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Amniotic band syndrome (ABS) and limb body wall complex (LBWC) have an overlapping phenotype of multiple congenital anomalies and their etiology is unknown. We aimed to determine the prevalence of ABS and LBWC in Europe from 1980 to 2019and to describe the spectrum of congenital anomalies. In addition, we investigated maternal age and multiple birth as possible risk factors for the occurrence of ABS and LBWC. We used data from the European surveillance of congenital anomalies (EUROCAT) network including data from 30 registries over 1980–2019. We included all pregnancy outcomes, including live births, stillbirths, and terminations of pregnancy for fetal anomalies. ABS and LBWC cases were extracted from the central EUROCAT database using coding information responses from the registries. In total, 866 ABS cases and 451 LBWC cases were included in this study. The mean prevalence was 0.53/10,000 births for ABS and 0.34/10,000 births for LBWC during the 40 years. Prevalence of both ABS and LBWC was lower in the 1980s and higher in the United Kingdom. Limb anomalies and neural tube defects were commonly see in ABS, whereas in LBWC abdominal and thoracic wall defects and limb anomalies were most prevalent. Twinning was confirmed as a risk factor for both ABS and LBWC. This study includes the largest cohort of ABS and LBWC cases ever reported over a large time period using standardized EUROCAT data. Prevalence, clinical characteristics, and the phenotypic spectrum are described, and twinning is confirmed as a risk factor. info:eu-repo/semantics/publishedVersion more...

Background: Postmenstrual age for surviving infants without congenital anomalies born at 24–29 weeks’ gestational age from 2005 to 2018 in the USA increased 8 days, discharge weight increased 316 grams, and median discharge weight z-score increased 0.19 standard units. We asked whether increases were observed in other countries. Methods: We evaluated postmenstrual age, weight, and weight z-score at discharge of surviving infants without congenital anomalies born at 24–29 weeks’ gestational age admitted to Vermont Oxford Network member hospitals in Austria, Ireland, Italy, Switzerland, the UK, and the USA from 2012 to 2020. Results: After adjustment, the median postmenstrual age at discharge increased significantly in Austria (3.6 days, 99% CI [1.0, 6.3]), Italy (4.0 days [2.3, 5.6]), and the USA (5.4 days [5.0, 5.8]). Median discharge weight increased significantly in Austria (181 grams, 99% CI [95, 267]), Ireland (234 [143, 325]), Italy (133 [83, 182]), and the USA (207 [194, 220]). Median discharge weight z-score increased in Ireland (0.24 standard units, 99% CI [0.12, 0.36]) and the USA (0.15 [0.13, 0.16]). Discharge on human milk increased in Italy, Switzerland, and the UK, while going home on cardiorespiratory monitors decreased in Austria, Ireland, and USA and going home on oxygen decreased in Ireland. Conclusions: In this international cohort of neonatal intensive care units, postmenstrual discharge age and weight increased in some, but not all, countries. Processes of care at discharge did not change in conjunction with age and weight increases. more...

Background Methods for the economic evaluation of implementation initiatives to increase the uptake of cost-effective healthcare interventions are not standardised. Value of implementation and policy cost-effectiveness are two proposed approaches. This research aims to compare these two methods and propose a standardised approach. To illustrate this, we evaluated two implementation programmes to increase magnesium sulphate (MgSO4) uptake in preterm labour to reduce the risk of cerebral palsy: i) the National PReCePT Programme (NPP) which provided regional support and funded clinical time in maternity units in England, and ii) an enhanced support programme (ESP) with additional unit-level coaching and extra funded time, which was nested within NPP and subject to a cluster RCT. Methods After summarising value of implementation and policy cost-effectiveness methods, we explored the extent to which the two methods can be viewed as mathematically equivalent for the purpose of evaluating the NPP (versus pre-existing trends) and the ESP (versus the NPP) calculating their incremental cost-effectiveness ratios, net monetary benefits, and their probability of being cost-effective. Results We demonstrate that value of implementation and policy cost-effectiveness methods can be expressed in mathematically equivalent terms and propose a standardised stepwise approach. Both methods depend on the change in the uptake of the healthcare technology, cost of the implementation activity, size of the eligible population affected over time, and the cost-effectiveness of the healthcare technology. We illustrated our standardised approach in two economic evaluations: the NPP generated a societal lifetime net monetary benefit of £30,247 per maternity unit over 12 months, at a willingness-to-pay threshold of £20,000; the probability of being cost-effective was 98%. In contrast, the ESP generated a net monetary benefit of -£28,682 per maternity unit in comparison to the NPP; the probability of being cost-effective was 22%. Conclusions Policy cost-effectiveness and value of implementation approaches can be represented by a standardised stepwise method for the economic evaluation of implementation initiatives. Our illustrative examples show how the value of different quality improvement interventions for the same cost-effective treatment can be evaluated and compared. Our standardised method may facilitate a more systematic assessment of the value for money of implementation initiatives, which should be viewed as an important component of implementation research. more...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rarely fatal in children and young people (CYP

Background Aplasia cutis congenita (ACC) is a rare congenital anomaly characterized by localized or widespread absence of skin at birth, mainly affecting the scalp. Most information about ACC exists as individual case reports and medium-sized studies. Objectives This study aimed to investigate the epidemiology of ACC, using data from a large European network of population-based registries for congenital anomalies (EUROCAT). Methods Twenty-eight EUROCAT population-based registries in 16 European countries were involved. Poisson regression models were exploited to estimate the overall and live birth prevalence, to test time trends in prevalence between four 5-year periods and to evaluate the impact of the change of coding for ACC from the unspecific ICD9-BPA code to the specific ICD10 code. Proportions of ACC cases associated with other anomalies were reported. Results Five hundred cases were identified in the period 1998–2017 (prevalence: 5.10 per 100,000 births). Prevalence across 5-year periods did not differ significantly and no significant differences were evident due to the change from ICD9 to ICD10 in ACC coding. Heterogeneity in prevalence was observed across registries. The scalp was the most common site for ACC (96.4%) and associated congenital anomalies were present in 33.8% of cases. Patau and Adams–Oliver syndromes were the most frequent among the associated chromosomal anomalies (88.3%) and the associated genetic syndromes (57.7%), respectively. 16% of cases were associated with limb anomalies and 15.4% with congenital heart defects. A family history of ACC was found in 2% of cases. Conclusion To our knowledge, this is the only population-based study on ACC. The EUROCAT methodologies provide reliable prevalence estimates and proportions of associated anomalies. more...

