Search

Background Although maternal death is rare in the United Kingdom, 90% of these women had multiple health/social problems. This study aims to estimate the prevalence of pre-existing multimorbidity (two or more long-term physical or mental health conditions) in pregnant women in the United Kingdom (England, Northern Ireland, Wales and Scotland). Study design Pregnant women aged 15–49 years with a conception date 1/1/2018 to 31/12/2018 were included in this population-based cross-sectional study, using routine healthcare datasets from primary care: Clinical Practice Research Datalink (CPRD, United Kingdom, n = 37,641) and Secure Anonymized Information Linkage databank (SAIL, Wales, n = 27,782), and secondary care: Scottish Morbidity Records with linked community prescribing data (SMR, Tayside and Fife, n = 6099). Pre-existing multimorbidity preconception was defined from 79 long-term health conditions prioritised through a workshop with patient representatives and clinicians. Results The prevalence of multimorbidity was 44.2% (95% CI 43.7–44.7%), 46.2% (45.6–46.8%) and 19.8% (18.8–20.8%) in CPRD, SAIL and SMR respectively. When limited to health conditions that were active in the year before pregnancy, the prevalence of multimorbidity was still high (24.2% [23.8–24.6%], 23.5% [23.0–24.0%] and 17.0% [16.0 to 17.9%] in the respective datasets). Mental health conditions were highly prevalent and involved 70% of multimorbidity CPRD: multimorbidity with ≥one mental health condition/s 31.3% [30.8–31.8%]). After adjusting for age, ethnicity, gravidity, index of multiple deprivation, body mass index and smoking, logistic regression showed that pregnant women with multimorbidity were more likely to be older (CPRD England, adjusted OR 1.81 [95% CI 1.04–3.17] 45–49 years vs 15–19 years), multigravid (1.68 [1.50–1.89] gravidity ≥ five vs one), have raised body mass index (1.59 [1.44–1.76], body mass index 30+ vs body mass index 18.5–24.9) and smoked preconception (1.61 [1.46–1.77) vs non-smoker). Conclusion Multimorbidity is prevalent in pregnant women in the United Kingdom, they are more likely to be older, multigravid, have raised body mass index and smoked preconception. Secondary care and community prescribing dataset may only capture the severe spectrum of health conditions. Research is needed urgently to quantify the consequences of maternal multimorbidity for both mothers and children.

Objectives Preterm children are exposed to many medications in neonatal intensive care units, but little is known about the effect of prematurity on medication use throughout infancy and childhood. We examined prescriptions of cardiovascular medication (CVM), antiseizure medication (ASM), antiasthmatic medication and antibiotics issued/dispensed in the first 10 years of life for very and moderately preterm children compared with term. Design Population-based data linkage cohort study linking information from birth records to prescription records. Setting Six registries from five countries in the EUROlinkCAT study. Participants The study population included 1 722 912 children, of whom 10 820 (0.6%) were very preterm (= 37 weeks GA) and 0.7% had missing GA. Children with major or minor congenital anomalies were excluded (including patent ductus arteriosus). Main outcome measures Relative risk (RR) of receiving a prescription for CVM, ASM, antiasthmatic and antibiotics. Results Very preterm children had a higher RR of receiving a prescription for CVM and ASM than preterm children. For all preterm children, the RR of having a CVM prescription was 3.58 (95% CI 2.06 to 6.23); 2.06 (95% C11.73 to 2.41) for ASM; 1.13 (95% CI 0.99 to 1.29) for antiasthmatics and 0.96 (95% CI 0.93 to 0.99) for antibiotics in the first year of life. Increased prescription of CVM, ASM and antiasthmatics persisted for all 10 years of follow-up. Although the RR was highest for CVM and ASM, in absolute numbers more children received prescriptions for antibiotics (42.34%, 95% CI 38.81% to 45.91%) and antiasthmatics (28.40%, 95% CI 16.07% to 42.649%) than for CVM (0.18%, 95% CI 0.12% to 0.25%) and ASM (0.16%, 95% CI 0.13% to 0.20%) in the first year of life. Conclusion Preterm children had a higher risk of being prescribed/dispensed CUM, ASM and antiasthmatics up to age 10. This study highlights a need for further research into morbidity beyond age 10.

