-
Ingeborg Barisic,
Ljubica Odak,
Maria Loane,
Ester Garne,
Diana Wellesley,
Elisa Calzolari, Helen Dolk,
Marie-Claude Addor,
Larraitz Arriola,
Jorieke Bergman, [......],
Babak Khoshnood,
Anna Latos-Bielenska,
Bob McDonnell,
Anna Pierini,
Judith Rankin,
Anke Rissmann,
Annette Queisser-Luft,
Christine Verellen-Dumoulin,
David Stone,
Romano Tenconi
[show abstract]
[hide abstract]
ABSTRACT: Fraser syndrome is a rare autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, laryngeal, and urogenital malformations. We present a population-based epidemiological study using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network of birth defect registries. Between January 1990 and December 2008, we identified 26 cases of Fraser syndrome in the monitored population of 12,886,464 births (minimal estimated prevalence of 0.20 per 100,000 or 1:495,633 births). Most cases (18/26; 69%) were registered in the western part of Europe, where the mean prevalence is 1 in 230,695 births, compared to the prevalence 1 in 1,091,175 for the rest of Europe (P = 0.0003). Consanguinity was present in 7/26 (27%) families. Ten (38%) cases were liveborn, 14 (54%) pregnancies were terminated following prenatal detection of a serious anomaly, and 2 (8%) were stillborn. Eye anomalies were found in 20/24 (83%), syndactyly in 14/24 (58%), and laryngeal anomalies in 5/24 (21%) patients. Ambiguous genitalia were observed in 3/24 (13%) cases. Bilateral renal agenesis was present in 12/24 (50%) and unilateral in 4/24 (17%) cases. The frequency of anorectal anomalies was particularly high (42%). Most cases of Fraser syndrome (85%) are suspected prenatally, often due to the presence of the association of renal agenesis and cryptophthalmos. In the European population, a high proportion (82%) of pregnancies is terminated, thus reducing the live birth prevalence to a third of the total prevalence rate. © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A 03/2013; · 2.39 Impact Factor
-
Birth Defects Research Part A Clinical and Molecular Teratology 11/2012; · 2.27 Impact Factor
-
Babak Khoshnood,
Maria Loane,
Ester Garne,
Marie-Claude Addor,
Larraitz Arriola,
Marian Bakker,
Ingeborg Barisic,
Sebastiano Bianca,
Patricia Boyd,
Elisa Calzolari, [......],
Annette Queisser-Luft,
Hanitra Randrianaivo,
Judith Rankin,
Anke Rissmann,
Joaquin Salvador,
David Tucker,
Christine Verellen-Dumoulin,
Diana Wellesley,
Natalya Zymak-Zakutnya, Helen Dolk
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVES: To examine trends in the prevalence of congenital heart defects (CHDs) in Europe and to compare these trends with the recent decrease in the prevalence of CHDs in Canada (Quebec) that was attributed to the policy of mandatory folic acid fortification. STUDY DESIGN: We used data for the period 1990-2007 for 47 508 cases of CHD not associated with a chromosomal anomaly from 29 population-based European Surveillance of Congenital Anomalies registries in 16 countries covering 7.3 million births. We estimated trends for all CHDs combined and separately for 3 severity groups using random-effects Poisson regression models with splines. RESULTS: We found that the total prevalence of CHDs increased during the 1990s and the early 2000s until 2004 and decreased thereafter. We found essentially no trend in total prevalence of the most severe group (group I), whereas the prevalence of severity group II increased until about 2000 and decreased thereafter. Trends for severity group III (the most prevalent group) paralleled those for all CHDs combined. CONCLUSIONS: The prevalence of CHDs decreased in recent years in Europe in the absence of a policy for mandatory folic acid fortification. One possible explanation for this decrease may be an as-yet-undocumented increase in folic acid intake of women in Europe following recommendations for folic acid supplementation and/or voluntary fortification. However, alternative hypotheses, including reductions in risk factors of CHDs (eg, maternal smoking) and improved management of maternal chronic health conditions (eg, diabetes), must also be considered for explaining the observed decrease in the prevalence of CHDs in Europe or elsewhere.