Background A quality improvement strategy (PReCePT) was used in a standard and enhanced format to scale up a clinical intervention (administering magnesium sulphate to women in preterm labour) across all maternity units in England to protect prematurely born infants from neurodevelopmental disabilities. Formal evaluations reported the effectiveness of the standard package alone in increasing the administration of magnesium sulphate. In this paper, we focus on the findings of the process evaluations, using normalisation process theory to explain how different implementation contexts generated the observed outcomes relating to normative and relational restructuring and sustainment. Methods Interviews were conducted with key individuals in implementation of leadership positions nationally and locally. Interviews were analysed initially using the framework method. We then engaged recursively with NPT constructs to generate generalisable insights with pragmatic applicability in other settings. Results In total, 72 interviews were conducted with good representation from units across England and staff from the National Academic Health Science Network. We found that all units irrespective of whether they received a standard or enhanced QI package were successful in the ‘normative restructuring’ of their setting to enable magnesium sulphate to be administered. This suggests that this implementation outcome is necessary to achieve improvements. However, it may not be sufficient to sustain the changes once additional resources have been withdrawn. Sustainment, our findings suggest, required ‘relational restructuring’ to accommodate altered workflows and facilitate the sharing of responsibilities and tasks in daily practice. Relational restructuring was more likely to have been achieved units receiving enhanced QI support but also happened in units with standard QI support, especially in those where perinatal team working was already well established. Conclusion Unlike other large QI-focused spread-and-scale programmes which failed to show any impact on outcomes, the PReCePT programme in both the enhanced and standard support packages led to improvements in the uptake of magnesium sulphate. The findings suggest that QI programmes interact with the enabling factors, such as strong interprofessional team working, already present in the setting. A standard package with minimal support was therefore sufficient in settings with enabling factors, but enhanced support was required in units where these were absent. more...

Abstract Outcomes of neonatal encephalopathy (NE) have improved since the widespread implementation of therapeutic hypothermia (TH) in high-resource settings. While TH for NE in term and near-term infants has proven beneficial, 30–50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. There is therefore a critical need to find additional pharmacological and non-pharmacological interventions that improve the outcomes for these children. There are many potential candidates; however, it is unclear whether these interventions have additional benefits when used with TH. Although primary and delayed (secondary) brain injury starting in the latent phase after HI are major contributors to neurodisability, the very late evolving effects of tertiary brain injury likely require different interventions targeting neurorestoration. Clinical trials of seizure management and neuroprotection bundles are needed, in addition to current trials combining erythropoietin, stem cells, and melatonin with TH. Impact The widespread use of therapeutic hypothermia (TH) in the treatment of neonatal encephalopathy (NE) has reduced the associated morbidity and mortality. However, 30–50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. This review details the pathophysiology of NE along with the evidence for the use of TH and other beneficial neuroprotective strategies used in term infants. We also discuss treatment strategies undergoing evaluation at present as potential adjuvant treatments to TH in NE. more...

Background: Pierre Robin sequence (PRS) is a rare congenital anomaly. Respiratory disorders and feeding difficulties represent the main burden. Objective: The aim of this study was to investigate the epidemiology of PRS using a cohort of cases from EUROCAT, the European network of population-based registries of congenital anomalies. Methods: We analysed cases of PRS born in the period 1998-2017 collected by 29 population-based congenital anomaly registries in 17 different countries. We calculated prevalence estimates, prenatal detection rate, survival up to 1 week, and proportions of associated anomalies. The effect of maternal age was tested using a Poisson regression model. Results: Out of 11 669 155 surveyed births, a total of 1294 cases of PRS were identified. The estimate of the overall prevalence was 12.0 per 100 000 births (95% CI 9.9, 14.5). There was a total of 882 (68.2%) isolated cases, and the prevalence was 7.8 per 100 000 births (95% CI 6.7, 9.2). A total of 250 cases (19.3%) were associated with other structural congenital anomalies, 77 cases (6.0%) were associated with chromosomal anomalies and 77 (6.0%) with genetic syndromes. The prenatal detection rate in isolated cases was 12.0% (95% CI 9.8, 14.5) and increased to 16.0% (95% CI 12.7, 19.7) in the sub-period 2008-2017. The prevalence rate ratio of non-chromosomal cases with maternal age ≥35 was higher than in cases with maternal age more...

ObjectivesThe aim of this analysis is to identify and report the patterns of social deprivation in relation to childhood mortality; and identify potential points where public health, social and education interventions or health policy may be best targeted.DesignDecile of deprivation and underlying population distribution was derived using Office for National Statistics (ONS) data. The risk of death was then derived using a Poisson regression model, calculating the increasing risk of death for each increasing deprivation decile.SettingEnglandParticipants2688 childhood deaths in England reviewed between the April 2019 and March 2020.Main Outcome MeasuresThe relationship between deprivation and risk of death; for deaths with, and without modifiable factors.ResultsThere was evidence of increasing mortality risk with increase in deprivation decile (RR 1.08 (1.07 to 1.10)), with the gradient of risk stronger in children who died with modifiable factors than those without (RR 1.12 (1.09 to 1.15)) vs (RR 1.07 (1.05 to 1.08)). Deprivation sub-domains of Employment, Adult Education, Barriers to Housing and Services, and Indoor Living Environments appeared to be the most important predictors of child mortalityConclusionsThere is a clear gradient of increasing child mortality across England as measures of deprivation increase; with a striking finding that this varied little by area, age or other demographic factor. Over a fifth of all child deaths may be avoided if the most deprived half of the population had the same mortality as the least deprived. Children dying in more deprived areas may have a greater proportion of avoidable deaths. Adult employment and education, and improvements to housing, may be the most efficient place to target resources to reduce these inequalities. more...

