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.

Congenital diaphragmatic hernia subtypes: Comparing birth prevalence, occurrence by maternal age, and mortality in a national birth cohort.

BACKGROUND: Population-based administrative data have rarely been used to compare the birth prevalence, risk factors for occurrence, and mortality of congenital diaphragmatic hernia (CDH) subtypes. OBJECTIVES: We used a national birth cohort to identify CDH subtypes and compared their birth prevalence, relationship with maternal age after accounting for sociodemographic factors, and 1-year mortality rates. METHODS: Linked hospital admission and death records were used to identify isolated and complex CDH cases (involving additional anomalies) among singleton livebirths in England between 2002 and 2018. The prevalence of each CDH subtype per 10,000 livebirths was estimated overall and by infant, birth and maternal characteristics. The relationship between maternal age and each subtype relative to no CDH was examined using multivariable log-binomial regression to estimate risk ratios (RRs). One-year mortality rates were examined using Kaplan-Meier curves and the hazard ratio (HR) of complex versus isolated CDH was calculated using Cox regression. RESULTS: Among 9.5 million livebirths, we identified 1285 with isolated CDH and 1150 with complex CDH. The overall prevalence of isolated and complex CDH was 1.4 (95% confidence interval [CI] 1.3, 1.4) and 1.2 (95% CI 1.1, 1.3) per 10,000 livebirths, respectively. Only complex CDH was associated with maternal age. Compared with maternal age 25-34 years, complex CDH risk was elevated for maternal age < 20 years (RR 1.31, 95% CI 1.00, 1.72). Risk was highest for maternal age ≥ 40 years (RR 1.61, 95% CI 1.21, 2.15) although accounting for chromosomal anomalies attenuated the risk (RR 1.39, 95% CI 1.00, 1.92). The 1-year mortality rate for complex CDH (33.1%, 95% CI 30.5, 35.9) was slightly higher than for isolated CDH (29.7%, 95% CI 27.3, 32.3) (HR 1.10, 95% CI 0.96, 1.27). CONCLUSIONS: Mechanisms of occurrence differed between and within CDH subtypes and 1-year mortality of complex CDH was slightly higher than for isolated CDH.

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.

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.

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.

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).

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.

Trends in hospital admissions during transition from paediatric to adult services for young people with learning disabilities or autism: Population-based cohort study.

Background: Transition from paediatric to adult health care may disrupt continuity of care, and result in unmet health needs. We describe changes in planned and unplanned hospital admission rates before, during and after transition for young people with learning disability (LD), or autism spectrum disorders (ASD) indicated in hospital records, who are likely to have more complex health needs. Methods: We developed two mutually exclusive cohorts of young people with LD, and with ASD without LD, born between 1990 and 2001 in England using national hospital admission data. We determined the annual rate of change in planned and unplanned hospital admission rates before (age 10-15 years), during (16-18 years) and after (19-24 years) transition to adult care using multilevel negative binomial regression models, accounting for area-level deprivation, sex, birth year and presence of comorbidities. Findings: The cohorts included 51,291 young people with LD, and 46,270 autistic young people. Admission rates at ages 10-24 years old were higher for young people with LD (54 planned and 25 unplanned admissions per 100 person-years) than for autistic young people (17/100 and 16/100, respectively). For young people with LD, planned admission rates were highest and constant before transition (rate ratio [RR]: 0.99, 95% confidence interval [CI] 0.98-0.99), declined by 14% per year of age during (RR: 0.86, 95% CI: 0.85-0.88), and remained constant after transition (RR: 0.99, 95% CI: 0.99-1.00), mainly due to fewer admissions for non-surgical care, including respite care. Unplanned admission rates increased by 3% per year of age before (RR: 1.03, 95% CI: 1.02-1.03), remained constant during (RR: 1.01, 95% CI: 1.00-1.03) and increased by 3% per year after transition (RR: 1.03, 95% CI: 1.02-1.04). For autistic young people, planned admission rates increased before (RR: 1.06, 95% CI: 1.05-1.06), decreased during (RR: 0.95, 95% CI: 0.93-0.97), and increased after transition (RR: 1.05, 95%: 1.04-1.07). Unplanned admission rates increased most rapidly before (RR: 1.16, 95% CI: 1.15-1.17), remained constant during (RR: 1.01, 95% CI: 0.99-1.03), and increased moderately after transition (RR: 1.03, 95% CI: 1.02-1.04). Interpretation: Decreases in planned admission rates during transition were paralleled by small but consistent increases in unplanned admission rates with age for young people with LD and autistic young people. Decreases in non-surgical planned care during transition could reflect disruptions to continuity of planned/respite care or a shift towards provision of healthcare in primary care and community settings and non-hospital arrangements for respite care. Funding: National Institute for Health Research Policy Research Programme.

Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.

INTRODUCTION: One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes. METHODS: The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation. ETHICS AND DISSEMINATION: Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.

Birth prevalence of anorectal malformations in England and 5-year survival: a national birth cohort study.

OBJECTIVE: To determine the birth prevalence, maternal risk factors and 5-year survival for isolated and complex anorectal malformations. DESIGN: National birth cohort using hospital admission data and death records. SETTING: All National Health Service England hospitals. PATIENTS: Live-born singletons delivered from 2002 through 2018, with evidence in the first year of life of a diagnosis of an anorectal malformation and repair during a hospital admission, or anorectal malformation recorded on the death certificate. Cases were further classified as isolated or complex depending on the presence of additional anomalies. MAIN OUTCOME MEASURES: Birth prevalence of anorectal malformations per 10 000 live births, risk ratios for isolated and complex anorectal malformation by maternal, infant and birth characteristics, and 5-year survival. RESULTS: We identified 3325 infants with anorectal malformations among 9 474 147 live-born singletons; 61.7% (n=2050) of cases were complex. Birth prevalence was 3.5 per 10 000 live births (95% CI 3.4 to 3.6). Complex anorectal malformations were associated with maternal age extremes after accounting for other sociodemographic factors. Compared with maternal ages 25-34 years, the risk of complex anorectal malformations was 31% higher for ≥35 years (95% CI 17 to 48) and 13% higher for ≤24 years (95% CI 0 to 27). Among 2376 anorectal malformation cases (n=1450 complex) born from 2002 through 2014, 5-year survival was lower for complex (86.9%; 95% CI 85.1% to 88.5%) than isolated anorectal malformations (98.2%; 95% CI 97.1% to 98.9%). Preterm infants with complex anorectal malformations had the lowest survival (73.4%; 95% CI 68.1% to 78.0%). CONCLUSIONS: Differences in maternal risk factors for isolated and complex anorectal malformations may reflect different underlying mechanisms for occurrence. Five-year survival is high but lowest for preterm children with complex anorectal malformations.

What makes administrative data "research-ready"? A systematic review and thematic analysis of published literature.

Introduction: Administrative data are a valuable research resource, but are under-utilised in the UK due to governance, technical and other barriers (e.g., the time and effort taken to gain secure data access). In recent years, there has been considerable government investment in making administrative data "research-ready", but there is no definition of what this term means. A common understanding of what constitutes research-ready administrative data is needed to establish clear principles and frameworks for their development and the realisation of their full research potential. Objective: To define the characteristics of research-ready administrative data based on a systematic review and synthesis of existing literature. Methods: On 29th June 2021, we systematically searched seven electronic databases for (1) peer-reviewed literature (2) related to research-ready administrative data (3) written in the English language. Following supplementary searches and snowball screening, we conducted a thematic analysis of the identified relevant literature. Results: Overall, we screened 2,375 records and identified 38 relevant studies published between 2012 and 2021. Most related to administrative data from the UK and US and particularly to health data. The term research-ready was used inconsistently in the literature and there was some conflation with the concept of data being ready for statistical analysis. From the thematic analysis, we identified five defining characteristics of research-ready administrative data: (a) accessible, (b) broad, (c) curated, (d) documented and (e) enhanced for research purposes. Conclusions: Our proposed characteristics of research-ready administrative data could act as a starting point to help data owners and researchers develop common principles and standards. In the more immediate term, the proposed characteristics are a useful framework for cataloguing existing research-ready administrative databases and relevant resources that can support their development.

Factors predicting amoxicillin prescribing in primary care among children: a cohort study.

