Linking a European cohort of children born with congenital anomalies to vital statistics and mortality records: A EUROlinkCAT study.

EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed.

Intrapartum-related perinatal deaths in births planned in midwifery-led settings in Great Britain: findings and recommendations from the ESMiE confidential enquiry.

OBJECTIVE: To review quality of care in births planned in midwifery-led settings, resulting in an intrapartum-related perinatal death. DESIGN: Confidential enquiry. SETTING: England, Scotland and Wales. SAMPLE: Intrapartum stillbirths and intrapartum-related neonatal deaths in births planned in alongside midwifery units, freestanding midwifery units or at home, sampled from national perinatal surveillance data for 2015/16 (alongside midwifery units) and 2013-16 (freestanding midwifery units and home births). METHODS: Multidisciplinary panels reviewed medical notes for each death, assessing and grading quality of care by consensus, with reference to national standards and guidance. Data were analysed using thematic analysis and descriptive statistics. RESULTS: Sixty-four deaths were reviewed, 30 stillbirths and 34 neonatal deaths. At the start of labour care, 23 women were planning birth in an alongside midwifery unit, 26 in a freestanding midwifery unit and 15 at home. In 75% of deaths, improvements in care were identified that may have made a difference to the outcome for the baby. Improvements in care were identified that may have made a difference to the mother's physical and psychological health and wellbeing in 75% of deaths. Issues with care were identified around risk assessment and decisions about planning place of birth, intermittent auscultation, transfer during labour, resuscitation and neonatal transfer, follow up and local review. CONCLUSIONS: These confidential enquiry findings do not address the overall safety of midwifery-led settings for healthy women with straightforward pregnancies, but suggest areas where the safety of care can be improved. Maternity services should review their care with respect to our recommendations. TWEETABLE ABSTRACT: Confidential enquiry of intrapartum-related baby deaths highlights areas where care in midwifery-led settings can be made even safer.

Evaluation of mericon E. coli O157 Screen Plus and mericon E. coli STEC O-Type Pathogen Detection Assays in Select Foods: Collaborative Study, First Action 2017.05.

QIAGEN mericon Escherichia coli O157 Screen Plus and mericon E. coli Shiga toxin-producing E. coli (STEC) O-Type Pathogen Detection Assays use Real-Time PCR technology for the rapid, accurate detection of E. coli O157 and the "big six" (O26, O45, O103, O111, O121, O145) (non-O157 STEC) in select food types. Using a paired study design, the assays were compared with the U.S. Department of Agriculture, Food Safety Inspection Service Microbiology Laboratory Guidebook Chapter 5.09 reference method for the detection of E. coli O157:H7 in raw ground beef. Both mericon assays were evaluated using the manual and an automated DNA extraction method. Thirteen technicians from five laboratories located within the continental United States participated in the collaborative study. Three levels of contamination were evaluated. Statistical analysis was conducted according to the probability of detection (POD) statistical model. Results obtained for the low-inoculum level test portions produced a difference between laboratories POD (dLPOD) value with a 95% confidence interval of 0.00 (-0.12, 0.12) for the mericon E. coli O157 Screen Plus with manual and automated extraction and mericon E. coli STEC O-Type with manual extraction and -0.01 (-0.13, 0.10) for the mericon E. coli STEC O-Type with automated extraction. The dLPOD results indicate equivalence between the candidate methods and the reference method.

Making stillbirths visible: a systematic review of globally reported causes of stillbirth.

