Ten-year survival of children with trisomy 13 or trisomy 18: a multi-registry European cohort study

Objective To investigate the survival to 10 years of age of children with trisomy 13 (T13) and children with trisomy 18 (T18), born 1995–2014. Design Population-based cohort study that linked mortality data to data on children born with T13 or T18, including translocations and mosaicisms, from 13 member registries of EUROCAT, a European network for the surveillance of congenital anomalies. Setting 13 regions in nine Western European countries. Patients 252 live births with T13 and 602 with T18. Main outcome measures Survival at 1 week, 4 weeks and 1, 5 and 10 years of age estimated by random-effects meta-analyses of registry-specific Kaplan-Meier survival estimates. Results Survival estimates of children with T13 were 34% (95% CI 26% to 46%), 17% (95% CI 11% to 29%) and 11% (95% CI 6% to 18%) at 4 weeks, 1 and 10 years, respectively. The corresponding survival estimates were 38% (95% CI 31% to 45%), 13% (95% CI 10% to 17%) and 8% (95% CI 5% to 13%) for children with T18. The 10-year survival conditional on surviving to 4 weeks was 32% (95% CI 23% to 41%) and 21% (95% CI 15% to 28%) for children with T13 and T18, respectively. Conclusions This multi-registry European study found that despite extremely high neonatal mortality in children with T13 and T18, 32% and 21%, respectively, of those who survived to 4 weeks were likely to survive to age 10 years. These reliable survival estimates are useful to inform counselling of parents after prenatal diagnosis

Gastrostomy and congenital anomalies: a European population-based study

Objective To report and compare the proportion of children with and without congenital anomalies undergoing gastrostomy for tube feeding in their first 5 years. Methods A European, population-based data-linkage cohort study (EUROlinkCAT). Children up to 5 years of age registered in nine EUROCAT registries (national and regional) in six countries and children without congenital anomalies (reference children) living in the same geographical areas were included. Data on hospitalisation and surgical procedures for all children were obtained by electronic linkage to hospital databases. Results The study included 91 504 EUROCAT children and 1 960 272 reference children. Overall, 1200 (1.3%, 95% CI 1.2% to 1.6%) EUROCAT children and 374 (0.016%, 95% CI 0.009% to 0.026%) reference children had a surgical code for gastrostomy within the first 5 years of life. There were geographical variations across Europe with higher rates in Northern Europe compared with Southern Europe. Around one in four children with Cornelia de Lange syndrome and Wolf-Hirschhorn syndrome had a gastrostomy. Among children with structural anomalies, those with oesophageal atresia had the highest proportion of gastrostomy (15.9%). Conclusions This study including almost 2 million reference children in Europe found that only 0.016% of these children had a surgery code for gastrostomy before age 5 years. The children with congenital anomalies were on average 80 times more likely to need a gastrostomy before age 5 years than children without congenital anomalies. More than two-thirds of gastrostomy procedures performed within the first 5 years of life were in children with congenital anomalies

The Mayer-Rokitansky-Küster-Hauser syndrome (congenital absence of uterus and vagina) – phenotypic manifestations and genetic approaches

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome affects at least 1 out of 4500 women and has for a long time been considered as a sporadic anomaly. Congenital absence of upper vagina and uterus is the prime feature of the disease which, in addition, is often found associated with unilateral renal agenesis or adysplasia as well as skeletal malformations (MURCS association). The phenotypic manifestations of MRKH overlap various other syndromes or associations and thus require accurate delineation. Since MRKH manifests itself in males, the term GRES syndrome (Genital, Renal, Ear, Skeletal) might be more appropriate when applied to both sexes. The MRKH syndrome, when described in familial aggregates, seems to be transmitted as an autosomal dominant trait with an incomplete degree of penetrance and variable expressivity. This suggests the involvement of either mutations in a major developmental gene or a limited chromosomal deletion. Until recently progress in understanding the genetics of MRKH syndrome has been slow, however, now HOX genes have been shown to play key roles in body patterning and organogenesis, and in particular during genital tract development. Expression and/or function defects of one or several HOX genes may account for this syndrome

Evaluation of the prenatal diagnosis of neural tube defects by ultrasonographic examination in different centres across Europe.

OBJECTIVE: Evaluation of prenatal diagnosis of neural tube defects by ultrasound examination in unselected populations across Europe. SETTING: Prenatal ultrasound units in areas that report to contributing congenital malformation registers. METHODS: All cases with a suspected or confirmed neural tube defect and delivered within the 30 month study period were identified from 18 Congenital Malformation Registers from 11 European countries. Data on the pregnancy, prenatal scans, outcome of pregnancy, and information on different screening policies for each country were analysed. RESULTS: 670766 deliveries occurred in the area covered by the registers during the study period. A neural tube defect was diagnosed at delivery in 542 cases. In 84% of these, the lesion was isolated (166 anencephaly, 252 spina bifida, 35 encephalocele). Of the 166 isolated cases with anencephaly, 96% were correctly identified prenatally; one was missed on scan, two were wrongly diagnosed, and four were not scanned (sensitivity 98%). 84% of the prenatal diagnoses were made before 24 weeks' gestation; 86% of isolated anencephalic pregnancies were terminated. Of the 252 cases of isolated spina bifida, 171 (68%) were correctly identified prenatally; 66% of these before 24 weeks' gestation. The diagnosis was missed on scan in 60 cases and 21 were not scanned (sensitivity 75%). The mean reduction in birth prevalence because of termination of pregnancy for spina bifida was 49% (range 6-100%). There was a wide variation between centres in prenatal detection rate (33-100%), termination of pregnancy of prenatally diagnosed cases (17-100%), and gestation both at diagnosis and termination of pregnancy. CONCLUSION: A high prenatal detection rate for anencephaly was reported by all registers. There is a large variation in prenatal detection and termination rates for spina bifida between centres, reflecting differences both in policy and culture

Evaluation of the prenatal diagnosis of neural tube defects by fetal ultrasonographic examination in different centres across Europe

Objective-Evaluation of prenatal diagnosis of neural tube defects by ultrasound examination in unselected populations across Europe. Setting-Prenatal ultrasound units in areas that report to contributing congenital malformation registers. Methods-All cases with a suspected or confirmed neural tube defect and delivered within the 30 month study period were identified from 18 Congenital Malformation Registers from 11 European countries. Data on the pregnancy, prenatal scans, outcome of pregnancy, and information on different screening policies for each country were analysed. Results-670 766 deliveries occurred in the area covered by the registers during the study period. A neural tube defect was diagnosed at delivery in 542 cases. In 84% of these, the lesion was isolated (166 anencephaly, 252 spina bifida, 35 encephalocele). Of the 166 isolated cases with anencephaly, 96% were correctly identified prenatally; one was missed on scan, two were wrongly diagnosed, and four were not scanned (sensitivity 98%). 84% of the prenatal diagnoses were made before 24 weeks' gestation; 86% of isolated anencephalic pregnancies were terminated. Of the 252 cases of isolated spina bifida, 171 (68%) were correctly identified prenatally; 66% of these before 24 weeks' gestation. The diagnosis was missed on scan in 60 cases and 21 were not scanned (sensitivity 75%). The mean reduction in birth prevalence because of termination of pregnancy for spina bifida was 49% (range 6-100%). There was a wide variation between centres in prenatal detection rate (33-100%), termination of pregnancy of prenatally diagnosed cases (17-100%), and gestation both at diagnosis and termination of pregnancy. Conclusion-A high prenatal detection rate for anencephaly was reported by all registers. There is a large variation in prenatal detection and termination rates for spina bifida between centres, reflecting differences both in policy and culture