Clinical Impact of Serious Respiratory Disease in Children Under the Age of 2 Years During the 2021-2022 Bronchiolitis Season in England, Scotland, and Ireland.

BACKGROUND: Interventions introduced to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a widespread reduction in childhood infections. However, from spring 2021 onwards the United Kingdom and Ireland experienced an unusual out-of-season epidemic of respiratory disease. METHODS: We conducted a prospective observational study (BronchStart), enrolling children 0-23 months of age presenting with bronchiolitis, lower respiratory tract infection, or first episode of wheeze to 59 emergency departments across England, Scotland, and Ireland from May 2021 to April 2022. We combined testing data with national admissions datasets to infer the impact of respiratory syncytial virus (RSV) disease. RESULTS: The BronchStart study collected data on 17 899 presentations for 17 164 children. Risk factors for admission and escalation of care included prematurity and congenital heart disease, but most admissions were for previously healthy term-born children. Of those aged 0-11 months who were admitted and tested for RSV, 1907 of 3912 (48.7%) tested positive. We estimate that every year in England and Scotland 28 561 (95% confidence interval, 27 637-29 486) infants are admitted with RSV infection. CONCLUSIONS: RSV infection was the main cause of hospitalizations in this cohort, but 51.3% of admissions in infants were not associated with the virus. The majority of admissions were in previously healthy term-born infants.

Housing Characteristics and Hospital Admissions due to Falls on Stairs: A National Birth Cohort Study.

OBJECTIVE: To assess associations between housing characteristics and risk of hospital admissions related to falls on/from stairs in children, to help inform prevention measures. STUDY DESIGN: An existing dataset of birth records linked to hospital admissions up to age 5 for a cohort of 3 925 737 children born in England between 2008 and 2014, was linked to postcode-level housing data from Energy Performance Certificates. Association between housing construction age, tenure (eg, owner occupied), and built form and risk of stair fall-related hospital admissions was estimated using Poisson regression. We stratified by age (<1 and 1-4 years), and adjusted for geographic region, Index of Multiple Deprivation, and maternal age. RESULTS: The incidence was higher in both age strata for children in neighborhoods with homes built before 1900 compared with homes built in 2003 or later (incidence rate ratio [IRR], 1.40; 95% CI, 1.10-1.77 [age <1 year], 1.20; 95% CI, 1.05-1.36 [age 1-4 years]). For those aged 1-4 years, the incidence was higher for those in neighborhoods with housing built between 1900 and 1929, compared with 2003 or later (IRR, 1.26; 95% CI, 1.13-1.41), or with predominantly social-rented homes compared with owner occupied (IRR, 1.21; 95% CI, 1.13-1.29). Neighborhoods with predominantly houses compared with flats had higher incidence (IRR, 1.24; 95% CI, 1.08-1.42 [<1 year] and IRR 1.16; 95% CI, 1.08-1.25 [1-4 years]). CONCLUSIONS: Changes in building regulations may explain the lower fall incidence in newer homes compared with older homes. Fall prevention campaigns should consider targeting neighborhoods with older or social-rented housing. Future analyses would benefit from data linkage to individual homes, as opposed to local area level.

Uptake of intra-muscular vitamin K administration after birth: A national cohort study.

AIM: A long-acting monoclonal antibody against RSV (nirsevimab), given as an injection shortly after birth, is currently being rolled out globally. Carer acceptance of intra-muscular (IM) vitamin K, another injection given shortly after birth, could serve to indicate the acceptability of nirsevimab. METHODS: We analysed a national dataset of postnatal health visitor visits in Scotland; individual-level data on gestation were not available. The primary outcome measure was the modality of administration of vitamin K; potential explanatory variables were maternal age, infant ethnicity, English as a first language, and measures of socio-economic deprivation. We examined associations between IM vitamin K administration or oral/no vitamin K and each explanatory variable. RESULTS: From 2019 to 2021, questionnaires were available for 142 857 infants; data was missing for 2.7%. IM Vitamin K uptake was high: 95.5% of carers consented, with 1.1% requesting oral vitamin K and 0.9% refusing vitamin K altogether. Infant ethnicity, use of English as a first language, socio-economic status and maternal age were not associated with reduced uptake of IM vitamin K. CONCLUSION: If IM Vitamin K administration is a valid proxy measure for nirsevimab acceptance, we did not identify groups that might require increased engagement prior to nirsevimab roll-out.

