Amniotic band syndrome and limb body wall complex in Europe 1980–2019

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 2019 and 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 seen 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.     

Congenital clubfoot in Europe: A population‐based study

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.     

Epidemiology of orofacial clefts in a Danish county over 35 years – Before and after implementation of a prenatal screening programme for congenital anomalies

In 2004 the Danish National Board of Health changed its screening recommendations. Since 2005 a first trimester screening for Down syndrome and a prenatal ultrasound screening for congenital anomalies in the second trimester of pregnancy has been offered to all pregnant women.The aim of this study was to describe the prevalence of cleft lip with or without cleft palate and cleft palate in a Danish area and to describe associated anomalies and the development in prenatal diagnosis over time. The study was based on data from the EUROCAT Registry for Funen County. The registry is based on multiple data sources and includes information about live births, fetal deaths with a gestational age >20 weeks and terminations of pregnancy after prenatal diagnosis of severe fetal anomaly. The study included all fetuses/infants out of a population of 182,907 births diagnosed with orofacial clefts born between 1980 and 2014. There were 271 cases diagnosed with cleft lip with or without cleft palate and 127 cases diagnosed with cleft palate, giving a prevalence of 14.8 per 10,000 births for cleft lip with or without cleft palate and 6.9 per 10,000 births for cleft palate. There were no significant changes in prevalence over time for the two anomalies, calculated with and without inclusion of genetic and chromosomal cases. Overall 66 cases were diagnosed prenatally (17% of total). For isolated cleft lip with or without cleft palate none of the 157 cases born before 2005 were diagnosed prenatally compared to 34 of 58 cases (59%) born in 2005–2014 (p?<?0.01). The proportion of liveborn infants with multiple congenital anomalies also changed after 2005 with 15% (39/266) of all liveborn infants with orofacial clefts born 1980–2004 having multiple anomalies compared to 7% (7/96) in 2005–2014 (p?<?0.05).The implementation of the new screening programme in 2005 has given a major change in prenatal detection rate and reduced the proportion of liveborn infants with orofacial clefts classified as multiple congenital anomaly cases. The prevalence of cleft lip with or without cleft palate was higher than reported from many other countries.     

Prevalence and associated factors for agenesis of corpus callosum in Emilia Romagna (1981–2015)

Agenesis and hypoplasia of the corpus callosum (ACC and HCC) are heterogeneous group with a large variation in published prevalence based on few population based studies. The aim of this work is to describe prevalence, associated factors and other malformations present in cases with either agenesis or hypoplasia of the corpus callosum, using a population-based database of all malformations diagnosed in Emilia-Romagna, Italy, (the Emilia-Romagna Registry on Congenital Malformations, IMER).This registry links and integrates hospital discharge records, birth certificates with cases reported by referral clinicians to identify all structural malformations diagnosed within one year of life regarding live birth, fetal death or termination of pregnancy due to fetal malformations (TOPFA). During the study period (1981–2015) the number of cases with ACC or HCC was 255, in a reference population of 1,023,784 live births, giving an overall prevalence of 2.49 per 10,000 (1.47 per 10,000 only live birth). After 1996, with the inclusion of TOPFA in IMER registry, the overall prevalence rate increase significantly from 1.42 to 3.03 cases per 10,000 birth (p-value<0.001). Prenatal diagnosis was made in 192 cases (75.3%), at a median gestational age of 20.7 [IQR: 19.71–22.71]. Termination of pregnancy occurred in 105 of the 255 cases (41,2%). Where a prenatal diagnosis was available, 55% of cases ended in TOPFA (105/192), with higher prevalence of cases associated to central nervous system malformations and multiple birth defects, and median gestational age at diagnosis significantly less than in live birth cases (20.3 vs 29 weeks). Agenesis/hypoplasia ratio was 5.7 (217/38). The most frequently associated malformations were musculoskeletal. Trisomies were the most frequent chromosomal anomalies, in particularly trisomy18 and 13 (respectively 9/32 and 4/32 cases). Our study showed an increased risk for male infants (RR of 1.68, RR 95% CI 1.19–2.37). No differences were detected analyzing maternal age and ethnicity, and the increased risk associated to preterm birth disappeared when compared with other malformed infants.This is one of the few population based studies dealing with prevalence of agenesis and hypoplasia of corpus callosum. Prevalence is still debated, but this study adds comprehensive data, in particular inclusion of TOPFA cases. Early prenatal diagnosis, not always possible, could be crucial for decision making regarding continuation of pregnancy.     

