The role of maternal stress in early pregnancy in the aetiology of gastroschisis : An incident case control study

We wish to thank all the women who took the time to take part in this study, the research nurses who undertook interviews and data collection: Sandra Edwards-Fenton, Anne Chamberlain, Marit Bodley, Sharon Brown, Isobel Clegg, Catherine Collins and the British Isles Network of Congenital Anomaly Registers (BINOCAR) for their support in facilitating this study.Peer reviewedPublisher PD

The Vehicle, Fall 2004

Table of Contents Six-Billion to One AgainstRyan Maneypage 5 May 25th, 2004Megan Rankinpage 6 Summer DeliveryAnthony Shootpage 7 A Young Family, Smithland, Kentucky. October 1935.Clementinepage 8 UntitledJonathan M. Cookpage 9 October 23, 2021Ryan Maneypage 10 Last NightKaty Dwigginspage 11 UntitledMegan Rankinpage 12 Clever DisguiseSarah Johnsonpage 13 conspiracy against grandmaClementinepage 14 ThunderKitty Apodacapage 15 UntitledJonathan M. Cookpage 16 Self PortraitAnnette Carlinpage 17 LeavesAnthony Shootpage 18 UntitledKaty Dwigginspage 19 The Woman I Almost UnderstoodGreg Lyonspage 20 Flesh and SandJonathan M. Cookpage 21 Lunch DateAlisa Habelpage 22 Like and Unlike Everyone ElseC. Alan Doughtypage 23 Thankfully SwayedSarah Johnsonpage 24 A Warm Winter DayJoshua D. Andersonpage 25-26 Oak, Maple, SassafrasClementinepage 27-30https://thekeep.eiu.edu/vehicle/1080/thumbnail.jp

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

Prevalence, prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe

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-auriculovertebral 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

First Contact Practitioners' (FCPs) and General Practitioners' Perceptions Towards FCPs Delivering Vocational Advice to Patients with Musculoskeletal Conditions: A Qualitative Investigation of the Implementation Potential of the I-SWAP Initiative.

Purpose Musculoskeletal (MSK) pain is a common cause of work absence. The recent SWAP (Study of Work And Pain) randomised controlled trial (RCT) found that a brief vocational advice service for primary care patients with MSK pain led to fewer days' work absence and provided good return-on-investment. The I-SWAP (Implementation of the Study of Work And Pain) initiative aimed to deliver an implementation test-bed of the SWAP vocational advice intervention with First Contact Practitioners (FCP). This entailed adapting the SWAP vocational advice training to fit the FCP role. This qualitative investigation explored the implementation potential of FCPs delivering vocational advice for patients with MSK pain. Methods Semi-structured interviews and focus groups were conducted with 10 FCPs and 5 GPs. Data were analysed thematically and findings explored using Normalisation Process Theory (NPT). Results I-SWAP achieved a degree of 'coherence' (i.e. made sense), with both FCPs and GPs feeling FCPs were well-placed to discuss work issues with these patients. However, for many of the FCPs, addressing or modifying psychosocial and occupational barriers to return-to-work was not considered feasible within FCP consultations, and improving physical function was prioritised. Concerns were also raised that employers would not act on FCPs' recommendations regarding return-to-work. Conclusion FCPs appear well-placed to discuss work issues with MSK patients, and signpost/refer to other services; however, because they often only see patients once they are less suited to deliver other aspects of vocational advice. Future research is needed to explore how best to provide vocational advice in primary care settings

Epidemiology of Multiple Congenital Anomalies in Europe: A EUROCAT Population-Based Registry Study

