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Objectives Preterm children are exposed to many medications in neonatal intensive care units, but little is known about the effect of prematurity on medication use throughout infancy and childhood. We examined prescriptions of cardiovascular medication (CVM), antiseizure medication (ASM), antiasthmatic medication and antibiotics issued/dispensed in the first 10 years of life for very and moderately preterm children compared with term. Design Population-based data linkage cohort study linking information from birth records to prescription records. Setting Six registries from five countries in the EUROlinkCAT study. Participants The study population included 1 722 912 children, of whom 10 820 (0.6%) were very preterm (= 37 weeks GA) and 0.7% had missing GA. Children with major or minor congenital anomalies were excluded (including patent ductus arteriosus). Main outcome measures Relative risk (RR) of receiving a prescription for CVM, ASM, antiasthmatic and antibiotics. Results Very preterm children had a higher RR of receiving a prescription for CVM and ASM than preterm children. For all preterm children, the RR of having a CVM prescription was 3.58 (95% CI 2.06 to 6.23); 2.06 (95% C11.73 to 2.41) for ASM; 1.13 (95% CI 0.99 to 1.29) for antiasthmatics and 0.96 (95% CI 0.93 to 0.99) for antibiotics in the first year of life. Increased prescription of CVM, ASM and antiasthmatics persisted for all 10 years of follow-up. Although the RR was highest for CVM and ASM, in absolute numbers more children received prescriptions for antibiotics (42.34%, 95% CI 38.81% to 45.91%) and antiasthmatics (28.40%, 95% CI 16.07% to 42.649%) than for CVM (0.18%, 95% CI 0.12% to 0.25%) and ASM (0.16%, 95% CI 0.13% to 0.20%) in the first year of life. Conclusion Preterm children had a higher risk of being prescribed/dispensed CUM, ASM and antiasthmatics up to age 10. This study highlights a need for further research into morbidity beyond age 10.

BACKGROUND: Parents of children who have a congenital anomaly can experience significant worry about their child's health. Access to clear, helpful, and trustworthy information can provide a valuable source of support. In this study the aim was to explore the information needs of parents/carers of children with congenital anomalies across Europe. METHOD: A cross-sectional online survey was developed in nine languages to measure parents' information needs, including: (1) the 'helpfulness'/'trustworthiness' of information received from eight relevant sources, and (2) overall satisfaction with information received. Parents/carers of children (0-10 years) with cleft lip, spina bifida, congenital heart defect [CHD] requiring surgery, and/or Down syndrome were recruited online via relevant organisations in 10 European countries from March-July 2021. Quantitative analyses using multivariable logistic regressions were performed. RESULTS: One thousand seventy parents/carers of children with a cleft lip (n = 247), spina bifida (n = 118), CHD (n = 366), Down syndrome (n = 281), and Down syndrome with CHD (n = 58) were recruited in Poland (n = 476), the UK (n = 120), Germany (n = 97), the Netherlands/Belgium (n = 74), Croatia (n = 68), Italy (n = 59), other European countries (n = 92), and not specified/non-European countries (n = 84). Most participants were mothers (92%) and aged 31-40 years (71%). Participants were most likely to rate support groups (63%), patient organisations (60%), specialist doctors/nurses (58%), and social media (57%) as 'very helpful' information sources. 'Very trustworthy' ratings remained high for specialist doctors/nurses (61%), however, they declined for support groups (47%), patient organisations (48%), and social media (35%). Germany had the highest proportion of participants who were 'very satisfied' (44%, 95% CI = 34%-54%) with information, whereas this percentage was lowest in Croatia (11%, 95% CI = 3%-19%) and Poland (15%, 95% CI = 11%-18%). Parents of children with Down syndrome had significantly lower satisfaction ratings than parents of children with CHD; 13% (95% CI = 8%-18%) reported being 'very satisfied' compared to 28% (95% CI = 23%-33%) in the CHD group. CONCLUSIONS: Findings suggest that informal sources of information (e.g. support groups) are of value to parents, however, they are not deemed as trustworthy as specialist medical sources. Satisfaction ratings differed across countries and by anomaly, and were particularly low in Croatia and Poland, as well as for parents of children with Down syndrome, which warrants further investigation.

