Spectrum of congenital anomalies among VACTERL cases: a EUROCAT population-based study.

BACKGROUND: The VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, Limb abnormalities) association is the non-random occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheo-esophageal, renal, and limb anomalies. Diagnosing VACTERL patients is difficult, as many disorders have multiple features in common with VACTERL. The aims of this study were to clearly outline component features, describe the phenotypic spectrum among the largest group of VACTERL patients thus far reported, and to identify phenotypically similar subtypes. METHODS: A case-only study was performed assessing data on 501 cases recorded with VACTERL in the JRC-EUROCAT (Joint Research Centre-European Surveillance of Congenital Anomalies) central database (birth years: 1980-2015). We differentiated between major and minor VACTERL features and anomalies outside the VACTERL spectrum to create a clear definition of VACTERL. RESULTS: In total, 397 cases (79%) fulfilled our VACTERL diagnostic criteria. The most commonly observed major VACTERL features were anorectal malformations and esophageal atresia/tracheo-esophageal fistula (both occurring in 62% of VACTERL cases), followed by cardiac (57%), renal (51%), vertebral (33%), and limb anomalies (25%), in every possible combination. Three VACTERL subtypes were defined: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, based on severity and presence of additional congenital anomalies. CONCLUSION: The clearly defined VACTERL component features and the VACTERL subtypes introduced will improve both clinical practice and etiologic research.

Use of hierarchical models to analyze European trends in congenital anomaly prevalence.

BACKGROUND: Surveillance of congenital anomalies is important to identify potential teratogens. Despite known associations between different anomalies, current surveillance methods examine trends within each subgroup separately. We aimed to evaluate whether hierarchical statistical methods that combine information from several subgroups simultaneously would enhance current surveillance methods using data collected by EUROCAT, a European network of population-based congenital anomaly registries. METHODS: Ten-year trends (2003 to 2012) in 18 EUROCAT registries over 11 countries were analyzed for the following groups of anomalies: neural tube defects, congenital heart defects, digestive system, and chromosomal anomalies. Hierarchical Poisson regression models that combined related subgroups together according to EUROCAT's hierarchy of subgroup coding were applied. Results from hierarchical models were compared with those from Poisson models that consider each congenital anomaly separately. RESULTS: Hierarchical models gave similar results as those obtained when considering each anomaly subgroup in a separate analysis. Hierarchical models that included only around three subgroups showed poor convergence and were generally found to be over-parameterized. Larger sets of anomaly subgroups were found to be too heterogeneous to group together in this way. CONCLUSION: There were no substantial differences between independent analyses of each subgroup and hierarchical models when using the EUROCAT anomaly subgroups. Considering each anomaly separately, therefore, remains an appropriate method for the detection of potential changes in prevalence by surveillance systems. Hierarchical models do, however, remain an interesting alternative method of analysis when considering the risks of specific exposures in relation to the prevalence of congenital anomalies, which could be investigated in other studies. Birth Defects Research (Part A) 106:480-10, 2016. © 2016 Wiley Periodicals, Inc.

Transition from hospital to home care for preterm babies: A qualitative study of the experiences of caregivers in Uganda.

Improving care for preterm babies could significantly increase child survival in low-and middle income countries. However, attention has mainly focused on facility-based care with little emphasis on transition from hospital to home after discharge. Our aim was to understand the experiences of the transition process among caregivers of preterm infants in Uganda in order to improve support systems. A qualitative study among caregivers of preterm infants in Iganga and Jinja districts in eastern Uganda was conducted in June 2019 through February 2020, involving seven focus group discussions and five in-depth interviews. We used thematic-content analysis to identify emergent themes related to the transition process. We included 56 caregivers, mainly mothers and fathers, from a range of socio-demographic backgrounds. Four themes emerged: caregivers' experiences through the transition process from preparation in the hospital to providing care at home; appropriate communication; unmet information needs; and managing community expectations and perceptions. In addition, caregivers' views on 'peer-support' was explored. Caregivers' experiences, and their confidence and ability to provide care were related to preparation in the hospital after birth and until discharge, the information they received and the manner in which healthcare providers communicated. Healthcare workers were a trusted source of information while in the hospital, but there was no continuity of care after discharge which increased their fears and worries about the survival of their infant. They often felt confused, anxious and discouraged by the negative perceptions and expectations from the community. Fathers felt left-out as there was very little communication between them and the healthcare providers. Peer-support could enable a smooth transition from hospital to home care. Interventions to advance preterm care beyond the health facility through a well-supported transition from facility to home care are urgently required to improve health and survival of preterm infants in Uganda and other similar settings.

