongitudinal 0 0
2De LangeTerminal 1 1
1Fanconi anemiaTerminal 1 1
1FFULongitudinal 0 0
2HanhartTerminal 0 0
1Holt OramTerminal 0 0
3Limb–body wallTerminal 2 2
1RobertsTerminal 0 0
1Orofaciodigital type IIIntercalary 1 1
2PolandTerminal 0 0
1Carey-Fineman-ZiterTerminal 0 0
2TARLongitudinal 1 1
Total 38  1212

Abdominal wall defects

There were 243 cases of abdominal wall defects and 57 of them had recognized syndromes, 48 with omphalocele and 9 with gastroschisis. Among the 48 with omphalocele, there were 34 chromosomal syndromes, 5 omphalocele-exstrophy-imperforate anus-spinal defects (OEIS), 2 caudal regression, 2 osteochondrodysplasia and 5 others: De Lange, amniotic band, megacystic-microcolon, schisis association, and Beckwith-Wiedemann. Among the 9 with gastroschisis, there were 4 limb-body wall complex, 2 amniotic band, 1 OEIS and 2 chromosomal aberrations: one trisomy 21 and one trisomy 13. Forty-eight of these 57 recognized syndromes were diagnosed prenatally (84.2%) (Table 8).

Table 8. Chromosomal anomalies and non-chromosomal recognized syndromes associated with omphalocele and gastroschisis
 Omphalocele (n)PND (n)TOP (n)Gastroschisis (n)PND (n)TOP (n)
  1. PND, prenatal detection; TOP, termination of pregnancy; OEIS, omphalocele-exstrophy-imperforate anus-spinal defects.

Chromosomal anomalies
 Trisomy 21 1 0 0111
 Trisomy 13 5 4 3111
 Trisomy 18211716   
 Trisomy 16 1 1 1   
 Additional 15 1 1 1   
 Turner (45,X) 1 1 0   
 Deletion 18p 1 1 1   
 Deletion 21p 1 0 0   
 Triploidy 2 2 1   
 Total342723222
Non-chromosomal syndromes
 OEIS 5 3 0110
 Skeletal dysplasia 2 2 2   
 Caudal regression 2 2 2   
 Cornelia de Lange 1 1 0   
 Amniotic band 1 1 1222
 Megacystis-microcolon 1 1 0   
 Schisis association 1 1 1   
 Limb–body wall   444
 Beckwith–Wiedemann 1 1 0   
 Total1412 6776

Diaphragmatic hernia

There were 187 cases of congenital diaphragmatic hernia (CDH). Of these, 116 had isolated CDH, 45 had multiple malformations but no recognized syndrome and 26 had recognized syndromes; 20 of these were chromosomal aberrations and 6 were syndromes without chromosomal anomalies (Table 9). Sixteen of the 20 (80%) chromosomal anomalies were detected prenatally as were all 6 non-chromosomal syndromes (100%). Termination of pregnancy was performed in 11 of the cases with chromosomal anomalies and in 4 of the 6 syndromes without chromosomal anomalies.

Table 9. Chromosomal anomalies and non-chromosomal recognized syndromes associated with diaphragmatic hernia
Diagnosisn
Chromosomal anomalies
 Trisomy 18 8
 Trisomy 13 3
 Trisomy 21 1
 45,X 1
 45,X/46,XX 1
 Other karyotype anomalies 6
Non-chromosomal syndromes
 Fryns 3
 Cornelia de Lange 1
 Meckel–Gruber 1
 VATER association 1
Total26

Intestinal anomalies

There were 349 cases with intestinal anomalies and 64 of them were recognized syndromes, 24 of which were diagnosed prenatally (37.5%). Thirty-two of the 64 were chromosomal anomalies and 32 had normal chromosomes (Table 10). Termination of pregnancy was performed in 4 of the 20 with trisomy 21, in 4 of the 8 with trisomy 18, in the 2 with trisomy 13 and in the 1 with deletion 7q. Among the syndromes without chromosomal anomalies there were 13 VATER association, 4 of which were diagnosed prenatally, 4 caudal regression and 4 OEIS.

Table 10. Chromosomal anomalies and non-chromosomal recognized syndromes associated with intestinal atresia
 EsophagusDuodenumSmall intestineLarge intestineTotal n
nPND (n)TOP (n)nPND (n)TOP (n)nPND (n)TOP (n)nPND (n)TOP (n)
  1. PND, prenatal diagnosis; TOP, termination of pregnancy; OEIS, omphalocele-exstrophy-imperforate anus-spinal defects; TAR, radial aplasia–thrombocytopenia syndrome.

