The limitations of some European healthcare databases for monitoring the effectiveness of pregnancy prevention programmes as risk minimisation measures.

PURPOSE: Pregnancy prevention programmes (PPPs) exist for some medicines known to be highly teratogenic. It is increasingly recognised that the impact of these risk minimisation measures requires periodic evaluation. This study aimed to assess the extent to which some of the data needed to monitor the effectiveness of PPPs may be present in European healthcare databases. METHODS: An inventory was completed for databases contributing to EUROmediCAT capturing pregnancy and prescription data in Denmark, Norway, the Netherlands, Italy (Tuscany/Emilia Romagna), Wales and the rest of the UK, to determine the extent of data collected that could be used to evaluate the impact of PPPs. RESULTS: Data availability varied between databases. All databases could be used to identify the frequency and duration of prescriptions to women of childbearing age from primary care, but there were specific issues with availability of data from secondary care and private care. To estimate the frequency of exposed pregnancies, all databases could be linked to pregnancy data, but the accuracy of timing of the start of pregnancy was variable, and data on pregnancies ending in induced abortions were often not available. Data availability on contraception to estimate compliance with contraception requirements was variable and no data were available on pregnancy tests. CONCLUSION: Current electronic healthcare databases do not contain all the data necessary to fully monitor the effectiveness of PPP implementation, and thus, special data collection measures need to be instituted.

Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study.

OBJECTIVE: To examine the effect of maternal exposure to asthma medications on the risk of congenital anomalies. DESIGN: Meta-analysis of aggregated data from three cohort studies. SETTING: Linkage between healthcare databases and EUROCAT congenital anomaly registries. POPULATION: 519 242 pregnancies in Norway (2004-2010), Wales (2000-2010) and Funen, Denmark (2000-2010). METHODS: Exposure defined as having at least one prescription for asthma medications issued (Wales) or dispensed (Norway, Denmark) from 91 days before to 91 days after the pregnancy start date. Odds ratios (ORs) were estimated separately for each register and combined in meta-analyses. MAIN OUTCOME MEASURES: ORs for all congenital anomalies and specific congenital anomalies. RESULTS: Overall exposure prevalence was 3.76%. For exposure to asthma medication in general, the adjusted OR (adjOR) for a major congenital anomaly was 1.21 (99% CI 1.09-1.34) after adjustment for maternal age and socioeconomic position. The OR of anal atresia was significantly increased in pregnancies exposed to inhaled corticosteroids (3.40; 99% CI 1.15-10.04). For severe congenital heart defects, an increased OR (1.97; 1.12-3.49) was associated with exposure to combination treatment with inhaled corticosteroids and long-acting beta-2-agonists. Associations with renal dysplasia were driven by exposure to short-acting beta-2-agonists (2.37; 1.20-4.67). CONCLUSION: The increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status. The study confirmed the association of inhaled corticosteroids with anal atresia found in earlier research and found potential new associations with combination treatment. The potential new associations should be interpreted with caution due to the large number of comparisons undertaken. TWEETABLE ABSTRACT: This cohort study found a small increased risk of congenital anomalies for women taking asthma medication.

Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy: a population-based study in six European regions.

OBJECTIVE: To explore the prescribing patterns of selective serotonin reuptake inhibitors (SSRIs) before, during and after pregnancy in six European population-based databases. DESIGN: Descriptive drug utilisation study. SETTING: Six electronic healthcare databases in Denmark, the Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK. POPULATION: All women with a pregnancy ending in a live or stillbirth starting and ending between 2004 and 2010. METHODS: A common protocol was implemented across databases to identify SSRI prescriptions issued (UK) or dispensed (non-UK) in the year before, during or in the year following pregnancy. MAIN OUTCOME MEASURES: The percentage of deliveries in which the woman received an SSRI prescription in the year before, during or in the year following pregnancy. We also compared the choice of SSRIs and changes in prescribing over the study period. RESULTS: In total, 721 632 women and 862,943 deliveries were identified. In the year preceding pregnancy, the prevalence of SSRI prescribing was highest in Wales [9.6%; 95% confidence interval (CI95 ), 9.4-9.8%] and lowest in Emilia Romagna (3.3%; CI95 , 3.2-3.4%). During pregnancy, SSRI prescribing had dropped to between 1.2% (CI95 , 1.1-1.3%) in Emilia Romagna and 4.5% (CI95 , 4.3-4.6%) in Wales. The higher UK pre-pregnancy prescribing rates resulted in higher first trimester exposures. After pregnancy, SSRI prescribing increased most rapidly in the UK. Paroxetine was more commonly prescribed in the Netherlands and Italian regions than in Denmark and the UK. CONCLUSIONS: The higher SSRI prescribing rates in the UK, compared with other European regions, raise questions about differences in the prevalence and severity of depression and its management in pregnancy across Europe.

