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Chromoanagenesis are complex chromosomal rearrangements that are supposed to occur during a single catastrophic event. They may result in loss or gain of genetic material and may be responsible for various phenotypes. These rearrangements are usually sporadic. However, some familial cases have been reported. Here, we studied six families in which a healthy parent carrying a chromoanagenesis transmitted its rearrangement in an unbalanced manner to its descent. The rearrangements were characterized by karyotype, fluorescent in situ hybridization, chromosomal microarray and whole genome sequencing (WGS) in the parents and their offspring. We then hypothesized meiosis-pairing figures of parental chromosomes that may have led to meiotic recombination between normal and abnormal homologous chromosomes, resulting in the formation of new unbalanced rearrangements. This work underlines that chromoanagenesis can be associated with a normal phenotype and a normal fertility, even in males, and that WGS may be the unique way to identify these rearrangements in some cases. Chromoanagenesis can be transmitted in an unbalanced and unpredictable way because of meiotic recombination. Thus, genetic counseling and technical choice for prenatal diagnosis are complex. Finally this work questions the meiotic pairing mechanisms of complex rearrangements, still poorly understood.

Amniotic band syndrome (ABS) and limb body wall complex (LBWC) have an overlapping phenotype of multiple congenital anomalies and their etiology is unknown. We aimed to determine the prevalence of ABS and LBWC in Europe from 1980 to 2019and to describe the spectrum of congenital anomalies. In addition, we investigated maternal age and multiple birth as possible risk factors for the occurrence of ABS and LBWC. We used data from the European surveillance of congenital anomalies (EUROCAT) network including data from 30 registries over 1980–2019. We included all pregnancy outcomes, including live births, stillbirths, and terminations of pregnancy for fetal anomalies. ABS and LBWC cases were extracted from the central EUROCAT database using coding information responses from the registries. In total, 866 ABS cases and 451 LBWC cases were included in this study. The mean prevalence was 0.53/10,000 births for ABS and 0.34/10,000 births for LBWC during the 40 years. Prevalence of both ABS and LBWC was lower in the 1980s and higher in the United Kingdom. Limb anomalies and neural tube defects were commonly see in ABS, whereas in LBWC abdominal and thoracic wall defects and limb anomalies were most prevalent. Twinning was confirmed as a risk factor for both ABS and LBWC. This study includes the largest cohort of ABS and LBWC cases ever reported over a large time period using standardized EUROCAT data. Prevalence, clinical characteristics, and the phenotypic spectrum are described, and twinning is confirmed as a risk factor. info:eu-repo/semantics/publishedVersion

