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)

A machine-learning approach to identify cerebral palsy cases using primary care database

Introduction Cerebral palsy (CP) is a complex condition that can manifest in different ways and is likely to be under-recorded in primary care databases. As identification based only on diagnostic codes will underestimate the incidence of cerebral palsy, an approach is needed to use all available information to identify more cases. Objectives and Approach We used a machine-learning approach to identify likely CP cases in the Clinical Practice Research Datalink (CPRD), a UK primary-care database: i) we selected potential codes (symptoms, therapies and managements) to identify CP cases by comparing relative frequencies of codes associated with known cases versus non-cases; ii) codes with higher discriminative ability were further selected using a Random Forest method based on a resampled, balanced population; iii) we calculated the predictive score for each patient employing the discriminative ability of selected codes; and iv) manually reviewed the full medical records of likely cases (i.e. patients with higher predictive score). Results Primary care records were available for 343,199 young people aged 2000 were identified as likely cases (n=365, 0.1% of previously non-cases). Their full medical records in CPRD were manually reviewed by experts and 85 children (23.3% of likely cases) were validated as CP cases additional to the 341 initially identified by diagnostic codes, resulting in a 20% increase of CP cases. Conclusion/Implications Data-driven schemes, such as the machine learning methods applied here, have the potential of identifying the most informative predictors in a cost-effective and rapid way to identify likely CP cases or other complex medical conditions in primary care database

Hospital admissions for stress-related presentations among school-aged adolescents during term time versus holidays in England: weekly time series and retrospective cross-sectional analysis

BACKGROUND: Schools are a potential stressor for adolescents and may contribute to emergency hospital admissions. AIMS: We describe rates of stress-related presentations (SRPs) among school-aged adolescents (11-17 years) during school terms and holidays, and explore differences by age and gender. METHOD: Using national administrative hospital data, we defined an SRP as an emergency hospital admission with a primary diagnosis related to pain, psychosomatic symptoms (e.g. fatigue) or mental health problems, or with self-harm indicated in any diagnostic position. We estimated incidence rate ratios for weekly SRPs in term time versus holidays from 2014-2015 to 2017-2018, using negative binomial regression models, stratified by age and gender. We estimated the cumulative incidence of any SRP between 11 and 17 years by analysing prior hospital admission histories of adolescents with an SRP in 2017-2018. RESULTS: Over the 4-year study period, 305 491 SRPs in 171 013 school-aged adolescents accounted for 31% of emergency admissions for this group. SRPs were predominantly for mental health problems or self-harm (38%), or pain (35%). Weekly admission rates for SRPs were higher in term time than holidays for all ages (age-specific incidence rate ratios were 1.15-1.49 for girls and 1.08-1.60 for boys). Rates were highest for girls aged 14 and 15 years. The estimated cumulative incidence of any SRP between 11 and 17 years was 7.9% for girls and 4.1% for boys. CONCLUSIONS: Hospital admissions for SRPs are common among adolescents, affecting around two girls and one boy in every classroom. Higher rates in term time than holidays suggest that school factors may contribute

Associations between use of macrolide antibiotics during pregnancy and adverse child outcomes: A systematic review and meta-analysis

BACKGROUND: Evidence on adverse effects of maternal macrolide use during pregnancy is inconsistent. We conducted a systematic review and meta-analysis to investigate the association between macrolide use during pregnancy and adverse fetal and child outcomes. METHODS AND FINDINGS: We included observational studies and randomised controlled trials (RCTs) that recorded macrolide use during pregnancy and child outcomes. We prioritized comparisons of macrolides with alternative antibiotics (mainly penicillins or cephalosporins) for comparability of indication and effect. Random effects meta-analysis was used to derive pooled odds ratios (OR) for each outcome. Subgroup analyses were performed according to specific types (generic forms) of macrolide. Of 11,186 citations identified, 19 (10 observational, 9 RCTs) studies were included (21 articles including 228,556 participants). Macrolide prescribing during pregnancy was associated with an increased risk of miscarriage (pooled ORobs 1·82, 95% CI 1·57-2·11, three studies, I2 = 0%), cerebral palsy and/or epilepsy (ORobs 1·78, 1·18-2·69; one study), epilepsy alone (ORobs 2·02, 1·30-3·14, one study; ORRCT 1.03, 0.79-1.35, two studies), and gastrointestinal malformations (ORobs 1·56, 1·05-2·32, two studies) compared with alternative antibiotics. We found no evidence of an adverse effect on 12 other malformations, stillbirth, or neonatal death. Results were robust to excluding studies with high risk of bias. CONCLUSIONS: Consistent evidence of an increased risk of miscarriage in observational studies and uncertain risks of cerebral palsy and epilepsy warrant cautious use of macrolide in pregnancy with warnings in drug safety leaflets and use of alternative antibiotics where appropriate. As macrolides are the third most commonly used class of antibiotics, it is important to confirm these results with high quality studies