This study investigated the risk of congenital heart defects (CHD) and other congenital anomalies (CA) associated with first trimester use of macrolide antibiotics (mainly erythromycin, spiramycin, clarithromycin and azithromycin) and lincosamides (clindamycin) using a case-malformed control design. Data included 145,936 babies with a CA diagnosis (livebirths, stillbirths and terminations of pregnancy for CA) from 15 population-based EUROCAT registries in 13 European countries, covering 9 million births 1995-2012. Cases were babies with CHD, anencephaly, orofacial clefts, genital and limb reduction anomalies associated with antibiotic exposure in the literature. Controls were babies with other CA or genetic conditions. Main outcomes were odds ratios adjusted (AOR) for maternal age and registry, with 95 % Confidence Intervals (95 %CI). Macrolide and lincosamide exposure was recorded for 307 and 28 cases, 72 and 4 non-genetic controls, 57 and 7 genetic controls, respectively. AOR for CHD was not significantly raised (AOR 0.94, 95 %CI: 0.70-1.26 vs non genetic controls; AOR 1.01, 95 %CI: 0.73-1.41 vs genetic controls), nor significantly raised for any specific macrolide. The risk of atrioventricular septal defect was significantly raised with exposure to any macrolide (AOR 2.98; 95 %CI: 1.48-6.01), erythromycin (AOR 3.68, 95 %CI: 1.28-10.61), and azithromycin (AOR 4.50, 95 %CI: 1.30-15.58). Erythromycin, clarithromycin, azithromycin, and clindamycin were associated with an increased risk of at least one other CA. Further research is needed on the risk of specific CA associated with macrolide and lincosamide use in the first trimester, particularly relevant for the potential use of azithromycin in the treatment of COVID-19.

Purpose\ud To study patterns of antiepileptic drugs (AED) prescribing, particularly valproate, during pregnancy over a 10‐year period in the UK, Italy, and France.\ud \ud Methods\ud Data on pregnancies conceived after 1 January 2007 with outcomes before 31 December 2016 were extracted from four European electronic health care databases (380 499 in the United Kingdom (UK), 66 681 in France, and 649 918 in Italy [355 767 in Emilia Romagna and 294 151 in Tuscany]). Prevalence of AEDs with an ATC code starting N03A and clobazam (N05BA09) were stratified by country and calendar year.\ud \ud Results\ud AED prescribing during pregnancy varied from 3.0 (2.8‐3.1) per 1000 pregnancies in Emilia Romagna to 7.8 (7.5‐8.0) in the UK, 5.9 (5.6‐6.1) in Tuscany, and 6.3 (5.7‐6.9) in France. Lamotrigine was commonly prescribed in all regions with a third of women exposed to an AED during pregnancy taking lamotrigine in the UK and France. Valproate was prescribed to 28.6% of AED exposed pregnant women in Tuscany, 21.6% in France, 16.7% in Emilia Romagna, and 11.9% in the UK. Over the study period, the prevalence of AED prescribing increased in the UK mainly due to increases in pregabalin and gabapentin, declined in France mainly related to decreases in clonazepam, and remained constant in Italy. Valproate prescriptions declined to a prevalence

OBJECTIVES: In November 2014, the CMDh (a regulatory body representing EU Member States) advised doctors not to prescribe sodium valproate for epilepsy or bipolar disorder in preg nant women, in women who can become pregnant, or in girls unless other treatments are ineffective or not tolerated. This study aimed to determine if this warning led to changes in prescription patterns. DESIGN AND SETTING: Cohort of 5.4 million women aged between 10 and 50 years identified in electronic health care data from United Kingdom, France, and Italy (2007-2016). MAIN OUTCOME MEASURES: Anti-epileptic drug (AED) prescriptions. RESULTS: The prevalence of women receiving AED prescriptions in 2016 varied from 12.2 per 1000 to 29 per 1000 in the four regions. The incidence of prescribing any AED (excluding clonazepam, gabapentin, and pregabalin) fell each year on average by 7.5% (95% CI, 7.0%-8.0%; Emilia Romagna), 9.6% (8.3%-11.0%; France), 7.1% (6.7%-7.6%; Tuscany), and 0.4% (0.2%-1.0%; United Kingdom). The relative odds of prescribing sodium valproate rather than any other AED decreased more after 2014 compared with before the end of 2014 in France (OR = 0.77; 95% CI, 0.60-0.98), Tuscany (0.81; 0.76-0.86), Emilia Romagna (0.83; 0.76-0.90), and the United Kingdom (0.92; 0.80-1.06; not statistically significant). CONCLUSIONS: There is evidence that the CMDh warning did lead to changes in prescription patterns of sodium valproate in women of childbearing age. There were considerable differences in prescribing practice amongst regions of Europe.