Background Evidence on the direction and strength of association between maternal age and the prevalence of congenital heart defects (CHD) in different age group categories is conflicting. Some studies have illustrated different trends with an increase in prevalence in younger and older age groups while other studies have reported a linear relationship. Given the increase in maternal age over recent years, it is important to study the CHD prevalence by maternal age. Objectives To examine the association between maternal age and the prevalence of CHD in Europe between 1995 and 2015 using population-based data from 24 registries belonging to the European Surveillance of Congenital Anomalies (EUROCAT) network. Methods Associations over time of all nonsyndromic CHD according to maternal age category and for three CHD severity groupings (severity group I: very severe; severity group II: severe; severity group III: less severe) were examined using Bayesian multilevel Poisson regression modeling. Further subgroup analyses were undertaken within four maternal age-bands: ≤24, 25–29, 30–34 and 35–44 years. Descriptive summaries are also presented. Results There were 51,608 nonsyndromic CHD cases in Europe over the 20-year study period. Total prevalence for all CHD combined was increased for younger mothers (≤24 years) and for mothers 35–44 years of age when compared with mothers aged 25–29 years (reference group) (IRR: 1.05, 95% CI: 1.02, 1.07). The total prevalence was increased for severity group I (very severe) only for younger mothers compared to those aged 25–29 years (IRR: 1.14, 95% CI: 1.04, 1.23). We found an increased prevalence of the following CHD subtypes: double outlet right ventricle (IRR:1.33, 95% CI: 1.09, 1.60), hypoplastic left heart syndrome (IRR: 1.18, 95% CI: 1.05, 1.32), hypoplastic right heart syndrome (IRR: 1.41, 95% CI: 1.05, 1.84), atrioventricular septal defect (IRR: 1.15, 95% CI: 1.01, 1.32), coarctation of aorta (IRR: 1.15, 95% CI: 1.03, 1.28) and atrial septal defect (IRR: 1.08, 95% CI: 1.02, 1.13). For older mothers (35–44 years) compared to the reference category, we observed an increased risk in the prevalence for severity group II (IRR: 1.09, 95% CI: 1.03, 1.14), severity group III (IRR: 1.05, 95% CI: 1.01, 1.08) and an increased prevalence of the CHD subtypes: Pulmonary valve stenosis (IRR: 1.22, 95% CI: 1.09, 1.34), ASD (IRR: 1.07, 95% CI: 1.02, 1.13), CoA (IRR: 1.18, 95% CI: 1.06, 1.32) and Tetralogy of Fallot (IRR: 1.14, 95% CI: 1.01, 1.28). Finally, for all age categories compared to the reference category, different associations of ASD and an increased prevalence of CoA was also observed. Conclusions Based on data for cases of CHD from 24 European population-based registries, evidence of a positive association between maternal age and the total prevalence of CHD for younger (≤24 years old) and older (35–44 years old) mothers was observed. The results suggest that young maternal age (≤24 years old) is a factor associated with severe CHD phenotypes while a positive association between advanced maternal age (35–44 years old) and mild CHD phenotypes was observed. publishedVersion

[Corrections added after online publication, 16 November 2022: The last name of Dr. Jennifer M. Broughan was incorrectly spelled in the initial publication. It has been corrected.] Background: Younger mothers are at a greater risk of having a pregnancy with gastroschisis and the risk is higher in the United Kingdom than other European countries. Gastroschisis is thought to be a vascular disruption anomaly and the aim of this study was to analyze the prevalence of other possible vascular disruption anomalies to determine whether both the younger maternal age and the UK associations also occur with these anomalies. Methods: All pregnancies with anomalies considered potentially due to vascular disruption from January 1, 2005 to December 31, 2017 from 26 European population-based congenital anomaly registries who were members of EUROCAT were analyzed. Multilevel models were used to allow for differences between registries when analyzing associations with maternal age, year of birth and whether the registry was in the United Kingdom. Results: There were 5,220 cases with potential vascular disruption anomalies, excluding chromosomal and genetic conditions, with a prevalence of 8.85 per 10,000 births in the United Kingdom and 5.44 in the other European countries. The prevalence per 10,000 births of gastroschisis (4.45 vs. 1.56) and congenital constriction bands (0.83 vs. 0.42) was significantly higher in the United Kingdom, even after adjusting for maternal age. However, transverse limb reduction defects had a similar prevalence (2.16 vs. 2.14 per 10,000). The expected increased prevalence in younger mothers was observed for vascular disruption anomalies overall and for the individual anomalies: gastroschisis and congenital constriction bands. Conclusion: Vascular disruption anomalies that had an increased risk for younger mothers (such as gastroschisis) had a higher maternal age standardized prevalence in the United Kingdom, while vascular disruption anomalies with weaker associations with younger mothers (such as transverse limb reduction defects) did not have an increased prevalence in the United Kingdom, which may indicate a different etiology for these anomalies. European Commission info:eu-repo/semantics/publishedVersion