ObjectiveTo evaluate the effectiveness and cost-effectiveness of the National PReCePT Programme (NPP) in increasing use of magnesium sulfate (MgSO4) in preterm births.DesignBefore-and-after study.SettingMaternity units (N=137) within NHS England and the Academic Health Science Network (AHSN) in 2018.ParticipantsBabies born ≤30 weeks’ gestation admitted to neonatal units in England.InterventionsThe NPP was a quality improvement (QI) intervention including the PReCePT (Preventing Cerebral Palsy in Pre Term labour) QI toolkit and materials (preterm labour proforma, staff training presentations, parent leaflet, posters for the unit and learning log), regional AHSN-level support, and up to 90 hours funded backfill for a midwife ‘champion’ to lead implementation.Main outcome measuresMgSO4uptake post implementation was compared with pre-NPP implementation uptake. Implementation and lifetime costs were estimated.ResultsCompared with pre-implementation estimates, the average MgSO4uptake for babies born ≤30 weeks’ gestation, in 137 maternity units in England, increased by 6.3 percentage points (95% CI 2.6 to 10.0 percentage points) to 83.1% post implementation, accounting for unit size, maternal, baby and maternity unit factors, time trends, and AHSN. Further adjustment for early/late initiation of NPP activities increased the estimate to 9.5 percentage points (95% CI 4.3 to 14.7 percentage points). From a societal and lifetime perspective, the health gains and cost savings associated with the NPP effectiveness generated a net monetary benefit of £866 per preterm baby and the probability of the NPP being cost-effective was greater than 95%.ConclusionThis national QI programme was effective and cost-effective. National programmes delivered via coordinated regional clinical networks can accelerate uptake of evidence-based therapies in perinatal care. more...

ObjectiveTo evaluate the effectiveness and cost-effectiveness of the National PreCePT Programme (NPP) in increasing magnesium sulphate (MgSO4) in pre-term births.DesignA quasi-experimental before-and-after designSettingMaternity units within NHS England and the AHSN network in 2018.ParticipantsMaternity units in England (n=137) who participated in the NPP.InterventionsNPP support which included the PReCePT QI toolkit and materials (pre-term labour proforma, staff training presentations, parent leaflet, posters for the unit, learning log), regional AHSN level support, and up to 90 hours funded backfill for a midwife ‘champion’ to lead implementation.Main outcome measuresMgSO4 post-implementation uptake compared to pre-implementation uptake. Implementation and lifetime costs were estimated.ResultsCompared to pre-implementation estimates, the average MgSO4 uptake in 137 maternity units in England increased by 6.3 percentage points (95% CI 2.6 to 10.0 percentage points) to 83.1% post-implementation, accounting for unit size, maternal, baby, and maternity unit factors, time trends, and AHSN. Further adjustment for early or late initiation of NPP activities increased the estimate to 9.5 percentage points (95% CI 4.3 to 14.7 percentage points). From a societal and lifetime perspective, the health gains and cost-savings associated with the NPP effectiveness generated a net monetary benefit of £866 per preterm baby and the probability of the NPP being cost-effective was greater than 95%.ConclusionThis national QI programme was effective and cost-effective. National programmes delivered via coordinated regional clinical networks can accelerate uptake of evidence-based therapies in perinatal care.WHAT IS ALREADY KNOWN ON THIS TOPICSince 2015 the UK National Institute for Health and Care Excellence (NICE) has recommended administration of Magnesium Sulphate (MgSO4) for fetal neuroprotection in very preterm deliveries as a core part of maternity care. By 2017, only two-thirds of all eligible women in England were being given MgSO4, with wide regional variation. The PReCePT pilot study showed an increase in uptake from 21% (2012-2013) to 88% after the introduction of the tool in2015 in 5 units. The National PReCePT Programme (NPP) was rolled out in 2018 by the national network of Academic Health Science Networks with a target to increase MgSO4 administration in England to 85% by 2020.WHAT THIS STUDY ADDSThe study has shown that the nationwide implementation of the NPP, which provided a Quality Improvement (QI) toolkit and materials, cross unit AHSN regional level support, and funded backfill for a unit midwife ‘champion’ through local regional support was effective and cost-effective. Scaling-up of network supported QI programmes at national level can accelerate uptake of new therapies and promote improvements in perinatal care delivery. more...

ObjectiveTo compare the impact of the National PReCePT Programme (NPP) versus an enhanced Quality Improvement (QI) support programme in improving magnesium sulfate (MgSO4) uptake in English maternity units.DesignUnblinded cluster randomised controlled trial.SettingEngland, Academic Health Sciences Network (AHSN), 2018.ParticipantsMaternity units with ≥10 preterm deliveries annually and MgSO4uptake ≤70%. 40 maternity units (27 NPP, 13 enhanced support) were included (randomisation stratified by MgSO4uptake).InterventionsNHS England commissioned the NPP to increase MgSO4uptake in very preterm deliveries to reduce risk of cerebral palsy. NPP maternity units received PReCePT QI materials, regional support, and midwife backfill funding. Enhanced support units received this plus extra backfill funding and unit-level QI coaching.Outcome measuresMgSO4uptake post-implementation was compared between groups using routine data and multivariable linear regression. Net monetary benefit was estimated, based on implementation costs, lifetime quality-adjusted life-years and societal costs. The implementation process was assessed through qualitative process evaluation.ResultsMgSO4uptake increased in all units, with no evidence of difference between groups (0.84 percentage points lower uptake in the enhanced group, 95% Confidence Interval -5.03 to 3.35 percentage points). The probability of enhanced support being cost-effective was ConclusionPReCePT improved MgSO4uptake in all maternity units. Enhanced support did not further improve uptake but may improve teamwork, and more accurately represented the time needed for implementation. Targeted enhanced support, sustainability of improvements and the possible indirect benefits of stronger teamwork associated with enhanced support should be explored further.Trial registrationISRCTN 40938673 (https://www.isrctn.com/ISRCTN40938673)WHAT IS ALREADY KNOWN ON THIS TOPICDespite long-standing evidence that Magnesium Sulfate (MgSO4) confers fetal neuroprotection and reduces risk of cerebral palsy in very preterm babies, by 2017 only two-thirds of eligible women in England were receiving it, with wide regional variation.The pilot PReCePT (Prevention of Cerebral Palsy in preterm labour) Quality Improvement (QI) study appeared to effectively accelerate uptake of MgSO4,and a version of this support model was rolled-out nationwide in 2018.WHAT THIS STUDY ADDSPReCePT improved MgSO4uptake in all maternity units, and the full (‘enhanced’) support model did not appear to improve uptake beyond the achievements of the standard support model used in the National PReCePT Programme. However, enhanced support may be associated with improved perinatal team working, and the funding more accurately represented the staff time needed for implementation.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYPReCePT may serve as a blueprint for other improvement programs to accelerate uptake of evidence-based interventions, and future studies should consider the potential for indirect but far-reaching benefits to staff and patients. more...