BACKGROUND: Stillbirth is a global health problem. The World Health Organization (WHO) application of the International Classification of Diseases for perinatal mortality (ICD-PM) aims to improve data on stillbirth to enable prevention. OBJECTIVES: To identify globally reported causes of stillbirth, classification systems, and alignment with the ICD-PM. SEARCH STRATEGY: We searched CINAHL, EMBASE, Medline, Global Health, and Pubmed from 2009 to 2016. SELECTION CRITERIA: Reports of stillbirth causes in unselective cohorts. DATA COLLECTION AND ANALYSIS: Pooled estimates of causes were derived for country representative reports. Systems and causes were assessed for alignment with the ICD-PM. Data are presented by income setting (low, middle, and high income countries; LIC, MIC, HIC). MAIN RESULTS: Eighty-five reports from 50 countries (489 089 stillbirths) were included. The most frequent categories were Unexplained, Antepartum haemorrhage, and Other (all settings); Infection and Hypoxic peripartum (LIC), and Placental (MIC, HIC). Overall report quality was low. Only one classification system fully aligned with ICD-PM. All stillbirth causes mapped to ICD-PM. In a subset from HIC, mapping obscured major causes. CONCLUSIONS: There is a paucity of quality information on causes of stillbirth globally. Improving investigation of stillbirths and standardisation of audit and classification is urgently needed and should be achievable in all well-resourced settings. Implementation of the WHO Perinatal Mortality Audit and Review guide is needed, particularly across high burden settings. FUNDING: HR, SH, SHL, and AW were supported by an NHMRC-CRE grant (APP1116640). VF was funded by an NHMRC-CDF (APP1123611). TWEETABLE ABSTRACT: Urgent need to improve data on causes of stillbirths across all settings to meet global targets. PLAIN LANGUAGE SUMMARY: Background and methods Nearly three million babies are stillborn every year. These deaths have deep and long-lasting effects on parents, healthcare providers, and the society. One of the major challenges to preventing stillbirths is the lack of information about why they happen. In this study, we collected reports on the causes of stillbirth from high-, middle-, and low-income countries to: (1) Understand the causes of stillbirth, and (2) Understand how to improve reporting of stillbirths. Findings We found 85 reports from 50 different countries. The information available from the reports was inconsistent and often of poor quality, so it was hard to get a clear picture about what are the causes of stillbirth across the world. Many different definitions of stillbirth were used. There was also wide variation in what investigations of the mother and baby were undertaken to identify the cause of stillbirth. Stillbirths in all income settings (low-, middle-, and high-income countries) were most frequently reported as Unexplained, Other, and Haemorrhage (bleeding). Unexplained and Other are not helpful in understanding why a baby was stillborn. In low-income countries, stillbirths were often attributed to Infection and Complications during labour and birth. In middle- and high-income countries, stillbirths were often reported as Placental complications. Limitations We may have missed some reports as searches were carried out in English only. The available reports were of poor quality. Implications Many countries, particularly those where the majority of stillbirths occur, do not report any information about these deaths. Where there are reports, the quality is often poor. It is important to improve the investigation and reporting of stillbirth using a standardised system so that policy makers and healthcare workers can develop effective stillbirth prevention programs. All stillbirths should be investigated and reported in line with the World Health Organization standards.

Changes in management policies for extremely preterm births and neonatal outcomes from 2003 to 2012: two population-based studies in ten European regions.

OBJECTIVE: To investigate changes in maternity and neonatal unit policies towards extremely preterm infants (EPTIs) between 2003 and 2012, and concurrent trends in their mortality and morbidity in ten European regions. DESIGN: Population-based cohort studies in 2003 (MOSAIC study) and 2011/2012 (EPICE study) and questionnaires from hospitals. SETTING: 70 hospitals in ten European regions. POPULATION: Infants born at <27 weeks of gestational age (GA) in hospitals participating in both the MOSAIC and EPICE studies (1240 in 2003, 1293 in 2011/2012). METHODS: We used McNemar's Chi2 test, paired t-tests and conditional logistic regression for comparisons over time. MAIN OUTCOMES MEASURES: Reported policies, mortality and morbidity of EPTIs. RESULTS: The lowest GA at which maternity units reported performing a caesarean section for acute distress of a singleton non-malformed fetus decreased from an average of 24.7 to 24.1 weeks (P < 0.01) when parents were in favour of active management, and 26.1 to 25.2 weeks (P = 0.01) when parents were against. Units reported that neonatologists were called more often for spontaneous deliveries starting at 22 weeks GA in 2012 and more often made decisions about active resuscitation alone, rather than in multidisciplinary teams. In-hospital mortality after live birth for EPTIs decreased from 50% to 42% (P < 0.01). Units reporting more active management in 2012 than 2003 had higher mortality in 2003 (55% versus 43%; P < 0.01) and experienced larger declines (55 to 44%; P < 0.001) than units where policies stayed the same (43 to 37%; P = 0.1). CONCLUSIONS: European hospitals reporting changes in management policies experienced larger survival gains for EPTIs. TWEETABLE ABSTRACT: Changes in reported policies for management of extremely preterm births were related to mortality declines.