Long-term mortality in mothers of infants with neonatal abstinence syndrome: A population-based parallel-cohort study in England and Ontario, Canada

Background Opioid addiction is a major public health threat to healthy life expectancy; however, little is known of long-term mortality for mothers with opioid use in pregnancy. Pregnancy and delivery care are opportunities to improve access to addiction and supportive services. Treating neonatal abstinence syndrome (NAS) as a marker of opioid-use during pregnancy, this study reports long-term maternal mortality among mothers with a birth affected by NAS in relation to those mothers without a NAS-affected-birth in two high prevalence jurisdictions, England and Ontario, Canada. Methods and Findings We conducted a population-based study using linked administrative health data to develop parallel cohorts of mother-infant dyads in England and Ontario between 2002 and 2013. The study population comprised 13,577 and 4,966 mothers of infants with NAS and 4,205,675 and 929,985 control mothers in England and Ontario, respectively. Death records captured all-cause maternal mortality after delivery through March 31, 2016, and cause-specific maternal mortality to December 31, 2014. The primary exposure was a livebirth of an infant with NAS and the main outcome was all deaths among mothers following their date of delivery. We modelled the association between NAS and all-cause maternal mortality using Cox regression, and the cumulative incidence of cause-specific mortality within a competing risks framework. All-cause mortality rates, 10-year cumulative incidence risk of death, and crude and age-adjusted hazard ratios were calculated. Estimated crude 10-year mortality based on Kaplan-Meier curves in mothers of infants with NAS was 5.1% (95% CI: 4.7-5.6%) for England and 4.6% (95% CI: 3.8-5.5%) for Ontario versus 0.4% (95% CI: 0.41-0.42) for England and 0.4% (95% CI: 0.38-0.41) in Ontario for controls (p<0.0001 for all rates). Survival curves showed no clear inflection point or period of heightened risk. Crude hazard ratios for all-cause mortality were 12.1 (95% confidence intervals (11.1–13.2) in England and 11.4 (9.7–13.4) in Ontario; age adjustment did not reduce the hazard ratios. Relative to controls, the cumulative incidence of death was higher among NAS mothers for almost all causes of death. The majority of deaths were by avoidable causes, defined as those that are either preventable, amenable to care, or both. Limitations included lack of direct measures of maternal opioid use, other substance misuse, and treatments or supports received. Conclusions In this study, we found that approximately one in 20 mothers of infants with NAS died within 10 years of delivery in both England and Canada— a mortality risk 11–12 times higher than for control mothers. Risk of death was not limited to the early postpartum period targeted by most public health programs. Policy responses to the current opioid epidemic require effective strategies for long-term support to improve the health and welfare of opioid using mothers and their children

Evaluating the real-world implementation of the Family Nurse Partnership in England: protocol for a data linkage study.