Descriptive epidemiology of Cornelia de Lange syndrome in Europe

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome consisting of characteristic dysmorphic features, microcephaly, hypertrichosis, upper limb defects, growth retardation, developmental delay, and a variety of associated malformations. We present a population-based epidemiological study of the classical form of CdLS. The data were extracted from the database of European Surveillance of Congenital Anomalies (EUROCAT) database, a European network of birth defect registries which follow a standard methodology. Based on 23 years of epidemiologic monitoring (8,558,346 births in the 1980-2002 period), we found the prevalence of the classical form of CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS prevalence at 1.6-2.2/100,000. Live born children accounted for 91.5% (97/106) of cases, fetal deaths 2.8% (3/106), and terminations of pregnancy following prenatal diagnosis 5.7% (6/106). The most frequent associated congenital malformations were limb defects (73.1%), congenital heart defects (45.6%), central nervous system malformations (40.2%), and cleft palate (21.7%). In the last 11 years, as much as 68% of cases with major malformations were not detected by routine prenatal US. Live born infants with CdLS have a high first week survival (91.4%). All patients were sporadic. Maternal and paternal age did not seem to be risk factors for CdLS. Almost 70% of patients, born after the 37th week of gestation, weighed 相似文献   

Associated anomalies in cases with achondroplasia

Associated congenital anomalies may be observed in cases with achondroplasia. The prevalence reported in the literature and the types of co-occurring congenital anomalies are variable between the reported studies. The aim of this study was to establish the prevalence and to describe the associated anomalies in cases with achondroplasia. This study included 25 cases ascertained from our registry of congenital anomalies including all terminations of pregnancy, stillbirths and live births between 1979 and 2007 in 387,067 consecutive births (the prevalence of achondroplasia was 6.4 per 100,000 births), and 223 cases ascertained from the French Little People organization built on the model of LPA (Little People of America, Inc.). Out of these 248 cases of achondroplasia 37 (14.9%) had associated anomalies including 4 (1.6%) cases with chromosomal abnormalities (2 trisomies 21, one 22 q11.2 deletion, and one 47, XXX), 2 (0.8%) cases with recognizable non-chromosomal conditions (one Moebius syndrome and one Pierre Robin sequence) and 31(12.5%) cases with MCA (multiple congenital anomalies). The 31 cases with MCA had 45 anomalies. Anomalies in the urogenital system (24.4%), the cardiovascular system (20.0%), the musculoskeletal system (15.5%), the central nervous system (11.1%), the eye (11.1%), and the orofacial system (8.8%) were the most common MCA. The overall prevalence of associated anomalies shows that the individuals with achondroplasia need a careful screening for other congenital anomalies.     

Associated anomalies in multi-malformed infants with cleft lip and palate: An epidemiologic study of nearly 6 million births in 23 EUROCAT registries

We studied 5,449 cases of cleft lip (CL) with or without cleft palate (CL/P) identified between 1980 and 2000 from the EUROCAT network of 23 registers (nearly 6 million births) in 14 European countries. We investigated specific types of defects associated with clefts. Among CL/P cases (prevalence = 9.1 per 10,000), 1,996 (36.6%) affected only the lip (CL) and 3,453 (63.4%) involved CL and palate (CLP). A total of 3,860 CL/P cases (70.8%) occurred as isolated anomalies and 1,589 (29.2%) were associated with other defects such as multiple congenital anomalies of unknown origin (970), chromosomal (455) and recognized syndromes (164). Associated malformations were more frequent in infants who had CLP (34.0%) than in infants with CL only (20.8%). Among multi-malformed infants, 2 unrelated anomalies were found in 351 cases, 3 in 242 cases, and 4 or more in 377 cases. Among 5,449 CL/P cases, 4,719 were live births (LB) (86.6%), 203 stillbirths (SB) (3.7%), while 508 (9.3%) were terminations of pregnancy (ToP). CL/P occurred significantly more frequently in males (M/F = 1.70), especially among total isolated cases (M/F = 1.87) and CLP isolated cases (M/F = 1.92). The study confirmed that musculoskeletal, cardiovascular, and central nervous system defects are frequently associated with CL/P. An association with reduction anomalies of the brain was found. This association suggests that clinicians should seek to identify structural brain anomalies in these patients with CL/P as the potential functional consequences may be important for rehabilitation and clinical management.     

Sex chromosome trisomies in Europe: prevalence, prenatal detection and outcome of pregnancy

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.     