Methadone is a vital treatment for women with opioid use disorder in pregnancy. Previous reports suggested an association between methadone exposure and Pierre Robin sequence (PRS), a rare craniofacial anomaly. We assessed the association between gestational methadone exposure and PRS.

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990-2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ ear anomalies and at least one major characteristic anomaly, was 3.8 per 100 000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.

Objectives: The aim of this study was to describe the epidemiology of Ebstein's anomaly in Europe and its association with maternal health and medication exposure during pregnancy. Design: We carried out a descriptive epidemiological analysis of population-based data. Setting: We included data from 15 European Surveillance of Congenital Anomalies Congenital Anomaly Registries in 12 European countries, with a population of 5.6 million births during 1982-2011. Participants: Cases included live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. Main outcome measures: We estimated total prevalence per 10,000 births. Odds ratios for exposure to maternal illnesses/medications in the first trimester of pregnancy were calculated by comparing Ebstein's anomaly cases with cardiac and non-cardiac malformed controls, excluding cases with genetic syndromes and adjusting for time period and country. Results: In total, 264 Ebstein's anomaly cases were recorded; 81% were live births, 2% of which were diagnosed after the 1st year of life; 54% of cases with Ebstein's anomaly or a co-existing congenital anomaly were prenatally diagnosed. Total prevalence rose over time from 0.29 (95% confidence interval (CI) 0.20-0.41) to 0.48 (95% CI 0.40-0.57) (p < 0.01). In all, nine cases were exposed to maternal mental health conditions/medications (adjusted odds ratio (adjOR) 2.64, 95% CI 1.33-5.21) compared with cardiac controls. Cases were more likely to be exposed to maternal beta-thalassemia (adjOR 10.5, 95% CI 3.13-35.3, n = 3) and haemorrhage in early pregnancy (adjOR 1.77, 95% CI 0.93-3.38, n = 11) compared with cardiac controls. Conclusions: The increasing prevalence of Ebstein's anomaly may be related to better and earlier diagnosis. Our data suggest that Ebstein's anomaly is associated with maternal mental health problems generally rather than lithium or benzodiazepines specifically; therefore, changing or stopping medications may not be preventative. We found new associations requiring confirmation.

BackgroundGastroschisis, a congenital anomaly of the abdomen, is associated with young maternal age and has increased in prevalence in many countries. Maternal illness and medication exposure are among environmental risk factors implicated in its aetiology. MethodsA population-based case-malformed control study was conducted using data from 18 European congenital anomaly registries, with information on first trimester medication use, covering 8 million births 1995-2012. 1577 gastroschisis cases (of which 4% stillbirths, 11% terminations of pregnancy) were compared to 153357 non-chromosomal/monogenic controls. Literature review identified previous associations concerning maternal illness and medication exposure to be tested as signals. Logistic regression adjusted for maternal age group, registry, and time period was used to evaluate associations. ResultsComparing gastroschisis to other congenital anomalies, the data supported signals concerning maternal depression (aOR 2.52, 95% CI 1.45, 4.39), antidepressant use (aOR 2.03, 95% CI 1.22, 3.38), postnatal depression/psychosis following a previous pregnancy (aOR 8.32, 95% CI 2.56, 27.01), sexually transmitted infections (aOR 2.85, 95% CI 1.13, 7.24), topical antivirals (aOR 5.31, 95% CI 1.63, 17.33), and continuation of oral contraceptives in early pregnancy (aOR 2.17, 95% CI 1.13, 4.18). Exploratory analyses suggested associations with a wider range of maternal infections and medications, including tonsillitis and the expectorant bromhexine. ConclusionsWhile it is difficult to disentangle the effects of the medication and underlying indication, our results add to the evidence base on preventable risk factors for gastroschisis. These risk factors may contribute to the higher risk among young mothers, and geographical and temporal variation in prevalence.

The European Surveillance of Congenital Anomalies (EUROCAT) network of population-based congenital anomaly registries is an important source of epidemiologic information on congenital anomalies in Europe covering live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. EUROCAT's policy is to strive for high-quality data, while ensuring consistency and transparency across all member registries. A set of 30 data quality indicators (DQIs) was developed to assess five key elements of data quality: completeness of case ascertainment, accuracy of diagnosis, completeness of information on EUROCAT variables, timeliness of data transmission, and availability of population denominator information. This article describes each of the individual DQIs and presents the output for each registry as well as the EUROCAT (unweighted) average, for 29 full member registries for 2004-2008. This information is also available on the EUROCAT website for previous years. The EUROCAT DQIs allow registries to evaluate their performance in relation to other registries and allows appropriate interpretations to be made of the data collected. The DQIs provide direction for improving data collection and ascertainment, and they allow annual assessment for monitoring continuous improvement. The DQI are constantly reviewed and refined to best document registry procedures and processes regarding data collection, to ensure appropriateness of DQI, and to ensure transparency so that the data collected can make a substantial and useful contribution to epidemiologic research on congenital anomalies. Birth Defects Research (Part A) 91: S23-S30, 2011. (C) 2011 Wiley-Liss, Inc.