The effects of a one-to-one nurse-to-patient ratio on the mortality rate in neonatal intensive care: a retrospective, longitudinal, population-based study.

OBJECTIVE: To estimate the effect of the provision of a one-to-one nurse-to-patient ratio on mortality rates in neonatal intensive care units. DESIGN: A population-based analysis of operational clinical data using an instrumental variable method. SETTING: National Health Service neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit and participating in the Neonatal Economic, Staffing, and Clinical Outcomes Project. PARTICIPANTS: 43 tertiary-level neonatal units observed monthly over the period January 2008 to December 2012. INTERVENTION: Proportion of neonatal intensive care days or proportion of intensive care admissions for which one-to-one nursing was provided. OUTCOMES: Monthly in-hospital intensive care mortality rate. RESULTS: Over the study period, the provision of one-to-one nursing in tertiary neonatal units declined from a median of 9.1% of intensive care days in 2008 to 5.9% in 2012. A 10 percentage point decrease in the proportion of intensive care days on which one-to-one nursing was provided was associated with an increase in the in-hospital mortality rate of 0.6 (95% CI 1.2 to 0.0) deaths per 100 infants receiving neonatal intensive care per month compared with a median monthly mortality rate of 4.5 deaths per 100 infants per month. The results remained robust to sensitivity analyses that varied the estimation sample of units, the choice of instrumental variables, unit classification and the selection of control variables. CONCLUSIONS: Our study suggests that decreases in the provision of one-to-one nursing in tertiary-level neonatal intensive care units increase the in-hospital mortality rate.

Prevention of neural tube defects in the UK: a missed opportunity.

OBJECTIVE: In 1991, the Medical Research Council (MRC) Vitamin Study demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). We aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in the UK from 1998 as it had been in the USA. DESIGN: Estimates of NTD prevalence, the preventive effect of folic acid and the proportion of women taking folic acid supplements before pregnancy were used to predict the number of NTD pregnancies that would have been prevented if folic acid fortification had been implemented. SETTING: Eight congenital anomaly registers in England and Wales. MAIN OUTCOME MEASURES: The prevalence of pregnancies with an NTD in the UK and the number of these pregnancies that would have been prevented if folic acid fortification had been implemented. RESULTS: From 1991 to 2012, the prevalence of NTD pregnancies was 1.28 (95% CI 1.24 to 1.31) per 1000 total births (19% live births, 81% terminations and 0.5% stillbirths and fetal deaths ≥20 weeks' gestation). If the USA levels of folic acid fortification from 1998 onwards had been adopted in the UK, an estimated 2014 fewer NTD pregnancies would have occurred. CONCLUSIONS: Failure to implement folic acid fortification in the UK has caused, and continues to cause, avoidable terminations of pregnancy, stillbirths, neonatal deaths and permanent serious disability in surviving children.

Combining 3D human in vitro methods for a 3Rs evaluation of novel titanium surfaces in orthopaedic applications.