Chromosomal anomalies
 Trisomy 21 1001444100 40020
 Trisomy 18 633 111100    8
 Trisomy 13          222 2
 Triploidy          100 1
 Deletion 7q          111 1
 Total 7331555200 83332
Non-chromosomal syndromes
 VATER1044       30013
 Caudal regression          422 4
 OEIS 100       311 4
 Chondrodystrophia (Majewski)          111 1
 Osteogenesis imperfecta type III 100          1
 Fryns    111       1
 Limb–body wall          111 1
 Fetal alcoholism          100 1
 TAR 110          1
 CHARGE          100 1
 Fanconi anemia    110       1
 Orofaciodigital type II      111    1
 Di George 100          1
 Goldenhar          100 1
 Total1454 221111155532

Cleft lip and palate and cleft palate

There were 553 cases with cleft lip and palate (CL(P)) and 198 with cleft palate (CP) including 74 chromosomal aberrations, of which 66 were common anomalies, and 49 common recognized syndromes without chromosomal anomalies (Table 11). Fifty-one cases of CL(P) (53.7%) and 7 cases of CP (13.7%) were diagnosed prenatally.

Table 11. Common chromosomal anomalies and non-chromosomal recognized syndromes associated with cleft lip/palate (CL(P)) and cleft palate (CP)
 nCL(P)CP
PNDTOP nPNDTOP n
n%n%
  1. PND, prenatal diagnosis; TOP, termination of pregnancy.

Chromosomal syndromes
 Trisomy 134132/3397.0198/81003
 Trisomy 18137/1353.9 80  
 Autosomal deletions 54/4  21/1 1
 Trisomy 21 31/2  10/1 0
 Triploidy 44/4  40  
 Total6648/56 349/10 4
Non-chromosomal syndromes
 Pierre Robin230/2  02/219.50
 Holoprosencephaly1111/11100 50  
 Amniotic band 74/5  42/2 2
 Meckel–Gruber 43/3  31/1 1
 Orofaciodigital 21/1  11/1 1
 Van der Woude 21/2  00  
 Total4920/24 136/25 4

Neural tube defects

There were 188 anencephalic cases and 22 of them were syndromic (Table 12). All were detected prenatally and 21 of them were terminated. There were 290 cases with spina bifida and 18 of them were recognized syndromes; 15 were chromosomal syndromes, all detected prenatally, and 3 were without chromosomal anomalies, including one osteogenesis imperfecta not detected prenatally. All 11 of the syndromic encephaloceles were diagnosed prenatally.

Table 12. Chromosomal anomalies and non-chromosomal recognized syndromes associated with neural tube defects
 nPND (n)TOP (n)
  1. PND, prenatal diagnosis; TOP, termination of pregnancy; OEIS, omphalocele-exstrophy-imperforate anus-spinal defects.

Anencephaly
 Amniotic band776
 Facial cleft333
 Abdominal wall defects777
 Diaphragmatic hernia333
 Renal agenesis111
 46,XX,der (3)111
Spina bifida
 Osteogenesis imperfecta100
 Meckel–Gruber111
 OEIS111
 Trisomy 18664
 Trisomy 13444
 Trisomy 9111
 Triploidy332
 22q-110
Encephalocele
 Amniotic band333
 Meckel–Gruber555
 Schisis association111
 Trisomy 18221

Discussion

Most birth defects occur in an unpredictable way in couples having no prior risk. Routine ultrasound screening offered to all women provides a potential means for their detection13.

There have been many studies on prenatal diagnosis by ultrasound examination in high-risk groups1–3, 5, 14, but few studies have been done on routine prenatal screening at the population level15–17. Due to widely different levels of expertise and equipment, there is a large discrepancy in the results of such screening13, with prenatal detection rates ranging from 0 to 60% for congenital heart disease16. An overview of the European experience shows a detection rate of about 28% for major congenital anomalies18. The purpose of the Eurofetus study, which was performed in 61 obstetric units over a 3-year period (1990–1993) was to evaluate the prenatal detection of malformations by routine ultrasound examination in unselected populations3. Overall 55% of the major abnormalities were detected in 3685 fetuses. The detection rate varied from 88.3% for the central nervous system to 38.8% for the heart and great vessels. However, the Eurofetus study was not population-based and so cannot be compared with the current study. In this report 709 030 fetuses were screened. Our calculations for detection rate of structural defects by routine ultrasound examination used data from congenital anomalies registers, 18/20 of which were population-based. Several studies involving most or all 20 of the registries have already been published which indicate that the detection rate varies widely between registries: 62–97% for neural tube defects19, 11–48% for congenital heart disease20, 21, 0–64% for limb reduction defects22, 7–55% for cleft lip and palate23, 16–45% for chromosomal anomalies24, 38–72% for gastrointestinal anomalies25, 46–100% for omphalocele and 50–100% for gastroschisis26, and 36–96% for renal anomalies (unpubl. data) despite the fact that the participating registries used the same methodology. How can such a large variation be explained? Variations in detection rate may result from differences in operator skill, equipment used, or the gestational age at which examinations are done8.

As the policies regarding prenatal scanning were country-specific (Table 2), it is possible to assess the diverse policies in Europe. As can be seen in Table 1, those registries in countries with no routine scanning policy (The Netherlands and Denmark) had some of the lowest detection rates. The highest detection rates were found in the registries of three European countries with three routine scans (France, Germany and Spain) and in the UK registries, where there is only one routine anomaly scan between 18 and 22 weeks of gestation. In the five other European countries there is also only one anomaly scan to search for congenital anomalies between 16 and 22 weeks of gestation and one or two scans for biometric purposes, in early and/or in late pregnancy.