BACKGROUND: Antibiotic prescribing during childhood, most commonly for respiratory tract infections (RTIs), contributes to antimicrobial resistance, which is a major public health concern. AIM: To identify factors associated with amoxicillin prescribing and RTI consultation attendance in young children in primary care. DESIGN AND SETTING: Cohort study in Bradford spanning pregnancy to age 24 months, collected 2007-2013, linked to electronic primary care and air pollution data. METHOD: Amoxicillin prescribing and RTI consultation rates/1000 child-years were calculated. Mixed-effects logistic regression models were fitted with general practice (GP) surgery as the random effect. RESULTS: The amoxicillin prescribing rate among 2493 children was 710/1000 child-years during year 1 (95% confidence interval [CI] = 677 to 744) and 780/1000 (95% CI = 745 to 816) during year 2. During year 1, odds of amoxicillin prescribing were higher for boys (adjusted odds ratio [aOR] 1.36, 95% CI = 1.14 to 1.61), infants from socioeconomically deprived households (aOR 1.36, 95% CI = 1.00 to 1.86), and infants with a Pakistani ethnic background (with mothers born in the UK [aOR 1.44, 95% CI = 1.06 to 1.94] and outside [aOR 1.42, 95% CI = 1.07 to 1.90]). During year 2, odds of amoxicillin prescribing were higher for infants with a Pakistani ethnic background (with mothers born in the UK [aOR 1.46, 95% CI = 1.10 to 1.94] and outside [aOR 1.56, 95% CI = 1.19 to 2.04]) and those born <39 weeks gestation (aOR 1.20, 95% CI = 1.00 to 1.45). Additional risk factors included caesarean delivery, congenital anomalies, overcrowding, birth season, and childcare attendance, with GP surgery explaining 7%-9% of variation. CONCLUSION: Socioeconomic status and ethnic background were associated with amoxicillin prescribing during childhood. Efforts to reduce RTI spread in household and childcare settings may reduce antibiotic prescribing in primary care.

Developing a national birth cohort for child health research using a hospital admissions database in England: The impact of changes to data collection practices.

BACKGROUND: National birth cohorts derived from administrative health databases constitute unique resources for child health research due to whole country coverage, ongoing follow-up and linkage to other data sources. In England, a national birth cohort can be developed using Hospital Episode Statistics (HES), an administrative database covering details of all publicly funded hospital activity, including 97% of births, with longitudinal follow-up via linkage to hospital and mortality records. We present methods for developing a national birth cohort using HES and assess the impact of changes to data collection over time on coverage and completeness of linked follow-up records for children. METHODS: We developed a national cohort of singleton live births in 1998-2015, with information on key risk factors at birth (birth weight, gestational age, maternal age, ethnicity, area-level deprivation). We identified three changes to data collection, which could affect linkage of births to follow-up records: (1) the introduction of the "NHS Numbers for Babies (NN4B)", an on-line system which enabled maternity staff to request a unique healthcare patient identifier (NHS number) immediately at birth rather than at civil registration, in Q4 2002; (2) the introduction of additional data quality checks at civil registration in Q3 2009; and (3) correcting a postcode extraction error for births by the data provider in Q2 2013. We evaluated the impact of these changes on trends in two outcomes in infancy: hospital readmissions after birth (using interrupted time series analyses) and mortality rates (compared to published national statistics). RESULTS: The cohort covered 10,653,998 babies, accounting for 96% of singleton live births in England in 1998-2015. Overall, 2,077,929 infants (19.5%) had at least one hospital readmission after birth. Readmission rates declined by 0.2% percentage points per annual quarter in Q1 1998 to Q3 2002, shifted up by 6.1% percentage points (compared to the expected value based on the trend before Q4 2002) to 17.7% in Q4 2002 when NN4B was introduced, and increased by 0.1% percentage points per annual quarter thereafter. Infant mortality rates were under-reported by 16% for births in 1998-2002 and similar to published national mortality statistics for births in 2003-2015. The trends in infant readmission were not affected by changes to data collection practices in Q3 2009 and Q2 2013, but the proportion of unlinked mortality records in HES and in ONS further declined after 2009. DISCUSSION: HES can be used to develop a national birth cohort for child health research with follow-up via linkage to hospital and mortality records for children born from 2003 onwards. Re-linking births before 2003 to their follow-up records would maximise potential benefits of this rich resource, enabling studies of outcomes in adolescents with over 20 years of follow-up.

Origins of disparities in preventable child mortality in England and Sweden: a birth cohort study.