In the newborn brain, moderate-severe hypoxia–ischaemia induces glutamate excitotoxicity and inflammation, possibly via dysregulation of candidate astrocytic glutamate transporter ( Glt1) and pro-inflammatory cytokines (e.g. Tnfα, Il1β, Il6). Epigenetic mechanisms may mediate dysregulation. Hypotheses: (1) hypoxia–ischaemia dysregulates mRNA expression of these candidate genes; (2) expression changes in Glt1 are mediated by DNA methylation changes; and (3) methylation values in brain and blood are correlated. Seven-day-old rat pups ( n = 42) were assigned to nine groups based on treatment (for each timepoint: naïve ( n = 3), sham ( n = 3), hypoxia–ischaemia ( n = 8) and timepoint for tissue collection (6, 12 and 24 h post-hypoxia). Moderate hypoxic–ischemic brain injury was induced via ligation of the left common carotid artery followed by 100 min hypoxia (8% O2, 36°C). mRNA was quantified in cortex and hippocampus for the candidate genes, myelin ( Mbp), astrocytic ( Gfap) and neuronal ( Map2) markers (qPCR). DNA methylation was measured for Glt1 in cortex and blood (bisulphite pyrosequencing). Hypoxia–ischaemia induced pro-inflammatory cytokine upregulation in both brain regions at 6 h. This was accompanied by gene expression changes potentially indicating onset of astrogliosis and myelin injury. There were no significant changes in expression or promoter DNA methylation of Glt1. This pilot study supports accumulating evidence that hypoxia–ischaemia causes neuroinflammation in the newborn brain and prioritises further expression and DNA methylation analyses focusing on this pathway. Epigenetic blood biomarkers may facilitate identification of high-risk newborns at birth, maximising chances of neuroprotective interventions. more...

Background: Preterm birth is the biggest cause of child mortality and morbidity in the UK and although we have seen an overall reduction in stillbirth and neonatal mortality in recent years there is still significant variation across the UK. PERIPrem, is a care bundle that brings together 11 best-practice interventions for mothers and preterm babies. A structured and supportive implementation approach using primarily Quality Improvement methodology has been found to significantly increase adherence to the whole bundle and its individual interventions. Methods: This was a qualitative exploration of the barriers and enablers to implementation and the behaviour change techniques used to encourage adherence to the bundle, using semi-structured interviews. The COM-B model for behaviour change was used as a framework for the interviews and the Theoretical Domains Framework and Behaviour Change Techniques Taxonomy to guide the analysis. Results: Across two timepoints, 47 interviews were conducted with 29 staff from Maternity, Obstetrics and Neonatology. The data revealed that capability, opportunity, and motivation acted as both barriers and enablers to the implementation of the bundle. The qualitative interviews revealed that this was achieved through improvements in perinatal team culture, increasing knowledge and skills, having strong leadership and access to the right resources. But above all else implementation depended upon having a care bundle that was evidence-based and a supportive and credible team. Implementation did not come without its challenges; notwithstanding the global pandemic and the effects this had on staff, challenges included the complexity and size of the bundle, limited dedicated time and resource, and the impact of hierarchical perinatal structures. These findings have provided insights that will advance our understanding about the processes that underpin successful implementation of a complex perinatal care bundle.Conclusions: Several factors interacted to enhance as well as hinder the implementation of this complex perinatal care bundle. Over time, adherence to the PERIPrem bundle was enabled by the application of theoretically informed behaviour change techniques. To improve future delivery of complex care bundles, like PERIPrem, the processes and support provided to aid implementation should reflect on how these barriers can be overcome and the enablers enhanced. more...

ImportanceDuring the first year of the COVID-19 pandemic, child mortality in England was the lowest on record, but if this trend will continue, or if unrecognized morbidity during the first year of the pandemic will manifest as increased deaths over the next few years is unclear.ObjectiveTo examine the risks and patterns of childhood deaths before and during the COVID-19 pandemic.Design, Setting, and ParticipantsThis population-based cohort study includes all child deaths in England from April 1, 2019, to March 31, 2022.ExposuresThe year of death.Main Outcomes and MeasuresThe primary outcome measure is risk of death.ResultsOf the 9983 child deaths reported during the study period, 9872 (98.8%) were linked to demographic and population data with 3409 deaths (34.5%) between April 2019 and March 2020, 3035 (30.7%) between April 2020 and March 2021, and 3428 (34.7%) between April 2021 and March 2022. Most deaths occurred in children who were younger than 1 year (6257 of 9872 [62.7%]), the majority were male (5534 of 9760 [56.7%]), and lived in an urban area (8766 of 9872 [88.8%]). The risk of death was lower between April 2020 and March 2021 (relative risk [RR], 0.89 [95% CI, 0.84-0.93]), but not between April 2021 and March 2022 (RR, 1.00 [95% CI, 0.95-1.05]) when compared with April 2019 to March 2020. A population attributable risk (PAF) of 4.0% (95% CI, 0.1%-6.8%) suggested fewer deaths occurred during the whole 3-year period than expected. Reductions were seen in risk of dying by infection (PAF, 22.8% [95% CI, 8.2%-37.0%]) and underlying disease (PAF, 13.3% [95% CI, 8.1%-18.8%]), but there was evidence of an increasing risk of death by trauma (PAF, 14.7% [95% CI, 2.9%-25.2%]). Any reduction in the risk of death was greater in rural areas than in urban areas (RR, 0.73 [95% CI, 0.63-0.85] vs RR, 0.91 [95% CI, 0.86-0.95]) and was not seen in children older than 9 years.Conclusions and RelevanceIn this cohort study, there was a significant reduction in all-cause child mortality during the first year of the COVID-19 pandemic (2020-2021), which returned to close to prepandemic levels the following year (2021-2022). However, there was a net reduction in deaths despite this, with 4% fewer deaths during the 3-year period than would have been expected from the 2019 to 2020 risks. The reductions were largest in rural areas and in children younger than 10 years. more...