Effect of SARS-CoV-2 infection in neonates or in pregnancy on developmental outcomes at 21-24 months (SINEPOST): study protocol for a prospective cohort study.

INTRODUCTION: Exposure to SARS-CoV-2 during pregnancy or in the neonatal period may impact fetal or neonatal brain development either through direct central nervous system infection or indirectly through the adverse effects of viral infection-related inflammation in the mother or newborn infant. This study aims to determine whether there are early neurodevelopmental effects of SARS-CoV-2 infection. METHODS AND ANALYSIS: We will conduct a prospective national population-based cohort study of children aged 21-24 months who were born at term (≥37 weeks' gestation) between 1 March 2020 and 28 February 2021 and were either antenatally exposed, neonatally exposed or unexposed (comparison cohort) to SARS-CoV-2. Nationally, hospitals will identify and approach parents of children eligible for inclusion in the antenatally and neonatally exposed cohorts using information from the UK Obstetric Surveillance System (UKOSS) and British Paediatric Surveillance Unit (BPSU) national surveillance studies and will identify and approach eligible children for the comparison cohort through routine birth records. Parents will be asked to complete questionnaires to assess their child's development at 21-24 months of age. Outcome measures comprise the Ages and Stages Questionnaire, Third Edition (ASQ-3), Ages and Stages Questionnaire Social-Emotional, Second Edition (ASQ-SE-2), Liverpool respiratory symptoms questionnaire and questionnaire items to elicit information about healthcare usage. With parental consent, study data will be linked to routine health and education records for future follow-up. Regression models will compare ASQ-3 and ASQ-SE-2 scores and proportions, frequency of respiratory symptoms and healthcare usage between the exposed and comparison cohorts, adjusting for potential confounders. ETHICS AND DISSEMINATION: Ethics approval was obtained from the London-Westminster Research Ethics Committee. Findings will be disseminated in scientific conference presentations and peer-reviewed publications. ISRCTN REGISTRATION NUMBER: ISRCTN99910769.

Maternal and perinatal Health Research Collaboration, India (MaatHRI): methodology for establishing a hospital-based research platform in a low and middle income country setting.

Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidence-based pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India - Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, real-time monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently being undertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs.

Maternal risk factors for the VACTERL association: A EUROCAT case-control study.

BACKGROUND: The VACTERL association (VACTERL) is the nonrandom occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Despite suggestions for involvement of several genes and nongenetic risk factors from small studies, the etiology of VACTERL remains largely unknown. OBJECTIVE: To identify maternal risk factors for VACTERL in offspring in a large European study. METHODS: A case-control study was performed using data from 28 EUROCAT registries over the period 1997-2015 with case and control ascertainment through hospital records, birth and death certificates, questionnaires, and/or postmortem examinations. Cases were diagnosed with VACTERL, while controls had a genetic syndrome and/or chromosomal abnormality. Data collected included type of birth defect and maternal characteristics, such as age, use of assisted reproductive techniques (ART), and chronic illnesses. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). RESULTS: The study population consisted of 329 VACTERL cases and 49,724 controls with recognized syndromes or chromosomal abnormality. For couples who conceived through ART, we found an increased risk of VACTERL (aOR 2.3 [95% CI 1.3, 3.9]) in offspring. Pregestational diabetes (aOR 3.1 [95% CI 1.1, 8.6]) and chronic lower obstructive pulmonary diseases (aOR 3.9 [95% CI 2.2, 6.7]) also increased the risk of having a child with VACTERL. Twin pregnancies were not associated with VACTERL (aOR 0.6 [95% CI 0.3, 1.4]). CONCLUSION: We identified several maternal risk factors for VACTERL in offspring befitting a multifactorial etiology.

'I haven't met them, I don't have any trust in them. It just feels like a big unknown': a qualitative study exploring the determinants of consent to use Human Fertilisation and Embryology Authority registry data in research.