The Journal of pediatrics 07/2012; · 4.02 Impact Factor
-
Maria Loane,
Joan K Morris,
Marie-Claude Addor,
Larraitz Arriola,
Judith Budd,
Berenice Doray,
Ester Garne,
Miriam Gatt,
Martin Haeusler,
Babak Khoshnood, [......],
Mary O'Mahony,
Annette Queißer-Wahrendorf,
Judith Rankin,
Anke Rissmann,
Catherine Rounding,
Joaquin Salvador,
David Tucker,
Diana Wellesley,
Lyubov Yevtushok, Helen Dolk
[show abstract]
[hide abstract]
ABSTRACT: This study examines trends and geographical differences in total and live birth prevalence of trisomies 21, 18 and 13 with regard to increasing maternal age and prenatal diagnosis in Europe. Twenty-one population-based EUROCAT registries covering 6.1 million births between 1990 and 2009 participated. Trisomy cases included live births, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly. We present correction to 20 weeks gestational age (ie, correcting early terminations for the probability of fetal survival to 20 weeks) to allow for artefactual screening-related differences in total prevalence. Poisson regression was used. The proportion of births in the population to mothers aged 35+ years in the participating registries increased from 13% in 1990 to 19% in 2009. Total prevalence per 10 000 births was 22.0 (95% CI 21.7-22.4) for trisomy 21, 5.0 (95% CI 4.8-5.1) for trisomy 18 and 2.0 (95% CI 1.9-2.2) for trisomy 13; live birth prevalence was 11.2 (95% CI 10.9-11.5) for trisomy 21, 1.04 (95% CI 0.96-1.12) for trisomy 18 and 0.48 (95% CI 0.43-0.54) for trisomy 13. There was an increase in total and total corrected prevalence of all three trisomies over time, mainly explained by increasing maternal age. Live birth prevalence remained stable over time. For trisomy 21, there was a three-fold variation in live birth prevalence between countries. The rise in maternal age has led to an increase in the number of trisomy-affected pregnancies in Europe. Live birth prevalence has remained stable overall. Differences in prenatal screening and termination between countries lead to wide variation in live birth prevalence.European Journal of Human Genetics advance online publication, 20 June 2012; doi:10.1038/ejhg.2012.94.
European journal of human genetics: EJHG 06/2012; · 3.56 Impact Factor
-
Ester Garne,
Maria Loane, Helen Dolk,
Ingeborg Barisic,
Marie-Claude Addor,
Larraitz Arriola,
Marian Bakker,
Elisa Calzolari,
Carlos Matias Dias,
Berenice Doray, [......],
Kari Klyungsoyr Melve,
Vera Nelen,
Mary O'Mahony,
Anna Pierini,
Hanitra Randrianaivo-Ranjatoelina,
Judith Rankin,
Anke Rissmann,
David Tucker,
Christine Verellun-Dumoulin,
Awi Wiesel
[show abstract]
[hide abstract]
ABSTRACT: Maternal pregestational diabetes is a well-known risk factor for congenital anomalies. This study analyses the spectrum of congenital anomalies associated with maternal diabetes using data from a large European database for the population-based surveillance of congenital anomalies.
Data from 18 population-based EUROCAT registries of congenital anomalies in 1990-2005. All malformed cases occurring to mothers with pregestational diabetes (diabetes cases) were compared to all malformed cases in the same registry areas to mothers without diabetes (non-diabetes cases).
There were 669 diabetes cases and 92,976 non diabetes cases. Odds ratios in diabetes pregnancies relative to non-diabetes pregnancies comparing each EUROCAT subgroup to all other non-chromosomal anomalies combined showed significantly increased odds ratios for neural tube defects (anencephaly and encephalocele, but not spina bifida) and several subgroups of congenital heart defects. Other subgroups with significantly increased odds ratios were anotia, omphalocele and bilateral renal agenesis. Frequency of hip dislocation was significantly lower among diabetes (odds ratio 0.15, 95% CI 0.05-0.39) than non-diabetes cases. Multiple congenital anomalies were present in 13.6 % of diabetes cases and 6.1 % of non-diabetes cases. The odds ratio for caudal regression sequence was very high (26.40,95% CI 8.98-77.64), but only 17% of all caudal regression cases resulted from a pregnancy with pregestational diabetes.