Objectives To quantify the relative risk (RR) of childhood deaths across the whole of England during the first year of the COVID-19 pandemic, compared with a similar period of 2019. Design This work is based on data collected by the National Child Mortality Database (NCMD). Deaths from 1 April 2020 until 31 March 2021 (2020–2021) were compared with those from the same period of 2019–2020. RR and excess mortality were derived for deaths in 2020–2021 vs 2019–2020. Setting All deaths reported to NCMD in England of children under 18 years of age, between April 2019 and March 2021. Participants 6490 deaths of children, under the age of 18 years, reported to the NCMD over the study period. Results Children had similar demographics in the 2 years. There were 356 (198–514) fewer deaths in 2020–2021 than in 2019–2020 (RR 0.90 (0.85 to 0.94), p, Using data from the National Child Mortality Database, associations between deaths during and before the pandemic were explored. more...

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. more...

ObjectivesTo describe the epidemiology and geographical differences in prevalence of congenital cerebral anomalies in Europe.Design and settingCongenital cerebral anomalies (International Classification of Diseases, 10th Revision code Q04) recorded in 29 population-based EUROCAT registries conducting surveillance of 1.7 million births per annum (29% of all European births).ParticipantsAll birth outcomes (live births, fetal deaths from 20 weeks gestation and terminations of pregnancy after prenatal diagnosis of a fetal anomaly (TOPFA)) from 2005 to 2014.Main outcome measuresPrevalence, proportion of associated non-cerebral anomalies, prenatal detection rate.Results4927 cases with congenital cerebral anomalies were identified; a prevalence (adjusted for under-reporting) of 9.8 (95% CI: 8.5 to 11.2) per 10 000 births. There was a sixfold difference in prevalence across the registries. Registries with higher proportions of prenatal diagnoses had higher prevalence. Overall, 55% of all cases were liveborn, 3% were fetal deaths and 41% resulted in TOPFA. Forty-eight per cent of all cases were an isolated cerebral anomaly, 25% had associated non-cerebral anomalies and 27% were chromosomal or part of a syndrome (genetic or teratogenic). The prevalence excluding genetic or chromosomal conditions increased by 2.4% per annum (95% CI: 1.3% to 3.5%), with the increases occurring only for congenital malformations of the corpus callosum (3.0% per annum) and ‘other reduction deformities of the brain’ (2.8% per annum).ConclusionsOnly half of the cases were isolated cerebral anomalies. Improved prenatal and postnatal diagnosis may account for the increase in prevalence of congenital cerebral anomalies from 2005 to 2014. However, major differences in prevalence remain between regions. more...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rarely fatal in children and young people (CYP,18 years old), but quantifying the risk of death is challenging because CYP are often infected with SARS-CoV-2 exhibiting no or minimal symptoms. To distinguish between CYP who died as a result of SARS-CoV-2 infection and those who died of another cause but were coincidentally infected with the virus, we undertook a clinical review of all CYP deaths with a positive SARS-CoV-2 test from March 2020 to February 2021. The predominant SARS-CoV-2 variants were wild-type and Alpha. Here we show that, of 12,023,568 CYP living in England, 3,105 died, including 61 who were positive for SARS-CoV-2. Of these deaths, 25 were due to SARS-CoV-2 infection (mortality rate, two per million), including 22 due to coronavirus disease 2019-the clinical disease associated with SARS-CoV-2 infection-and 3 were due to pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. In total, 99.995% of CYP with a positive SARS-CoV-2 test survived. CYP older than 10 years, Asian and Black ethnic backgrounds and comorbidities were over-represented in SARS-CoV-2-related deaths compared with other CYP deaths. These results are important for guiding decisions on shielding and vaccinating children. New variants might have different mortality risks and should be evaluated in a similar way. more...

BackgroundDeaths in children and young people (CYP) following SARS-CoV-2 infection are rare. Quantifying the risk of mortality is challenging because of high relative prevalence of asymptomatic and non-specific disease manifestations. Therefore, it is important to differentiate between CYP who have died of SARS-CoV-2 and those who have died of an alternative disease process but coincidentally tested positive.MethodsDuring the pandemic, the mandatory National Child Mortality Database (NCMD) was linked to Public Health England (PHE) testing data to identify CYP (Findings3105 CYP died from all causes during the first pandemic year in England. 61 of these deaths occurred in CYP who tested positive for SARS-CoV-2. 25 CYP died of SARS-CoV-2 infection; 22 from acute infection and three from PIMS-TS. 99·995% of CYP with a positive SARS-CoV-2 test survived. The 25 CYP who died of SARS-CoV-2 equates to a mortality rate of 2/million for the 12,023,568 CYP living in England. CYP >10 years, of Asian and Black ethnic backgrounds, and with comorbidities were over-represented compared to other children.InterpretationSARS-CoV-2 is very rarely fatal in CYP, even among those with underlying comorbidities. These findings are important to guide families, clinicians and policy makers about future shielding and vaccination. more...