In this study, we report on a group of complementary human osteoblast in vitro test methods for the preclinical evaluation of 3D porous titanium surfaces. The surfaces were prepared by additive manufacturing (electron beam melting [EBM]) and plasma spraying, allowing the creation of complex lattice surface geometries. Physical properties of the surfaces were characterized by SEM and profilometry and 3D in vitro cell culture using human osteoblasts. Primary human osteoblast cells were found to elicit greater differences between titanium sample surfaces than an MG63 osteoblast-like cell line, particularly in terms of cell survival. Surface morphology was associated with higher osteoblast metabolic activity and mineralization on rougher titanium plasma spray coated surfaces than smoother surfaces. Differences in osteoblast survival and metabolic activity on titanium lattice structures were also found, despite analogous surface morphology at the cellular level. 3D confocal microscopy identified osteoblast organization within complex titanium surface geometries, adhesion, spreading, and alignment to the biomaterial strut geometries. Mineralized nodule formation throughout the lattice structures was also observed, and indicative of early markers of bone in-growth on such materials. Testing methods such as those presented are not traditionally considered by medical device manufacturers, but we suggest have value as an increasingly vital tool in efficiently translating pre-clinical studies, especially in balance with current regulatory practice, commercial demands, the 3Rs, and the relative merits of in vitro and in vivo studies. Biotechnol. Bioeng. 2016;113: 1586-1599. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

Economic costs associated with moderate and late preterm birth: a prospective population-based study.

OBJECTIVE: We sought to determine the economic costs associated with moderate and late preterm birth. DESIGN: An economic study was nested within a prospective cohort study. SAMPLE: Infants born between 32(+0) and 36(+6)  weeks of gestation in the East Midlands of England. A sample of infants born at ≥37 weeks of gestation acted as controls. METHODS: Data on resource use, estimated from a National Health Service (NHS) and personal social services perspective, and separately from a societal perspective, were collected between birth and 24 months corrected age (or death), and valued in pounds sterling, at 2010-11 prices. Descriptive statistics and multivariable analyses were used to estimate the relationship between gestational age at birth and economic costs. MAIN OUTCOME MEASURES: Cumulative resource use and economic costs over the first two years of life. RESULTS: Of all eligible births, 1146 (83%) preterm and 1258 (79%) term infants were recruited. Mean (standard error) total societal costs from birth to 24 months were £12 037 (£1114) and £5823 (£1232) for children born moderately preterm (32(+0) -33(+6)  weeks of gestation) and late preterm (34(+0) -36(+6)  weeks of gestation), respectively, compared with £2056 (£132) for children born at term. The mean societal cost difference between moderate and late preterm and term infants was £4657 (bootstrap 95% confidence interval, 95% CI £2513-6803; P < 0.001). Multivariable regressions revealed that, after controlling for clinical and sociodemographic characteristics, moderate and late preterm birth increased societal costs by £7583 (£874) and £1963 (£337), respectively, compared with birth at full term. CONCLUSIONS: Moderate and late preterm birth is associated with significantly increased economic costs over the first 2 years of life. Our economic estimates can be used to inform budgetary and service planning by clinical decision-makers, and economic evaluations of interventions aimed at preventing moderate and late preterm birth or alleviating its adverse consequences. TWEETABLE ABSTRACT: Moderate and late preterm birth is associated with increased economic costs over the first 2 years of life.

Observational study of children admitted to United Kingdom and Republic of Ireland Paediatric Intensive Care Units after out-of-hospital cardiac arrest.

AIMS: To estimate the prevalence of children admitted after out-of-hospital cardiac arrest (OHCA) to UK and Republic of Ireland (RoI) Paediatric Intensive Care Units (PICUs) and factors associated with mortality to inform future clinical trial feasibility. METHOD: Observational study using a prospectively collected dataset of the Paediatric Intensive Care Audit Network (PICANet) of 33 UK and RoI PICUs (January 2003 to June 2010). Cases (0 to <16 years), with documented OHCA surviving to PICU admission and requiring mechanical ventilation were included. Main outcomes were prevalence for admission and death within PICU. Factors associated with mortality were examined with multiple logistic regression analysis. RESULTS: 827 of 111,170 admissions (0.73%; 95% CI [0.48 to 0.98%]) were identified as children admitted following OHCA. PICU mortality for OHCA was 50.5% (418/827). Recruitment into an adequately sized clinical trial would not be feasible with the current prevalence rate. Characteristics at PICU admission associated with increased risk of death included; bilateral unreactive pupils, genetically inherited condition, inter-hospital transfer to PICU, requirement for vasoactive drugs and greater base deficit. Factors associated with reduced risk of death were submersion or a respiratory aetiology and pre-existing respiratory or cardiac conditions. CONCLUSIONS: Less than 120 children a year are admitted to PICUs in the UK and RoI after OHCA, limiting options for conducting UK intervention trials. The risk factors associated with mortality identified in this study will allow risk stratification in future studies.