This study investigated the risk of congenital heart defects (CHD) and other congenital anomalies (CA) associated with first trimester use of macrolide antibiotics (mainly erythromycin, spiramycin, clarithromycin and azithromycin) and lincosamides (clindamycin) using a case-malformed control design. Data included 145,936 babies with a CA diagnosis (livebirths, stillbirths and terminations of pregnancy for CA) from 15 population-based EUROCAT registries in 13 European countries, covering 9 million births 1995-2012. Cases were babies with CHD, anencephaly, orofacial clefts, genital and limb reduction anomalies associated with antibiotic exposure in the literature. Controls were babies with other CA or genetic conditions. Main outcomes were odds ratios adjusted (AOR) for maternal age and registry, with 95 % Confidence Intervals (95 %CI). Macrolide and lincosamide exposure was recorded for 307 and 28 cases, 72 and 4 non-genetic controls, 57 and 7 genetic controls, respectively. AOR for CHD was not significantly raised (AOR 0.94, 95 %CI: 0.70-1.26 vs non genetic controls; AOR 1.01, 95 %CI: 0.73-1.41 vs genetic controls), nor significantly raised for any specific macrolide. The risk of atrioventricular septal defect was significantly raised with exposure to any macrolide (AOR 2.98; 95 %CI: 1.48-6.01), erythromycin (AOR 3.68, 95 %CI: 1.28-10.61), and azithromycin (AOR 4.50, 95 %CI: 1.30-15.58). Erythromycin, clarithromycin, azithromycin, and clindamycin were associated with an increased risk of at least one other CA. Further research is needed on the risk of specific CA associated with macrolide and lincosamide use in the first trimester, particularly relevant for the potential use of azithromycin in the treatment of COVID-19.

EUROlinkCAT aims to investigate the health and educational outcomes of children with congenital anomalies for the first 10 years of their lives. We also aim to facilitate the development of a more reciprocal relationship between families with children with congenital anomalies, health and social care professionals, and researchers by conducting focus groups. The aim of the focus groups and parent interviews was to investigate parental experiences of having a child with a heart defect requiring surgery, cleft lip, spina bifida or Down Syndrome and to identify their research priorities. In total, seven interviews with 12 parents and eight focus groups with 58 parents and two caregivers were conducted in four European countries. We found that parents request more positive information with a focus on quality of life and what the children can achieve rather than solely on the negative aspects and limitations of the congenital anomaly. Some parents also highlighted discrepancies between the family's need for support and the lack of support received from the local authority. Finally, it was challenging for the parents to address specific research priorities. Future research should therefore focus on the potential of a child with a congenital anomaly.

Objectives: The aim of this study was to describe the epidemiology of Ebstein's anomaly in Europe and its association with maternal health and medication exposure during pregnancy. Design: We carried out a descriptive epidemiological analysis of population-based data. Setting: We included data from 15 European Surveillance of Congenital Anomalies Congenital Anomaly Registries in 12 European countries, with a population of 5.6 million births during 1982-2011. Participants: Cases included live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. Main outcome measures: We estimated total prevalence per 10,000 births. Odds ratios for exposure to maternal illnesses/medications in the first trimester of pregnancy were calculated by comparing Ebstein's anomaly cases with cardiac and non-cardiac malformed controls, excluding cases with genetic syndromes and adjusting for time period and country. Results: In total, 264 Ebstein's anomaly cases were recorded; 81% were live births, 2% of which were diagnosed after the 1st year of life; 54% of cases with Ebstein's anomaly or a co-existing congenital anomaly were prenatally diagnosed. Total prevalence rose over time from 0.29 (95% confidence interval (CI) 0.20-0.41) to 0.48 (95% CI 0.40-0.57) (p < 0.01). In all, nine cases were exposed to maternal mental health conditions/medications (adjusted odds ratio (adjOR) 2.64, 95% CI 1.33-5.21) compared with cardiac controls. Cases were more likely to be exposed to maternal beta-thalassemia (adjOR 10.5, 95% CI 3.13-35.3, n = 3) and haemorrhage in early pregnancy (adjOR 1.77, 95% CI 0.93-3.38, n = 11) compared with cardiac controls. Conclusions: The increasing prevalence of Ebstein's anomaly may be related to better and earlier diagnosis. Our data suggest that Ebstein's anomaly is associated with maternal mental health problems generally rather than lithium or benzodiazepines specifically; therefore, changing or stopping medications may not be preventative. We found new associations requiring confirmation.

