Epidemiology of septo-optic dysplasia with focus on prevalence and maternal age – a EUROCAT study

Septo-optic nerve dysplasia is a rare congenital anomaly known to be caused by a midline developmental defect in the prosencephalon. The clinical findings are visual impairment, hypopituitarism and developmental delays and severity is related to the extent of the cerebral anomalies in septum pellucidum, optic nerves and hypothalamus. The aim of this study was to report prevalence, associated anomalies, maternal age and other epidemiology factors from a large European population based network of congenital anomaly registries (EUROCAT). Data from 29 full member registries for the years 2005-2014 were included, covering 6.4 million births. There were 99 cases with a diagnosis of septo-optic dysplasia. There was evidence of under-reporting in some registries. If underreporting was assumed to occur in the 14 registries with the lowest prevalences, the overall prevalence in the top 15 registries would be a good estimate of the overall prevalence. It was 2.51 per 100,000 births (95%CI: 1.60-3.58), with clear evidence of heterogeneity; I2=59.9%. If there was no under-reporting the estimated prevalence for all registries would be 2.51/1.35 = 1.9 per 100,000 births with 95% CI approximately (1.2 - 2.6) (The 1.35 adjusts for taking the prevalence of the highest 15 registries). The prevalence of septo-optic dysplasia in Europe is therefore likely to be between 1.9 to 2.5 per 100,000 births. The prevalence was highest for mothers aged 20 to 24 years of age and was significantly higher in UK registries compared with other EUROCAT registries (P = 0.021 in the multilevel model) and the increase was greater for younger mothers in the UK (P=0.027). The majority of septo-optic dysplasia cases were classified as isolated cerebral anomaly (77%) and only two cases had a genetic diagnosis. The anomaly may not be apparent at birth and this is reflected in that 57% of the postnatal diagnoses occurred over 1 month after birth. Septo-optic dysplasia share patterns with gastroschisis and this strengthen the hypothesis of vascular disruption being an aetiological factor for septo-optic dysplasia.JRC.F.1-Health in Societ

Epidemiology of achondroplasia: a population-based study in Europe

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.JRC.F.1-Health in Societ

Epidemiology of Dandy-Walker malformation in Europe: a EUROCAT population-based study.

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. 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 EUROCAT network. 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. 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% fetal deaths from 20 weeks gestational age, and 56.5% terminations of pregnancy after prenatal diagnosis of fetal 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). 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 necessary in epidemiology studies of rare and severe congenital anomalies.JRC.F.1-Health in Societ

Epidemiology of congenital cerebral anomalies in Europe: a multicentre, population-based EUROCAT study

Objectives: To describe the epidemiology and geographical differences in prevalence of congenital cerebral anomalies in Europe. Design and setting: Congenital cerebral anomalies (International Classification of Diseases, 10th Revision code Q04) recorded in 29 population-based EUROCAT registries conducting surveillance of 1.7 million births per annum (29% of all European births). Participants: All birth outcomes (live births, fetal deaths from 20 weeks gestation and terminations of pregnancy after prenatal diagnosis of a fetal anomaly (TOPFA)) from 2005 to 2014. Main outcome measures: Prevalence, proportion of associated non-cerebral anomalies, prenatal detection rate. Results: 4927 cases with congenital cerebral anomalies were identified; a prevalence (adjusted for under-reporting) of 9.8 (95% CI: 8.5 to 11.2) per 10 000 births. There was a sixfold difference in prevalence across the registries. Registries with higher proportions of prenatal diagnoses had higher prevalence. Overall, 55% of all cases were liveborn, 3% were fetal deaths and 41% resulted in TOPFA. Forty-eight per cent of all cases were an isolated cerebral anomaly, 25% had associated non-cerebral anomalies and 27% were chromosomal or part of a syndrome (genetic or teratogenic). The prevalence excluding genetic or chromosomal conditions increased by 2.4% per annum (95% CI: 1.3% to 3.5%), with the increases occurring only for congenital malformations of the corpus callosum (3.0% per annum) and ‘other reduction deformities of the brain’ (2.8% per annum). Conclusions: Only half of the cases were isolated cerebral anomalies. Improved prenatal and postnatal diagnosis may account for the increase in prevalence of congenital cerebral anomalies from 2005 to 2014. However, major differences in prevalence remain between regions