OBJECTIVE The purpose of this article is to present the specific public health indicators recently developed by EUROCAT that aim to summarize important aspects of the public health impact of congenital anomalies in a few quantitative measures. METHODS The six indicators are: (1) congenital anomaly perinatal mortality, (2) congenital anomaly prenatal diagnosis prevalence, (3) congenital anomaly termination of pregnancy, (4) Down syndrome livebirth prevalence, (5) congenital anomaly pediatric surgery, and (6) neural tube defects (NTD) total prevalence. Data presented for this report pertained to all cases (livebirths, fetal deaths, or stillbirths after 20 weeks of gestation and terminations of pregnancy for fetal anomaly [TOPFA]) of congenital anomaly from 27 full member registries of EUROCAT that could provide data for at least 3 years during the period 2004 to 2008. Prevalence of anomalies, prenatal diagnosis, TOPFA, pediatric surgery, and perinatal mortality were calculated per 1000 births. RESULTS The overall perinatal mortality was approximately 1.0 per 1000 births for EUROCAT registries with almost half due to fetal and the other half due to first week deaths. There were wide variations in perinatal mortality across the registries with the highest rates observed in Dublin and Malta, registries in countries where TOPFA are illegal, and in Ukraine. The overall perinatal mortality across EUROCAT registries slightly decreased between 2004 and 2008 due to a decrease in first week deaths. The prevalence of TOPFA was fairly stable at about 4 per 1000 births. There were variations in livebirth prevalence of cases typically requiring surgery across the registries; however, for most registries this prevalence was between 3 and 5 per 1000 births. Prevalence of NTD decreased by about 10% from 1.05 in 2004 to 0.94 per 1000 in 2008. CONCLUSION It is hoped that by publishing the data on EUROCAT indicators, the public health importance of congenital anomalies can be clearly summarized to policy makers, the need for accurate data from registries emphasized, the need for primary prevention and treatment services highlighted, and the impact of current services measured. Birth Defects Research (Part A), 2011.© 2011 Wiley-Liss, Inc.

OBJECTIVE: To investigate whether first trimester exposure to lamotrigine (LTG) monotherapy is specifically associated with an increased risk of orofacial clefts (OCs) relative to other malformations, in response to a signal regarding increased OC risk.METHODS: Population-based case-control study with malformed controls based on EUROCAT congenital anomaly registers. The study population covered 3.9 million births from 19 registries 1995-2005. Registrations included congenital anomaly among livebirths, stillbirths, and terminations of pregnancy following prenatal diagnosis. Cases were 5,511 nonsyndromic OC registrations, of whom 4,571 were isolated, 1,969 were cleft palate (CP), and 1,532 were isolated CP. Controls were 80,052 nonchromosomal, non-OC registrations. We compared first trimester LTG and antiepileptic drug (AED) use vs nonepileptic non-AED use, for mono and polytherapy, adjusting for maternal age. An additional exploratory analysis compared the observed and expected distribution of malformation types associated with LTG use.RESULTS: There were 72 LTG exposed (40 mono- and 32 polytherapy) registrations. The ORs for LTG monotherapy vs no AED use were 0.67 (95% CI 0.10-2.34) for OC relative to other malformations, 0.80 (95% CI 0.11-2.85) for isolated OC, 0.79 (95% CI 0.03-4.35) for CP, and 1.01 (95% CI 0.03-5.57) for isolated CP. ORs for any AED use vs no AED use were 1.43 (95% CI 1.03-1.93) for OC, 1.21 (95% CI 0.82-1.72) for isolated OC, 2.37 (95% CI 1.54-3.43) for CP, and 1.86 (95% CI 1.07-2.94) for isolated CP. The distribution of other nonchromosomal malformation types with LTG exposure was similar to non-AED exposed.CONCLUSION: We find no evidence of a specific increased risk of isolated orofacial clefts relative to other malformations due to lamotrigine (LTG) monotherapy. Our study is not designed to assess whether there is a generalized increased risk of malformations with LTG exposure.

