Evaluation of standard and enhanced quality improvement methods to increase the uptake of magnesium sulphate in pre-term deliveries for the prevention of neurodisability (PReCePT Study): a cluster randomized controlled trial (preprint)

ABSTRACT Objective To investigate the impact of an enhanced QI support programme (ESP) in further improving the magnesium sulphate (MgSO 4 ) uptake compared to the National PReCePT Programme (NPP) model. Design An unblinded cluster randomised controlled trial. Setting NHS England and the AHSN network in 2018. Participants Maternity units with ≥10 pre-term deliveries annually and MgSO 4 uptake ≤70%. 40 maternity units (27 NPP, 13 ESP) were included. Randomisation was stratified by MgSO 4 uptake. Interventions MgSO 4 reduces the risk of cerebral palsy by 30%. NHS England commissioned the AHSN network in 2018 to deliver the NPP to increase MgSO 4 uptake in all maternity units in England. NPP units received PReCePT QI materials, regional support, and midwife backfill funding. ESP units received NPP plus backfill funding, unit-level QI coaching, and tablet computer Main outcome measures MgSO 4 uptake post-implementation was compared between trial groups. Implementation and lifetime costs, and quality-adjusted life-years were estimated. The implementation process, fidelity, and local adaptations were assessed through a qualitative process evaluation. Results Using routine data and multivariable linear regression, both ESP and NPP units increased uptake between pre- and post-implementation. Post-implementation uptake increase in ESP units was similar to NPP units (−0.84 percentage points difference, 95% Confidence Interval -5.03 to 3.35 percentage points). Decision tree and probabilistic analyses were used to estimate cost-effectiveness and the probability ESP cost-effective was < 30%. Midwives implementing the NPP allocated more than their funded hours. Implementers of the ESP had better overall understanding of and collective engagement in PReCePT QI and made more use of QI methods. Units varied in amount and kind of support required to successfully implement the intervention. Conclusion This trial did not find additional benefit from the ESP compared with the NPP. Units with low uptake of MgSO 4 were found to experience a range of local challenges and targeted enhanced support may improve performance and represent good value. Trial registration ISRCTN 40938673 ( https://www.isrctn.com/ISRCTN40938673 ) WHAT IS ALREADY KNOWN ON THIS TOPIC Since 2009 there has been strong evidence for the fetal neuroprotective benefits of antenatal MgSO 4 in women at risk of pre-term birth. This took a further 6 years to become a NICE recommended intervention. By 2017, only two-thirds of all eligible women in England were being given MgSO 4 , with wide regional variations. The PReCePT pilot study in 2015 demonstrated that uptake could be increased significantly using a Quality Improvement (QI) intervention to increase maternity staff awareness of MgSO 4 , and investment in staff time for training. In 2018, NHS England funded the National PReCePT Programme (NPP) in maternity units nationally, which provided a QI toolkit, backfill funding for a unit-level support for a midwife ‘champion’ and regional-level clinical champion. WHAT THIS STUDY ADDS The study has shown that national quality improvement programmes are effective in increasing MgSO 4 across maternity units in England. While overall uptake increased in both groups between baseline and follow-up, the study did not demonstrate additional benefit of the ESP compared to the NPP. Enhanced support can be delivered to units who are struggling or those with low improvement capability. Instead of delivering enhanced support to all units, a targeted intervention might be valuable for units who have low MgSO 4 implementation rates despite the national QI programme. Assessing individual organisations’ support needs based on factors including their readiness to change may help focus support to local needs.

Child Mortality in England During the First Year of the COVID-19 Pandemic (preprint)

OBJECTIVESThe aim of this analysis was to quantify the relative risk of childhood deaths across the whole of England during the first year of the COVID pandemic, compared to a similar period of 2019. DESIGNThis work is based on data collected by the National Child Mortality Database (NCMD) which collates data on all children who die in England. The number of deaths, and their characteristics, from 1st April 2020 until 31st of March 2021 (2020-21), were compared to those from the same period of 2019-20. Relative risk and excess mortality were derived for deaths in 2020-21 vs 2019-20. 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 who died between April 2020 and March 2021 had similar demographics to those who died in 2019-20. Overall, there were 356 (198 to 514) fewer deaths in 2020-21 than in 2019-20 (RR 0.90 (0.85-0.94), p<0.001). Repeating the analysis by category of death, suggested that deaths from infection (RR 0.49 (0.38-0.64)) and from other underlying medical conditions (RR 0.75 (0.68-0.82)) were lower in 2020-21 than 2019-20, and weak evidence (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 the lowest on record, with over 300 fewer deaths than the preceding 12 months. The greatest reduction was seen 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.