INTRODUCTION: Almost 20 000 babies are born to teenage mothers each year in England, with poorer outcomes for mothers and babies than among older mothers. A nurse home visitation programme in the USA was found to improve a wide range of outcomes for young mothers and their children. However, a randomised controlled trial in England found no effect on short-term primary outcomes, although cognitive development up to age 2 showed improvement. Our study will use linked routinely collected health, education and social care data to evaluate the real-world effects of the Family Nurse Partnership (FNP) on child outcomes up to age 7, with a focus on identifying whether the FNP works better for particular groups of families, thereby informing programme targeting and resource allocation. METHODS AND ANALYSIS: We will construct a retrospective cohort of all women aged 13-24 years giving birth in English NHS hospitals between 2010 and 2017, linking information on mothers and children from FNP programme data, Hospital Episodes Statistics and the National Pupil Database. To assess the effectiveness of FNP, we will compare outcomes for eligible mothers ever and never enrolled in FNP, and their children, using two analysis strategies to adjust for measured confounding: propensity score matching and analyses adjusting for maternal characteristics up to enrolment/28 weeks gestation. Outcomes of interest include early childhood development, childhood unplanned hospital admissions for injury or maltreatment-related diagnoses and children in care. Subgroup analyses will determine whether the effect of FNP varied according to maternal characteristics (eg, age and education). ETHICS AND DISSEMINATION: The Nottingham Research Ethics Committee approved this study. Mothers participating in FNP were supportive of our planned research. Results will inform policy-makers for targeting home visiting programmes. Methodological findings on the accuracy and reliability of cross-sectoral data linkage will be of interest to researchers

A multi-national comparison of antipsychotic drug use in children and adolescents, 2005-2012

Over the last decades, an increase in antipsychotic (AP) prescribing and a shift from first-generation antipsychotics (FGA) to second-generation antipsychotics (SGA) among youth have been reported. However, most AP prescriptions for youth are off-label, and there are worrying long-term safety data in youth. The objective of this study was to assess multinational trends in AP use among children and adolescents. A repeated cross-sectional design was applied to cohorts from varied sources from Denmark, Germany, the Netherlands, the United Kingdom (UK) and the United States (US) for calendar years 2005/2006–2012. The annual prevalence of AP use was assessed, stratified by age group, sex and subclass (FGA/SGA). The prevalence of AP use increased from 0.78 to 1.03% in the Netherlands’ data, from 0.26 to 0.48% in the Danish cohort, from 0.23 to 0.32% in the German cohort, and from 0.1 to 0.14% in the UK cohort. In the US cohort, AP use decreased from 0.94 to 0.79%. In the US cohort, nearly all ATP dispensings were for SGA, while among the European cohorts the proportion of SGA dispensings grew to nearly 75% of all AP dispensings. With the exception of the Netherlands, AP use prevalence was highest in 15–19 year-olds. So, from 2005/6 to 2012, AP use prevalence increased in all youth cohorts from European countries and decreased in the US cohort. SGA were favoured in all countries’ cohorts

Air Pollution, housing and respiratory tract Infections in Children: NatIonal birth Cohort study (PICNIC) - study protocol

INTRODUCTION: Respiratory tract infections (RTIs) are the most common reason for hospital admission among children <5 years in the UK. The relative contribution of ambient air pollution exposure and adverse housing conditions to RTI admissions in young children is unclear and has not been assessed in a UK context. METHODS AND ANALYSIS: The aim of the PICNIC study (Air Pollution, housing and respiratory tract Infections in Children: NatIonal birth Cohort Study) is to quantify the extent to which in-utero, infant and childhood exposures to ambient air pollution and adverse housing conditions are associated with risk of RTI admissions in children <5 years old. We will use national administrative data birth cohorts, including data from all children born in England in 2005-2014 and in Scotland in 1997-2020, created via linkage between civil registration, maternity and hospital admission data sets. We will further enhance these cohorts via linkage to census data on housing conditions and socioeconomic position and small area-level data on ambient air pollution and building characteristics. We will use time-to-event analyses to examine the association between air pollution, housing characteristics and the risk of RTI admissions in children, calculate population attributable fractions for ambient air pollution and housing characteristics, and use causal mediation analyses to explore the mechanisms through which housing and air pollution influence the risk of infant RTI admission. ETHICS, EXPECTED IMPACT AND DISSEMINATION: To date, we have obtained approval from six ethics and information governance committees in England and two in Scotland. Our results will inform parents, national and local governments, the National Health Service and voluntary sector organisations of the relative contribution of adverse housing conditions and air pollution to RTI admissions in young children. We will publish our results in open-access journals and present our results to the public via parent groups and social media and on the PICNIC website. Code and metadata will be published on GitHub