OBJECTIVE: To compare mortality in children aged <5 years from two causes amenable to healthcare prevention in England and Sweden: respiratory tract infection (RTI) and sudden unexpected death in infancy (SUDI). DESIGN: Birth cohort study using linked administrative health databases from England and Sweden. SETTING AND PARTICIPANTS: Singleton live births between 2003 and 2012 in England and Sweden, followed up from age 31 days until the fifth birthday, death or 31 December 2013. MAIN OUTCOME MEASURES: The main outcome measures were HR for RTI-related mortality at 31-364 days and at 1-4 years and SUDI mortality at 31-364 days in England versus Sweden estimated using Cox proportional hazards models. We calculated unadjusted HRs and HRs adjusted for birth characteristics (gestational age, birth weight, sex and congenital anomalies) and socioeconomic factors (maternal age and socioeconomic status). RESULTS: The English cohort comprised 3 928 483 births, 768 RTI-related deaths at 31-364 days, 691 RTI-related deaths at 1-4 years and 1166 SUDIs; the corresponding figures for the Swedish cohort were 1 012 682, 131, 118 and 189. At 31-364 days, unadjusted HR for RTI-related death in England versus Sweden was 1.52 (95% CI 1.26 to 1.82). After adjusting for birth characteristics, the HR reduced to 1.16 (95% CI 0.96 to 1.40) and for socioeconomic factors to 1.11 (95% CI 0.92 to 1.34). At 1-4 years, unadjusted HR was 1.58 (95% CI 1.30 to 1.92) and decreased to 1.32 (95% CI 1.09 to 1.61) after adjusting for birth characteristics and to 1.30 (95% CI 1.07 to 1.59) after further adjustment for socioeconomic factors. For SUDI, the respective HRs were 1.59 (95% CI 1.36 to 1.85) in the unadjusted model, and 1.40 (95% CI 1.20 to 1.63) after accounting for birth characteristics and 1.19 (95% CI 1.02 to 1.39) in the fully adjusted model. CONCLUSION: Interventions that improve maternal health before and during pregnancy to reduce the prevalence of adverse birth characteristics and address poverty could reduce child mortality due to RTIs and SUDIs in England.

Deprivation and mortality related to pediatric respiratory tract infection: a cohort study in 3 high-income jurisdictions.

BACKGROUND: Deaths from respiratory tract infections (RTIs) in children are preventable through timely access to public health and medical interventions. We aimed to assess whether socioeconomic disparities in mortality related to pediatric RTI persisted after accounting for health status at birth. METHODS: We compared the prevalence of and risk factors for RTI-related death in singletons aged 28 days to 4 years across Ontario (Canada), Scotland and England (jurisdictions with universal health care) using linked administrative data for 2003-2013. We estimated rates of RTI-related mortality for children living in deprived areas and those born to teenage girls; we estimated both crude rates and those adjusted for health status at birth. RESULTS: A total of 1 299 240 (Ontario), 547 556 (Scotland) and 3 910 401 (England) children were included in the study. Across all jurisdictions, children born in the most deprived areas experienced the highest rates of RTI-related mortality. After adjustment for high-risk chronic conditions and prematurity, we observed differences in mortality according to area-level deprivation in Ontario and England but not in Scotland. In Ontario, teenage motherhood was also an independent risk factor for RTI-related mortality. INTERPRETATION: Socioeconomic disparities played a substantial role in child mortality related to RTI in all 3 jurisdictions. Context-specific investigations around the mechanisms of this increased risk and development of programs to address socioeconomic disparities are needed.

Temporal trends and socioeconomic differences in acute respiratory infection hospitalisations in children: an intercountry comparison of birth cohort studies in Western Australia, England and Scotland.

OBJECTIVES: Acute respiratory infections (ARIs) are a global cause of childhood morbidity. We compared temporal trends and socioeconomic disparities for ARI hospitalisations in young children across Western Australia, England and Scotland. DESIGN: Retrospective population-based cohort studies using linked birth, death and hospitalisation data. SETTING AND PARTICIPANTS: Population birth cohorts spanning 2000-2012 (Western Australia and Scotland) and 2003-2012 (England). OUTCOME MEASURES: ARI hospitalisations in infants (<12 months) and children (1-4 years) were identified through International Classification of Diseases, 10th edition diagnosis codes. We calculated admission rates per 1000 child-years by diagnosis and jurisdiction-specific socioeconomic deprivation and used negative binomial regression to assess temporal trends. RESULTS: The overall infant ARI admission rate was 44.3/1000 child-years in Western Australia, 40.7/1000 in Scotland and 40.1/1000 in England. Equivalent rates in children aged 1-4 years were 9.0, 7.6 and 7.6. Bronchiolitis was the most common diagnosis. Compared with the least socioeconomically deprived, those most deprived had higher ARI hospitalisation risk (incidence rate ratio 3.9 (95% CI 3.5 to 4.2) for Western Australia; 1.9 (1.7 to 2.1) for England; 1.3 (1.1 to 1.4) for Scotland. ARI admissions in infants were stable in Western Australia but increased annually in England (5%) and Scotland (3%) after adjusting for non-ARI admissions, sex and deprivation. CONCLUSIONS: Admissions for ARI were higher in Western Australia and displayed greater socioeconomic disparities than England and Scotland, where ARI rates are increasing. Prevention programmes focusing on disadvantaged populations in all three countries are likely to translate into real improvements in the burden of ARI in children.