Background: The use of topiramate (TPM) has been increased among pregnant women. Safety data for TPM in human pregnancy are limited. Recent studies have suggested that exposure to TPM early in gestation has a higher risk of orofacial clefts (OCs), particularly cleft lip with or without palate, and there has been a Food Drug Administration (FDA) alert. Objectives: The aim of this study was to assess the risk of OCs relative to other malformations in infants whose mothers had taken TPM during the first trimester of pregnancy. Methods: A population-based case-control study with malformed controls was performed using the EUROCAT Antiepileptic (AED) Drug Database including data from 19 population-based registries of congenital anomaly in Europe with a total coverage of 8.0 million births from 1995 to 2011. Cases were 10 802 nonsyndromic OC registrations, of whom 8919 were isolated, and 6827 were cleft lip with or without cleft palate (CL/P). Controls were 136 838 nonchromosomal, non-OC registrations. We compared first trimester TPM use versus no-AED use, for monotherapy and polytherapy. Results: Exposure to TPM monotherapy was recorded for a total of 12 registrations, with one registration in the case group (isolated cleft palate) and 11 in the control group (odds ratio (OR) 1.15, 95% CI 0.03-7.95 for OC relative to other malformations, OR 4.03, 95%CI 0.09-27.8 for isolated cleft palate). No registration of CL/P was in TPM monotherapy exposure. There were 36 registrations exposed to TPM polytherapy, of whom six with isolated CL/P, three with cleft palate. Out of 36 of TPM polytherapy, 19 included valproic acid, 8 included carbamazepine and 4 included lamotrigine. The OR for TPM polytherapy versus no-AED use was 4.23 (95%CI 1.75-9.28) for OC, 4.35 (95%CI 1.31- 11.5) for isolated CL/P and 3.85 (95%CI 0.75- 12.5) for isolated cleft palate. Conclusions: The prevalence of TPM monotherapy exposure was five times lower in these data than reported in the United States, which limited our ability to confirm or refute previous findings. We found an excess of OCs, particularly CL/P, associated with TPM polytherapy. Further attention to TPM polytherapy is warranted.

Advancing rare disease research: the use of network of congenital anomaly registries in the study of rare genetic syndromes

Joint Action EUROCAT 2011-2013 Funded by the Public Health Programme 2008-2013 of the European Commission

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by macroglossia, high birth weight, omphalocele, visceromegaly, hypoglycaemia, tumour predisposition, and congenital malformations. AIM: To determine relevant epidemiological and clinical characteristics in a large series of patients with BWS in Europe PATIENTS AND METHODS: We present clinical and epidemiological characteristics of 197 patients with BWS that were identified by retrospective analysis among 13 546 771 pregnancies that were monitored in EUROCAT network of population based registries in 1980-2007period. RESULTS: The clinical manifestations of BWS patients reflect the variable presentation of the syndrome. The infants had a high birth weight for their gestational age. Prematurity was present in 74/166 (44.57%) cases. The most frequent features were omphalocele (54.72% ; 81/148) and macroglossia (52.7% ; 78/148). Associated anomalies were present in 68 (46%) patients and included mainly cardiovascular (30/148 ; 20.28 %), urinary (26/148 ; 17.56%) and limb defects (14/148 ; 9.15%). Of the 70 cases detected prenatally, 12 (17.1%) were terminated due to severe anomalies. The overall recorded number of late foetal deaths/stillbirths with BWS was 8, and of deaths in the first week of life 7, resulting in a total perinatal mortality rate associated with BWS of 76.14 per 1000 births. The minimal estimated prevalence rate of BWS in Europe is 1 in 69930 births. All cases were sporadic. CONCLUSION: Beckwith Wiedemann syndrome is a rare disorder. Presence of various associated anomalies decreases overall first week survival rate in this patients to 86.14% (170/197).