Prevalence and risk of Down syndrome in monozygotic and dizygotic multiple pregnancies in Europe: implications for prenatal screening.

OBJECTIVE: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome. DESIGN: Population-based prevalence study based on EUROCAT congenital anomaly registries. SETTING: Eight European countries. POPULATION: 14.8 million births 1990-2009; 2.89% multiple births. METHODS: DS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases. MAIN OUTCOME MEASURES: Relative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome. STATISTICAL ANALYSIS: Poisson and logistic regression stratified for maternal age, country and time. RESULTS: Overall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59]). CONCLUSIONS: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening.

Trends in the prevalence, risk and pregnancy outcome of multiple births with congenital anomaly: a registry-based study in 14 European countries 1984-2007.

OBJECTIVE: To assess the public health consequences of the rise in multiple births with respect to congenital anomalies. DESIGN: Descriptive epidemiological analysis of data from population-based congenital anomaly registries. SETTING: Fourteen European countries. POPULATION: A total of 5.4 million births 1984-2007, of which 3% were multiple births. METHODS: Cases of congenital anomaly included live births, fetal deaths from 20 weeks of gestation and terminations of pregnancy for fetal anomaly. MAIN OUTCOME MEASURES: Prevalence rates per 10,000 births and relative risk of congenital anomaly in multiple versus singleton births (1984-2007); proportion prenatally diagnosed, proportion by pregnancy outcome (2000-07). Proportion of pairs where both co-twins were cases. RESULTS: Prevalence of congenital anomalies from multiple births increased from 5.9 (1984-87) to 10.7 per 10,000 births (2004-07). Relative risk of nonchromosomal anomaly in multiple births was 1.35 (95% CI 1.31-1.39), increasing over time, and of chromosomal anomalies was 0.72 (95% CI 0.65-0.80), decreasing over time. In 11.4% of affected twin pairs both babies had congenital anomalies (2000-07). The prenatal diagnosis rate was similar for multiple and singleton pregnancies. Cases from multiple pregnancies were less likely to be terminations of pregnancy for fetal anomaly, odds ratio 0.41 (95% CI 0.35-0.48) and more likely to be stillbirths and neonatal deaths. CONCLUSIONS: The increase in babies who are both from a multiple pregnancy and affected by a congenital anomaly has implications for prenatal and postnatal service provision. The contribution of assisted reproductive technologies to the increase in risk needs further research. The deficit of chromosomal anomalies among multiple births has relevance for prenatal risk counselling.

Linking a European cohort of children born with congenital anomalies to vital statistics and mortality records: A EUROlinkCAT study.

EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed.

Termination of pregnancy for fetal anomaly after 23 weeks of gestation: a European register-based study.

OBJECTIVE: To determine the prevalence of termination of pregnancy for fetal anomaly (TOPFA) after 23 weeks of gestation in European countries, and describe the spectrum of anomalies for which late TOPFA is recorded. DESIGN: Population-based study. SETTING: Twelve European countries. POPULATION: Nineteen registries of congenital anomaly in 12 European countries between 2000 and 2005. The number of total births covered was 2 695 832. METHODS: TOPFAs in singleton pregnancies from the European Surveillance of Congenital Anomalies and Twins (EUROCAT) database. MAIN OUTCOME MEASURES: The prevalence of TOPFA and type of anomaly. RESULTS: There were 10 233 TOPFAs, 678 (6.6%) of which were performed at 24 weeks or more. The rate of TOPFA before 24 weeks was 3.4 per 1000 births, at 24-25 weeks 0.14 per 1000 births and at 26 weeks or more 0.11 per 1000 births. There was significant variation in the prevalence of TOPFA at >or=24 weeks between countries (P < 0.001), with all countries in the range 0-0.55 per 1000 births, except France (Paris) at 2.65 per 1000 births. The large majority of late TOPFAs had a gestational age of 24-27 weeks (516/678, 76%). The proportion of TOPFAs from 24 weeks or more varied by type of anomaly, with 4% of all TOPFAs for chromosomal anomalies and 9% of all TOPFAs for nonchromosomal anomalies resulting in late TOPFA (P < 0.001). For transposition of the great arteries, single ventricle, hypoplastic left heart and hydrocephaly, the percentage of late TOPFA was 12-23%. The median time interval between diagnosis and late TOPFA was 2 weeks for most anomalies, but longer (>or=5 weeks) for diaphragmatic hernia, omphalocoele, arthrogryposis multiplex and Turner's syndrome. CONCLUSION: Late TOPFA is rare in Europe, and varies in prevalence between countries. Compared with earlier TOPFA, late TOPFA is more often performed for a nonchromosomal isolated major structural anomaly and less often for a fetus with a chromosomal syndrome or multiple anomalies.