The increased risk of congenital anomalies in pregnancies with pregestational diabetes is related to specific non-chromosomal congenital anomalies and multiple congenital anomalies and not a general increased risk.
Birth Defects Research Part A Clinical and Molecular Teratology 02/2012; 94(3):134-40. · 2.27 Impact Factor
-
Diana Wellesley, Helen Dolk,
Patricia A Boyd,
Ruth Greenlees,
Martin Haeusler,
Vera Nelen,
Ester Garne,
Babak Khoshnood,
Berenice Doray,
Anke Rissmann,
Carmel Mullaney,
Elisa Calzolari,
Marian Bakker,
Joaquin Salvador,
Marie-Claude Addor,
Elizabeth Draper,
Judith Rankin,
David Tucker
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study is to quantify the prevalence and types of rare chromosome abnormalities (RCAs) in Europe for 2000-2006 inclusive, and to describe prenatal diagnosis rates and pregnancy outcome. Data held by the European Surveillance of Congenital Anomalies database were analysed on all the cases from 16 population-based registries in 11 European countries diagnosed prenatally or before 1 year of age, and delivered between 2000 and 2006. Cases were all unbalanced chromosome abnormalities and included live births, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. There were 10,323 cases with a chromosome abnormality, giving a total birth prevalence rate of 43.8/10,000 births. Of these, 7335 cases had trisomy 21,18 or 13, giving individual prevalence rates of 23.0, 5.9 and 2.3/10,000 births, respectively (53, 13 and 5% of all reported chromosome errors, respectively). In all, 473 cases (5%) had a sex chromosome trisomy, and 778 (8%) had 45,X, giving prevalence rates of 2.0 and 3.3/10,000 births, respectively. There were 1,737 RCA cases (17%), giving a prevalence of 7.4/10,000 births. These included triploidy, other trisomies, marker chromosomes, unbalanced translocations, deletions and duplications. There was a wide variation between the registers in both the overall prenatal diagnosis rate of RCA, an average of 65% (range 5-92%) and the prevalence of RCA (range 2.4-12.9/10,000 births). In all, 49% were liveborn. The data provide the prevalence of families currently requiring specialised genetic counselling services in the perinatal period for these conditions and, for some, long-term care.
European journal of human genetics: EJHG 01/2012; 20(5):521-6. · 3.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Improving the health of expectant mothers and reductions in health inequalities, are repeatedly prioritised in policy reports in England and Northern Ireland. Measurement of underlying rates, and geographical variation in rates, of adverse birth outcomes are tools in monitoring these priorities.
Northern Ireland data on stillbirths, infant mortality and low birth weight (1992-2002) were linked to board (n=4), district council (n=26) and 1991 census wards (n=568). Underlying variations in rates were estimated at each geographical level, unadjusted and controlling for year, ward-level deprivation, settlement size and higher geographical levels. Impacts on geographical variation of individual social class, maternal age, multiple birth and smoking were assessed.
There was significant variation in underlying rates of low birth weight (<2500 g) at all three geographical levels. Controlling for smoking reduced variation between wards. Geographical variation proved more robust for medium than for very low birth weight. No variation was seen between boards for other outcomes, nor between district level rates of infant mortality. Evidence was weak for variation in district rates of neonatal deaths and stillbirths, and variation in ward-level adjusted stillbirth rates was not significant. Variation in ward-level infant death rates was robust to all adjustments, with risks tripling (infant mortality) or quadrupling (neonatal mortality) between the 10th and 90th percentile.
Strong evidence was found of geographical variation in infant mortality and low birth weight, unexplained by individual risk factors or by area-level deprivation. Geographical targeting or area-level interventions might look beyond deprivation scores, to other environmental and social factors.