The clinical impact of serious respiratory disease in children under the age of two years during the 2021-2022 bronchiolitis season in England, Scotland and Ireland.

BACKGROUND: Interventions introduced to reduce the spread of SARS-CoV-2 led to a widespread reduction in childhood infections. However, from spring 2021 onwards the United Kingdom and Ireland experienced an unusual out-of-season epidemic of respiratory disease. METHODS: We conducted a prospective observational study (BronchStart), enrolling children 0-23 months of age presenting with bronchiolitis, lower respiratory tract infection or first episode of wheeze to 59 Emergency Departments across England, Scotland and Ireland from May 2021 to April 2022. We combined testing data with national admissions datasets to infer the impact of respiratory syncytial virus (RSV) disease. RESULTS: The BronchStart study collected data on 17,899 presentations for 17,164 children. Risk factors for admission and escalation of care included prematurity and congenital heart disease, but most admissions were for previously healthy term-born children. Of those aged 0-11 months who were admitted and tested for RSV, 1,907/3,912 (48.7%) tested positive. We estimate that every year in England and Scotland 28,561 (95% confidence interval 27,637-29,486) infants are admitted with RSV infection. CONCLUSIONS: RSV infection was the main cause of hospitalisations in this cohort, but 51.3% of admissions in infants were not associated with the virus. The majority of admissions were in previously healthy term-born infants.

Target Trial Emulation and Bias Through Missing Eligibility Data: An Application to a Study of Palivizumab for the Prevention of Hospitalization Due to Infant Respiratory Illness.

Target trial emulation (TTE) applies the principles of randomized controlled trials to the causal analysis of observational data sets. One challenge that is rarely considered in TTE is the sources of bias that may arise if the variables involved in the definition of eligibility for the trial are missing. We highlight patterns of bias that might arise when estimating the causal effect of a point exposure when restricting the target trial to individuals with complete eligibility data. Simulations consider realistic scenarios where the variables affecting eligibility modify the causal effect of the exposure and are missing at random or missing not at random. We discuss means to address these patterns of bias, namely: 1) controlling for the collider bias induced by the missing data on eligibility, and 2) imputing the missing values of the eligibility variables prior to selection into the target trial. Results are compared with the results when TTE is performed ignoring the impact of missing eligibility. A study of palivizumab, a monoclonal antibody recommended for the prevention of respiratory hospital admissions due to respiratory syncytial virus in high-risk infants, is used for illustration.

Access to palivizumab among children at high risk of respiratory syncytial virus complications in English hospitals.

AIMS: Palivizumab is a monoclonal antibody which can prevent infection with respiratory syncytial virus (RSV). Due to its high cost, it is recommended for high-risk infants only. We aimed to determine the proportion of infants eligible for palivizumab treatment in England who receive at least one dose. METHODS: We used the Hospital Treatment Insights database, which contains hospital admission records linked to hospital pharmacy dispensing data for 43 out of 153 hospitals in England. Infants born between 2010 and 2016 were considered eligible for palivizumab if their medical records indicated chronic lung disease (CLD), congenital heart disease (CHD) or severe immunodeficiency (SCID), and they met additional criteria based on gestational age at birth and age at start of the RSV season (beginning of October). We calculated the proportion of infants who received at least one dose of palivizumab in their first RSV season, and modelled the odds of treatment according to multiple child characteristics using logistic regression models. RESULTS: We identified 3712 eligible children, of whom 2479 (67%) had complete information on all risk factors. Palivizumab was prescribed to 832 of eligible children (34%). Being born at <30 weeks' gestation, aged <6 months at the start of RSV season, and having two or more of CLD, CHD or SCID were associated with higher odds of treatment. CONCLUSION: In England, palivizumab is not prescribed to the majority of children who are eligible to receive it. Doctors managing these infants may be unfamiliar with the eligibility criteria or constrained by other considerations, such as cost.

Determinants of accident and emergency attendances and emergency admissions in infants: birth cohort study.