Admissions to paediatric intensive care units (PICU) with refractory convulsive status epilepticus (RCSE): A two-year multi-centre study.

AIMS: To obtain national epidemiological data on the aetiology, management and outcome of refractory convulsive status epilepticus (RCSE) in children. METHODS: Data on children admitted with RCSE between 01.01.2008 and 31.12.2009, to eight paediatric intensive care units (PICUs) were retrospectively collected using a standard proforma designed with and co-ordinated by PICANet. RESULTS: Data were collected on 245 (male, 179) patients aged between <1 month and 16.5 years (median 2.8 years, IQR 1-7.43 years), of which: One hundred and fifty-one patients (male, 89) aged between <1 month and 16.5 years (median 2.3 years, IQR 1-7.17 years) met the study criteria for a diagnosis of RCSE. Causes included acute symptomatic (15.2%), remote symptomatic (29.0%), epilepsy-related (10.6%), progressive encephalopathy (10.6%) febrile seizures (18.2%); no cause was identified in 16.4%. First line treatments included lorazepam (118 patients, 78.1%), diazepam (72, 47.7%) and midazolam (37, 24.5%). Second-line treatments included phenytoin (125 patients, 82.8%) and phenobarbital (seven patients, 4.6%). Third-line treatments included a thiopentone bolus (99 patients, 65.6%), thiopentone infusion (20, 13.2%) midazolam infusion (56, 37.1%) phenobarbital (18, 11.9%), propofol (6, 4.0%) and clonazepam (2, 1.3%). Deviation from the national advanced paediatric life support (APLS) protocol was noted in approximately one quarter of all patients. Six patients died (4.0%). Seventeen patients (11.3%) developed a new neurological deficit on discharge from PICU, of which eight (5.3%) continued to show this deficit at a 30-day follow-up and 12 patients (7.9%) developed de novo epilepsy. CONCLUSIONS: Thiopentone was the most commonly used anticonvulsant to treat RCSE on admission to PICU. Mortality was low and approximately 1 in 25 showed a new neurological deficit at the 30-day follow-up.

Experiences with maternal and perinatal death reviews in the UK--the MBRRACE-UK programme.

Established in 1952, the programme of surveillance and Confidential Enquiries into Maternal Deaths in the UK is the longest running such programme worldwide. Although more recently instituted, surveillance and confidential enquiries into perinatal deaths are also now well established nationally. Recent changes to funding and commissioning of the Enquiries have enabled both a reinvigoration of the processes and improvements to the methodology with an increased frequency of future reporting. Close engagement with stakeholders and a regulator requirement for doctors to participate have both supported the impetus for involvement of all professionals leading to greater potential for improved quality of care for women and babies.

The effects of designation and volume of neonatal care on mortality and morbidity outcomes of very preterm infants in England: retrospective population-based cohort study.