Journal of epidemiology and community health 12/2011; 65(12):1159-65. · 3.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: As part of EUROCAT's surveillance of congenital anomalies in Europe, a statistical monitoring system has been developed to detect recent clusters or long-term (10 year) time trends. The purpose of this article is to describe the system for the identification and investigation of 10-year time trends, conceived as a "screening" tool ultimately leading to the identification of trends which may be due to changing teratogenic factors.
The EUROCAT database consists of all cases of congenital anomalies including livebirths, fetal deaths from 20 weeks gestational age, and terminations of pregnancy for fetal anomaly. Monitoring of 10-year trends is performed for each registry for each of 96 non-independent EUROCAT congenital anomaly subgroups, while Pan-Europe analysis combines data from all registries. The monitoring results are reviewed, prioritized according to a prioritization strategy, and communicated to registries for investigation. Twenty-one registries covering over 4 million births, from 1999 to 2008, were included in monitoring in 2010.
Significant increasing trends were detected for abdominal wall anomalies, gastroschisis, hypospadias, Trisomy 18 and renal dysplasia in the Pan-Europe analysis while 68 increasing trends were identified in individual registries. A decreasing trend was detected in over one-third of anomaly subgroups in the Pan-Europe analysis, and 16.9% of individual registry tests. Registry preliminary investigations indicated that many trends are due to changes in data quality, ascertainment, screening, or diagnostic methods. Some trends are inevitably chance phenomena related to multiple testing, while others seem to represent real and continuing change needing further investigation and response by regional/national public health authorities.
Birth Defects Research Part A Clinical and Molecular Teratology 03/2011; 91 Suppl 1:S31-43. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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 Clinical and Molecular Teratology 03/2011; 91 Suppl 1:S23-30. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The European Surveillance of Congenital Anomalies (EUROCAT) is a network of population-based congenital anomaly registries in Europe, funded by the European Union, which has been in operation for more than 30 years. It currently surveys more than 1.7 million births per year, including 31% of births in the European Union, and includes almost all population-based European congenital anomaly registries as its members. EUROCAT member registries collect data, ascertained from multiple sources, on all major structural congenital and chromosomal anomalies. EUROCAT surveillance relates to three areas: prevalence, primary prevention, and prenatal screening. This article describes the history of EUROCAT and gives an overview of the current methodology and work of EUROCAT covering the database content and management, coding and classification of anomalies, core surveillance, prevalence tables, statistical monitoring. The monitoring of new developments in prenatal diagnosis, medication during pregnancy, use of folic acid, and investigation of clusters and exposures are overseen by working groups responsible for organizing research and producing regular reports. The EUROCAT Web site includes current data on prevalence rates and prenatal detection rates-an example of information useful to clinicians, public health service managers, and patients.
Birth Defects Research Part A Clinical and Molecular Teratology 03/2011; 91 Suppl 1:S2-15. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE
The purpose of this article is to present the specific public health indicators recently developed by EUROCAT that aim to summarize important aspects of the public health impact of congenital anomalies in a few quantitative measures.METHODS
The six indicators are: (1) congenital anomaly perinatal mortality, (2) congenital anomaly prenatal diagnosis prevalence, (3) congenital anomaly termination of pregnancy, (4) Down syndrome livebirth prevalence, (5) congenital anomaly pediatric surgery, and (6) neural tube defects (NTD) total prevalence. Data presented for this report pertained to all cases (livebirths, fetal deaths, or stillbirths after 20 weeks of gestation and terminations of pregnancy for fetal anomaly [TOPFA]) of congenital anomaly from 27 full member registries of EUROCAT that could provide data for at least 3 years during the period 2004 to 2008. Prevalence of anomalies, prenatal diagnosis, TOPFA, pediatric surgery, and perinatal mortality were calculated per 1000 births.RESULTSThe overall perinatal mortality was approximately 1.0 per 1000 births for EUROCAT registries with almost half due to fetal and the other half due to first week deaths. There were wide variations in perinatal mortality across the registries with the highest rates observed in Dublin and Malta, registries in countries where TOPFA are illegal, and in Ukraine. The overall perinatal mortality across EUROCAT registries slightly decreased between 2004 and 2008 due to a decrease in first week deaths. The prevalence of TOPFA was fairly stable at about 4 per 1000 births. There were variations in livebirth prevalence of cases typically requiring surgery across the registries; however, for most registries this prevalence was between 3 and 5 per 1000 births. Prevalence of NTD decreased by about 10% from 1.05 in 2004 to 0.94 per 1000 in 2008.CONCLUSION
It is hoped that by publishing the data on EUROCAT indicators, the public health importance of congenital anomalies can be clearly summarized to policy makers, the need for accurate data from registries emphasized, the need for primary prevention and treatment services highlighted, and the impact of current services measured. Birth Defects Research (Part A), 2011.© 2011 Wiley-Liss, Inc.