Background Aplasia cutis congenita (ACC) is a rare congenital anomaly characterized by localized or widespread absence of skin at birth, mainly affecting the scalp. Most information about ACC exists as individual case reports and medium-sized studies. Objectives This study aimed to investigate the epidemiology of ACC, using data from a large European network of population-based registries for congenital anomalies (EUROCAT). Methods Twenty-eight EUROCAT population-based registries in 16 European countries were involved. Poisson regression models were exploited to estimate the overall and live birth prevalence, to test time trends in prevalence between four 5-year periods and to evaluate the impact of the change of coding for ACC from the unspecific ICD9-BPA code to the specific ICD10 code. Proportions of ACC cases associated with other anomalies were reported. Results Five hundred cases were identified in the period 1998–2017 (prevalence: 5.10 per 100,000 births). Prevalence across 5-year periods did not differ significantly and no significant differences were evident due to the change from ICD9 to ICD10 in ACC coding. Heterogeneity in prevalence was observed across registries. The scalp was the most common site for ACC (96.4%) and associated congenital anomalies were present in 33.8% of cases. Patau and Adams–Oliver syndromes were the most frequent among the associated chromosomal anomalies (88.3%) and the associated genetic syndromes (57.7%), respectively. 16% of cases were associated with limb anomalies and 15.4% with congenital heart defects. A family history of ACC was found in 2% of cases. Conclusion To our knowledge, this is the only population-based study on ACC. The EUROCAT methodologies provide reliable prevalence estimates and proportions of associated anomalies.

Background: Pierre Robin sequence (PRS) is a rare congenital anomaly. Respiratory disorders and feeding difficulties represent the main burden. Objective: The aim of this study was to investigate the epidemiology of PRS using a cohort of cases from EUROCAT, the European network of population-based registries of congenital anomalies. Methods: We analysed cases of PRS born in the period 1998-2017 collected by 29 population-based congenital anomaly registries in 17 different countries. We calculated prevalence estimates, prenatal detection rate, survival up to 1 week, and proportions of associated anomalies. The effect of maternal age was tested using a Poisson regression model. Results: Out of 11 669 155 surveyed births, a total of 1294 cases of PRS were identified. The estimate of the overall prevalence was 12.0 per 100 000 births (95% CI 9.9, 14.5). There was a total of 882 (68.2%) isolated cases, and the prevalence was 7.8 per 100 000 births (95% CI 6.7, 9.2). A total of 250 cases (19.3%) were associated with other structural congenital anomalies, 77 cases (6.0%) were associated with chromosomal anomalies and 77 (6.0%) with genetic syndromes. The prenatal detection rate in isolated cases was 12.0% (95% CI 9.8, 14.5) and increased to 16.0% (95% CI 12.7, 19.7) in the sub-period 2008-2017. The prevalence rate ratio of non-chromosomal cases with maternal age ≥35 was higher than in cases with maternal age

Background The VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, Limb abnormalities) association is the non-random occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheo-esophageal, renal, and limb anomalies. Diagnosing VACTERL patients is difficult, as many disorders have multiple features in common with VACTERL. The aims of this study were to clearly outline component features, describe the phenotypic spectrum among the largest group of VACTERL patients thus far reported, and to identify phenotypically similar subtypes. Methods A case-only study was performed assessing data on 501 cases recorded with VACTERL in the JRC-EUROCAT (Joint Research Centre-European Surveillance of Congenital Anomalies) central database (birth years: 1980-2015). We differentiated between major and minor VACTERL features and anomalies outside the VACTERL spectrum to create a clear definition of VACTERL. Results In total, 397 cases (79%) fulfilled our VACTERL diagnostic criteria. The most commonly observed major VACTERL features were anorectal malformations and esophageal atresia/tracheo-esophageal fistula (both occurring in 62% of VACTERL cases), followed by cardiac (57%), renal (51%), vertebral (33%), and limb anomalies (25%), in every possible combination. Three VACTERL subtypes were defined: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, based on severity and presence of additional congenital anomalies. Conclusion The clearly defined VACTERL component features and the VACTERL subtypes introduced will improve both clinical practice and etiologic research.