Detection rate varies with the type of syndrome and increases with increasing numbers of abnormalities in the fetus. For all categories of congenital anomalies apart from renal ones, the detection rate is much higher for associated anomalies, (when the fetus has two or more congenital anomalies) than it is for isolated anomalies27.

The reason for adopting a routine scanning policy is not to increase the termination of pregnancy rate but to provide information and the best care for the fetus and for the mother. In some cases prenatal diagnosis may provide optimum care for the delivery of the liveborn infant and may help prepare the parents for the birth of an affected infant.

This study focused on the prenatal detection of syndromes. It is therefore difficult to compare these results with those of studies which studied the overall outcome of liveborn infants over a long period after birth. For example, concerning the most frequent congenital anomalies, cardiac defects, Meberg et al.28 studied the main outcomes of congenital heart defects in an unselected population of 35 218 liveborn infants over the 15-year period 1982–1996, 3–18 years after birth. Of 360 children with congenital heart defects, 72 (20%) had congenital heart defects associated with chromosomal disorders, other recognizable syndromes or extracardiac malformations. Trisomy 21 accounted for 15 (20.8%) of these. In our series, 479 of 2454 cases with congenital heart defects had recognized syndromes including 375 chromosomal anomalies of which 239 were trisomy 21 (49.9% of those with recognized syndromes), twice as many as in the study of Meberg et al.28. This difference is due to the fact that in our series many cases were diagnosed prenatally and the pregnancy was terminated; 86 of 375 cases with chromosomal anomalies were terminated (22.9%).

In the series of Meberg et al.28 non-isolated disorders occurred significantly less often in children with ventricular septal defects (24/211 = 11.4%) than they did in children with other types of congenital heart defect. In our series, 276 (36.2%) of 761 cases of non-isolated congenital heart defect had ventricular septal defect.

In interpreting these results one should take into consideration the limitations and strengths of the study. The registries participating in this study are selected registries from each country. For example, in France only two of four congenital anomalies registries participated in this study, similarly for Germany, Spain and Italy. Some of the variations seen in types of malformation and their detection rates may have been due to the fact that some of the participating registries cover a small population. The sensitivity of prenatal diagnosis depends on when, where, by whom and on whom the screening is performed. Higher detection rates may be obtained by trained sonographers using the most recent equipment and working on women at high risk for birth defects. The timing of screening is an important factor to take into consideration as screening in early pregnancy may miss the detection of certain malformations that become apparent later in pregnancy and may thus reduce the overall sensitivity of sonographic screening. Some congenital anomalies, for example congenital heart disease and intestinal and renal malformations, are not apparent at birth or during the first week of postnatal life. Therefore, their detection rates may be overestimated. The gestational age at the time of ultrasound examination was not the same for all the registries participating in this study. This may account for some of the discrepancies between countries.

Major strengths of this study are that it evaluated large numbers of births, that it was population-based and that participating registries used the same epidemiological methods. Case fetuses/infants were actively ascertained through multiple sources from geographically defined residential populations. The same definitions and coding system for the malformations were used by all participants. The validation was performed at a local and at a central database level, and analysis of the data was performed centrally.

In conclusion, this study categorized different types of anomaly (e.g. cardiac, renal, gastrointestinal) and identified those with a syndrome to determine the number identified prenatally by ultrasound examination. Some syndromes will not have been identified because they will not have been diagnosed until after the first week of postnatal life. However, it is clear that prenatal ultrasound screening allows diagnosis of a large proportion of chromosomal syndromes and recognized syndromes without chromosomal anomalies. In fetuses with associated congenital anomalies the main purpose of prenatal diagnosis is to give parents as much information about the likely outcome and prognosis as possible.

Acknowledgements

This work was a BIOMED 2 Concerted Action, funded by the European Union.

Appendix

Members of the Euroscan study group:

  • Participants and registries of congenital malformation contributing to the Euroscan study of prenatal diagnosis of congenital anomalies by fetal ultrasonographic examination: Austria (Styria) Häusler M; Croatia (Zagreb) Barisic I , Matejic R; Denmark (Funen County) Garne E; France (Paris) De Vigan C, Vodovar V; (Strasbourg) Stoll C, Alembik Y, Dott B; Germany (Leipzig) Froster UG ; (Mainz) Queisser-Luft A, Wiesel A; Italy (North-east Italy) Tenconi R, Clementi M, Benedicenti F ; (Sicily) Bianca S, Ettore G ; (Tuscany) Cariati E, Bianchi F ; Lithuania : Kucinskas V, Utkus A; Netherlands (Northern Netherlands) De Walle HEK ; (South-west Netherlands) Zandwijken GRJ; Spain (Basque Country) Garcia-Minaur S, Aranguren G ; (Barcelona) Joaquim S ; (El Valles) Baena N; Switzerland (Lausanne) Addor MC, Pescia G; South-west Ukraine (Vinnitsa) Oshovska T, Gordienko I; UK (Oxford) Boyd PA; (Wessex) Wellesley DG.

Ancillary