BACKGROUND: There is limited understanding of the drivers of increasing infant accident and emergency (A&E) attendances and emergency hospital admissions across England. We examine variations in use of emergency hospital services among infants by local areas in England and investigate the extent to which infant and socio-economic factors explain these variations. METHODS: Birth cohort study using linked administrative Hospital Episode Statistics data in England. Singleton live births between 1-April-2012 and 31-March-2019 were followed up for 1 year; from 1-April-2013 (from the discharge date of their birth admission) until their first birthday, death or 31-March-2019. Mixed effects negative binomial models were used to calculate incidence rate ratios for A&E attendances and emergency admissions and mixed effects logistic regression models estimated odds ratio of conversion (the proportion of infants subsequently admitted after attending A&E). Models were adjusted for individual-level factors and included a random effect for local authority (LA). RESULTS: The cohort comprised 3,665,414 births in 150 English LAs. Rates of A&E attendances and emergency admissions were highest amongst: infants born < 32 weeks gestation; with presence of congenital anomaly; and to mothers < 20-years-old. Area-level deprivation was positively associated with A&E attendance rates, but not associated with conversion probability. A&E attendance rates were highest in the North East (916 per 1000 child-years, 95%CI: 911 to 921) and London (876 per 1000, 95%CI: 874 to 879), yet London had the lowest emergency admission rates (232 per 1000, 95%CI: 231 to 234) and conversion probability (25% vs 39% in South West). Adjusting for individual-level factors did not significantly affect variability in A&E attendance and emergency admission rates by local authority. CONCLUSIONS: Drivers of A&E attendances and emergency admissions include individual-level factors such being born premature, with congenital anomaly and from socio-economically disadvantaged young parent families. Support for such vulnerable infants and families should be provided alongside preventative health care in primary and community care settings. The impact of these services requires further investigation. Substantial geographical variations in rates were not explained by individual-level factors. This suggests more detailed understanding of local and underlying service-level factors would provide targets for further research on mechanisms and policy priority.

Community-Based Antibiotic Prescribing Attributable to Respiratory Syncytial Virus and Other Common Respiratory Viruses in Young Children: A Population-Based Time-series Study of Scottish Children.

BACKGROUND: Inappropriate antibiotic prescribing, such as for viral illness, remains common in primary care. The objective of this study was to estimate the proportion of community-prescribed antibiotics to children aged less than 5 years attributable to common respiratory viruses. METHODS: We fitted time-series negative binomial models to predict weekly antibiotic prescribing rates from positive viral pathogen tests for the period 1 April 2009 through 27 December 2017 using comprehensive, population-based administrative data for all children (<5 years) living in Scotland. Multiple respiratory viral pathogens were considered, including respiratory syncytial virus (RSV), influenza, human metapneumovirus (HMPV), rhinovirus, and human parainfluenza (HPIV) types 1-4. We estimated the proportion of antibiotic prescriptions explained by virus circulation according to type of virus, by age group, presence of high-risk chronic conditions, and antibiotic class. RESULTS: We included data on 6 066 492 antibiotic prescriptions among 452 877 children. The antibiotic-prescribing rate among all Scottish children (<5 years) was 609.7 per 1000 child-years. Our final model included RSV, influenza, HMPV, HPIV-1, and HPIV-3. An estimated 6.9% (95% confidence interval, 5.6-8.3%), 2.4% (1.7-3.1%), and 2.3% (.8-3.9%) of antibiotics were attributable to RSV, influenza, and HMPV, respectively. RSV was consistently associated with the highest proportion of prescribed antibiotics, particularly among children without chronic conditions and for amoxicillin and macrolide prescriptions. CONCLUSIONS: Nearly 14% of antibiotics prescribed to children in this study were estimated to be attributable to common viruses for which antibiotics are not recommended. A future RSV vaccine could substantially reduce unnecessary antibiotic prescribing among children.

Are infant mortality rates increasing in England? The effect of extreme prematurity and early neonatal deaths.