Background We aimed to use individual patient data to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in children and young people (CYP) in hospital. Methods We searched Pubmed, European PMC, Medline and Embase for case series and cohort studies that included all CYP admitted to hospital with ≥30 CYP with SARS-CoV-2 or ≥5 CYP with PIMS-TS or MIS-C. Eligible studies contained 1) details of age, sex, ethnicity or co-morbidities, and 2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted grouping of co-morbidities were eligible for narrative review. Authors of eligible studies were approached for individual patient data (IPD). We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI). Findings 81 studies were included, 57 in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years, infants had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)). Number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a dose-related fashion. For critical care admission odds ratios were: 1 comorbidity 1.49 (1.45-1.53); 2 comorbidities 2.58 (2.41-2.75); ≥3 comorbidities 2.97 (2.04-4.32), and for death: 1 comorbidity 2.15 (1.98-2.34); 2 comorbidities 4.63 (4.54-4.74); ≥3 co-morbidities 4.98 (3.78-6.65). Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities. Interpretation Hospitalised CYP at greatest vulnerability of severe disease or death from SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions. Funding RH is in receipt of a funded fellowship from Kidney Research UK. JW is in receipt of a Medical Research Council Fellowship. Putting Research Into Context Evidence before this study The risk factors for severe disease following SARS-CoV-2 infection in adults has been extensively studied and reported, with good evidence that increasing age, non-white ethnicity, male gender and co-morbidities increase the risk. SARS-CoV-2 infection in children and young people (CYP) infrequently results in hospital admission and very rarely causes severe disease and death, making it difficult to discern the impact of a range of potential risk factors for severe disease in the many small to moderate sized published studies. More recent larger publications have aimed to address this question in specific populations but the global experience has not been described. We searched Pubmed, European PMC, Medline and Embase from the 1st January 2020 to 21st May 2021 for case series and cohort studies that included all CYP admitted to hospital with 30 children with reverse transcriptase-PCR confirmed SARS-CoV-2 or 5 CYP defined as having PIMS-TS or MIS-C. 57 studies met the eligibility criteria for meta-analysis. Added value of this study To our knowledge, this is the first meta-analysis to use individual patient data to compare the odds and risk of critical care admission and death in CYP with COVID-19 and PIMS-TS. We find that the odds of severe disease in hospitalised children is increased in those with multiple co-morbidities, cardiac and neurological co-morbidities and those who are obese. However, the additional risk compared to children without co-morbidity is small. Implications of all the available evidence Severe COVID-19 and PIMS-TS, whilst rare, can occur in CYP. We have identified pre-existing risk factors for severe disease after SARS-CoV-2 and recommend that those with co-orbidities which place them in the highest risk groups are prioritised for vaccination. more...

Identifying which children and young people (CYP) are vulnerable to severe disease following SARS-CoV-2 is important to guide shielding and vaccination policy.MethodsWe used data for all inpatient hospital admissions in England in CYP aged 0-17 between March 1st2015 to Feb 28th2021, linked to paediatric intensive care unit (PICU), SARS-CoV-2 PCR testing, and mortality data. We examined associations between PICU admission and death by sociodemographic factors and comorbidities within COVID-19 and PIMS-TS admissions. We calculated odds ratios and predicted probability of PICU admission using generalized estimation equations, and compared these between COVID-19, PIMS-TS, other admissions in 2020/21, all admissions in 2019/20, and admissions due to influenza in 20219/20. Analyses of deaths were descriptive due to low numbers.FindingsWithin COVID-19, there were 6,338 hospital admissions, 259 PICU admissions and 8 deaths. Within PIMS-TS there were 712 hospital admissions 312 PICU admissions and InterpretationCYP were at very low risk of severe disease and death from COVID-19 or PIMS-TS. PICU admission due to PIMS-TS was associated with older non-white CYP. Patterns of vulnerability for severe COVID-19 appear to magnify background risk factors for serious illness in CYP.Evidence before this studyWe conducted a systematic review and meta-analysis of studies investigating risk factors associated with severe disease among children and young people admitted with COVID-19 and PIMS-TS, [Harwood, R et al. 2021 (submission to the Lancet linked with this paper)]. We identified 81 studies. Infants were found to have increased odds of PICU admission compared with 1-4, but there were no associations by sex. Other factors associated with PICU admission included number of co-morbid conditions, with neurological, cardiac and gastrointestinal associated with the greatest risk. Low numbers of serious SARS-CoV-2 infections or deaths amongst CYP limit these analyses, yet national studies of CYP have not yet been published. Importantly, we found these studies did not take into account background risks for severe illness in CYP who are known to be vulnerable before the pandemic.What this study addsThis is the first population base study of risk factors for severe disease following SARS-CoV-2 infection in CYP in England. We analyse all admissions to hospital amongst 0-17 year olds nationally between 2015-2021 linked to multiple other health datasets. We explore how socioeconomic factors and co-morbidities are associated with Paediatric Intensive Care Unit (PICU) admission and death amongst CYP admitted with COVID-19 and PIMS-TS, and compare this with other causes for admission during the pandemic and in the year prior. As CYP with PIMS-TS are highly likely to require hospitalization, we were able to analyse total national cases of the condition during 2020/21.We found extremely low numbers of CYP required PICU or died as a result of SARS-CoV-2 in the first pandemic year. CYP admitted due to COVID-19 disease were older and more likely to be non-white with pre-existing conditions, similar to patterns seen in adults. Patterns of associations between comorbidities and risk of PICU admission amongst COVID-19 were similar to those seen for all admissions and influenza admissions in the year prior to the pandemic. However, the increase in risk associated with comorbidities for COVID-19 admissions were greater than in these cohorts.We found most cases of PIMS-TS were amongst non-white male adolescents without previous hospital admissions. Interpreting associations between comorbidities and PICU admission for PIMS-TS was complicated by the multi-system nature of the disease.Implications of all the available evidenceCYP with most vulnerable to COVID-19 were also those most at risk of prior to the pandemic due to other illnesses such as influenza, although COVID-19 appears to amplify this risk profile. It is important to consider this context when advising parents and carers regarding the risk posed by COVID-19, considering potential harms to CYP as a result of shielding precautions. more...

The UK’s National Institute for Health and Care Excellence Preterm labour and birth guideline recommends use of magnesium sulfate (MgSO4) in deliveries below 30 weeks’ gestation to prevent cerebral palsy and other neurological problems associated with preterm delivery. Despite national guidance, the uptake of MgSO4 administration in eligible women has been slow. National Health Service England has rolled out the PReCePT (PRevention of Cerebral Palsy in Pre-Term labour) quality improvement (QI) toolkit to increase uptake of MgSO4 in preterm deliveries. The toolkit is designed to increase maternity staff knowledge about MgSO4 and provides training and practical tools to help staff consider use in eligible women. The PReCePT trial compares the effectiveness of two different methods of implementing the QI toolkit (standard versus enhanced support). The standard support arm (control) receives the QI toolkit and regional-level support for a midwife/obstetric ‘champion’. The enhanced support arm (intervention) receives this plus additional clinical backfill funding and unit-level QI microcoaching. It is funded by The Health Foundation. This is a cluster randomised controlled trial designed to include 48 maternity units randomised (2:1 ratio) to standard or enhanced support. Units are eligible for inclusion if they have 10 or more preterm (4 uptake of 70% or less. Randomisation is stratified by previous level of MgSO4 uptake. The QI intervention is implemented over 9 months. All units are followed up for a further 9 months. Blinding is not possible due to the nature of the intervention. The primary outcome is the proportion of MgSO4 uptake among eligible women at follow-up, adjusting for uptake before implementation of the toolkit. The effectiveness of the intervention will be assessed using weighted linear regression on data from the National Neonatal Research Database. Semistructured qualitative staff interviews will inform understanding of the process and outcomes. Economic evaluation will describe total costs and cost-effectiveness.Trial registration number SRCTN 40938673. more...