OBJECTIVE: To examine the effects of designation and volume of neonatal care at the hospital of birth on mortality and morbidity outcomes in very preterm infants in a managed clinical network setting. DESIGN: A retrospective, population-based analysis of operational clinical data using adjusted logistic regression and instrumental variables (IV) analyses. SETTING: 165 National Health Service neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit and participating in the Neonatal Economic, Staffing and Clinical Outcomes Project. PARTICIPANTS: 20 554 infants born at <33 weeks completed gestation (17 995 born at 27-32 weeks; 2559 born at <27 weeks), admitted to neonatal care and either discharged or died, over the period 1 January 2009-31 December 2011. INTERVENTION: Tertiary designation or high-volume neonatal care at the hospital of birth. OUTCOMES: Neonatal mortality, any in-hospital mortality, surgery for necrotising enterocolitis, surgery for retinopathy of prematurity, bronchopulmonary dysplasia and postmenstrual age at discharge. RESULTS: Infants born at <33 weeks gestation and admitted to a high-volume neonatal unit at the hospital of birth were at reduced odds of neonatal mortality (IV regression odds ratio (OR) 0.70, 95% CI 0.53 to 0.92) and any in-hospital mortality (IV regression OR 0.68, 95% CI 0.54 to 0.85). The effect of volume on any in-hospital mortality was most acute among infants born at <27 weeks gestation (IV regression OR 0.51, 95% CI 0.33 to 0.79). A negative association between tertiary-level unit designation and mortality was also observed with adjusted logistic regression for infants born at <27 weeks gestation. CONCLUSIONS: High-volume neonatal care provided at the hospital of birth may protect against in-hospital mortality in very preterm infants. Future developments of neonatal services should promote delivery of very preterm infants at hospitals with high-volume neonatal units.

Perinatal outcomes for extremely preterm babies in relation to place of birth in England: the EPICure 2 study.

BACKGROUND: Expertise and resources may be important determinants of outcome for extremely preterm babies. We evaluated the effect of place of birth and perinatal transfer on survival and neonatal morbidity within a prospective cohort of births between 22 and 26 weeks of gestation in England during 2006. METHODS: We studied the whole population of 2460 births where the fetus was alive at the admission of the mother to hospital for delivery. Outcomes to discharge were compared between level 3 (most intensive) and level 2 maternity services, with and without transfers, and by activity level of level 3 neonatal unit; ORs were adjusted for gestation at birth and birthweight for gestation (adjusted ORs (aOR)). FINDINGS: Of this national birth cohort, 56% were born in maternity services with level 3 and 34% with level 2 neonatal units; 10% were born in a setting without ongoing intensive care facilities (level 1). When compared with level 2 settings, risk of death in level 3 services was reduced (aOR 0.73 (95% CI 0.59 to 0.90)), but the proportion surviving without neonatal morbidity was similar (aOR 1.27 (0.93 to 1.74)). Analysis by intended hospital of birth confirmed reduced mortality in level 3 services. Following antenatal transfer into a level 3 setting, there were fewer intrapartum or labour ward deaths, and overall mortality was higher for those remaining in level 2 services (aOR 1.44 (1.09 to 1.90)). Among level 3 services, those with higher activity had fewer deaths overall (aOR 0.68 (0.52 to 0.89)). INTERPRETATION: Despite national policy, only 56% of births between 22 and 26 weeks of gestation occurred in maternity services with a level 3 neonatal facility. Survival was significantly enhanced following birth in level 3 services, particularly those with high activity; this was not at the cost of increased neonatal morbidity.

Contemporary management and outcomes for infants born with oesophageal atresia.

BACKGROUND: Reports on the management and outcome of rare conditions, such as oesophageal atresia, are frequently limited to case series reporting single-centre experience over many years. The aim of this study was to identify all infants born with oesophageal atresia in the UK and Ireland to describe current clinical practice and outcomes. METHODS: This was a prospective multicentre cohort study of all infants born with oesophageal atresia and/or tracheo-oesophageal fistula in 2008-2009 in the UK and Ireland to record current clinical management and early outcomes. RESULTS: A total of 151 infants admitted to 28 paediatric surgical units were identified. Some aspects of perioperative management were universal, including oesophageal decompression, operative technique and the use of transanastomotic tubes. However, there were a number of areas where clinical practice varied considerably, including the routine use of perioperative chest drains, postoperative contrast studies and antireflux medication, with each of these being employed in 30-50 per cent of patients. There was a trend towards routine postoperative ventilation. CONCLUSION: The prospective methodology used in this study can help identify practices that all surgeons employ and also those that few surgeons use. Areas of clinical equipoise can be recognized and avenues for further research identified.

An investigation into the reporting and management of late terminations of pregnancy (between 22 +0 and 26 +6 weeks of gestation) within NHS Hospitals in England in 2006: the EPICure preterm cohort study.