Background: The total prevalence of congenital heart defects (CHDs) varies by populations and over time. Studies that examine trends in the prevalence of CHD in different regions may shed light on our understanding of the occurrence of CHD and the impact of different risk factors. Objectives: To examine trends in total and live birth prevalence of nonsyndromic CHD in Europe between the years 2008 and 2015 and to investigate if the decreasing trend reported by previous studies is continuing. Methods: Cases of CHD delivered between January 1, 2008 and December 31, 2015 notified to 25 population-based EUROCAT (European Surveillance of Congenital Anomalies) registries in 14 countries, formed the population-based case-series. Prevalence (total/live) rates and 95% confidence intervals were calculated as the number of cases per 10,000 births (live and stillbirths). Time trends in prevalence of all nonsyndromic CHDs and for three CHD severity groups (very severe, severe, and less severe) were plotted using a Poisson regression multilevel approach. Results: The total prevalence of nonsyndromic CHD was 57.1 per 10,000 births (live births and stillbirths) for the 8-year period and remained stable across the three CHD severity groups while the live birth prevalence was 60.2 per 10,000 births. There was considerable variation in the reported total CHD prevalence and the direction of trends by registry. A decreasing prevalence ofCHD was observed for the Norway and England/Wales registries, whereas the CHD prevalence increased for registries in Italy and Croatia. Conclusions: The total prevalence of CHD in Europe between the years 2008 and 2015 remained stable for all CHD and across the three CHD severity groups. The decreasing trend reported by previous studies has not continued. However, we found significant differences in the total and live birth prevalence by registry. info:eu-repo/semantics/publishedVersion

Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA.Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation.Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 μg/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements.Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 pregnancies every year.

ObjectiveTo assess trends in the average costs and effectiveness of the French ultrasound screening programme for birth defects.DesignA population-based study.SettingNational Public Health Insurance claim database.ParticipantsAll pregnant women in the ‘Echantillon Généraliste des Bénéficiaires’, a permanent representative sample of 1/97 of the individuals covered by the French Health Insurance System.Main outcomes measuresTrends in the costs and in the average cost-effectiveness ratio (ACER) of the screening programme (in € per case detected antenatally), per year, between 2006 and 2014. incremental cost-effectiveness ratio (ICER) from 1 year to another were also estimated. We assessed costs related to the ultrasound screening programme of birth defects excluding the specific screening of Down’s syndrome. The outcome for effectiveness was the prenatal detection rate of birth defects, assessed in a previous study. Linear and logistic regressions were used to analyse time trends.ResultsDuring the study period, there was a slight decrease in prenatal detection rates (from 58.2% in 2006 to 55.2% in 2014; p=0.015). The cost of ultrasound screening increased from €168 in 2006 to €258 per pregnancy in 2014 (p=0.001). We found a 61% increase in the ACER for ultrasound screening during the study period. ACERs increased from €9050 per case detected in 2006 to €14 580 per case detected in 2014 (p=0.001). ICERs had an erratic pattern, with a strong tendency to show that any increment in the cost of screening was highly cost ineffective.ConclusionEven if the increase in costs may be partly justified, we observed a diminishing returns for costs associated with the prenatal ultrasound screening of birth defects, in France, between 2006 and 2014.

Introduction Congenital anomalies (CA) are responsible for high rates of mortality and long-term disabilities. Research on their risk factors including environmental factors is needed. Studies on exposure to arsenic (As) in tap water and the risk of CA have not provided conclusive evidence, particularly when levels of exposure were low (from 10 to 50 μg As/L). The main objective of this study was to assess the association between exposure to As in tap water and the risk of any major CA. The secondary objectives were to assess this association for the most common types of congenital anomalies (in the heart, musculoskeletal, urinary and nervous systems). Methods A semi-ecological study was conducted from births recorded at the University Hospital of Clermont-Ferrand, France, in 2003, 2006 and 2010. The medico-obstetric data were available at individual level. Children with congenital anomalies were identified from the database of the regional registry of congenital anomalies: the Centre d’Etudes des Malformations Congenitales Auvergne (CEMC-Auvergne). As exposure was estimated from the concentrations of As measured during sanitary control of tap water supplied in the mothers' commune of residence (aggregate data). French guidelines for As in tap water were used to identify the two groups: “≥ 10 μg As/L group” and “[0–10) μg As/L group”. Multivariable logistic regression models were fit. Results 5263 children (5.1% with a CA) were included. In stratified analysis by gender of the child, positive associations between As exposure exceeding 10 μg/L and risk of any major CA (adjusted OR = 2.41; 95%CI: 1.36–4.14) and of congenital heart anomalies (adjusted OR = 3.66; 95%CI: 1.62–7.64) were only shown for girls. No association was found for boys. Conclusion This French semi-ecological study provides additional arguments for the association between exposure to As exceeding 10 μg/L in tap water and the risk of CA especially in a context of low exposure. Further studies are needed to better understand the interaction between arsenic exposure and child gender.