Objectives Using the National Child Mortality Database (NCMD), this work aims to investigate and quantify the characteristics of children dying of COVID-19, and to identify any changes in rate of childhood mortality during the pandemic. Design We compared the characteristics of the children who died in 2020, split by SARS-CoV-2 status. A negative binomial regression model was used to compare mortality rates in lockdown (23 March–28 June), with those children who died in the preceding period (6 January–22 March), as well as a comparable period in 2019. Setting England. Participants Children (0–17 years). Main outcome measures Characteristics and number of the children who died in 2020, split by SARS-CoV-2 status. Results 1550 deaths of children between 6th of January and 28 June 2020 were notified to the NCMD; 437 of the deaths were linked to SARS-CoV-2 virology records, 25 (5.7%) had a positive PCR result. PCR-positive children were less likely to be white (37.5% vs 69.4%, p=0.003) and were older (12.2 vs 0.7 years, p, Child mortality was lower in 2020 than in 2019 . Older children and those from Black, Asian and minority ethnic groups were more likely to have a SARS-CoV-2 positive test. more...

PReCePT (PRevention of Cerebral Palsy in Pre Term Labour) is the first perinatal Quality Improvement (QI) programme delivered at scale across England, bringing together midwives, obstetricians and neonatologists in every maternity unit in the country. It aims to reduce incidence of cerebral palsy (CP) in preterm babies. Commissioned by NHS England, the two-year programme is led by the West of England AHSN on behalf of the AHSN Network. PReCePT was developed in 2014 by the West of England AHSN with University Hospitals Bristol NHS Foundation Trust, involving both patients and staff. The intervention was adopted by five maternity units, using a QI approach to support uptake. Each unit increased MgSO4 uptake to >85% during the project and sustained these levels. A retrospective audit showed the project had avoided seven cases of preterm CP, representing a lifetime health and social care cost of around £5.6million. PReCePT is now being spread across the country by all 15 AHSNs during 2018–2020. A suite of standardised QI resources has been developed, available on the AHSN Network website. Taking a network-of-networks approach, each AHSN works with maternity units in their region, supporting them to deliver QI projects to increase MgSO4 uptake, with backfill funding for midwife and regional clinical leads. We are currently halfway through the PReCePT programme. From available data received so far, administration rates of MgSO4 in participating units is already consistently above 80%. more...

Aim: The aim of this work is to test if three single nucleotide polymorphisms (SNPs) implicated in glutamate homeostasis or signalling and cellular survival are associated with birth condition. Methods: This study is drawn from the Avon Longitudinal Study of Parents and Children. 7611 term infants were genotyped and patient outcome data retrieved from routine medical records. Exposure measures were the presence of one or more minor alleles in one of 3 SNPs (rs2284411, rs2498804, rs1835740). The primary outcome was the need for resuscitation at birth. Results: For SNP rs1835740, infants homozygous for the minor allele compared to wild-type were more likely to need resuscitation (9.2% vs. 7.0%, p=0.041) while the odds ratio for resuscitation was associated with each increasing minor allele (OR 1.17 (1.01 to 1.35)). Population attributable risk fraction was 6.5%. There was no evidence that the other two SNPs investigated were associated with birth condition. Conclusions: We have tested three candidate SNPs to measure any association with birth condition. The study revealed that the rs1835740 was associated with the need for resuscitation and Apgar scores, with a substantial population impact. This article is protected by copyright. All rights reserved. more...

Achondroplasia is a rare genetic disorder resulting in short-limb skeletal dysplasia. We present the largest European population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. All cases of achondroplasia notified to 28 EUROCAT registries (1991-2015) were included in the study. Prevalence, birth outcomes, prenatal diagnosis, associated anomalies, and the impact of paternal and maternal age on de novo achondroplasia were presented. The study population consisted of 434 achondroplasia cases with a prevalence of 3.72 per 100,000 births (95%CIs: 3.14-4.39). There were 350 live births, 82 terminations of pregnancy after prenatal diagnosis, and two fetal deaths. The prenatal detection rate was significantly higher in recent years (71% in 2011-2015 vs. 36% in 1991-1995). Major associated congenital anomalies were present in 10% of cases. About 20% of cases were familial. After adjusting for maternal age, fathers >34 years had a significantly higher risk of having infants with de novo achondroplasia than younger fathers. Prevalence was stable over time, but regional differences were observed. All pregnancy outcomes were included in the prevalence estimate with 80.6% being live born. The study confirmed the increased risk for older fathers of having infants with de novo achondroplasia. Funding for the JRC-EUROCAT Central Registry is described in Kinsner-Ovaskainen et al. (2018). We thank Prof. Joan Morris (St. George's University of London) for her helpful suggestions. info:eu-repo/semantics/publishedVersion more...

Background: Dandy-Walker (DW) malformation is a rare and severe congenital anomaly of the posterior fossa affecting the development of the cerebellum and the fourth ventricle. Objective: The aim of this study was to investigate the epidemiology of DW malformation, using data from the European population-based registries of congenital anomalies in the European Surveillance of Congenital Anomalies network. Methods: Anonymous individual data on cases of DW malformation diagnosed in 2002–2015 from 28 registries in 17 countries were included. Prevalence, prenatal detection rate, proportions and types of associated anomalies were estimated. Cases of DW variant were considered and analysed separately. Results: Out of 8,028,454 surveyed births we identified a total of 734 cases, including 562 DW malformation cases and 172 DW variant cases. The overall prevalence of DW malformation was 6.79 per 100,000 births (95% CI 5.79–7.96) with 39.2% livebirths, 4.3% foetal deaths from 20 weeks gestational age, and 56.5% terminations of pregnancy after prenatal diagnosis of foetal anomaly at any gestation (TOPFA). The livebirth prevalence was 2.74 per 100,000 births (95% CI 2.08–3.61). The prenatal detection rate was 87.6%. Two-hundred and seventy-three cases (48.6%) had an isolated cerebral anomaly and 24.2, 19.2 and 5.5% cases were associated with other structural non-cerebral anomalies, chromosomal anomalies and genetic syndromes respectively. The prevalence of DW variant was 2.08 per 100,000 (95% CI 1.39–3.13). Conclusions: This European population-based study provides the epidemiological profile of DW malformation. All birth outcomes were analysed and TOPFA represented more than half of the cases. About 50% of the cases of DW malformation were associated with other non-cerebral anomalies. Large populations and all birth outcomes are essential in epidemiological studies of rare and severe congenital anomalies. more...