Beckwith Wiedemann syndrome: A population-based study on prevalence,prenatal diagnosis,associated anomalies and survival in Europe

Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. We present epidemiological and clinical aspects of patients with Beckwith Wiedemann syndrome diagnosed prenatally or in the early years of life, using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. The study population consisted of 371 cases identified between January 1990 and December 2015 in 34 registries from 16 European countries. There were 15 (4.0%) terminations of pregnancy after prenatal detection of severe anomaly/anomalies, 10 fetal deaths (2.7%), and 346 (93.3%) live-births. Twelve (3.6%) of the 330 live-births with available information on survival died in the first week of life, of those eleven (91.6%) were preterm. First-year survival rate was 90.9%. Prematurity was present in 40.6% of males and 33.9% of females. Macrosomia was found in 49.2% and 43.3% of preterm males and females, respectively. Of term newborns, 41.1% of males and 24% of females were macrosomic. Out of 353 cases with known time of diagnosis, 39.9% were suspected prenatally, 36.3% at birth, 7.6% were diagnosed in the first week of life, and 16.2% in the first year of life. The mean gestational age at prenatal diagnosis by obstetric ultrasound was 19.8?±?6.2 (11–39) gestational weeks. The mean prenatal diagnosis of cases where parents opted for termination of pregnancy was 15.3?±?2.4 (11–22) gestational weeks, and the mean gestational age at termination was 19.3?±?4.1 (13–26) gestational weeks. The prenatal detection rate was 64.1% (141/220) with no significant change over time. There were 12.7% of familial cases. The study confirmed the association of assisted reproductive technologies with Beckwith Wiedemann syndrome, as 7.2% (13/181) of patients were conceived by one of the methods of assisted reproductive technologies, which was three times higher compared to the general population of the countries included in the study. Twin pregnancies of undetermined zygosity were recorded in 5.7% (21/365) cases, and were on average three to four times more common than in European countries that participated in the study. The estimated mean prevalence of classical Beckwith Wiedemann syndrome in Europe was 3.8 per 100,000 births or 1:26,000 births.     

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

Septo-optic nerve dysplasia is a rare congenital anomaly with optic nerve hypoplasia, pituitary hormone deficiencies and midline developmental defects of the brain. The clinical findings are visual impairment, hypopituitarism and developmental delays. The aim of this study was to report prevalence, associated anomalies, maternal age and other epidemiological 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. The prevalence of septo-optic dysplasia in Europe was calculated to lie between 1.9 and 2.5 per 100,000 births after adjusting for potential under-reporting in some registries. The prevalence was highest in babies of mothers aged 20–24 years of age and was significantly higher in UK registries compared with other EUROCAT registries (P?=?0.021 in the multilevel model) and the additional risk for younger mothers was significantly greater in the UK compared to the rest of Europe (P?=?0.027). The majority of septo-optic dysplasia cases were classified as an isolated cerebral anomaly (N?=?76, 77%). Forty percent of diagnoses occurred in fetuses with a prenatal diagnosis. The anomaly may not be visible at birth, which is reflected in that 57% of the postnatal diagnoses occurred over 1 month after birth.This is the first population based study to describe the prevalence of septo-optic dysplasia in Europe. Septo-optic dysplasia shares epidemiological patterns with gastroschisis and this strengthens the hypothesis of vascular disruption being an aetiological factor for septo-optic dysplasia.     

Meckel–Gruber Syndrome: a population-based study on prevalence,prenatal diagnosis,clinical features,and survival in Europe

Meckel–Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11–36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.     

The impact of prenatal diagnosis on congenital anomaly outcomes: Data from 1997 to 2016