BackgroundGastroschisis, a congenital anomaly of the abdomen, is associated with young maternal age and has increased in prevalence in many countries. Maternal illness and medication exposure are among environmental risk factors implicated in its aetiology. MethodsA population-based case-malformed control study was conducted using data from 18 European congenital anomaly registries, with information on first trimester medication use, covering 8 million births 1995-2012. 1577 gastroschisis cases (of which 4% stillbirths, 11% terminations of pregnancy) were compared to 153357 non-chromosomal/monogenic controls. Literature review identified previous associations concerning maternal illness and medication exposure to be tested as signals. Logistic regression adjusted for maternal age group, registry, and time period was used to evaluate associations. ResultsComparing gastroschisis to other congenital anomalies, the data supported signals concerning maternal depression (aOR 2.52, 95% CI 1.45, 4.39), antidepressant use (aOR 2.03, 95% CI 1.22, 3.38), postnatal depression/psychosis following a previous pregnancy (aOR 8.32, 95% CI 2.56, 27.01), sexually transmitted infections (aOR 2.85, 95% CI 1.13, 7.24), topical antivirals (aOR 5.31, 95% CI 1.63, 17.33), and continuation of oral contraceptives in early pregnancy (aOR 2.17, 95% CI 1.13, 4.18). Exploratory analyses suggested associations with a wider range of maternal infections and medications, including tonsillitis and the expectorant bromhexine. ConclusionsWhile it is difficult to disentangle the effects of the medication and underlying indication, our results add to the evidence base on preventable risk factors for gastroschisis. These risk factors may contribute to the higher risk among young mothers, and geographical and temporal variation in prevalence.

Background: Surveillance of congenital anomalies is important to identify potential teratogens. Despite known associations between different anomalies, current surveillance methods examine trends within each subgroup separately. We aimed to evaluate whether hierarchical statistical methods that combine information from several subgroups simultaneously would enhance current surveillance methods using data collected by EUROCAT, a European network of population-based congenital anomaly registries. Methods: Ten year trends (2003 to 2012) in 18 EUROCAT registries over 11 countries were analysed for the following groups of anomalies: neural tube defects, congenital heart defects, digestive system and chromosomal anomalies. Hierarchical Poisson regression models that combined related subgroups together according to EUROCAT’s hierarchy of subgroup coding were applied. Results from hierarchical models were compared to those from Poisson models that consider each congenital anomaly separately. Results: Hierarchical models gave similar results as those obtained when considering each anomaly subgroup in a separate analysis. Hierarchical models that included only around three subgroups showed poor convergence and were generally found to be over-parameterised. Larger sets of anomaly subgroups were found to be too heterogeneous to group together in this way. Conclusions: There were no substantial differences between independent analyses of each subgroup and hierarchical models when using the EUROCAT anomaly subgroups. Considering each anomaly separately therefore remains an appropriate method for the detection of potential changes in prevalence by surveillance systems. Hierarchical models do, however, remain an interesting alternative method of analysis when considering the risks of specific exposures in relation to the prevalence of congenital anomalies, which could be investigated in other studies.

The European Surveillance of Congenital Anomalies (EUROCAT) network of population-based congenital anomaly registries is an important source of epidemiologic information on congenital anomalies in Europe covering live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. EUROCAT's policy is to strive for high-quality data, while ensuring consistency and transparency across all member registries. A set of 30 data quality indicators (DQIs) was developed to assess five key elements of data quality: completeness of case ascertainment, accuracy of diagnosis, completeness of information on EUROCAT variables, timeliness of data transmission, and availability of population denominator information. This article describes each of the individual DQIs and presents the output for each registry as well as the EUROCAT (unweighted) average, for 29 full member registries for 2004-2008. This information is also available on the EUROCAT website for previous years. The EUROCAT DQIs allow registries to evaluate their performance in relation to other registries and allows appropriate interpretations to be made of the data collected. The DQIs provide direction for improving data collection and ascertainment, and they allow annual assessment for monitoring continuous improvement. The DQI are constantly reviewed and refined to best document registry procedures and processes regarding data collection, to ensure appropriateness of DQI, and to ensure transparency so that the data collected can make a substantial and useful contribution to epidemiologic research on congenital anomalies. Birth Defects Research (Part A) 91: S23-S30, 2011. (C) 2011 Wiley-Liss, Inc.