In a population-based study, we found an overall false-positive rate of 8.8% for the second and third trimester ultrasounds. Although numerous studies have been performed to examine factors which lead to false negatives, the same is not true for the factors associated with false positives. The principal objective of this study was to look for risk factors for false-positive diagnoses of fetal malformations on obstetric ultrasound scans.In this nested case-control study, the case infants were those whose mother had a false-positive antenatal ultrasound diagnosis of a malformation during the second or third trimester (ultrasound false-positives) and who were live - or stillborn in Auvergne in 2006-2010. The control group comprised all children who were ultrasound true-negatives in 2005 and 2007. The study included 46 cases and 184 controls, matched according to the level of the maternity unit in which they were born.Most false-positive diagnoses were minor malformations. The mean term at this false-positive diagnosis was 27.7±5.4 weeks; in 46.8% of cases, the diagnosis was made during the second-trimester ultrasound. A single malformation was suspected in 95.7% of the cases. In 97.9% of cases, only one anatomical system was affected. In all, 49 malformations were identified among the 46 cases and their distribution differed according to anatomical system. The only risk factor identified was a body mass index (BMI)25 (ORa=1.7; 95%CI: 1.2-2.4).A maternal BMI25 was the only risk factor identified for a false-positive ultrasound diagnosis of a fetal malformation.

Background The different mechanisms leading to a solitary kidney should be differentiated because the long-term outcome might be different. The fetal period is the best moment to make a true diagnosis of congenital unilateral renal agenesis (URA). The objective was to determine the prevalence of URA at birth. The secondary objectives were to describe the evolution of sensitivity of prenatal diagnosis over time and the different forms of URA (isolated and associated with other malformations) detected up to 1 year. Methods The cases were retrospectively identified through two French population-based birth defect registries (Auvergne and Bas-Rhin) between 1995 and 2013. Stillbirths and fetuses up to 22 weeks of gestation and infants up to 1 year old with URA were included. Results A total of 177 cases of URA were registered. The prevalence at birth was 4.0/10,000. The overall prenatal prevalence was 3.6/10,000 (isolated URA: 2.8/10,000). URA were isolated (59.9%), associated with isolated contralateral congenital anomaly of kidney or urinary tract (CAKUT) (7.3%) and with other extra-renal anomalies (32.8%). The total proportion of contralateral CAKUT was 15%. Only three cases presented an aneuploidy, prenatally detected and conducting to a termination of pregnancy. The sensitivity of prenatal diagnosis improved over time (from 54.2% in 1995 to 1997 to 95.8% in 2010 to 2013; p = 0.002). Conclusion Our study provides estimates of prevalence of URA at birth. A longitudinal cohort from the antenatal period to puberty should be performed to determine the prognosis of the contralateral kidney among these children with isolated, associated with contralateral CAKUT and URA with extra-renal anomalies. Birth Defects Research 109:1204-1211, 2017. © 2017 Wiley Periodicals, Inc.

ObjectiveTo assess the association between exposure to monotherapy with 10 different antiepileptic drugs (AEDs) during the first 2 months of pregnancy and the risk of 23 major congenital malformations (MCMs).MethodsThis nationwide cohort study, based on the French health care databases, included all pregnancies ≥20 weeks and ending between January 2011 and March 2015. Women were considered to be exposed when an AED had been dispensed between 1 month before and 2 months after the beginning of pregnancy. The reference group included pregnant women with no reimbursement for AEDs. MCMs were detected up to 12 months after birth (24 months for microcephaly, hypospadias, and epispadias). Odds ratios (ORs) were adjusted for potential confounders for MCMs with at least 5 cases. Otherwise, we calculated crude ORs with exact confidence intervals (CIs).ResultsThe cohort included 1,886,825 pregnancies, 2,997 of which were exposed to lamotrigine, 1,671 to pregabalin, 980 to clonazepam, 913 to valproic acid, 579 to levetiracetam, 517 to topiramate, 512 to carbamazepine, 365 to gabapentin, 139 to oxcarbazepine, and 80 to phenobarbital. Exposure to valproic acid was associated with 8 specific types of MCMs (e.g., spina bifida, OR 19.4, 95% CI 8.6–43.5), and exposure to topiramate was associated with an increased risk of cleft lip (6.8, 95% CI 1.4–20.0). We identified 3 other signals. We found no significant association for lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, and gabapentin.ConclusionsThese results confirm the teratogenicity of valproic acid and topiramate. Because of the small numbers of cases and possible confounding, the other 3 signals should be interpreted with appropriate caution.