OBJECTIVE: To review all late terminations of pregnancy, between 22(+0) and 26(+6) weeks of gestation, collected as part of the EPICure2 study. DESIGN: Prospective cohort study. SETTING: All National Health Service (NHS) hospitals providing perinatal services for extremely preterm infants. POPULATION: All births between 22(+0) and 26(+6) weeks of gestation in England during 2006. METHODS: Data were collected for the defined cohort of births, including terminations of pregnancy, by designated unit staff using a standardised questionnaire. Rigorous validation processes were established to ensure comprehensive data collection. Gestational age was validated using a hierarchical classification of scan dates, certain date of last menstrual period and working gestation. Data for terminations of pregnancy (TOPs) were categorised into two groups, terminations for fetal abnormality and for maternal or fetal compromise, and were analysed in terms of their reporting, management and outcomes. MAIN OUTCOME MEASURES: Classification, rate of feticide and outcome following TOP. RESULTS: Of 3782 births between 22(+0) and 26(+6) weeks of gestation, 647 (17.1%) were TOPs; of these 584 (90.3%) were for fetal abnormality and 63 (9.7%) for maternal or fetal compromise. Feticide was carried out in 489 of 584 (83.7%) TOPs for fetal abnormality, and in 38 of 63 (60.3%) of the TOPs for maternal or fetal compromise. Live births resulted following 2.2% TOPs for fetal abnormality and 4.8% TOPs for maternal or fetal compromise. CONCLUSION: Terminations of pregnancy represent a relatively large proportion of very preterm births. Fetal abnormalities are the main cause for these terminations, and most include feticide. Better screening strategies are required to avoid the need for late terminations of pregnancy for fetal abnormalities.

Schizencephaly prevalence, prenatal diagnosis and clues to etiology: a register-based study.

OBJECTIVES: To establish the prevalence and antenatal diagnosis of schizencephaly in the UK. METHODS: Data on schizencephaly were extracted from six regional congenital anomaly registers. RESULTS: Thirty-eight cases of schizencephaly were identified in 2 567 165 livebirths and stillbirths, giving a total prevalence of 1.48/100 000 births (95% CI, 1.01-1.95). Eighteen (47% (95% CI, 31-63%)) of the 38 cases were identified antenatally. No affected fetus had an abnormal karyotype identified. A high proportion of cases of schizencephaly occurred in younger mothers: 63% were aged 24 years or less, significantly higher (P < 0.0001) than the corresponding proportion (26%) of mothers in England and Wales. The majority of cases were not identified until after 22 weeks of pregnancy. Additional anomalies associated with vascular disruption sequences were found in eight cases which had septo-optic dysplasia or absent septum pellucidum, one of which also had gastroschisis. CONCLUSIONS: Schizencephaly occurs more frequently in the fetuses of younger mothers. It is often associated with septo-optic dysplasia, suggesting that the two conditions may share a common origin, arising as a result of destructive processes that cause changes in the brain which only become apparent on ultrasound in the second half of pregnancy.

Neonatal intensive care outcomes and resource utilisation of infants born <26 weeks in the former Trent region: 2001-2003 compared with 1991-1993.

OBJECTIVES: To provide survival data and rates of severe disability at 2 years of corrected age in infants born prior to 26 weeks' gestation in 2001-2003 and to compare these outcomes with an earlier cohort from 1991 to 1993. DESIGN: Population-based prospective cohort study. SETTING: Former Trent region of UK covering a population of approximately five million and around 55 000 births per annum. PARTICIPANTS: The authors identified a 3-year cohort of infants born before 26 weeks' gestation between 1 January 2001 and 31 December 2003 from The Neonatal Survey (TNS). Questionnaires based on the Oxford minimum dataset were completed. MAIN OUTCOME MEASURES: Survival, service use and disability levels were compared between the 2001- 2003 cohort and the cohort from 1991 to 1993. RESULTS: In 2001-2003, 0%, 18% and 35% of live born babies were alive at 2 years without any evidence of severe disability at 23, 24 and 25 weeks' gestation, respectively. Overall, of those children admitted to neonatal care, the proportion with no evidence of severe disability at 2 years corrected age improved from 14.5% in 1991-1993 to 26.5% in 2001-2003. There was an increase in the proportion of children with at least one severe disability, out of total admissions to neonatal unit (8% vs 17%) and of those assessed at 2 years (35% vs 39%). CONCLUSIONS: This study has shown an improvement in survival to discharge in babies admitted for neonatal care. However, this improved survival has been associated with an increase in the proportion of children with at least one severe disability at a corrected age of 2 years.