BACKGROUND: Infant mortality has been rising in England since 2014. We examined potential drivers of these trends. METHODS: We used aggregate data on all live births, stillbirths and linked infant deaths in England in 2006-2016 from the Office for National Statistics. We compared trends in infant mortality rates overall, excluding births at <24 weeks of gestation, by quintile of SES and gestational age. RESULTS: Infant mortality decreased from 4.78 deaths/1000 live births in 2006 to 3.54/1000 in 2014 (annual decrease of 0.15/1000) and increased to 3.67/1000 in 2016 (annual increase of 0.07/1000). This rise was driven by increases in deaths at 0-6 days of life. After excluding infants born at <24 weeks of gestation, infant mortality continued to decrease after 2014. The risk of infant death was 94% higher in the most versus least deprived SES quintile, which reduced to a 55% higher risk after adjusting for gestational age. CONCLUSIONS: The observed increase in infant mortality rates since 2014 is wholly explained by an increasing number of deaths at 0-6 days of age among babies born at <24 weeks of gestation. Policies focused on improving maternal health to reduce preterm birth could substantially reduce the socio-economic gap in infant survival.

Respiratory syncytial virus in young children: community cohort study integrating serological surveys, questionnaire and electronic health records, Born in Bradford cohort, England, 2008 to 2013.

BackgroundBronchiolitis caused by respiratory syncytial virus (RSV) is a major cause of mortality and morbidity in infants.AimTo describe RSV epidemiology in children in the community in a high-income setting.MethodsWe used stored blood samples from the United Kingdom Born in Bradford cohort study that had been collected at birth, age 1 and 2 years old, tested for IgG RSV postfusion F antibody and linked to questionnaires and primary and hospital care records. We used finite mixture models to classify children as RSV infected/not infected according to their antibody concentrations at age 1 and 2 years. We assessed risk factors for primary RSV infection at each age using Poisson regression models.ResultsThe study cohort included 700 children with cord blood samples; 490 had additional blood samples taken at both ages 1 and 2 years old. Of these 490 children, 258 (53%; 95% confidence interval (CI): 48-57%) were first infected with RSV at age 1, 99 of whom (38%; 95% CI: 33-43%) had been in contact with healthcare during peak RSV season (November-January). Having older siblings, birth in October-June and attending formal childcare were associated with risk of RSV infection in infancy. By age 2, a further 164 of 490 children (33%; 95% CI: 29-38%) had been infected.ConclusionOver half of children experienced RSV infection in infancy, a further one third had evidence of primary RSV infection by age 2, and one in seven remained seronegative by their second birthday. These findings will inform future analyses to assess the cost-effectiveness of RSV vaccination programmes in high-income settings.

Geospatial and seasonal variation of bronchiolitis in England: a cohort study using hospital episode statistics.

BACKGROUND: Rates of hospital admissions for bronchiolitis vary seasonally and geographically across England; however, seasonal differences by area remain unexplored. We sought to describe spatial variation in the seasonality of hospital admissions for bronchiolitis and its association with local demographic characteristics. METHODS: Singleton children born in English National Health Service hospitals between 2011 and 2016 (n=3 727 013) were followed up for 1 year. Poisson regression models with harmonic functions to model seasonal variations were used to calculate weekly incidence rates and peak timing of bronchiolitis admissions across English regions and clinical commissioning groups (CCGs). Linear regression was used to estimate the joint association of population density and deprivation with incidence and peak timing of bronchiolitis admissions at the CCG level. RESULTS: Bronchiolitis admission rates ranged from 30.9 per 1000 infant-years (95% CI 30.4 to 31.3) in London to 68.7 per 1000 (95% CI 67.9 to 69.5) in the North West. Across CCGs, there was a 5.3-fold variation in incidence rates and the epidemic peak ranged from week 49.3 to 52.2. Admission rates were positively associated with area-level deprivation. CCGs with earlier peak epidemics had higher population densities, and both high and low levels of deprivation were associated with earlier peak timing. CONCLUSIONS: Approximately one quarter of the variation in admission rates and two-fifths of the variation in peak timing of hospital admissions for bronchiolitis were explained by local demographic characteristics. Implementation of an early warning system could help to prepare hospitals for peak activity and to time public health messages.