Birth Defects Research Part A Clinical and Molecular Teratology 02/2011; 91(S1):S16 - S22. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND
Surveillance of multiple congenital anomalies is considered to be more sensitive for the detection of new teratogens than surveillance of all or isolated congenital anomalies. Current literature proposes the manual review of all cases for classification into isolated or multiple congenital anomalies.METHODS
Multiple anomalies were defined as two or more major congenital anomalies, excluding sequences and syndromes. A computer algorithm for classification of major congenital anomaly cases in the EUROCAT database according to International Classification of Diseases (ICD)v10 codes was programmed, further developed, and implemented for 1 year's data (2004) from 25 registries. The group of cases classified with potential multiple congenital anomalies were manually reviewed by three geneticists to reach a final agreement of classification as “multiple congenital anomaly” cases.RESULTSA total of 17,733 cases with major congenital anomalies were reported giving an overall prevalence of major congenital anomalies at 2.17%. The computer algorithm classified 10.5% of all cases as “potentially multiple congenital anomalies”. After manual review of these cases, 7% were agreed to have true multiple congenital anomalies. Furthermore, the algorithm classified 15% of all cases as having chromosomal anomalies, 2% as monogenic syndromes, and 76% as isolated congenital anomalies. The proportion of multiple anomalies varies by congenital anomaly subgroup with up to 35% of cases with bilateral renal agenesis.CONCLUSIONS
The implementation of the EUROCAT computer algorithm is a feasible, efficient, and transparent way to improve classification of congenital anomalies for surveillance and research. Birth Defects Research (Part A), 2011. © 2011 Wiley-Liss, Inc.
Birth Defects Research Part A Clinical and Molecular Teratology 02/2011; 91(S1):S44 - S50. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study aims to assess prevalence and pregnancy outcome for sex chromosome trisomies (SCTs) diagnosed prenatally or in the first year of life. Data held by the European Surveillance of Congenital Anomalies (EUROCAT) database on SCT cases delivered 2000-2005 from 19 population-based registries in 11 European countries covering 2.5 million births were analysed. Cases included were livebirths diagnosed to 1 year of age, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly (TOPFA). In all, 465 cases of SCT were diagnosed between 2000 and 2005, a prevalence of 1.88 per 10,000 births (95% CI 1.71-2.06). Prevalence of XXX, XXY and XYY were 0.54 (95% CI 0.46-0.64), 1.04 (95% CI 0.92-1.17) and 0.30 (95% CI 0.24-0.38), respectively. In all, 415 (89%) were prenatally diagnosed and 151 (36%) of these resulted in TOPFA. There was wide country variation in prevalence (0.19-5.36 per 1000), proportion prenatally diagnosed (50-100%) and proportion of prenatally diagnosed resulting in TOPFA (13-67%). Prevalence of prenatally diagnosed cases was higher in countries with high prenatal detection rates of Down syndrome. The EUROCAT prevalence rate for SCTs diagnosed prenatally or up to 1 year of age represents 12% of the prevalence expected from cytogenetic studies of newborn babies, as the majority of cases are never diagnosed or are diagnosed later in life. There is a wide variation between European countries in prevalence, prenatal detection and TOPFA proportions, related to differences in screening policies as well as organizational and cultural factors.
European journal of human genetics: EJHG 02/2011; 19(2):231-4. · 3.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
Circulation 02/2011; 123(8):841-9. · 14.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The use of valproic acid in the first trimester of pregnancy is associated with an increased risk of spina bifida, but data on the risks of other congenital malformations are limited.
