Prenatal detection of rare chromosomal autosomal abnormalities in Europe.

The aim of the present study was to evaluate the prenatal detection of rare chromosomal autosomal abnormalities by ultrasound (US) examination. Data were obtained from 19 congenital malformation registries from 11 European countries, between 01/07/96 and 31/12/98. A total of 664,340 births were covered and 7,758 cases with congenital malformations were recorded. Rare autosomal abnormalities were diagnosed in 114 cases (6.6%) from a total of 1,738 chromosome abnormalities. There were a wide variety of autosomal abnormalities: the most common were deletions (33 cases), duplications (32 cases), trisomies of chromosomes 8, 9, 10, 14, 15, and 16 (23 cases), and unbalanced rearrangements (19 cases). Out of these cases, 45.6% were detected prenatally by US examination due to the presence of congenital anomaly. As for the types of chromosomal anomaly, unbalanced rearrangements and deletions were the most frequently detected by US. A high percentage of cases with balanced rearrangements were associated with severe congenital anomalies. The most frequent congenital anomalies detected by US were cystic hygroma (20.6%), central nervous system defects (17.6%), cardiac defects (13.2%), and diaphragm defects (10.3%). This large series offers useful information about prenatal diagnosis by US of congenital defects associated with rare autosomal abnormalities and it provides a valuable knowledge about outcome. Fetal anomalies detected by US that were associated with rare autosomal abnormalities were significantly more frequent than those associated with common chromosomal abnormalities (45.6 vs. 34.7%). This study indicates the need to increase the detection of congenital anomalies by US.

Oesophageal atresia: prevalence, prenatal diagnosis and associated anomalies in 23 European regions.

OBJECTIVE: To describe prevalence, prenatal diagnosis and epidemiological data on oesophageal atresia from 23 well-defined European regions and compare the prevalence between these regions. DESIGN: Population-based study using data from a large European database for surveillance of congenital anomalies (EUROCAT) for two decades (1987-2006). SETTINGS: Twenty-three participating registries based on multiple sources of information including information about live births, fetal deaths with gestational age ≥20 weeks and terminations of pregnancy. PATIENTS: 1222 cases of oesophageal atresia in a population of 5 019 804 births. RESULTS: The overall prevalence was 2.43 cases per 10 000 births (95% CI 2.30 to 2.57). There were regional differences in prevalence ranging from 1.27 to 4.55. Prenatal detection rates varied by registry from >50% of cases to <10% of cases. A total of 546 cases (44.7%) had an isolated oesophageal anomaly, 386 (31.6%) were multiple malformed and 290 (23.7%) had an association or a syndrome. There were 1084 live born cases (88.7%), 43 cases were fetal deaths and 95 cases were terminations of pregnancy. One-week survival for live births was 86.9% and 99.2% if the gestational age was ≥38 weeks and isolated oesophageal atresia was present. Males accounted for 57.3% of all cases and 38.5% of live born cases were born with gestational age <37 weeks. CONCLUSION: There were regional differences in prevalence of oesophageal atresia in Europe. Half of all cases had associated anomalies. Prenatal detection rate increased from 26% to 36.5% over the two decades. Survival in infants with isolated oesophageal atresia born at term is high.

Prenatal diagnosis and epidemiology of multicystic kidney dysplasia in Europe.

OBJECTIVES: The aim of this study is to describe the prenatal diagnosis and epidemiology of multicystic kidney dysplasia (MCKD). METHODS: The study is based on routinely collected data from a European database of major congenital anomalies including 13 registries with cases born in 1997-2006 and covering 1 458 552 births. RESULTS: There were 601 MCKD cases giving an overall prevalence of 4.12 per 10 000 births with regional variation. In live births, 87% of cases had an isolated renal anomaly and 13% had associated major nonrenal anomalies (chromosomal, syndrome or other major anomalies). For the cases with isolated renal anomalies, 51/386 (11%) and 7/386 (2%) choose to terminate the pregnancy or resulted in an intrauterine fetal death, respectively. The prenatal detection rate was 88% in both unilateral and bilateral cases. Birth outcome differed with 92% of unilateral MCKD cases being liveborn compared with 33% of bilateral MCKD cases. For unilateral MCKD cases, 84% had an isolated renal anomaly compared with 51% of bilateral MCKD cases (p < 0.001). CONCLUSIONS: Cases with unilateral MCKD are mainly liveborn, and only 16% have associated major malformations or a syndrome. Cases with bilateral MCKD are often associated with nonrenal major congenital anomalies or part of a syndrome, and only one third of bilateral MCKD cases in this study were liveborn. Prenatal detection rate of MCKD was high for both unilateral and bilateral cases. © 2014 John Wiley & Sons, Ltd.