OBJECTIVES: There has been much discussion about the relatively high perinatal mortality seen in the Netherlands (Buitendijk 2004, Europeristat 2009), for which congenital anomalies (CA) are known to be one of the four main risk factors. There was no nationwide routine prenatal screening for CA in the Netherlands until 2007. We have analysed data for a 14-year period from the EUROCAT registries to investigate the effect of the introduction of screening for CA on the perinatal mortality rate in the Netherlands and compared the results with those from other European registries. METHODS: We used data from the European Surveillance of Congenital Anomalies (EUROCAT) database covering the period 1998 to 2011. We included registries that had correctly coded the date of death for more than 80% of their cases. Perinatal mortality was defined as: deaths in the first week after birth plus late foetal deaths and stillbirths from 20 weeks' gestation onwards, excluding terminations of pregnancy for foetal anomalies (TOPFA). RESULTS: A total of 84.832 cases of CA were included from 13 European registries covering a total of 3.1million births. In Europe the perinatalmortality associated with CA decreased from an average of 1.35 per 1000 births in the period 1998-2006 to 1.15 per 1000 births in the period 2007-2011. In the northern Netherlands, it dropped from 1.73 per 1000 births in the period 1998-2006 to 1.00 per 1000 births in the period 2007- 2011. In 2011, the perinatal mortality associated with CA in the northern Netherlands was on the same level as the rest of Europe. Our data also showed that, since the introduction of prenatal screening, more parents have chosen to terminate a pregnancy if congenital anomalies are discovered. CONCLUSIONS: Perinatal mortality associated with congenital anomaly (CA) has decreased in the northern Netherlands since 2005. The introduction of prenatal screening in 2007 markedly contributed to this trend: pregnancies involving CA were terminated more often, leading to a decrease in the perinatal mortality rate. By 2011, the perinatal mortality rate associated with CA in the northern Netherlands was equal to that for the rest of Europe.

Objective / Background Use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with adverse pregnancy outcomes, including congenital heart disease. Objectives: To describe utilisation patterns of SSRIs 1 year before, during and 1 year after pregnancy in primary care in Wales and 5 other European databases. Methods A common protocol was implemented across 6 databases in: Denmark, The Netherlands, Tuscany, Emilia Romagna, Wales, and the Clinical Practice Research Datalink (CPRD) representing the rest of the UK. All pregnancies starting 2004-2010 (2009 Denmark) were identified in each database. For those ending in a birth (live or still), prescriptions for SSRIs issued (UK) or dispensed (Denmark, Italy, The Netherlands) between 1 year before and 1 year after pregnancy were identified. Prescribing patterns were described and compared between databases. Where available, data were explored for associations with material deprivation, as Townsend scores. Results In the six databases 721,632 eligible women with 862,943 deliveries were identified. SSRI use was higher in Wales and the UK than in the other European databases: in the year leading up to pregnancy 9.6 % (CI95 9.4-9.8 %) of women inWales and 8.8 % (8.6-8.9%) in the CPRD, UK were prescribed an SSRI compared with 3.3 % (3.2- 3.4 %) in Emilia Romagna. During pregnancy exposure ranged from 1.2 % (1.1-1.3 %) (Emilia Romagna) to 3.7 % (3.6-3.8 %) (CPRD, UK) and 4.5 % (4.3-4.6 %) (Wales). Prescribing was at a nadir in the 2nd and 3rd trimesters in all databases. After pregnancy, SSRI prescribing increased more rapidly in Wales and the CPRD, UK than elsewhere. Of those who discontinued SSRI prescriptions before pregnancy or in the first trimester, a minority restarted in the year after birth, ranging from 36.5 % (35.2-37.7 %) in Wales to 15.3 % (14.3-16.3 %) in Emilia Romagna. Where data were available, material deprivation (Wales) and socioeconomic status (Denmark) were associated with SSRI prescription. In Wales, between 1 year before and 1 year after pregnancy: 11777/58073 (20.3 %) women received a prescription for an SSRI, 8527 (72.4 %) of whom were diagnosed with depression; 13475/58073 (23.2 %) women were diagnosed with depression, 8527 (63.3%) of whom were prescribed an SSRI; 15.1 % in the least deprived 25.3 % and in the most deprived fifth received an SSRI prescription (chi sq 456.3, df 1, p