We first combined data from eight published cohort studies (1565 pregnancies in which the women were exposed to valproic acid, among which 118 major malformations were observed) and identified 14 malformations that were significantly more common among the offspring of women who had received valproic acid during the first trimester. We then assessed the associations between use of valproic acid during the first trimester and these 14 malformations by performing a case-control study with the use of the European Surveillance of Congenital Anomalies (EUROCAT) antiepileptic-study database, which is derived from population-based congenital-anomaly registries. Registrations (i.e., pregnancy outcomes with malformations included in EUROCAT) with any of these 14 malformations were compared with two control groups, one consisting of infants with malformations not previously linked to valproic acid use (control group 1), and one consisting of infants with chromosomal abnormalities (control group 2). The data set included 98,075 live births, stillbirths, or terminations with malformations among 3.8 million births in 14 European countries from 1995 through 2005.
Exposure to valproic acid monotherapy was recorded for a total of 180 registrations, with 122 registrations in the case group, 45 in control group 1, and 13 in control group 2. As compared with no use of an antiepileptic drug during the first trimester (control group 1), use of valproic acid monotherapy was associated with significantly increased risks for 6 of the 14 malformations under consideration; the adjusted odds ratios were as follows: spina bifida, 12.7 (95% confidence interval [CI], 7.7 to 20.7); atrial septal defect, 2.5 (95% CI, 1.4 to 4.4); cleft palate, 5.2 (95% CI, 2.8 to 9.9); hypospadias, 4.8 (95% CI, 2.9 to 8.1); polydactyly, 2.2 (95% CI, 1.0 to 4.5); and craniosynostosis, 6.8 (95% CI, 1.8 to 18.8). Results for exposure to valproic acid were similar to results for exposure to other antiepileptic drugs.
The use of valproic acid monotherapy in the first trimester was associated with significantly increased risks of several congenital malformations, as compared with no use of antiepileptic drugs or with use of other antiepileptic drugs.
New England Journal of Medicine 06/2010; 362(23):2185-93. · 53.30 Impact Factor
-
Epidemiology (Cambridge, Mass.) 03/2010; 21(2):275-7; author reply 277. · 5.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Evidence is unclear as to whether there is a socio-economic gradient in cerebral palsy (CP) prevalence beyond what would be expected from the socio-economic gradient for low birthweight, a strong risk factor for CP. We conducted a population-based study in five regions of the UK with CP registers, to investigate the relationship between CP prevalence and socio-economic deprivation, and how it varies by region, by birthweight and by severity and type of CP. The total study population was 1 657 569 livebirths, born between 1984 and 1997. Wards of residence were classified into five quintiles according to a census-based deprivation index, from Q1 (least deprived) to Q5 (most deprived). Socio-economic gradients were modelled by Poisson regression, and region-specific estimates combined by meta-analysis. The prevalence of postneonatally acquired CP was 0.14 per 1000 livebirths overall. The mean deprivation gradient, expressed as the relative risk in the most deprived vs. the least deprived quintile, was 1.86 (95% confidence interval [95% CI 1.19, 2.88]). The prevalence of non-acquired CP was 2.22 per 1000 livebirths. For non-acquired CP the gradient was 1.16 [95% CI 1.00, 1.35]. Evidence for a socio-economic gradient was strongest for spastic bilateral cases (1.32 [95% CI 1.09, 1.59]) and cases with severe intellectual impairment (1.59 [95% CI 1.06, 2.39]). There was evidence for differences in gradient between regions. The gradient of risk of CP among normal birthweight births was not statistically significant overall (1.21 [95% CI 0.95, 1.54]), but was significant in two regions. There was non-significant evidence of a reduction in gradients over time. The reduction of the higher rates of postneonatally acquired CP in the more socioeconomically deprived areas is a clear goal for prevention. While we found evidence for a socio-economic gradient for non-acquired CP of antenatal or perinatal origin, the picture was not consistent across regions, and there was some evidence of a decline in inequalities over time. The steeper gradients in some regions for normal birthweight cases and cases with severe intellectual impairment require further investigation.