Dyssegmental dysplasia, Silverman-Handmaker type: prenatal ultrasound findings and molecular analysis.

OBJECTIVES: The objective of this study is to describe the prenatal sonographic features and the results of DNA analysis on three fetuses with dyssegmental dysplasia, Silverman-Handmaker type (DD-SH). METHODS: A retrospective review of three fetuses with confirmed DD-SH was conducted. The fetal ultrasound findings, the radiological characteristics, and the results of the mutation analysis of the heparan sulphate perlecan gene 2 (HSPG2) were reviewed. RESULTS: There were three cases in two families with DD-SH diagnosed prenatally. The main prenatal ultrasound and the radiological features of DD-SH were severe limb shortening and vertebral segmentation and fusion defects (anisospondyly). The DNA analysis of the HSPG2 gene showed that the two affected fetuses in a nonconsanguineous family had a compound heterozygote for the c.646G > T transversion in exon 7 and a c.5788C > T transition in exon 46. The fetus born to the consanguineous couple had a homozygous mutation c.1356-27_1507 + 59del. CONCLUSION: DD-SH can be diagnosed prenatally using fetal ultrasound as early as 13 weeks. Xrays and DNA analysis of the HSPG2 gene are important for the confirmation of the diagnosis and for the preimplantation and prenatal diagnosis in pregnancies at risk. © 2013 John Wiley & Sons, Ltd.

Evaluation of the prenatal diagnosis of limb reduction deficiencies. EUROSCAN Study Group.

Ultrasound scans in the mid-trimester of pregnancy are now a routine part of antenatal care in most European countries. Using data from registries of congenital anomalies a study was undertaken in Europe. The objective of the study was to evaluate prenatal detection of limb reduction deficiencies (LRD) by routine ultrasonographic examination of the fetus. All LRDs suspected prenatally and all LRDs (including chromosome anomalies) confirmed at birth were identified from 20 Congenital Malformation Registers from the following 12 European countries: Austria, Croatia, Denmark, France, Germany, Italy, Lithuania, Spain, Switzerland, The Netherlands, UK and Ukrainia. These registries are following the same methodology. During the study period (1996-98) there were 709,030 births, and 7,758 cases with congenital malformations including LRDs. If more than one LRD was present the case was coded as complex LRD; 250 cases of LRDs with 63 (25.2%) termination of pregnancies were identified including 138 cases with isolated LRD, 112 with associated malformations, 16 with chromosomal anomalies and 38 non chromosomal recognized syndromes. The prenatal detection rate of isolated LRD was 24.6% (34 out of 138 cases) compared with 49.1% for associated malformations (55 out of 112; p<0.01). The prenatal detection of isolated terminal transverse LRD was 22.7% (22 out of 97), 50% (3 out of 6) for proximal intercalary LRD, 8.3% (1 out of 12) for longitudinal LRD and 0 for split hand/foot; for multipli-malformed children with LRD those percentages were 46.1% (30 out of 65), 66.6% (6 out of 9), 57.1% (8 out of 14) and 0 (0 out of 2), respectively. The prenatal detection rate of LRDs varied in relation with the ultrasound screening policies from 20.0% to 64.0% in countries with at least one routine fetal scan.

Anxiety and Psychological Stress Before Prenatal Screening in First-Time Mothers Who Conceived Through IVF/ICSI or Spontaneously.