Background— This study determines the prevalence of Congenital Heart Defects (CHD), diagnosed prenatally or in infancy, and fetal and perinatal mortality associated with CHD in Europe. Methods and Results— Data were extracted from the European Surveillance of Congenital Anomalies central database for 29 population-based congenital anomaly registries in 16 European countries covering 3.3 million births during the period 2000 to 2005. CHD cases (n=26 598) comprised live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly (TOPFA). The average total prevalence of CHD was 8.0 per 1000 births, and live birth prevalence was 7.2 per 1000 births, varying between countries. The total prevalence of nonchromosomal CHD was 7.0 per 1000 births, of which 3.6% were perinatal deaths, 20% prenatally diagnosed, and 5.6% TOPFA. Severe nonchromosomal CHD (ie, excluding ventricular septal defects, atrial septal defects, and pulmonary valve stenosis) occurred in 2.0 per 1000 births, of which 8.1% were perinatal deaths, 40% were prenatally diagnosed, and 14% were TOPFA (TOPFA range between countries 0% to 32%). Live-born CHD associated with Down syndrome occurred in 0.5 per 1000 births, with >4-fold variation between countries. Conclusion— Annually in the European Union, we estimate 36 000 children are live born with CHD and 3000 who are diagnosed with CHD die as a TOFPA, late fetal death, or early neonatal death. Investing in primary prevention and pathogenetic research is essential to reduce this burden, as well as continuing to improve cardiac services from in utero to adulthood.

Prenatal ultrasound diagnosis of oculoauriculovertebral spectrum disorder

Beckwith Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by growth disregulation, risk of tumour development and congenital anomalies. In this study we analysed 197 patients registered in EUROCAT network of congenital anomaly registries in 1980-2007 period by monitoring population of 13 546 771 births. The prevalence was 1.45 per 100 000 births. Male to female ratio was 1.3:1. High proportion of patients was diagnosed by prenatal ultrasound examination (70/166 ; 42.1%), 41 patient was discovered at birth (41/166 ; 24.69%) and 55 patients (33.3%) were diagnosed during the first month of life. Most patients were live births (177/197 ; 89.8%), eight were stillbirths (8/166 ; 4.81%), and twelve pregnancies were terminated after prenatal diagnosis (12/70 ; 17.4%) due to heart, kidney or limb anomalies. Seven live births didn’t survive the first week of life (7/177 ; 3.9%). In 148 (75.12 %) of patients major malformations were present, with the hallmarks of the syndrome, omphalocele (54.72% ; 81/148) and macroglossia (52.7% ; 78/148), being the most common. Other associated anomalies were present in 68 (46%) patients: cardiovascular in 20.28 % (30/148), urinary in 17.56% (26/148), limb defects in 9.15% (14/148), and central nervous system malformations and cleft lip in 2.0% (3/148). In thirteen patients more than one congenital anomaly was present. In conclusion, with estimated frequency of 1 in 69930 births, BWS is a rare congenital anomaly disorder, often associated with major congenital anomalies. Pregnancies that are carried out to term mainly result in live births with high survival rate.

U sažetku je prikazano multicentrično istraživanje Treacher Collinsovoga sindroma u europskoj populaciji. Prikazane su kliničke i epidemiološke osobitosti Treacher Collins sindroma.

Prenatal ultrasound diangosis of genetic syndromes.

To assess at a population-based level the frequency with which severe structural congenital malformations are detected prenatally in Europe and the gestational age at detection, and to describe regional variation in these indicators. In the period 1995-1999, data were obtained from 17 European population-based registries of congenital malformations (EUROCAT). Included were all live births, fetal deaths and terminations of pregnancy diagnosed with one or more of the following malformations: anencephalus, encephalocele, spina bifida, hydrocephalus, transposition of great arteries, hypoplastic left heart, limb reduction defect, bilateral renal agenesis, diaphragmatic hernia, omphalocele and gastroschisis. The 17 registries reported 4366 cases diagnosed with the 11 severe structural malformations and of these 2300 were live births (53%), 181 were fetal deaths (4%) and 1863 were terminations of pregnancy (43%) ; in 22 cases pregnancy outcome was unknown. The overall prenatal detection rate was 64% (range, 25-88% across regions). The proportion of terminations of pregnancy varied between regions from 15% to 59% of all cases. Gestational age at discovery for prenatally diagnosed cases was less than 24 weeks for 68% (range, 36-88%) of cases. There was a significant relationship between high prenatal detection rate and early diagnosis (P < 0.0001). For individual malformations, the prenatal detection rate was highest for anencephalus (469/498, 94%) and lowest for transposition of the great arteries (89/324, 27%). Termination of pregnancy was performed in more than half of the prenatally diagnosed cases, except for those with transposition of the great arteries, diaphragmatic hernia and gastroschisis, in which 30-40% of the pregnancies with a prenatal diagnosis were terminated. European countries currently vary widely in the provision and uptake of prenatal screening and its quality, as well as the "culture" in terms of decision to continue the pregnancy. This inevitably contributes to variation between countries in perinatal and infant mortality and in childhood prevalence and cost to health services of congenital anomalies.