ß2-integrin LFA1 mediates airway damage following neutrophil transepithelial migration during respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) bronchiolitis is the most common cause of infant hospital admissions, but there is limited understanding of the mechanisms of disease, and no specific antiviral treatment. Using a novel in vitro primary transepithelial neutrophil migration model and innovative imaging methods, we show that RSV infection of nasal airway epithelium increased neutrophil transepithelial migration and adhesion to infected epithelial cells, which is associated with epithelial cell damage and reduced ciliary beat frequency, but also with a reduction in infectious viral load.Following migration, RSV infection results in greater neutrophil activation, degranulation and release of neutrophil elastase into the airway surface media compared to neutrophils that migrated across mock-infected nasal epithelial cells. Blocking of the interaction between the ligand on neutrophils (the ß2-integrin LFA-1) for intracellular adhesion molecule (ICAM)-1 on epithelial cells reduced neutrophil adherence to RSV-infected cells and epithelial cell damage to pre-infection levels, but did not reduce the numbers of neutrophils that migrated or prevent the reduction in infectious viral load.These findings have provided important insights into the contribution of neutrophils to airway damage and viral clearance, which are relevant to the pathophysiology of RSV bronchiolitis. This model is a convenient, quantitative preclinical model that will further elucidate mechanisms that drive disease severity and has utility in antiviral drug discovery.

Phenotyping congenital anomalies in administrative hospital records.

BACKGROUND: Congenital anomalies are a major cause of co-morbidity in children. Diagnostic code lists are increasingly used to identify congenital anomalies in administrative health records. Evidence is lacking on comparability of these code lists. OBJECTIVES: To compare prevalence of congenital anomalies and prognostic outcomes for children with congenital anomalies identified in administrative health records using three different code lists. METHODS: We developed national cohorts of singleton livebirths in England (n = 7 354 363, 2003-2014) and Scotland (n = 493 556, 2003-2011). Children with congenital anomalies were identified if congenital anomaly diagnosis was recorded at birth, during subsequent hospital admission or as cause of death before 2 years old. We used three code lists: the EUROCAT list for congenital anomaly surveillance in Europe; the Hardelid list developed to identify children with chronic conditions (including congenital anomalies) admitted to hospital in England; and the Feudtner list developed to indicate children with complex chronic conditions (including congenital anomalies) admitted to hospitals in the United States. We compared prevalence, and risks of postnatal hospital readmission and death according to each code list in England and Scotland. RESULTS: Prevalence of congenital anomalies was highest using the EUROCAT list (4.1% of livebirths in England, 3.7% in Scotland), followed by Hardelid (3.1% and 3.0% of livebirths, respectively) and Feudtner (1.8% and 1.5% of livebirths, respectively). 67.2%-73.3% of children with congenital anomalies in England and 65.2%-77.0% in Scotland had at least one postnatal hospital admission across the three code lists; mortality ranged between 42.6-75.4 and 41.5-88.7 deaths per 1000 births in England Scotland, respectively. The risk of these adverse outcomes was highest using Feudtner and lowest using EUROCAT code lists. CONCLUSIONS: The prevalence of congenital anomalies varied by congenital anomaly code list, over time and between countries, reflecting in part differences in hospital coding practices and admission thresholds. As a minimum, researchers using administrative health data to study congenital anomalies should report sensitivity analyses using different code lists.

Profile of severely growth-restricted births undelivered at 40 weeks in Western Australia.

PURPOSE: To investigate the proportion of severely growth-restricted singleton births < 3rd percentile (proxy for severe fetal growth restriction; FGR) undelivered at 40 weeks (FGR_40), and compare maternal characteristics and outcomes of FGR_40 births and FGR births at 37-39 weeks' (FGR_37-39) to those not born small-for-gestational-age at term (Not SGA_37+). METHODS: The annual rates of singleton FGR_40 births from 2006 to 2015 were calculated using data from linked Western Australian population health datasets. Using 2013-2015 data, maternal factors associated with FGR births were investigated using multinomial logistic regression to estimate odds ratios (OR) with 95% confidence intervals (CI) while relative risks (RR) of birth outcomes between each group were calculated using Poisson regression. Neonatal adverse outcomes were identified using a published composite indicator (diagnoses, procedures and other factors). RESULTS: The rate of singleton FGR_40 births decreased by 23.0% between 2006 and 2015. Factors strongly associated with FGR_40 and FGR_37-39 births compared to Not SGA_37+ births included the mother being primiparous (ORs 3.13: 95% CI 2.59-3.79; 1.69, 95% CI 1.47, 1.94, respectively) and ante-natal smoking (ORs 2.55, 95% CI 1.97, 3.32; 4.48, 95% CI 3.74, 5.36, respectively). FGR_40 and FGR_37-39 infants were more likely to have a neonatal adverse outcome (RRs 1.70, 95% CI 1.41, 2.06 and 2.46 95% CI 2.18, 2.46, respectively) compared to Not SGA 37+ infants. CONCLUSIONS: Higher levels of poor perinatal outcomes among FGR births highlight the importance of appropriate management including fetal growth monitoring. Regular population-level monitoring of FGR_40 rates may lead to reduced numbers of poor outcomes.