Mothers' general anxiety, anxiety about the well-being of the child and psychological stress before prenatal testing was studied by comparing women who conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with women who conceived naturally. Before the first trimester screening test for Down's syndrome, a group of 51 women who conceived through IVF/ICSI and a group of 54 women who conceived spontaneously completed the State Scale of the State-Trait Anxiety Inventory (S-Anxiety; Spielberger, 1983), the Fear of Bearing a Physically or Mentally Handicapped Child Subscale of the Pregnancy-related Anxiety Questionnaire (PRAQ-R; Huizink et al., 2004), the Psychological Stress Measure (PSM; Lemyre & Tessier, 1988), and the Prenatal Psychosocial Profile (PPP; Curry, Campbell, & Christian, 1994). Women who conceived through IVF/ICSI had more elevated levels of general anxiety and psychological stress than the women who conceived naturally; however, no difference was observed between the two groups for anxiety specifically related to the health of the child. These results underline the need to monitor women's emotional state after conception via IVF/ICSI-when counseling usually ends-and around the time of the first trimester screening. Counseling might thus be extended.

Le suivi prénatal des femmes accouchant dans le canton de Vaud: etude rétrospective de 854 cas. [Prenatal care of women delivering in the Vaud canton: retrospective study of 854 cases].

The association between prenatal care and infant health has been shown in many studies. Therefore, accurate information on prenatal care is required to assess the organization of preventive measures aiming at a reducing in neonatal mortality any morbidity. We retrospectively collected data on 854 pregnancies. According to a classification scheme developed by Kessner, 61.6% of women had access to adequate prenatal care. Overall, the proportion of adequate prenatal care was lower among multiparas, and in this subgroup we found a lower rate for women with base line insurance. In the primiparas subgroup we found a lower rate of adequate prenatal care for foreigners, women under 20 years or unmarried mothers, and for women without professional activity during pregnancy, besides preterm birth was more frequent amongst women in the group of prenatal care qualified as intermediate or inadequate. The frequency of pregnancy visits and the Kessner index are discussed in a literature review. The association between socio-economic indicators and prenatal care was unexpected considering the overall wealth of Switzerland. With a 6.8% infant mortality registered in 1989, this country can be considered to have one of the lowest rates in the world. These findings nevertheless suggest the way to possible additional gains by interventions targeted to specific socio-economic groups.

Prenatal ultrasonographic detection of gastrointestinal obstruction: results from 18 European congenital anomaly registries.

OBJECTIVES: We evaluated the prenatal detection of gastrointestinal obstruction (GIO, including atresia, stenosis, absence or fistula) by routine ultrasonographic examination in an unselected population all over Europe. METHODS: Data from 18 congenital malformation registries in 11 European countries were analysed. These multisource registries used the same methodology. All fetuses/neonates with GIO confirmed within 1 week after birth who had prenatal sonography and were born during the study period (1 July 1996 to 31 December 1998) were included. RESULTS: There were 670 793 births in the area covered and 349 fetuses/neonates had GIO. The prenatal detection rate of GIO was 34%; of these 40% were detected < or = 24 weeks of gestation (WG). A total of 31% (60/192) of the isolated GIO were detected prenatally, as were 38% (59/157) of the associated GIO (p=0.26). The detection rate was 25% for esophageal obstruction (31/122), 52% for duodenal obstruction (33/64), 40% for small intestine obstruction (27/68) and 29% for large intestine obstruction (28/95) (p=0.002). The detection rate was higher in countries with a policy of routine obstetric ultrasound. Fifteen percent of pregnancies were terminated (51/349). Eleven of these had chromosomal anomalies, 31 multiple malformations, eight non-chromosomal recognized syndromes, and one isolated GIO. The participating registries reflect the various national policies for termination of pregnancy (TOP), but TOPs after 24 WG (11/51) do not appear to be performed more frequently in countries with a liberal TOP policy. CONCLUSION: This European study shows that the detection rate of GIO depends on the screening policy and on the sonographic detectability of GIO subgroups.

EUROCAT website data on prenatal detection rates of congenital anomalies.

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.

Congenital diaphragmatic hernia : a European population-based study of epidemiology, prenatal diagnosis and mortality

Aim: To study the epidemiology and the impact of prenatal diagnosis on mortality and morbidity in infants with isolated congenital diaphragmatic hernia (CDH). Methods: Cases were identified in eight population-based registries of congenital malformations (Eurocat) in Europe. Results: A total of 183 live births were included in the study. Sixty per cent died and 67% of all deaths were during the first day of life. CDH was diagnosed prenatally in 39% of cases. Both mortality and morbidity were significantly higher for infants diagnosed prenatally compared to those diagnosed postnatally. The Apgar score was a very sensitive indicator for survival. Gestational age at birth was significantly lower for infants diagnosed prenatally compared to those diagnosed postnatally (37.6 weeks vs. 38.8 weeks, p < 0.01). At the end of follow-up, half of the survivors were leading a normal life. The most frequently reported health problems were respiratory and gastrointestinal symptoms. Conclusions: In this population-based study, mortality for infants with CDH was high (60%) and early prenatal diagnosis was a risk factor for survival. Intervention at the time of birth seems too late for the majority of newborn infants with CDH.

Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe.

OBJECTIVES: Ultrasound scan in the mid-trimester of pregnancy is now a routine part of prenatal care in most European countries. The objective of this study was to evaluate the prenatal diagnosis of dysmorphic syndromes by fetal ultrasound examination. METHODS: Data from 20 registries of congenital malformations in 12 European countries were included in the study. RESULTS: There were 2454 cases with congenital heart diseases, 479 of which were recognized syndromes, including 375 chromosomal anomalies and 104 syndromes without chromosomal anomalies. Fifty-one of the 104 were detected prenatally (49.0%). One hundred and ninety-two of 1130 cases with renal anomalies were recognized syndromes, including 128 chromosomal anomalies and 64 syndromes without chromosomal anomalies; 162 of them (84.4%) were diagnosed prenatally, including 109 chromosomal anomalies and 53 non-chromosomal syndromes. Fifty-four of the 250 cases with limb defects were recognized syndromes, including 16 chromosomal syndromes and 38 syndromes without chromosomal anomalies; 21 of these 54 syndromes were diagnosed prenatally (38.9%), including 9 chromosomal syndromes. There were 243 cases of abdominal wall defects including 57 recognizable syndromes, 48 with omphalocele and 9 with gastroschisis; 48 were diagnosed prenatally (84.2%). Twenty-six of the 187 cases with diaphragmatic hernia had recognized syndromes, including 20 chromosomal aberrations and 6 syndromes without chromosomal anomalies. Twenty-two of them (84.6%) were detected prenatally. Sixty-four of 349 cases with intestinal anomalies were recognized syndromes; 24 were diagnosed prenatally (37.5%). There were 553 cases of cleft lip and palate (CL(P)) and 198 of cleft palate (CP) including 74 chromosomal anomalies and 73 recognized non-chromosomal syndromes. Prenatal diagnosis was made in 51 cases of CL(P) (53.7%) and 7 of CP (13.7%). Twenty-two of 188 anencephalic cases were syndromic and all were diagnosed prenatally. Of 290 cases with spina bifida, 18 were recognized syndromes, and of them 17 were diagnosed prenatally. All 11 syndromic encephaloceles were diagnosed prenatally. CONCLUSIONS: Around 50% of the recognized syndromes which are associated with major congenital anomalies (cardiac, renal, intestinal, limb defects, abdominal wall defects and oral clefts) can be detected prenatally by the anomaly scan. However the detection rate varies with the type of syndrome and with the different countries' policies of prenatal screening.

Transient prenatal expression of NPY-Y1 receptor in trigeminal axons innervating the mystacial vibrissae.

Using immunohistochemistry in combination with confocal laser scanning microscopy, we studied the ontogeny of neuropeptide Y-Y1 receptor (Y1-R) expression in the trigeminal system of the rat. The study was limited to the nerve fibers innervating the mystacial pad and the trigeminal ganglia. In the trigeminal ganglia, Y1-R-immunoreactive (IR) neurons were first observed at E16.5. At this same stage some nerve fibers in the trigeminal ganglia also exhibited Y1-R-like immunoreactivity (LI). Strongly Y1-R-IR nerve fibers innervating the follicles of the mystacial vibrissae were first observed at E18. After double labeling, the Y1-R-LI was found to be colocalized with the neuronal marker protein gene product 9.5. At P1 only weak labeling for the Y1-R was found around the vibrissae follicles, whereas the neurons in the trigeminal ganglia were intensely labeled. The same was true for the adult rat, but at this stage no Y1-R labeling at all was observed in nerve fibers around the vibrissal follicles. These results strongly support an axonal localization of the Y1-R at this developmental stage. The transient expression of the Y1-R during prenatal mystacial pad development suggests a role for the Y1-R in the functional development of the vibrissae.