Achondroplasia is a rare genetic disorder resulting in short-limb skeletal dysplasia. We present the largest European population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. All cases of achondroplasia notified to 28 EUROCAT registries (1991-2015) were included in the study. Prevalence, birth outcomes, prenatal diagnosis, associated anomalies, and the impact of paternal and maternal age on de novo achondroplasia were presented. The study population consisted of 434 achondroplasia cases with a prevalence of 3.72 per 100,000 births (95%CIs: 3.14-4.39). There were 350 live births, 82 terminations of pregnancy after prenatal diagnosis, and two fetal deaths. The prenatal detection rate was significantly higher in recent years (71% in 2011-2015 vs. 36% in 1991-1995). Major associated congenital anomalies were present in 10% of cases. About 20% of cases were familial. After adjusting for maternal age, fathers >34 years had a significantly higher risk of having infants with de novo achondroplasia than younger fathers. Prevalence was stable over time, but regional differences were observed. All pregnancy outcomes were included in the prevalence estimate with 80.6% being live born. The study confirmed the increased risk for older fathers of having infants with de novo achondroplasia. Funding for the JRC-EUROCAT Central Registry is described in Kinsner-Ovaskainen et al. (2018). We thank Prof. Joan Morris (St. George's University of London) for her helpful suggestions. info:eu-repo/semantics/publishedVersion

Background: Dandy-Walker (DW) malformation is a rare and severe congenital anomaly of the posterior fossa affecting the development of the cerebellum and the fourth ventricle. Objective: The aim of this study was to investigate the epidemiology of DW malformation, using data from the European population-based registries of congenital anomalies in the European Surveillance of Congenital Anomalies network. Methods: Anonymous individual data on cases of DW malformation diagnosed in 2002–2015 from 28 registries in 17 countries were included. Prevalence, prenatal detection rate, proportions and types of associated anomalies were estimated. Cases of DW variant were considered and analysed separately. Results: Out of 8,028,454 surveyed births we identified a total of 734 cases, including 562 DW malformation cases and 172 DW variant cases. The overall prevalence of DW malformation was 6.79 per 100,000 births (95% CI 5.79–7.96) with 39.2% livebirths, 4.3% foetal deaths from 20 weeks gestational age, and 56.5% terminations of pregnancy after prenatal diagnosis of foetal anomaly at any gestation (TOPFA). The livebirth prevalence was 2.74 per 100,000 births (95% CI 2.08–3.61). The prenatal detection rate was 87.6%. Two-hundred and seventy-three cases (48.6%) had an isolated cerebral anomaly and 24.2, 19.2 and 5.5% cases were associated with other structural non-cerebral anomalies, chromosomal anomalies and genetic syndromes respectively. The prevalence of DW variant was 2.08 per 100,000 (95% CI 1.39–3.13). Conclusions: This European population-based study provides the epidemiological profile of DW malformation. All birth outcomes were analysed and TOPFA represented more than half of the cases. About 50% of the cases of DW malformation were associated with other non-cerebral anomalies. Large populations and all birth outcomes are essential in epidemiological studies of rare and severe congenital anomalies.