Correction to: EUROCAT: an update on its functions and activities.

The published online version contains the following errors: On the cover page "JRC Management Committee" - should be corrected to JRC-EUROCAT Management Committee. In the authors list under the title, same as above, "JRC Management Committee" should be corrected to JRC-EUROCAT Management Committee.

Survey of prenatal screening policies in Europe for structural malformations and chromosome anomalies, and their impact on detection and termination rates for neural tube defects and Down's syndrome.

OBJECTIVE: To 'map' the current (2004) state of prenatal screening in Europe. DESIGN: (i) Survey of country policies and (ii) analysis of data from EUROCAT (European Surveillance of Congenital Anomalies) population-based congenital anomaly registers. SETTING: Europe. POPULATION: Survey of prenatal screening policies in 18 countries and 1.13 million births in 12 countries in 2002-04. METHODS: (i) Questionnaire on national screening policies and termination of pregnancy for fetal anomaly (TOPFA) laws in 2004. (ii) Analysis of data on prenatal detection and termination for Down's syndrome and neural tube defects (NTDs) using the EUROCAT database. MAIN OUTCOME MEASURES: Existence of national prenatal screening policies, legal gestation limit for TOPFA, prenatal detection and termination rates for Down's syndrome and NTD. RESULTS: Ten of the 18 countries had a national country-wide policy for Down's syndrome screening and 14/18 for structural anomaly scanning. Sixty-eight percent of Down's syndrome cases (range 0-95%) were detected prenatally, of which 88% resulted in termination of pregnancy. Eighty-eight percent (range 25-94%) of cases of NTD were prenatally detected, of which 88% resulted in termination. Countries with a first-trimester screening policy had the highest proportion of prenatally diagnosed Down's syndrome cases. Countries with no official national Down's syndrome screening or structural anomaly scan policy had the lowest proportion of prenatally diagnosed Down's syndrome and NTD cases. Six of the 18 countries had a legal gestational age limit for TOPFA, and in two countries, termination of pregnancy was illegal at any gestation. CONCLUSIONS: There are large differences in screening policies between countries in Europe. These, as well as organisational and cultural factors, are associated with wide country variation in prenatal detection rates for Down's syndrome and NTD.

EUROCAT: an update on its functions and activities.

This paper provides an outline of the development and growth of EUROCAT, the European network of congenital anomaly registers. In recent years the network has been through a period of transition and change. The Central Register of data has transferred from the Ulster University to the EU Joint-Research-Centre, Ispra, Italy.The benefits of combining data from across Europe, from different populations and countries are described by the uses to which these data can be put. These uses include:. surveillance of anomalies at a local, regional or pan-European level. pharmacovigilance. registration of rare diseasesNew studies and projects are underway, including EUROlinkCAT (a Horizon 2020 funded data-linkage project), promising a fruitful future in further research of congenital anomalies.

Trends and geographic inequalities in the prevalence of Down syndrome in Europe, 1980-1999.

BACKGROUND: EUROCAT is a network of population-based registries for the epidemiologic surveillance of congenital anomalies covering approximately one quarter of births in the European Union. Down syndrome constitutes approximately 8% of cases of registered congenital anomaly in Europe, with over 7000 affected pregnancies in the 15 current member states of the European Union each year. In this paper, we aim to examine trends in the live birth prevalence of Down syndrome in Europe in the light of trends in maternal age and in prenatal diagnosis. METHODS: Descriptive analysis of data from 24 EUROCAT registries, covering 8.3 million births 1980-99. Cases include live births, stillbirths and terminations of pregnancy following prenatal diagnosis. RESULTS: Since 1980, the proportion of births to mothers of 35 years of age and over has risen quite dramatically from 8 to 14% for the European Union as a whole, with steeper rises in some regions. By 1995-1999, the proportion of "older" mothers varied between regions from 10% to 25%, and the total prevalence (including terminations of pregnancy) of Down syndrome varied from 1 to 3 per 1000 births. Some European regions have shown a more than twofold increase in total prevalence of Down syndrome since 1980. The proportion of cases of Down syndrome which were prenatally diagnosed followed by termination of pregnancy in 1995-1999 varied from 0% in the three regions of Ireland and Malta where termination of pregnancy is illegal, to less than 50% in 14 further regions, to 77% in Paris. The extent to which terminations of pregnancy were concen trated among older mothers varied between regions. The live birth prevalence has since 1980 increasingly diverged from the rising total prevalence, in some areas remaining approximately stable, in others decreasing over time. CONCLUSION: The rise in average maternal age in Europe has brought with it an increase in the number of pregnancies affected by Down syndrome. The widespread practice of prenatal screening and termination of pregnancy has in most of the regions covered by EUROCAT counteracted the effect of maternal age in its effect on live birth prevalence. Under the joint influences of maternal age and prenatal screening the pattern of geographic inequalities in Down syndrome live birth prevalence in Europe has also been changed.