The term prenatal diagnosis comprises a variety of techniques aimed to determine the health and condition of the embryo or foetus. Its main goal is to identify at an early stage of the pregnancy, if possible, malformations or other conditions that could increase the risk of a negative outcome in the pregnancy. The aim of this study was to assess the impact of prenatal diagnosis in Portugal in pregnancies with congenital anomalies. A cross sectional study was implemented using data for the years 1997 to 2016 from the Portuguese registry of congenital anomalies (RENAC), a population-based registry that follows EUROCAT guidelines. Analysis was restricted to malformations that are potentially detectable by prenatal diagnosis. The effect of prenatal diagnosis on outcome (death vs live birth) was estimated using a regression model. Main results indicate that prenatal diagnosis was performed in 56.1% (n?=?7605) of all registered cases. At least one malformation was detected for the first time through ultrasound (47.4%), invasive tests (5.6%) and other tests (2.2%). When analysed severe CA, 54.2% was detectible by prenatal ultrasound distributed as follows: 17.4% were diagnosed before 14 weeks of gestation, 47.6% between 14 and 23 weeks and 35.0% with 24 or more weeks of gestation. TOPFA was the option for 21.3% of these CA.Over the 20 years of analysis, there was a statistically significant increase trend in the detection rate of congenital anomalies through prenatal diagnosis compared to detection at birth or after birth (p?<?0.001).After adjusting for confounding (year, maternal age, presence of more than one malformation), prenatal diagnosis was associated with more severe outcomes (TOPFA, 40.3%; Death 3.5%) and increased the risk of the pregnancy ending in foetal death (OR?=?2.56; 95%CI?=?2.06–3.18). These results are in accordance that more severe anomalies are more easily detected prenatally.Considering the results, it is important to raise awareness about the importance of pregnancy planning and preventing the risk factors more associated with CA. More information about prognosis for children with congenital malformations is important for parents and health professionals after prenatal detection.     

A sustainable solution for the activities of the European network for surveillance of congenital anomalies: EUROCAT as part of the EU Platform on Rare Diseases Registration

The European Commission through its Directorates-General Joint Research Centre (DG JRC) and Health and Food Safety (DG SANTE) is developing the European Platform on Rare Diseases Registration (EU RD Platform) with the objective to set European-level standards for data collection and data sharing. In the field of rare diseases the EU RD Platform will be a source of information on available rare disease patient data with large transnational European coverage. One main function of the EU RD Platform is to enable interoperability for the >600 existing RD registries in Europe. The second function is to offer a sustainable solution for two large European surveillance networks: European Surveillance of Congenital Anomalies (EUROCAT) and Surveillance of Cerebral Palsy in Europe (SCPE).EUROCAT is European network of population-based registries for the epidemiological surveillance of congenital anomalies. It covers about one third of the European birth population. The Central Database contains about 800,000 cases with congenital anomalies among livebirths, stillbirths and terminations of pregnancy, reported using the same standardised classification and coding. These high quality data enables epidemiological surveillance of congenital anomalies, which includes estimating prevalence, prenatal diagnosis and perinatal mortality rates and the detection of teratogenic exposures among others. The network also develops recommendations for primary prevention in the Rare Diseases National Plans for medicinal drugs, food/nutrition, lifestyle, health services, and environmental pollution.The network has received the European Commission's support since its inception. In order to offer a sustainable solution for the continuation of EUROCAT activities, it was agreed that EUROCAT would become part of the EU RD Platform. In 2015, the European level-coordination activities and the Central Database were transferred to the DG JRC, where the JRC-EUROCAT Central Registry is now located. This paper describes the functioning of EUROCAT in the new setting, and gives an overview of the activities and the organisation of the JRC-EUROCAT Central Registry.     

Prevalence of valproate syndrome in Europe from 2005 to 2014: A registry based multi-centre study

Women with epilepsy need to continue to take anticonvulsants during their pregnancies to prevent seizures from occurring. Since the 1980's, it has been known that the use of valproate (an anticonvulsant) in the first trimester of pregnancy is associated with an increased risk of spina bifida. Recent studies have also demonstrated increased risks of other congenital anomalies as well as a risk of cognitive impairment. Doctors in the EU are now advised not to prescribe valproate in pregnant women, in women who can become pregnant or in girls unless other treatments are ineffective or not tolerated. This study aimed to determine if there has been a reduction in the numbers of babies born with valproate syndrome in Europe from 2005 to 2014. Data from 15 European congenital anomaly registries, who are members of EUROCAT (A European network of population-based registries for the epidemiologic surveillance of congenital anomalies), identified 28 cases of valproate syndrome in 2.74 million births from 2005 to 2014. The prevalence of valproate syndrome in Europe significantly decreased from 0.22 per 10,000 births in 2005/6 to 0.03 per 10,000 births in 2013/14. One registry, Ile de la Reunion, had the majority of cases (17). After excluding these cases there still remained a decreasing trend even though it no longer reached statistical significance due to the small number of cases. This study emphasises the continued need for European collaboration in analysing rare exposures and rare anomalies.     