Background Transposition of great arteries (TGA) defined as the combination of concordant atrioventricular and discordant ventriculo-arterial connections is one of the most common congenital heart defects. Prenatal diagnosis of TGA remains difficult. To determine the impact of antenatal diagnosis we evaluated the sensitivity of antenatal detection and the neonatal mortality of TGA considering two study periods and two major types of TGA. Methods A cross-sectional study was performed. Data were collected from a French population-based birth defect registry. From 1988 to 2012, 94 fetuses with TGA were registered. The study period was subdivided into the 1988 to 1999 period and the 2000 to 2012 period. Two types of TGA were considered: isolated TGA (n = 66) and associated TGA (n = 28). A stratified analysis was performed considering the study periods and the types of TGA. RESULTS Considering the study periods, the sensitivity of prenatal detection of TGA increased significantly (9.8% vs. 51.5%, p = 0.0001). The same trend was found for associated TGA (4.8% vs. 33.3%, p = 0.002) and isolated TGA (21.1% vs. 100%, p

Background The prognosis and early neonatal management of the VACTERL association depend mainly on the severity of malformations ascertained prenatally. Methods Here we reviewed the spectrum of clinical features observed in cases of VACTERL association ascertained prenatally through ultrasound examination but examined at birth and compared them with cases ascertained postnatally. Results From 1995 to 2011, a total of 19 cases of VACTERL association were observed in our center; 10 were ascertained prenatally and confirmed after birth whereas 9 were ascertained only after birth. The types and frequencies of malformations observed prenatally were as follows: renal malformations (45%), tracheoesophageal fistula (44%), cardiac malformations (20%), vertebral (13%), and limb (11%) defects. Anal atresia was never detected using routine prenatal ultrasound examination. Conclusion Further studies of fetuses with the VACTERL association are necessary to better delineate the malformations spectrum observed prenatally to improve the early recognition of the VACTERL association. Birth Defects Research (Part A) 103:880–886, 2015. © 2015 Wiley Periodicals, Inc.

ObjectiveTo analyse trends in the number of ultrasound examinations in relation to the effectiveness of prenatal detection of birth defects using population-based data in France.DesignA multiple registry-based study of time trends in resource use (number of ultrasounds) and effectiveness (proportion of cases prenatally diagnosed).SettingThree registries of congenital anomalies and claims data on ultrasounds for all pregnant women in France.ParticipantsThere were two samples of pregnant women. Effectiveness was assessed using data from three French birth defect registries. Resource use for ultrasound screening was based on the French national healthcare database.Main outcome measuresThe main outcome measures were prenatal diagnosis (effectiveness) and the average number of ultrasounds (resource use). Statistical analyses included linear and logistic regression models to assess trends in resource use and effectiveness of prenatal testing, respectively.ResultsThe average number of ultrasound examinations per pregnancy significantly increased over the study period, from 2.47 in 2006 to 2.98 in 2014 (p=0.005). However, there was no significant increase in the odds of prenatal diagnosis. The probability of prenatal diagnosis was substantially higher for cases associated with a chromosomal anomaly (91.2%) than those without (51.8%). However, there was no evidence of an increase in prenatal detection of either over time.ConclusionsThe average number of ultrasound examinations per pregnancy increased over time, whereas the probability of prenatal diagnosis of congenital anomalies did not. Hence, there is a need to implement policies such as high-quality training programmes which can improve the efficiency of ultrasound examinations for prenatal detection of congenital anomalies.

The prognosis and early neonatal management of the VACTERL association depend mainly on the severity of malformations ascertained prenatally.Here we reviewed the spectrum of clinical features observed in cases of VACTERL association ascertained prenatally through ultrasound examination but examined at birth and compared them with cases ascertained postnatally.From 1995 to 2011, a total of 19 cases of VACTERL association were observed in our center; 10 were ascertained prenatally and confirmed after birth whereas 9 were ascertained only after birth. The types and frequencies of malformations observed prenatally were as follows: renal malformations (45%), tracheoesophageal fistula (44%), cardiac malformations (20%), vertebral (13%), and limb (11%) defects. Anal atresia was never detected using routine prenatal ultrasound examination.Further studies of fetuses with the VACTERL association are necessary to better delineate the malformations spectrum observed prenatally to improve the early recognition of the VACTERL association.