Declining autopsy rates in stillbirths and infant deaths: results from Funen County, Denmark, 1986-96.

OBJECTIVE: The aim of this study was to describe the development of the autopsy rate in stillbirths and infant deaths in an 11-year period and evaluate the information gained by performing an autopsy. METHODS: Included in the study were all stillbirths and infant deaths in Funen County, Denmark, in 1986-96. Data sources were death certificates and autopsy reports. RESULTS: The study included 273 stillbirths and 351 deaths in infancy. The rates of stillbirth and infant death did not change significantly during the period. The overall autopsy rate for stillbirths was 70% and for infant deaths 57%. There was a significant decline in autopsy rate during the years 1991-96 as compared with 1986-90 for stillbirths, infant deaths and infant deaths excluding sudden infant death syndrome. In stillbirth, the autopsy changed the diagnosis in 9% of the cases. In 22%, the clinical diagnosis was maintained, but additional information was obtained. In infant death, the numbers were 10% and 40%, respectively. CONCLUSION: In 10% of the autopsies the diagnosis was changed completely, with an impact on genetic counseling as well as on statistical records of causes of death in fetuses and infants. With additional information in 22-40% of the autopsies, the study emphasizes autopsy as a useful investigation.

Gastrointestinal malformations in Funen county, Denmark--epidemiology, associated malformations, surgery and mortality.

AIM: To report the epidemiology, associated malformations, morbidity and mortality for the first 5 years of life for infants with gastrointestinal malformations (GIM). METHODS: Population-based study using data from a registry of congenital malformations (Eurocat) and follow-up data from hospital records. The study included livebirths, fetal deaths with a gestational age of 20 weeks and older and induced abortions after prenatal diagnosis of malformations born during the period 1980 - 1993. RESULTS: A total of 109 infants/fetuses with 118 GIM were included in the study giving a prevalence of 15.3 (12.6 - 18.5) cases per 10 000 births. Anal atresia was present in seven of the 9 cases with more than one GIM. There were 38 cases (35 %) with associated malformations and/or karyotype anomalies. Thirty-two of the 90 live-born infants died during the first 5 years of life with the majority of deaths during the first week of life. Mortality was significantly increased for infants with associated malformations or karyotype anomalies compared to infants with isolated GIM (p < 0.01). An uneventful surgical course was reported for 74 % of the 58 survivors. CONCLUSIONS: The prognosis for infants with GIM is highly dependent on the presence of associated malformations or karyotype anomalies. Surgery for GIM can be performed with low mortality. Morbidity is high for a small group of infants, but the majority of survivors have an uncomplicated surgical course.

[Complications of long-term treatment with vitamin K antagonists]. / Komplikationer til langtidsbehandling med vitamin K-antagonister.

Long-term treatment with vitamin K antagonists (vKA) frequently involves complications. The commonest complication is haemorrhage and cases of serious haemorrhage are stated in the literature to occur with a frequency per 1,000 treatment years of 12-108, of which 2-17 are fatal. The majority of deaths associated with haemorrhage are due to intracranial haemorrhage. Notifications of complications of vKA treatment in Denmark are considerably fewer than might be anticipated from the literature. The stability of anticoagulation treatment decreases with the number of drugs administered simultaneously and numerous drugs and other factors interact with the effect of vKA. A series of examples are reviewed and some known drugs which do not interact are mentioned. Non-haemorrhagic side effects of coumarin derivatives are rare. Anticoagulation treatment during pregnancy is associated with very special problems and must be regarded as a specialist task.

[Wound infection following heart surgery]. / Sårinfektioner efter hjertekirurgi.

Two hundred patients who had been submitted to cardiac surgery were subdivided at random into two groups with removal of the dressings on the first or fifth postoperative day. The risk of wound infection was demonstrated to be identical in the two groups. Early removal of the dressings is therefore recommended.

Agreement between Cochrane Neonatal reviews and clinical practice guidelines for newborns in Denmark: a cross-sectional study.