Background: Progressive ventricular dilatation after intraventricular haemorrhage (IVH) in preterm infants has a very high risk of severe disability and death. Drainage, irrigation and fibrinolytic therapy (DRIFT), in a randomised trial, reduced severe cognitive impairment at two years. No intervention has been shown objectively to improve cognitive outcome at school-age. Methods: Objective: To assess if the cognitive advantage of DRIFT seen at two years persisted until middle school-age. Participants: The randomised controlled trial in four neonatal intensive care units, recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow up was at a median age of ten years (range 8-12). Intervention: Intraventricular injection of a fibrinolytic followed by continuous ventricular drainage via one catheter and continuous infusion with artificial cerebrospinal fluid via a second catheter. Ventricular lavage was continued until the drainage was clear. Standard care consisted of controlling expansion by lumbar punctures and if expansion persisted via a ventricular access device. Primary outcome: Cognitive Quotient (CQ) derived from the British Ability Scales and Bayley Scales III and survival without severe cognitive disability. Findings: Of the 77 children randomized; 12 died, two could not be traced, ten did not respond and one declined at ten years follow up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blind to the intervention. Mean CQ was 69·3 (sd=30·1) in the DRIFT group and 53·7 (sd=35·7) in the standard treatment group (unadjusted p=0·1; after adjustment for the pre-specified variables sex, birthweight and grade of IVH, adjusted p=0·01). Survival without severe cognitive disability, over the ten-year period, was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0·019; adjusted p=0·003). Interpretation: DRIFT is the first intervention to objectively demonstrate sustained cognitive improvement. Trial registration: ISRCTN80286058 Funding: NIHR HTA Declaration of Interest: None reported. Ethical Approval: Research ethics approval (14/SW/1078) was granted by the NRES Committee South West-Central Bristol and by the Faculty of Psychology Research Ethics Committee (University of Warsaw). more...

Understanding how spatially remote brain regions interact to form functional brain networks, and how these develop during the neonatal period, provides fundamental insights into normal brain development, and how mechanisms of brain disorder and recovery may function in the immature brain. A key imaging tool in characterising functional brain networks is examination of T2*‐weighted fMRI signal during rest (resting state fMRI, rs‐fMRI). The majority of rs‐fMRI studies have concentrated on slow signal fluctuations occurring at more...

BACKGROUND: Mothers are increasingly given greater control over many of the choices around birth, although there is little robust evidence to inform these choices. After an infant is born with HIE the question of whether it was predictable, or preventable, is often raised. Intrapartum 'sentinel' events and antenatal predictors of HIE have been well described, however there is little evidence how antenatal and intrapartum factors interact. This is particularly important when elective delivery by lower segment caesarean section (LSCS) has been shown to be beneficial in high risk groups. AIM: To develop a clinical risk score to identify women with a higher risk of having an infant with HIE. PATIENTS AND METHODS: This study is based on the Avon Longitudinal Study of Parents and Children (ALSPAC). This dataset was split into two halves: with each infant being randomly allocated to either cohort one or two. The first cohort was used for the derivation of the model, while it was tested exclusively on the second. Logistic regression modelling was then performed to develop a predictive model. The final model was used to predict the outcome of infants in the second cohort and infants divided into four risk quartiles. To give some indication of possible avoidable disease, the proportion of infants with HIE, potentially avoided by earlier delivery, was estimated by assuming that medicalized delivery by elective LSCS at 37 weeks would remove intrapartum risk of HIE for those infants undelivered at this point. RESULTS: In the final model seven covariates remained (parity, preeclampsia, polyhydramnios, prelabor rupture of membranes, gender, concerns over fetal growth and prematurity). When applied to the second cohort, a ROC curve for the prediction of developing HIE in the newborn period showed good evidence for association (AUC 0.68 (0.60 to 0.77)) and the risk score derived was strongly associated with the risk of HIE, resuscitation and stillbirth, and neonatal death (all p < 0.05). Elective delivery of high risk infants at 37 weeks gestation could prevent 14% of all HIE, with a NNT of 41. CONCLUSION: It is possible to combine routine antenatal findings to identify infants at higher risk of neonatal HIE, thereby recognizing those infants who may benefit most from delivery by elective caesarean section. This work suggests a clinical risk score permits antenatal identification of high-risk infants whose outcome may be amenable to changes in clinical practice to potentially reduce HIE rates, and its devastating consequences. more...

Aim To determine the aetiological associations, neurological sequelae and role of magnetic resonance imaging (MRI) in term newborn infants with seizures. Methods Cohort study of infants ≥37 weeks' gestation delivered in a tertiary level centre, prospectively identified and followed longitudinally for 18–24 months. Results An underlying aetiology was found in 95% of the 77 infants identified with seizures (3.0/1000 live births). The most common diagnosis was hypoxic–ischaemic encephalopathy (HIE) (65%), followed by neonatal stroke (12%). Nine infants died, 28 of the 68 survivors developed neurodevelopmental impairment (NDI), and 15 had recurrent seizures in the first 2 years, with both outcomes more likely in those with a diagnosis other than HIE. Abnormal MRI findings were found in 45 of the 70 infants imaged. The absence of major cerebral lesions was highly predictive of a normal neurological outcome. Conclusion We report the first cohort of term infants with seizures fully investigated by MRI. The universal use of MRI enabled a cause to be identified in 95% of cases. The probability of having NDI or recurrence of seizures was extremely low with absence of major cerebral lesions on MRI. This study demonstrates the added value of MRI for diagnosis of aetiology and the prediction of neurological outcome. more...