Histopathology and computed tomography of age-associated degeneration of the equine temporohyoid joint.

REASONS FOR PERFORMING STUDY: The aetiology of temporohyoid osteoarthropathy (THO) is unknown; both primary infectious and degenerative causes have been suggested. HYPOTHESIS: There is a significant association between increasing age and severity of temporohyoid joint degeneration. To examine the histopathology of the temporohyoid articulation in aged horses and to compare the appearance of the joint with computed tomography (CT) and peripheral quantitative CT (pQCT). METHODS: pQCT scans of the temporohyoid articulations were obtained bilaterally from 31 horses (range age 1-44 years) post mortem and images were graded by 2 blinded observers on 2 occasions for the presence of osteophytes, irregularity of the joint surface and mineralisation. Eight heads had been examined previously by CT, with the images similarly graded for the shape and density of the proximal stylohyoid bones, bone proliferation surrounding the joint, mineralisation of the tympanohyoid cartilage and the relationship of the petrous temporal bone to the stylohyoid bone. Sixteen temporohyoid joints were then evaluated histologically. RESULTS: There was significant association between the mean pQCT degeneration score and age (rho = 0.75; P<0.0001), between the pQCT and CT score (rho = 0.63; P = 0.01) and between the degenerative changes identified within each temporohyoid joint within each horse (rho = 0.81; P<0.0001). Age-associated changes included the development of a club shape by the proximal stylohyoid bone, rounding of the synostosis with the petrous temporal bone and extension of osteophytes from the petrous temporal bone to envelope the stylohyoid head and bridge the joint. In no horse was there any evidence of osteomyelitis within the petrous temporal bone, stylohyoid bone or tympanohyoid cartilage. CONCLUSIONS: This study provides evidence that age is associated with increasing severity of degenerative changes in the equine temporohyoid joint and that similar changes are commonly found bilaterally. POTENTIAL RELEVANCE: The changes identified appear similar, albeit milder to the changes reported in horses with THO, suggesting that degenerative, rather than infectious causes may underlie the aetiology of THO. Future work should be directed at examining the histopathology of clinical THO cases.

Estimates of length of neonatal stay for very premature babies in the UK.

OBJECTIVE: To describe simple estimates of likely duration of stay for very premature babies born in the UK and discharged home. DESIGN: Statistical modelling of data from thirty neonatal units in a geographically defined region of the UK. PARTICIPANTS: All babies born at 23 to 32 completed weeks of gestation in 2005, 2006 and 2007 who were discharged home with the expectation that they would survive. MAIN OUTCOME MEASURE: Total duration of stay in the neonatal service. RESULTS: 5528 babies were initially identified. 558 (10.1%) who died or who did not follow a normal care pathway were excluded. In a further 27, data were either missing or inadequate, leaving a study population of 4702 babies. As expected, gestation and birthweight exhibited strong influence on length of stay. Of the other variables tested, initial reason for admission (need for early respiratory support) showed the most consistent association. These factors were combined to produce predictive tables. The predictive performance of the tables was found to fit the data well for various groups, with the exception of multiple births who tended to have longer stays. However, when tested against individual units, much greater variation was seen independent of unit size and case mix. CONCLUSION: The prediction tables should permit parents to make sensible estimates about the duration of their baby's stay in the neonatal service; however, there appear to be important differences between units. The variation noted in length of stay between otherwise similar units merits further investigation.