OBJECTIVE: To assess agreement between Cochrane Neonatal Group reviews and clinical practice guidelines in Denmark. DESIGN: Retrospective analysis of clinical guidelines for newborn infants. MATERIALS: All Cochrane neonatal reviews and Danish clinical guidelines for newborn infants. MAIN OUTCOME MEASURES: The recommendations from the Cochrane reviews and local clinical guidelines were compared and classified as being in agreement, in partial agreement or in disagreement. Authors of guidelines were asked whether Cochrane reviews had been considered during guideline development and reasons for any disagreements. Heterogeneity among departments was assessed. RESULTS: 173 interventions evaluated in Cochrane neonatal reviews were included. All 17 Danish neonatal departments agreed to participate, but only 14 (82%) delivered data. Agreement between reviews and guidelines was observed for a median of 132 interventions (76%) (range 129-134), partial agreement was observed for 31 interventions (18%) (range 29-33), and disagreement was observed for 10 interventions (6%) (range 8-13) (kappa = 0.56, range 0.53-0.59). Most of the latter 10 interventions were not recommended in the reviews but were recommended in the guidelines. There were numerous reasons for disagreement, the most common being usage of evidence with higher bias risks than randomised trials in guidelines development. Overall, Cochrane reviews were rarely (10%) used during guideline development. For nine guideline topics (5%) there was diversity among the Danish departments' recommendations. CONCLUSIONS: There is good agreement between Cochrane reviews and neonatal guidelines in Denmark. However, Cochrane reviews were rarely used for guideline development. Heterogeneity among guidelines produced by the various neonatal departments seems moderate.

Prenatal diagnosis of severe structural congenital malformations in Europe.

OBJECTIVES: To assess at a population-based level the frequency with which severe structural congenital malformations are detected prenatally in Europe and the gestational age at detection, and to describe regional variation in these indicators. METHODS: In the period 1995-1999, data were obtained from 17 European population-based registries of congenital malformations (EUROCAT). Included were all live births, fetal deaths and terminations of pregnancy diagnosed with one or more of the following malformations: anencephalus, encephalocele, spina bifida, hydrocephalus, transposition of great arteries, hypoplastic left heart, limb reduction defect, bilateral renal agenesis, diaphragmatic hernia, omphalocele and gastroschisis. RESULTS: The 17 registries reported 4366 cases diagnosed with the 11 severe structural malformations and of these 2300 were live births (53%), 181 were fetal deaths (4%) and 1863 were terminations of pregnancy (43%); in 22 cases pregnancy outcome was unknown. The overall prenatal detection rate was 64% (range, 25-88% across regions). The proportion of terminations of pregnancy varied between regions from 15% to 59% of all cases. Gestational age at discovery for prenatally diagnosed cases was less than 24 weeks for 68% (range, 36-88%) of cases. There was a significant relationship between high prenatal detection rate and early diagnosis (P < 0.0001). For individual malformations, the prenatal detection rate was highest for anencephalus (469/498, 94%) and lowest for transposition of the great arteries (89/324, 27%). Termination of pregnancy was performed in more than half of the prenatally diagnosed cases, except for those with transposition of the great arteries, diaphragmatic hernia and gastroschisis, in which 30-40% of the pregnancies with a prenatal diagnosis were terminated. CONCLUSION: European countries currently vary widely in the provision and uptake of prenatal screening and its quality, as well as the "culture" in terms of decision to continue the pregnancy. This inevitably contributes to variation between countries in perinatal and infant mortality and in childhood prevalence and cost to health services of congenital anomalies.

Prenatal diagnosis of six major cardiac malformations in Europe--a population based study.

AIM: To present data on prenatal diagnosis of six major cardiac malformations in low-risk European populations. METHODS: Data from 12 Eurocat registries on congenital malformations. All registries have multiple sources of information and use the same methods of data collection and coding. The six cardiac malformations included were hypoplastic left heart, tricuspid atresia, single ventricle, Tetralogy of Fallot, transposition of great arteries and common A-V-canal. RESULTS: There were significant differences in the proportion of cases diagnosed prenatally, with the highest detection rate in France (91% for single ventricle in Paris) and the lowest detection rate in countries without prenatal ultrasound screening (no cases diagnosed prenatally in the Danish registry area). Prenatal detection rate was significantly higher for the three malformations affecting the size of the ventricles (hypoplastic left heart, tricuspid atresia, single ventricle) compared to the other three malformations (46% versus 24%, p<0.001). Time of diagnosis was late, with only one third diagnosed before 24 weeks of gestation. The risk of fetal death seems to be low. CONCLUSION: There are significant regional differences in prenatal detection rate of major cardiac malformations in Europe.