Paediatric and Perinatal Epidemiology 03/2010; 24(2):149-55. · 2.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The EUROCAT website www.eurocat-network.eu publishes prenatal detection rates for major congenital anomalies using data from European population-based congenital anomaly registers, covering 28% of the EU population as well as non-EU countries. Data are updated annually. This information can be useful for comparative purposes to clinicians and public health service managers involved in the antenatal care of pregnant women as well as those interested in perinatal epidemiology.
Journal of Medical Screening 01/2010; 17(2):97-8. · 1.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: EUROCAT (European Surveillance of Congenital Anomalies) is the network of population-based registers of congenital anomaly in Europe, with a common protocol and data quality review, covering 1.5 million annual births in 22 countries. EUROCAT recorded a total prevalence of major congenital anomalies of 23.9 per 1,000 births for 2003-2007. 80% were livebirths. 2.5% of livebirths with congenital anomaly died in the first week of life. 2.0% were stillbirths or fetal deaths from 20 weeks gestation. 17.6% of all cases were terminations of pregnancy following prenatal diagnosis (TOPFA). Thus, congenital anomalies overwhelmingly concern children surviving the early neonatal period, who have important medical, social or educational needs. The prevalence of chromosomal anomalies was 3.6 per 1,000 births, contributing 28% of stillbirths/fetal deaths from 20 weeks gestation with congenital anomaly, and 48% of all TOPFA. Congenital heart defects (CHD) were the most common non-chromosomal subgroup, at 6.5 per 1,000 births, followed by limb defects (3.8 per 1,000), anomalies of urinary system (3.1 per 1,000) and nervous system defects (2.3 per 1,000). In 2004, perinatal mortality associated with congenital anomaly was 0.93 per 1,000 births, and TOPFA 4.4 per 1,000 births, with considerable country variation. Primary prevention of congenital anomalies in the population based on controlling environmental risk factors is a crucial policy priority, including preconceptional care and whole population approaches.
Advances in experimental medicine and biology 01/2010; 686:349-64. · 1.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy.
A review of all published cohort studies to identify key indications and a population based case-control study to test these indications.
Review of PubMed, Web of Science, and Embase for papers about carbamazepine exposure in the first trimester of pregnancy and specific malformations, and the EUROCAT Antiepileptic Study Database, including data from 19 European population based congenital anomaly registries, 1995-2005.
The literature review covered eight cohort studies of 2680 pregnancies with carbamazepine monotherapy exposure, and the EUROCAT dataset included 98 075 registrations of malformations covering over 3.8 million births.
Overall prevalence for a major congenital malformation after exposure to carbamazepine monotherapy in the first trimester. Odds ratios for malformations with exposure to carbamazepine among cases (five types of malformation identified in the literature review) compared with two groups of controls: other non-chromosomal registrations of malformations and chromosomal syndromes.
The literature review yielded an overall prevalence for a major congenital malformation of 3.3% (95% confidence interval 2.7 to 4.2) after exposure to carbamazepine monotherapy in the first trimester. In 131 registrations of malformations, the fetus had been exposed to carbamazepine monotherapy. Spina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy (odds ratio 2.6 (95% confidence interval 1.2 to 5.3) compared with no antiepileptic drug), but the risk was smaller for carbamazepine than for valproic acid (0.2, 0.1 to 0.6). There was no evidence for an association with total anomalous pulmonary venous return (no cases with carbamazepine exposure), cleft lip (with or without palate) (0.2, 0.0 to 1.3), diaphragmatic hernia (0.9, 0.1 to 6.6), or hypospadias (0.7, 0.3 to 1.6) compared with no exposure to antiepileptic drugs. Further exploratory analysis suggested a higher risk of single ventricle and atrioventricular septal defect.
Carbamazepine teratogenicity is relatively specific to spina bifida, though the risk is less than with valproic acid. Despite the large dataset, there was not enough power to detect moderate risks for some rare major congenital malformations.
BMJ (Clinical research ed.). 01/2010; 341:c6581.