Birth prevalence rates of skeletal dysplasias

This study establishes the prevalence rates at birth of the skeletal dysplasias which can be diagnosed in the perinatal period or during pregnancy. Using a population-based register of congenital anomalies, a prevalence rate of 3.22 0/000 was observed. The most frequent types of skeletal dysplasia were achondroplasia and osteogenesis imperfecta (0.64 0/000, 1/15,000 births), thanatophoric dysplasia and achondrogenesis (0.28 0/000). The mutation rate for achondroplasia was higher in our material than in the other studies: 3.3 x 10(-5) per gamete per generation. Our study demonstrates that prenatal diagnosis by ultrasound is possible in some skeletal dysplasias.     

Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening

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.     

Prevalence and descriptive epidemiology of Turner syndrome in the United States, 2000–2017: A report from the National Birth Defects Prevention Network

The lack of United States population-based data on Turner syndrome limits assessments of prevalence and associated characteristics for this sex chromosome abnormality. Therefore, we collated 2000–2017 data from seven birth defects surveillance programs within the National Birth Defects Prevention Network. We estimated the prevalence of karyotype-confirmed Turner syndrome diagnosed within the first year of life. We also calculated the proportion of cases with commonly ascertained birth defects, assessed associations with maternal and infant characteristics using prevalence ratios (PR) with 95% confidence intervals (CI), and estimated survival probability. The prevalence of Turner syndrome of any pregnancy outcome was 3.2 per 10,000 female live births (95% CI = 3.0–3.3, program range: 1.0–10.4), and 1.9 for live birth and stillbirth (≥20 weeks gestation) cases (95% CI = 1.8–2.1, program range: 0.2–3.9). Prevalence was lowest among cases born to non-Hispanic Black women compared to non-Hispanic White women (PR = 0.5, 95% CI = 0.4–0.6). Coarctation of the aorta was the most common defect (11.6% of cases), and across the cohort, individuals without hypoplastic left heart had a five-year survival probability of 94.6%. The findings from this population-based study may inform surveillance practices, prenatal counseling, and diagnosis. We also identified racial and ethnic disparities in prevalence, an observation that warrants further investigation.     

The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US

There have been no large population-based studies of the prevalence of achondroplasia and thanatophroic dysplasia in the United States. This study compared data from seven population-based birth defects monitoring programs in the United States. We also present data on the association between older paternal age and these birth defects, which has been described in earlier studies. The prevalence of achondroplasia ranged from 0.36 to 0.60 per 10,000 livebirths (1/27,780-1/16,670 livebirths). The prevalence of thanatophoric dysplasia ranged from 0.21 to 0.30 per 10,000 livebirths (1/33,330-1/47,620 livebirths). In Texas, fathers that were 25-29, 30-34, 35-39, and > or =40 years of age had significantly increased rates of de novo achondroplasia among their offspring compared with younger fathers. The adjusted prevalence odds ratios were 2.8 (95% CI; 1.2, 6.7), 2.8 (95% CI; 1.0, 7.6), 4.9 (95% CI; 1.7, 14.3), and 5.0 (95% CI; 1.5, 16.1), respectively. Using the same age categories, the crude prevalence odds ratios for de novo cases of thanatophoric dysplasia in Texas were 5.8 (95% CI; 1.7, 9.8), 3.9 (95% CI; 1.1, 6.7), 6.1 (95% CI; 1.6, 10.6), and 10.2 (95% CI; 2.6, 17.8), respectively. These data suggest that thanatophoric dysplasia is one-third to one-half as frequent as achondroplasia. The differences in the prevalence of these conditions across monitoring programs were consistent with random fluctuation. Birth defects monitoring programs may be a good source of ascertainment for population-based studies of achondroplasia and thanatophoric dysplasia, provided that diagnoses are confirmed by review of medical records.     

Equipoise of recent estimated Down syndrome live births in Japan

To support people with Down syndrome (DS), it is essential to know and predict the number of live births of children with this condition. In this study, we estimated DS live birth rates on the basis of maternal age distribution and numbers of births in the general population, the maternal‐age specific chance for a live birth of a child with DS, and the prenatal diagnosis/termination rate. The total number of live births in Japan decreased to less than 1 million in 2016 and the percentage of women aged 35 years old or over giving birth has increased by sixfold. Prenatal genetic testing in Japan has gradually become more widespread, and 20% of all cases of DS were diagnosed prenatally in 2016. Meanwhile, the annual projected number of DS live births has remained steady at around 2,200 (22 per 10,000 births). In 2016, it was estimated that 70% of all DS babies were born to women of advanced maternal age (AMA). Given that Japan is facing a decreasing birth rate and an aging population, adoption of the practice of prenatal genetic testing for AMA has balanced the number of DS births over the last 7 years from 2010.