Background: This study describes the prevalence, associated anomalies, and demographic characteristics of cases of multiple congenital anomalies (MCA) in 19 population-based European registries (EUROCAT) covering 959,446 births in 2004 and 2010. Methods: EUROCAT implemented a computer algorithm for classification of congenital anomaly cases followed by manual review of potential MCA cases by geneticists. MCA cases are defined as cases with two or more major anomalies of different organ systems, excluding sequences, chromosomal and monogenic syndromes. Results: The combination of an epidemiological and clinical approach for classification of cases has improved the quality and accuracy of the MCA data. Total prevalence of MCA cases was 15.8 per 10,000 births. Fetal deaths and termination of pregnancy were significantly more frequent in MCA cases compared with isolated cases (p<0.001) and MCA cases were more frequently prenatally diagnosed (p<0.001). Live born infants with MCA were more often born preterm (p<0.01) and with birth weight<2500 grams (p<0.01). Respiratory and ear, face, and neck anomalies were the most likely to occur with other anomalies (34% and 32%) and congenital heart defects and limb anomalies were the least likely to occur with other anomalies (13%) (p<0.01). However, due to their high prevalence, congenital heart defects were present in half of all MCA cases. Among males with MCA, the frequency of genital anomalies was significantly greater than the frequency of genital anomalies among females with MCA (p<0.001). Conclusion: Although rare, MCA cases are an important public health issue, because of their severity. The EUROCAT database of MCA cases will allow future investigation on the epidemiology of these conditions and related clinical and diagnostic problems

Long term trends in prevalence of neural tube defects in Europe:population based study

STUDY QUESTIONWhat are the long term trends in the total (live births, fetal deaths, and terminations of pregnancy for fetal anomaly) and live birth prevalence of neural tube defects (NTD) in Europe, where many countries have issued recommendations for folic acid supplementation but a policy for mandatory folic acid fortification of food does not exist?METHODSThis was a population based, observational study using data on 11 353 cases of NTD not associated with chromosomal anomalies, including 4162 cases of anencephaly and 5776 cases of spina bifida from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries covering approximately 12.5 million births in 19 countries between 1991 and 2011. The main outcome measures were total and live birth prevalence of NTD, as well as anencephaly and spina bifida, with time trends analysed using random effects Poisson regression models to account for heterogeneities across registries and splines to model non-linear time trends.SUMMARY ANSWER AND LIMITATIONSOverall, the pooled total prevalence of NTD during the study period was 9.1 per 10 000 births. Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991. Estimates from Poisson models that took registry heterogeneities into account showed an annual increase of 4% (prevalence ratio 1.04, 95% confidence interval 1.01 to 1.07) in 1995-99 and a decrease of 3% per year in 1999-2003 (0.97, 0.95 to 0.99), with stable rates thereafter. The trend patterns for anencephaly and spina bifida were similar, but neither anomaly decreased substantially over time. The live birth prevalence of NTD generally decreased, especially for anencephaly. Registration problems or other data artefacts cannot be excluded as a partial explanation of the observed trends (or lack thereof) in the prevalence of NTD.WHAT THIS STUDY ADDSIn the absence of mandatory fortification, the prevalence of NTD has not decreased in Europe despite longstanding recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification.</p

Cerebral arteriopathy associated with heterozygous variants in the casitas B-lineage lymphoma gene

Objective: To report a series of patients with cerebral arteriopathy associated with heterozygous variants in the casitas B-lineage lymphoma (CBL) gene and examine the functional role of the identified mutant Cbl protein. We hypothesized that mutated Cbl fails to act as a negative regulator of the RAS-mitogen-activated protein kinases (MAPK) signaling pathway, resulting in enhanced vascular fibroblast proliferation and migration and enhanced angiogenesis and collateral vessel formation. Methods: We performed whole-exome sequencing in 11 separate families referred to Great Ormond Street Hospital, London, with suspected genetic cause for clinical presentation with severe progressive cerebral arteriopathy. Results: We identified heterozygous variants in the CBL gene in 5 affected cases from 3 families. We show that impaired CBL-mediated degradation of cell surface tyrosine kinase receptors and dysregulated intracellular signaling through the RAS-MAPK pathway contribute to the pathogenesis of the observed arteriopathy. Mutated CBL failed to control the angiogenic signal relay of vascular endothelial growth factor receptor 2, leading to prolonged tyrosine kinase signaling, thus driving angiogenesis and collateral vessel formation. Mutant Cbl promoted myofibroblast migration and proliferation contributing to vascular occlusive disease; these effects were abrogated following treatment with a RAF-RAS-MAPK pathway inhibitor. Conclusions: We provide a possible mechanism for the arteriopathy associated with heterozygous CBL variants. Identification of the key role for the RAS-MAPK pathway in CBL-mediated cerebral arteriopathy could facilitate identification of novel or repurposed druggable targets for treating these patients and may also provide therapeutic clues for other cerebral arteriopathies.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.Y. Hong was supported for this work by Versus Arthritis (grant 21791) and Rosetrees Trust (grant A1700). D. Eleftheriou was supported by Versus Arthritis (grants 20164 and 21593). A. Keylock was supported by a BHF PhD studentship. B. Jensen is supported by a GOSH Children’s Charity grant (CP_RSRCH_003). P.A. Brogan and D. Eleftheriou also acknowledge support from Great Ormond Street Hospital Children’s Charity. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.accepted version (12 month embargo