Correction to: Profile of severely growth-restricted births undelivered at 40 weeks in Western Australia.

Unfortunately, after publication, we found errors in the extraction of data on gestational diabetes and threatened miscarriage.

Child mortality in England compared with Sweden: a birth cohort study.

BACKGROUND: Child mortality is almost twice as high in England compared with Sweden. We aimed to establish the extent to which adverse birth characteristics and socioeconomic factors explain this difference. METHODS: We developed nationally representative cohorts of singleton livebirths between Jan 1, 2003, and Dec 31, 2012, using the Hospital Episode Statistics in England, and the Swedish Medical Birth Register in Sweden, with longitudinal follow-up from linked hospital admissions and mortality records. We analysed mortality as the outcome, based on deaths from any cause at age 2-27 days, 28-364 days, and 1-4 years. We fitted Cox proportional hazard regression models to estimate the hazard ratios (HRs) for England compared with Sweden in all three age groups. The models were adjusted for birth characteristics (gestational age, birthweight, sex, and congenital anomalies), and for socioeconomic factors (maternal age and socioeconomic status). FINDINGS: The English cohort comprised 3 932 886 births and 11 392 deaths and the Swedish cohort comprised 1 013 360 births and 1927 deaths. The unadjusted HRs for England compared with Sweden were 1·66 (95% CI 1·53-1·81) at 2-27 days, 1·59 (1·47-1·71) at 28-364 days, and 1·27 (1·15-1·40) at 1-4 years. At 2-27 days, 77% of the excess risk of death in England was explained by birth characteristics and a further 3% by socioeconomic factors. At 28-364 days, 68% of the excess risk of death in England was explained by birth characteristics and a further 11% by socioeconomic factors. At 1-4 years, the adjusted HR did not indicate a significant difference between countries. INTERPRETATION: Excess child mortality in England compared with Sweden was largely explained by the unfavourable distribution of birth characteristics in England. Socioeconomic factors contributed to these differences through associations with adverse birth characteristics and increased mortality after 1 month of age. Policies to reduce child mortality in England could have most impact by reducing adverse birth characteristics through improving the health of women before and during pregnancy and reducing socioeconomic disadvantage. FUNDING: The Farr Institute of Health Informatics Research (through the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institute for Social Care and Health Research, and the Wellcome Trust).

The contribution of child, family and health service factors to respiratory syncytial virus (RSV) hospital admissions in the first 3 years of life: birth cohort study in Scotland, 2009 to 2015.

IntroductionSeveral vaccines for respiratory syncytial virus (RSV) are under development. Designing an effective vaccination programme for RSV requires information about the relative contribution of risk factors for severe RSV symptoms.AimTo inform preventive strategies in Europe by quantifying the contribution of key child, family and health service risk factors to the burden of RSV hospital admissions in young children.MethodsWe constructed a birth cohort study of all singleton children born in Scotland between October 2009 and September 2012 using linkage between birth registration, maternity, vaccination and hospital admission records, with follow-up until the age of 3 years. RSV-confirmed hospital admissions were defined using linkage to national laboratory surveillance data. We estimated hospital admission rates per 1,000 child years and length of stay according to each risk factor. Cox proportional hazard regression models were used to estimate adjusted hazard ratios.ResultsThere were 5,185 RSV admissions among the 169,726 children in the cohort: 48.6% of admissions occurred before the age of 6 months, and 29.6% after the age of 1 year. Children born prematurely, small for gestational age, between July and December, with chronic conditions, older siblings, mothers < 30 years old or delayed infant vaccination had a significantly increased risk of admission. Minimising the risk posed by older siblings could reduce RSV admissions by up to 34%.ConclusionFuture RSV vaccination programmes must protect children throughout early childhood. Vaccination and/or interventions to reduce transmission by older siblings could substantially reduce RSV hospital admissions.