OBJECTIVES: To explore why and how fertility patients decide to allow (or deny) the use of personal data held in the Human Fertilisation and Embryology Authority registry for linkage and research. DESIGN: A qualitative study was conducted using in-depth face-to-face interviews and an online survey to garner information on experience and opinions from fertility clinic patients and staff. Verbatim transcripts were analysed using the 'one sheet of paper' method to identify themes. SETTING: Women and men were recruited between September 2015 and December 2017, via fertility clinics across England and online advertising, then interviewed at a location convenient to them. PARTICIPANTS: 20 patients and 9 staff were interviewed, 40 patients completed the online survey. RESULTS: Consent for disclosure (CD) forms are completed at a stressful time, when patients often feel overwhelmed; these forms were considered a low priority. Perceptions of benefit (to individuals, to wider society) and harm (misuse of data, impact of disclosure on child) influenced consent. Important themes included: understanding of the forms; trust in those asking, in researchers, in the Human Fertilisation and Embryology Authority (HFEA); and wider attitudes to data use. Issues influencing response, and thus the representativeness of the HFEA data set, were highlighted. CONCLUSIONS: Understanding what is being asked, and trust in those organisations keeping and using personal data, affects individual decisions to consent to disclosure. Patients were influenced by the wider context of infertility, as well as general concerns about data sharing and security. Low consent rates, which vary by clinic and likely also by patients' characteristics, have adverse implications for research conducted using HFEA data collected after 2008. Public understanding of data use and security is relatively poor; increased public trust in, and awareness of, research based on routine data could improve consent to data use and reduce the risk of bias.

Towards optimising local reviews of severe incidents in maternity care: messages from a comparison of local and external reviews.

BACKGROUND: Detailed local case review is commonly used as a strategy to improve care. However, recent reports have highlighted concerns over quality of local reviews in maternity care. The aim of this project was to describe the methods used for conducting local reviews of care of women with severe maternal morbidity, and to compare lessons identified for future care through external and local reviews. METHODS: Thirty-three anonymised clinical records from women with severe maternal morbidities were obtained, together with the report of the local review of their care. The methodology used for the local reviews was described, including specific tools used, team members involved, their disciplines, report format and whether an action plan with recommendations for audit was produced. Multidisciplinary external reviewers considered the records using a standard confidential enquiry approach. A thematic analysis of lessons learned from the two approaches was undertaken. RESULTS: A formal report of the local review was produced for 11/33 cases; 4 of these used root cause analysis. A further 12 local reviews consisted of a group discussion with output noted in a spreadsheet; 5 consisted of a timeline with good practice points and 5 had no formal review. Patients were involved in five local reviews; only one was multidisciplinary. Action plans were recorded in 14 local reviews; 3 of these included a recommendation to audit the proposed changes. External reviews identified additional messages for care and highlighted aspects of good care in every case, whereas only 55% (n=18) of local reviews identified good care (p<0.0005). CONCLUSIONS: The quality of local reviews can clearly be improved. Very few of the reviews involved patients. Local reviews should be multidisciplinary, generate an action plan, and the implementation of recommendations should be audited. Improvements in local reviews may be achieved by standardised training or development of national protocols.

Epidemiology of partial urorectal septum malformation sequence (or 'persistent cloaca'): a population-based study in seven regions of England and Wales, 1985-2010.

BACKGROUND: Partial urorectal septum malformation (pURSM) sequence (or 'persistent cloaca') is a rare congenital anomaly characterised by a joining of the urethral, anal, and genital openings into a single common channel. This study describes the epidemiology of pURSM sequence in England and Wales including prevalence, additional anomalies, and pregnancy outcomes. METHODS: All cases of pURSM sequence prospectively notified to seven congenital anomaly registers in England and Wales during 1985-2010, whether delivered as live births, spontaneous fetal deaths (≥20 weeks' gestation), or elective terminations of pregnancy for fetal anomaly (TOPFA, any gestation), formed this population-based cohort. The risks of spontaneous fetal and infant death were examined by Kaplan-Meier analysis. Differences in prevalence over time, and between regions, were examined by multilevel Poisson regression. RESULTS: 117 cases were recorded among 4,251,241 total births. Six (5%) pregnancies resulted in spontaneous fetal deaths, 53 (45%) in TOPFA, and 58 (50%) in live births. The prevalence was 2.8 (95% CI 2.3 to 3.4) per 100,000 total births, increasing significantly over time (p=0.002) and differing significantly between regions (p=0.005). 77 cases (66%) had at least one additional major congenital anomaly outside the perineum, including 67 (57%) renal, 29 (25%) musculoskeletal, 26 (23%) digestive system, and 24 (21%) cardiovascular anomalies. The risks of spontaneous fetal and infant death were estimated as 8.9% (95% CI 4.1 to 18.8) and 26.3% (95% CI 15.1 to 43.4) respectively. CONCLUSIONS: This is the largest study of the epidemiology of pURSM sequence. The information will be valuable for families and health professionals whenever a case of pURSM sequence is diagnosed.