Child Suicide Rates During the COVID-19 pandemic in England (preprint)

Background: There is concern about the impact of COVID-19, and the control measures to prevent the spread, on children's mental health. The aim of this work was to identify if there had been a rise of childhood suicide during the COVID pandemic; using data from England's National Child Mortality Database (NCMD). Method: Child suicide rates between April to December 2020 were compared with those in 2019 using negative binomial regression models, and characteristics compared. In a subset (1st January to 17th May 2020) further characteristics and possible contributing factors were obtained. Results: A total of 193 likely childhood deaths by suicide were reported. There was no evidence overall suicide deaths were higher in 2020 than 2019 (RR 1.09 (0.80-1.48), p=0.584) but weak evidence that the rate in the first lockdown period (April to May 2020) was higher than the corresponding period in 2019 (RR 1.56 (0.86-2.81), p=0.144). Characteristics of individuals were similar between periods. Restriction to education and other activities, disruption to care and support services, tensions at home and isolation appeared to be contributing factors. Limitations: As child suicides are fortunately rare, the analysis is based on small numbers of deaths with limited statistical power to detect anything but major increases in incidence. Conclusion: We found no consistent evidence that child suicide deaths increased during the COVID-19 pandemic although there was a concerning signal they may have increased during the first UK lockdown. A similar peak was not seen during the following months, or the second lockdown.

Deaths in Children and Young People in England following SARS-CoV-2 infection during the first pandemic year: a national study using linked mandatory child death reporting data (preprint)

Background Deaths 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. Methods During the pandemic, the mandatory National Child Mortality Database (NCMD) was linked to Public Health England (PHE) testing data to identify CYP (<18 years) who died with a positive SARS-CoV-2 test. A clinical review of all deaths from March 2020 to February 2021 was undertaken to differentiate between those who died of SARS-CoV-2 infection and those who died of an alternative cause but coincidentally tested positive. Then, using linkage to national hospital admission data, demographic and comorbidity details of CYP who died of SARS-CoV-2 were compared to all other deaths. Absolute risk of death was estimated where denominator data were available. Findings 3105 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. Interpretation SARS-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.

Which children and young people are at higher risk of severe disease and death after SARS-CoV-2 infection: a systematic review and individual patient meta-analysis (preprint)

BackgroundWe 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. MethodsWe 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). Findings81 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. InterpretationHospitalised 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. FundingRH is in receipt of a funded fellowship from Kidney Research UK. JW is in receipt of a Medical Research Council Fellowship. Putting Research Into ContextO_ST_ABSEvidence before this studyC_ST_ABSThe 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 studyTo 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 evidenceSevere 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.

Which children and young people are at higher risk of severe disease and death after SARS-CoV-2 infection: a systematic review and individual patient meta-analysis (preprint)

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.

Deaths in Children and Young People in England following SARS-CoV-2 infection during the first pandemic year: a national study using linked mandatory child death reporting data (preprint)

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 (<18 years) who died with a positive SARS-CoV-2 test. A clinical review of all deaths from March 2020 to February 2021 was undertaken to differentiate between those who died of SARS-CoV-2 infection and those who died of an alternative cause but coincidentally tested positive. Then, using linkage to national hospital admission data, demographic and comorbidity details of CYP who died of SARS-CoV-2 were compared to all other deaths. Absolute risk of death was estimated where denominator data were available. 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.

Risk factors for intensive care admission and death amongst children and young people admitted to hospital with COVID-19 and PIMS-TS in England during the first pandemic year (preprint)

Identifying which children and young people (CYP) are vulnerable to severe disease following SARS-CoV-2 is important to guide shielding and vaccination policy. Methods We used data for all inpatient hospital admissions in England in CYP aged 0-17 between March 1st 2015 to Feb 28th 2021, linked to paediatric intensive care unit (PICU) admission, and SARS-CoV-2 PCR testing, and deaths. 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. Findings There were 6,338 COVID-19 hospitalisations, 259 PICU admissions and 8 deaths as well as 712 PIMS-TS hospitalisations, 312 PICU admissions and <5 deaths. Odds of PICU admission were increased amongst neonates and decreased amongst 15-17 compared with 1-4 year olds with COVID-19, increased in older CYP and females with PIMS-TS, and increased for Black compared with White ethnicity for both conditions. Odds of PICU admission with COVID-19 were increased for CYP with any comorbidity and were highest for CYP with multiple medical problems. Comorbidities associated with PICU admission among COVID-19 patients were similar to overall PICU admissions in 2019/20 and to influenza PICU admissions in 2019/20, but with higher odds. Interpreting associations with comorbidities within PIMS-TS was complex due to the multisystem nature of the disease. Interpretation CYP were at very low risk of severe disease and death from COVID-19 or PIMS-TS. Patterns of vulnerability for severe COVID-19 appear to magnify background risk factors for serious illness in CYP.