Effectiveness of live attenuated influenza vaccine in preventing amoxicillin prescribing in preschool children: a self-controlled case series study.

Objectives: To determine the effectiveness of live attenuated influenza vaccine (LAIV) in reducing amoxicillin prescribing in preschool children in primary care. Patients and methods: We used The Health Improvement Network (THIN), a large primary care database from the United Kingdom. We included children aged 2 to 4 years old at the start of either the 2013/14 or the 2014/15 winter season, with at least one amoxicillin prescription between September and May, irrespective of LAIV vaccination status. We used the self-controlled case series method to estimate influenza vaccine effectiveness (VE). Results: The total study sample included 33 137 children from 378 general practices during the two winter seasons. Of these children, 43.4% with at least one amoxicillin prescription had been vaccinated. The rate of amoxicillin prescribing was significantly reduced during periods of influenza vaccine immunity. The associated VE for amoxicillin prescribing was 12.8% (95% CI 6.9%, 18.3%) in 2013/14 and 14.5% (9.6%, 19.2%) in 2014/15. Given a VE of 14.5%, we estimated that amoxicillin prescribing could have been reduced by 5.6% if LAIV uptake in children aged 2-4 years increased to 50% in the 2014/15 winter season. Conclusions: Influenza vaccination of young children may contribute to a reduction in the prescribing of amoxicillin, one of the most commonly prescribed antibiotics in primary care. Further studies are required to confirm the size of the effect.

Risk factors for admission to hospital with laboratory-confirmed influenza in young children: birth cohort study.

We determined risk factors for influenza hospital admission in children aged <2 years to guide the design of paediatric vaccination programmes.We linked all singleton live births in Scotland from 2007 to 2015 to hospital administrative data and influenza laboratory reports. Cox proportional hazard models were used to identify birth and family risk factors for influenza admissions.There were 1115 influenza admissions among 424 048 children. 85.1% of admitted children were born at term and were not in a high-risk group. Presence of an older sibling was strongly associated with increased risk of influenza admission, particularly for children aged <6 months: hazard ratio for second- versus first-born child was 2.02 (95% CI 1.52-2.69). Maternal age <30 years and birth during autumn (age <6 months) or spring (age 6-23 months) were also associated with admission risk.Targeting vaccination programmes to high-risk children will not prevent the vast majority of influenza admissions. Parents of children aged <2 years should be advised that vaccination of older siblings will protect younger children against influenza infection. As evidence of the impact of the universal influenza vaccine programme emerges, there may be a need to reconsider universal influenza vaccination in children aged 6 months to 2 years in the UK.

How can we make international comparisons of infant mortality in high income countries based on aggregate data more relevant to policy?

BACKGROUND: Infant mortality rates are commonly used to compare the health of populations. Observed differences are often attributed to variation in child health care quality. However, any differences are at least partly explained by variation in the prevalence of risk factors at birth, such as low birth weight. This distinction is important for designing interventions to reduce infant mortality. We suggest a simple method for decomposing inter-country differences in crude infant mortality rates into two metrics representing risk factors operating before and after birth. METHODS: We used data from 7 European countries participating in the EURO-PERISTAT project in 2010. We calculated crude and birth weight-standardised stillbirth and infant mortality rates using Norway as the standard population. We decomposed between-country differences in crude stillbirth and infant mortality rates into the within-country difference in crude and birth weight-standardised stillbirth and infant mortality rates (metric 1), reflecting prenatal risk factors, and the between-country difference in birth weight-standardised stillbirth and infant mortality rates (metric 2), reflecting risk factors operating after birth. We also calculated birth weight-specific mortality. RESULTS: Using our metrics, we showed that for England, Wales and Scotland risk factors before and after birth contributed equally to the differences in crude stillbirth and infant mortality rates relative to Norway. In Austria, Czech Republic and Switzerland the differences were driven primarily by metric 1, reflecting high rate of low birth weight. The highest values of metric 2 observed in Poland partially reflected high rates of congenital anomalies. CONCLUSIONS: Our suggested metrics can be used to guide policy decisions on preventing infant deaths through reducing risk factors at birth or improving the care of babies after birth. Aggregate data tabulated by birth weight/gestational age should be routinely collected and published in high-income countries where birth weight is reported on birth certificates.