Major Congenital Anomalies in Babies Born With Down Syndrome: A EUROCAT Population-Based Registry Study

Previous studies have shown that over 40% of babies with Down syndrome have a major cardiac anomaly and are more likely to have other major congenital anomalies. Since 2000, many countries in Europe have introduced national antenatal screening programs for Down syndrome. This study aimed to determine if the introduction of these screening programs and the subsequent termination of prenatally detected pregnancies were associated with any decline in the prevalence of additional anomalies in babies born with Down syndrome. The study sample consisted of 7,044 live births and fetal deaths with Down syndrome registered in 28 European population-based congenital anomaly registries covering seven million births during 2000-2010. Overall, 43.6% (95% CI: 42.4-44.7%) of births with Down syndrome had a cardiac anomaly and 15.0% (14.2-15.8%) had a non-cardiac anomaly. Female babies with Down syndrome were significantly more likely to have a cardiac anomaly compared to male babies (47.6% compared with 40.4%, P&#8201;<&#8201;0.001) and significantly less likely to have a non-cardiac anomaly (12.9% compared with 16.7%, P&#8201;<&#8201;0.001). The prevalence of cardiac and non-cardiac congenital anomalies in babies with Down syndrome has remained constant, suggesting that population screening for Down syndrome and subsequent terminations has not influenced the prevalence of specific congenital anomalies in these babies.

Risk of infection following semi-invasive ultrasound procedures in Scotland, 2010 to 2016:A retrospective cohort study using linked national datasets

Introduction Outbreak reports indicate a risk of cross-infection following medical procedures using semi-invasive ultrasound probes. This study aimed to evaluate the risk of infection, using microbiological reports and antibiotic prescriptions as proxy measures, associated with semi-invasive ultrasound probe procedures, including transoesophageal echocardiography, transvaginal and transrectal ultrasound. Methods Patient records from the Electronic Communication of Surveillance in Scotland and the Prescribing Information System were linked with the Scottish Morbidity Records for cases in Scotland between 2010 and 2016. Three retrospective cohorts were created to include inpatients/day-cases and outpatients in the following specialties: Cardiology, Gynaecology and Urology. Cox regression was used to quantify the association between semi-invasive ultrasound probe procedures and the risk of positive microbiological reports and community antibiotic prescriptions in the 30-day period following the procedure. Results There was a greater hazard ratio of microbiological reports for patients who had undergone transoesophageal echocardiography (HR: 4.92; 95% CI: 3.17–7.63), transvaginal (HR: 1.41; 95% CI: 1.21–1.64) and transrectal ultrasound (HR: 3.40; 95% CI: 2.90–3.99), compared with unexposed cohort members after adjustment for age, co-morbidities, previous hospital admissions and past care home residence. Similarly, there was a greater hazard ratio of antibiotic prescribing for those who had received transvaginal (HR: 1.26; 95% CI: 1.20–1.32) and transrectal (HR: 1.75; 95% CI: 1.66–1.84) ultrasound, compared with unexposed patients. Conclusion Analysis of linked national datasets demonstrated a greater risk of infection within 30 days of undergoing semi-invasive ultrasound probe procedures, using microbiological reports and antibiotic prescriptions as proxy measures of infection