Objective / Background The Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants are widely prescribed in pregnancy, but there is evidence that they may cause congenital anomalies, particularly congenital heart defects (CHD). Objective: To determine the specificity of association between first trimester pregnancy exposure to individual SSRI and specific congenital anomalies (CAs). Methods Population-based case-malformed control study covering 3.3 million births from 12 EUROCAT registries 1995-2009. CAs included non-syndromic live births, fetal deaths and terminations of pregnancy for fetal anomaly (n=42,839). Three groups of CA were studied: CHD (n=12,828), 15 non-CHD "signals" derived from the literature (n=12,460), and other subgroups of CA not previously associated with SSRIs (controls, n=17,046). First trimester SSRI exposure was compared to no SSRI use. Odds ratios (OR) and 95% confidence intervals (CI) were calculated adjusted for registry. Results SSRI use in first trimester pregnancy was associated with CHD overall (OR 1.38, 95 % CI 1.05-1.82, n=109); and with severe CHDs (OR 1.56, 95 % CI 1.03-2.38, n=29). Specific associations between SSRI and Tetralogy of Fallot (OR 3.36, 95 % CI 1.67-6.75, n=9), and Ebstein's anomaly (OR 8.23, 95 % CI 2.91-23.28, n=4) were detected. Statistically significant associations between SSRI and four of the 15 non- CHDsignals (anorectal atresia and stenosis, gastroschisis, renal dysplasia, clubfoot) were found. In all the statistically significant associations identified there was little evidence of specificity in relation to SSRI type. Conclusion / Discussion These data support the previously reported association between SSRIs and CHDs and a number of other CAs, but do not suggest specificity of action in relation to SSRI type. This may indicate confounding or a common mechanism of teratogenic effect among SSRIs, the specificity of CA supporting the latter explanation. Preconceptional and pregnancy care for women should include weighing the benefits of SSRIs against the growing evidence of risk when assessing treatment options.

Background: The use of topiramate (TPM) has been increased among pregnant women. Safety data for TPM in human pregnancy are limited. Recent studies have suggested that exposure to TPM early in gestation has a higher risk of orofacial clefts (OCs), particularly cleft lip with or without palate, and there has been a Food Drug Administration (FDA) alert. Objectives: The aim of this study was to assess the risk of OCs relative to other malformations in infants whose mothers had taken TPM during the first trimester of pregnancy. Methods: A population-based case-control study with malformed controls was performed using the EUROCAT Antiepileptic (AED) Drug Database including data from 19 population-based registries of congenital anomaly in Europe with a total coverage of 8.0 million births from 1995 to 2011. Cases were 10 802 nonsyndromic OC registrations, of whom 8919 were isolated, and 6827 were cleft lip with or without cleft palate (CL/P). Controls were 136 838 nonchromosomal, non-OC registrations. We compared first trimester TPM use versus no-AED use, for monotherapy and polytherapy. Results: Exposure to TPM monotherapy was recorded for a total of 12 registrations, with one registration in the case group (isolated cleft palate) and 11 in the control group (odds ratio (OR) 1.15, 95% CI 0.03-7.95 for OC relative to other malformations, OR 4.03, 95%CI 0.09-27.8 for isolated cleft palate). No registration of CL/P was in TPM monotherapy exposure. There were 36 registrations exposed to TPM polytherapy, of whom six with isolated CL/P, three with cleft palate. Out of 36 of TPM polytherapy, 19 included valproic acid, 8 included carbamazepine and 4 included lamotrigine. The OR for TPM polytherapy versus no-AED use was 4.23 (95%CI 1.75-9.28) for OC, 4.35 (95%CI 1.31- 11.5) for isolated CL/P and 3.85 (95%CI 0.75- 12.5) for isolated cleft palate. Conclusions: The prevalence of TPM monotherapy exposure was five times lower in these data than reported in the United States, which limited our ability to confirm or refute previous findings. We found an excess of OCs, particularly CL/P, associated with TPM polytherapy. Further attention to TPM polytherapy is warranted.

