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ObjectivesTo determine the baseline trends in the total birth prevalence of neural tube defects (NTDs) in England (2000–2019) to enable the impact of folic acid fortification of non-wholemeal wheat flour to be monitored.DesignPopulation-based, observational study using congenital anomaly (CA) registration data for England curated by the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS).SettingRegions of England with active registration in the time period.ParticipantsBabies that were liveborn or stillborn and pregnancies that resulted in a termination of pregnancy or a late miscarriage (20–23 weeks’ gestation) with an NTD.Main outcome measuresTotal birth prevalence of anencephaly, spina bifida and all NTDs in England. Poisson regression analysis was used to evaluate time trends with regional register as a random effect. The progress of national registration across England was assessed.ResultsThere were 4541 NTD pregnancies out of 3 637 842 births in England; 1982 anencephaly and 2127 spina bifida. NTD prevalence was 12.5 (95% CI 12.1 to 12.9) per 10 000 total births. NTD prevalence per 10 000 total births was significantly higher in 2015–2019 (13.6, 95% CI 12.9 to 14.4) compared with 2010–2014 (12.1, 95% CI 11.7 to 12.5). An increasing trend in NTDs overall was detected (incidence rate ratio (IRR) 1.01, 1.00 to 1.02), although further analysis determined this effect was confined to 2015–2019 (compared against 2000–2004, IRR 1.14, 1.04 to 1.24). The birth prevalence of anencephaly reflected this pattern. The prevalence of spina bifida remained relatively stable over time.ConclusionsBaseline NTD prevalence for England has been established. National and standardised CA registration is in place, facilitating the systematic and consistent monitoring of pre-fortification and post-fortification NTD trends and evaluating the impact of fortification on NTD prevalence.

IMPORTANCE: Investigating how the risk of serious illness after SARS-CoV-2 infection in children and adolescents has changed as new variants have emerged is essential to inform public health interventions and clinical guidance. OBJECTIVE: To examine risk factors associated with hospitalization for COVID-19 or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) among children and adolescents during the first 2 years of the COVID-19 pandemic and change in risk factors over time. DESIGN, SETTING, AND PARTICIPANTS: This population-level analysis of hospitalizations after SARS-CoV-2 infection in England among children and adolescents aged 0 to 17 years was conducted from February 1, 2020, to January 31, 2022. National data on hospital activity were linked with data on SARS-CoV-2 testing, SARS-CoV-2 vaccination, pediatric intensive care unit (PICU) admissions, and mortality. Children and adolescents hospitalized with COVID-19 or PIMS-TS during this time were included. Maternal, elective, and injury-related hospitalizations were excluded. EXPOSURES: Previous medical comorbidities, sociodemographic factors, and timing of hospitalization when different SARS-CoV-2 variants (ie, wild type, Alpha, Delta, and Omicron) were dominant in England. MAIN OUTCOMES: PICU admission and death within 28 days of hospitalization with COVID-19 or PIMS-TS. RESULTS: A total of 10 540 hospitalizations due to COVID-19 and 997 due to PIMS-TS were identified within 1 125 010 emergency hospitalizations for other causes. The number of hospitalizations due to COVID-19 and PIMS-TS per new SARS-CoV-2 infections in England declined during the second year of the COVID-19 pandemic. Among 10 540 hospitalized children and adolescents, 448 (4.3%) required PICU admission due to COVID-19, declining from 162 of 1635 (9.9%) with wild type, 98 of 1616 (6.1%) with Alpha, and 129 of 3789 (3.4%) with Delta to 59 of 3500 (1.7%) with Omicron. Forty-eight children and adolescents died within 28 days of hospitalization due to COVID-19, and no children died of PIMS-TS (PIMS-S data were limited to November 2020 onward). Risk of severe COVID-19 in children and adolescents was associated with medical comorbidities and neurodisability regardless of SARS-CoV-2 variant. Results were similar when children and adolescents with prior SARS-CoV-2 exposure or vaccination were excluded. CONCLUSIONS: In this study of data across the first 2 years of the COVID-19 pandemic, risk of severe disease from SARS-CoV-2 infection in children and adolescents in England remained low. Children and adolescents with multiple medical problems, particularly neurodisability, were at increased risk and should be central to public health measures as further variants emerge.

Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008–2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the pvalue was estimated using a two-sided Fisher’s exact test. The Benjamini–Hochberg procedure adjusted pvalues to control the false discovery rate and pairs of anomalies with adjusted pvalues < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered “potential new associations” by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation.

ObjectivesUsing 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.DesignWe 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.SettingEngland.ParticipantsChildren (0–17 years).Main outcome measuresCharacteristics and number of the children who died in 2020, split by SARS-CoV-2 status.Results1550 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<0.0006) compared with child deaths without evidence of the virus. All-cause mortality rates were similar during lockdown compared with both the period before lockdown in 2020 (rate ratio (RR) 0.93 (0.84 to 1.02)) and a similar period in 2019 (RR 1.02 (0.92 to 1.13)).ConclusionsThere is little to suggest that there has been excess mortality during the period of lockdown. The apparent higher frequency of SARS-CoV-2-positive tests among children from black, Asian and minority ethnic groups is consistent with findings in adults. Ongoing surveillance is essential as the pandemic continues.