This work was funded as part of the Hospital Clinical Research Programme, in 2010, by the French Health Ministry.; International audience; BACKGROUND: Congenital malformations occur in 3-4% of live births. Their prenatal detection is performed by ultrasound screening. Any announcement about a suspected malformation is a source of stress for the parents, and misdiagnosis during ultrasound screening can lead to expensive and sometimes iatrogenic medical interventions. In this study, we aim to determine the false-positive rate, first overall and then by anatomical system, of ultrasound screening for congenital malformations in the second and third trimesters of pregnancy. METHODS: Our sample includes all children born between 1 January, 2006, and 31 December, 2009, in the French region of Auvergne, whose mother had a prenatal ultrasound diagnosis of a congenital malformation during the second or third trimester of pregnancy confirmed by a follow-up ultrasound examination by an expert consultant ultrasonographer. The study included 526 fetuses, divided in 3 groups: false positives, diagnostic misclassifications, and true positives. The rates of false positives and diagnostic misclassifications were calculated for the sample as a whole and then by anatomical system. RESULTS: Overall, the false-positive rate was 8.8% and the rate of diagnostic misclassification 9.2%. The highest false-positive rates were found for renal and gastrointestinal tract malformations, and the highest diagnostic misclassification rates for cerebral and cardiac malformations. The diagnostic misclassification rate was significantly higher than the false-positive rate for cardiac malformations. CONCLUSION: The false-positive rate during prenatal ultrasound is not insignificant; these misdiagnoses cause psychological stress for the parents and overmedicalisation of the pregnancy and the child.

International audience; BACKGROUND: Conventional power studies possess limited ability to assess the performance of cluster detection tests. In particular, they cannot evaluate the accuracy of the cluster location, which is essential in such assessments. Furthermore, they usually estimate power for one or a few particular alternative hypotheses and thus cannot assess performance over an entire region. Takahashi and Tango developed the concept of extended power that indicates both the rate of null hypothesis rejection and the accuracy of the cluster location. We propose a systematic assessment method, using here extended power, to produce a map showing the performance of cluster detection tests over an entire region. METHODS: To explore the behavior of a cluster detection test on identical cluster types at any possible location, we successively applied four different spatial and epidemiological parameters. These parameters determined four cluster collections, each covering the entire study region. We simulated 1,000 datasets for each cluster and analyzed them with Kulldorff's spatial scan statistic. From the area under the extended power curve, we constructed a map for each parameter set showing the performance of the test across the entire region. RESULTS: Consistent with previous studies, the performance of the spatial scan statistic increased with the baseline incidence of disease, the size of the at-risk population and the strength of the cluster (i.e., the relative risk). Performance was heterogeneous, however, even for very similar clusters (i.e., similar with respect to the aforementioned factors), suggesting the influence of other factors. CONCLUSIONS: The area under the extended power curve is a single measure of performance and, although needing further exploration, it is suitable to conduct a systematic spatial evaluation of performance. The performance map we propose enables epidemiologists to assess cluster detection tests across an entire study region.

To investigate prevalence of iron deficiency and examine the relationship between iron status and Health-related Quality of Life among female students.Cross-sectional study.Data were collected from 543 female students, aged 17 to 38 years, attending University or secondary schools in Clermont-Ferrand (France) and its metropolitan area. Three groups were defined, according to the rate of serum ferritin: iron deficient (serum ferritin15 microg/L), iron depletion borderline (serum ferritin 15-20 microg/L), and iron replete (serum ferritin20 microg/L). Those 3 groups of menstruating female students were compared in terms of health-related quality of life using univariate analysis.Health-related Quality of Life based on SF-36 questionnaire, and iron status measured by serum ferritin.The prevalence of iron deficiency was 19.3%, the prevalence of borderline iron status was 11.4%. Regarding the SF-36 questionnaire, the only significant difference between iron deficient and iron replete female students concerned the dimension reflecting 'general health', which was significantly lower in iron deficient group (p = 0.015).Iron deficiency seems to impair the perceived general health in female students. Further research should be conducted on this little known subject.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 33 - N° 4 - p. 355