Background: There is evidence that selective serotonin reuptake inhibitor (SSRI) antidepressants used in early pregnancy may cause congenital anomalies (CA), particularly congenital heart defects (CHD). Objectives: The aim of this study was to determine the association between first trimester pregnancy exposure to SSRI and specific CAs, using EUROCAT registry data enhanced with linkage to prescription databases. Methods: Population-based case-malformed control study covering 3.3 million births from 14 EUROCAT registries in 12 countries, 1995-2012. CAs included non-syndromic livebirths, fetal deaths and terminations of pregnancy for fetal anomaly (n =71 602 babies). Exposure to SSRI among cases of CHD (n=24 035) and 15 non-CHD CA signals (n =25 752) derived from the literature was compared with controls (babies with non-CHD, non-signal CA only, n=21 815). Medication exposure information was obtained from prospective medical records (13 registries), maternal interviews after delivery (two registries) and prescription records (five registries). Odds ratios (OR, 95%CI) were adjusted for registry and time. Results: SSRI exposure was associated with a low and non-significant risk of CHD overall (OR 1.12, 95%CI 0.90-1.37) and severe CHD (OR 1.27, 95%CI 0.94- 1.71) relative to control CA; specific associations for severe CHD with citalopram (OR 1.76, 95%CI 1.05- 2.95) and SSRI with Ebstein's anomaly (OR 4.24, 95%CI 1.69-10.6) were found. Elevated risks were found for four non-CHD signals: gastroschisis (OR 2.15, 95%CI 1.27-3.64), renal dyplasia (OR1.97, 95%CI 1.26-3.07), clubfoot (OR 1.56, 95%CI 1.12-2.17) and anorectal atresia (OR 1.79, 95%CI 0.96-3.32). Conclusions: The excess risk of CHD associated with SSRI use overall is small. The specific associations regarding citalopram and Ebstein's anomaly need confirmation in independent datasets. Evidence is accumulating that some other types of CA may also be associated with SSRI use. Further research is needed to explore the causality of these associations, particularly with regard to underlying condition and co-exposures.

Advancing rare disease research: the use of network of congenital anomaly registries in the study of rare genetic syndromes

Joint Action EUROCAT 2011-2013 Funded by the Public Health Programme 2008-2013 of the European Commission

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by macroglossia, high birth weight, omphalocele, visceromegaly, hypoglycaemia, tumour predisposition, and congenital malformations. AIM: To determine relevant epidemiological and clinical characteristics in a large series of patients with BWS in Europe PATIENTS AND METHODS: We present clinical and epidemiological characteristics of 197 patients with BWS that were identified by retrospective analysis among 13 546 771 pregnancies that were monitored in EUROCAT network of population based registries in 1980-2007period. RESULTS: The clinical manifestations of BWS patients reflect the variable presentation of the syndrome. The infants had a high birth weight for their gestational age. Prematurity was present in 74/166 (44.57%) cases. The most frequent features were omphalocele (54.72% ; 81/148) and macroglossia (52.7% ; 78/148). Associated anomalies were present in 68 (46%) patients and included mainly cardiovascular (30/148 ; 20.28 %), urinary (26/148 ; 17.56%) and limb defects (14/148 ; 9.15%). Of the 70 cases detected prenatally, 12 (17.1%) were terminated due to severe anomalies. The overall recorded number of late foetal deaths/stillbirths with BWS was 8, and of deaths in the first week of life 7, resulting in a total perinatal mortality rate associated with BWS of 76.14 per 1000 births. The minimal estimated prevalence rate of BWS in Europe is 1 in 69930 births. All cases were sporadic. CONCLUSION: Beckwith Wiedemann syndrome is a rare disorder. Presence of various associated anomalies decreases overall first week survival rate in this patients to 86.14% (170/197).

Background— This study determines the prevalence of Congenital Heart Defects (CHD), diagnosed prenatally or in infancy, and fetal and perinatal mortality associated with CHD in Europe. Methods and Results— Data were extracted from the European Surveillance of Congenital Anomalies central database for 29 population-based congenital anomaly registries in 16 European countries covering 3.3 million births during the period 2000 to 2005. CHD cases (n=26 598) comprised live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly (TOPFA). The average total prevalence of CHD was 8.0 per 1000 births, and live birth prevalence was 7.2 per 1000 births, varying between countries. The total prevalence of nonchromosomal CHD was 7.0 per 1000 births, of which 3.6% were perinatal deaths, 20% prenatally diagnosed, and 5.6% TOPFA. Severe nonchromosomal CHD (ie, excluding ventricular septal defects, atrial septal defects, and pulmonary valve stenosis) occurred in 2.0 per 1000 births, of which 8.1% were perinatal deaths, 40% were prenatally diagnosed, and 14% were TOPFA (TOPFA range between countries 0% to 32%). Live-born CHD associated with Down syndrome occurred in 0.5 per 1000 births, with >4-fold variation between countries. Conclusion— Annually in the European Union, we estimate 36 000 children are live born with CHD and 3000 who are diagnosed with CHD die as a TOFPA, late fetal death, or early neonatal death. Investing in primary prevention and pathogenetic research is essential to reduce this burden, as well as continuing to improve cardiac services from in utero to adulthood.