Identifying which children and young people (CYP) are most vulnerable to serious infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to guide protective interventions. To address this question, we used data for all hospitalizations in England among 0–17 year olds from 1 February 2019 to 31 January 2021. We examined how sociodemographic factors and comorbidities might be risk factors for pediatric intensive care unit (PICU) admission among hospitalizations due to the following causes: Coronavirus Disease 2019 (COVID-19) and pediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the first pandemic year (2020–2021); hospitalizations due to all other non-traumatic causes in 2020–2021; hospitalizations due to all non-traumatic causes in 2019–2020; and hospitalizations due to influenza in 2019–2020. Risk of PICU admission and death from COVID-19 or PIMS-TS in CYP was very low. We identified 6,338 hospitalizations with COVID-19, of which 259 were admitted to a PICU and eight CYP died. We identified 712 hospitalizations with PIMS-TS, of which 312 were admitted to a PICU and fewer than five CYP died. Hospitalizations with COVID-19 and PIMS-TS were more common among males, older CYP, those from socioeconomically deprived neighborhoods and those who were of non-White ethnicity (Black, Asian, Mixed or Other). The odds of PICU admission were increased in CYP younger than 1 month old and decreased among 15–17 year olds compared to 1–4 year olds with COVID-19; increased in older CYP and females with PIMS-TS; and increased for Black compared to White ethnicity in patients with COVID-19 and PIMS-TS. Odds of PICU admission in COVID-19 were increased for CYP with comorbidities and highest for CYP with multiple medical problems. Increases in odds of PICU admission associated with different comorbidities in COVID-19 showed a similar pattern to other causes of hospitalization examined and, thus, likely reflect background vulnerabilities. These findings identify distinct risk factors associated with PICU admission among CYP with COVID-19 or PIMS-TS that might aid treatment and prevention strategies.

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.

BackgroundProgressive 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 controlled trial (RCT), reduced severe cognitive impairment at 2 years.ObjectiveTo assess if the cognitive advantage of DRIFT seen at 2 years persisted until school age.ParticipantsThe RCT conducted in four centres recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow-up was at 10 years of age.InterventionIntraventricular injection of a fibrinolytic followed by continuous lavage, until the drainage was clear, and standard care consisting of control of expansion by lumbar punctures and if expansion persisted via a ventricular access device.Primary outcomeCognitive quotient (CQ), derived from the British Ability Scales and Bayley III Scales, and survival without severe cognitive disability.ResultsOf the 77 children randomised, 12 died, 2 could not be traced, 10 did not respond and 1 declined at 10-year follow-up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blinded to the intervention. The mean CQ score 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; adjusted p=0.01, after adjustment for the prespecified variables sex, birth weight and IVH grade). Survival without severe cognitive disability was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0.019; adjusted p=0.003).ConclusionDRIFT is the first intervention for posthaemorrhagic ventricular dilatation to objectively demonstrate sustained cognitive improvement.Trial registration numberISRCTN80286058.

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.

Following low incidence of invasive group A streptococcal (iGAS) infections during the COVID-19 pandemic, marked increases were noted in many countries during 2022, particularly in children. In November 2022, severe presentations of lower respiratory tract infections (LRTIs), including empyema, were notified by clinicians across the UK. UKHSA investigated this rise with the aim of informing clinical management and public health response.

Improving neurodevelopmental outcome for preterm infants is an important challenge for neonatal medicine. The disruption of normal brain growth and neurological development is a significant consequence of preterm birth and can result in physical and cognitive impairments. While advances in neonatal medicine have led to progressively better survival rates for preterm infants, there has only been a modest improvement in the proportion of surviving infants without neurological impairment, and no change in the proportion with severe disability. The overall number of children with neurodisability due to prematurity is increasing. Trials investigating novel therapies are underway and many have promising early results; however, in the interim, current treatments and management strategies that have proven benefit for neurodevelopment or reduction in neonatal brain injury are often underutilised. We collate the evidence for the efficacy of such interventions, recommended by guidelines or supported by large meta-analysis or randomised control trials. We address controversies that have hindered uptake and problems with translating research into practice. We then look to the future of preterm neuroprotective care.

ObjectivesTo 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.DesignThis 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.SettingAll deaths reported to NCMD in England of children under 18 years of age, between April 2019 and March 2021.Participants6490 deaths of children, under the age of 18 years, reported to the NCMD over the study period.ResultsChildren 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<0.001). Deaths from infection (RR 0.49 (0.38 to 0.64)) and from other underlying medical conditions (RR 0.75 (0.68 to 0.82)) were lower in 2020–2021 than 2019–2020, and weak evidence (RR 0.50 (0.23 to 1.07), p=0.074) that this was also true of deaths from substance abuse.ConclusionsChildhood mortality in England during the first year of the SARS-CoV-2 pandemic was lower than expected, with over 300 fewer deaths than the preceding 12 months. The greatest reduction was in children less than 10 years old. It is important that we learn from this effect that potentially offers alternative ways to improve the outcome for the most vulnerable children in our society.

To compare the overall performance of specially trained neonatal nurses acting autonomously, unsupervised, and without a protocol with specialist registrars when weaning neonates from mechanical ventilation.

AbstractTo compare differences in the management of the neonatal patent ductus arteriosus between neonatologists and paediatric cardiologists, physicians throughout the South-West were contacted. In treatment-refractory cases, neonatologists considered ligation less frequently than paediatric cardiologists (0% versus 40%; p<0.05) and held haemodynamic effects more important for ligation decisions [median: 5 (range 2–5) versus median: 4 (range 2–5); p<0.05]. Furthermore, 81% felt the current guidelines were insufficient.