Effects of pregnancy planning, fertility, and assisted reproductive treatment on child behavioral problems at 5 and 7 years: evidence from the Millennium Cohort Study.

OBJECTIVE: To examine the effects of pregnancy planning, time to conception (TTC), and assisted reproductive technologies (ART) on child behavior. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 12,380 singletons recruited at 9 months and followed-up at 5 and 7 years. Conceptions were divided into "unplanned" (unplanned, unhappy), "mistimed" (unplanned, happy), "planned" (planned, TTC <12 months), "subfertile" (planned, TTC ≥ 12 months), "ovulation induced" (received clomiphene citrate), and "ART" (IVF or intracytoplasmic sperm injection). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Child behavior (Strengths and Difficulties Questionnaire [SDQ]). RESULT(S): Mistimed and unplanned children had higher average SDQ scores at age 5 and 7 years and were significantly more likely to have a clinically relevant behavioral problem compared with the planned group. The ART children had significantly higher average SDQ scores at both 5 and 7 years compared with the planned group. An increase in clinically relevant behavioral problems was observed at 5 years (odds ratio 2.05 [95% confidence interval 0.96, 4.42]) but failed to reach statistical significance. No effects were observed in the subfertile and ovulation-induced groups. CONCLUSION(S): Unplanned and mistimed children exhibit more behavioral problems than their planned peers. Though ART children have higher mean total difficulties scores, this did not translate into a statistically significant increase in clinically relevant behavioral problems.

Reassured or fobbed off? Perspectives on infertility consultations in primary care: a qualitative study.

BACKGROUND: Infertility affects 9% of couples in the UK. Most couples who visit their GP because they are worried about their fertility will ultimately conceive, but a few will not. Treatment usually happens in secondary care, but GPs can have an invaluable role in starting investigations, referring, and giving support throughout treatment and beyond. AIM: To inform clinical practice by exploring primary care experiences of infertility treatment among females and males, and discussing findings with a reference group of GPs to explore practice experience. DESIGN AND SETTING: A qualitative patient interview and GP focus group study. Interviews were conducted in patients homes in England and Scotland; the focus group was held at a national conference. METHOD: An in-depth interview study was conducted with 27 females and 11 males. A maximum variation sample was sought and interviews were transcribed for thematic analysis. Results were discussed with a focus group of GPs to elicit their views. RESULTS: Feeling that they were being taken seriously was very important to patients. Some felt that their concerns were not taken seriously, or that their GP did not appear to be well informed about infertility. The focus group of GPs highlighted the role of protocols in their management of patients who are infertile, as well as the difficulty GPs faced in communicating both reassurance and engagement. CONCLUSION: Simple things that GPs say and do, such as describing the 'action plan' at the first consultation, could make a real difference to demonstrating that they are taking the fertility problem seriously.

Target decision to delivery intervals for emergency caesarean section based on neonatal outcomes and three year follow-up.

OBJECTIVE: To investigate current target decision to delivery intervals (DDIs) for 'emergency' caesarean section. STUDY DESIGN: Prospective observational cohort study in a teaching hospital providing district and tertiary maternity services delivering 6000 babies per annum. RESULTS: 68% Category 1 deliveries were achieved within 30min and 66% Category 2 within 75min (26% for antepartum Category 2 deliveries). Category 1 deliveries were quicker using general rather than regional anaesthesia (21 vs. 29min, odds ratio [OR] for delivery <30min 4.2, 95%CI 1.3-14.2). 8% Category 1 and 4% Category 2 neonates were acidotic or asphyxiated. The risk of acidosis was not reduced by delivery within 30min for Category 1 (OR 0.56; 0.11-2.81), or within 75min for Category 2 (OR 2.72; 0.6-25.1). Three babies were registered with developmental impairment by three years of age; none were Category 1 deliveries. CONCLUSIONS: Our data suggest that clinical triage is effective, with the more compromised fetus delivered more rapidly using general anaesthesia. For Category 1 deliveries a 30min target DDI is appropriate, although those born after longer DDI did not show developmental impairment. For Category 2 caesarean sections performed for acute fetal distress or concerns, failed instrumental delivery, failure to progress or placental bleeding, a 75min DDI may be an appropriate target but did not protect against acidosis, asphyxia or developmental impairment. Longer DDIs did not result in unfavourable outcomes for other Category 2 indications.