How are socioeconomic inequalities in preterm birth explained by maternal smoking and maternal body mass index: A mediation analysis.

BACKGROUND: Preterm birth affects between 7% and 8% of births in the UK and is a leading cause of infant mortality and childhood disability. Prevalence of preterm birth has been shown to have significant and consistent socioeconomic inequalities. OBJECTIVE: To estimate how much of the association between socioeconomic status (SES) and gestational age at birth is mediated by maternal smoking status and maternal body mass index (BMI). METHODS: Retrospective cohort study of a maternity hospital in the UK. The analysis included all singleton live births between April 2009 and March 2020 to mothers 18 years old and over, between 22 weeks and 43 weeks gestation. We estimate two measures of mediation for four low gestational age categories: (i) The proportion eliminated the percentage of the effect of SES on low gestational age at birth that would be eliminated by removing the mediators, through the Controlled Direct Effects estimated using serial log-binomial regressions; and (ii) The proportion mediated is the percentage of the effect removed by equalising the distribution of the mediators across socioeconomic groups, estimated using Interventional Disparity Measures calculated through Monte Carlo simulations. RESULTS: Overall, 81,219 births were included, with 63.7% low SES. The risk of extremely (0.3% of all births), very (0.7%) and moderately preterm birth (6.3%) was 1.71 (95% Confidence Interval [CI] 1.29, 2.31), 1.43 (95% CI 1.18, 1.73) and 1.26 (95% CI 1.19, 1.34) times higher in the low SES, compared to higher SES respectively. The proportion of this inequality eliminated by removing both maternal smoking and BMI was 43.4% for moderately preterm births. The proportion mediated for smoking was 33.9%, 43.0% and 48.4% respectively. CONCLUSIONS: Smoking during pregnancy is a key mediator of inequalities in preterm birth, representing an area for local action to reduce social inequalities in preterm birth.

Disadvantage in early-life and persistent asthma in adolescents: a UK cohort study.

OBJECTIVE: To determine how early-life risk factors explain socioeconomic inequalities in persistent asthma in adolescence. METHODS: We did a causal mediation analysis using data from 7487 children and young people in the UK Millennium Cohort Study. Persistent asthma was defined as having a diagnosis reported at any two or more time points at 7, 11 or 14 years. The main exposure was maternal education, a measure of early-life socioeconomic circumstances (SECs), used to calculate the relative index of inequality. We assessed how blocks of perinatal (maternal health behaviours, infant characteristics and duration of breastfeeding, measured at 9 months) and environmental risk factors (family housing conditions; potential exposure to infections through childcare type and sibling number, and neighbourhood characteristics, measured at 3 years) mediated the total effect of childhood SECs on persistent asthma risk, calculating the proportion mediated and natural indirect effect (NIE) via blocks of mediators. RESULTS: At age 14 the overall prevalence of persistent asthma was 15%. Children of mothers with lower educational qualifications were more likely to have persistent asthma, with a clear social gradient (degree plus: 12.8% vs no qualifications: 20.3%). The NIE gives the effect of SECs acting only via the mediators and shows a 31% increased odds of persistent asthma when SECs are fixed at the highest level, and mediators at the level which would naturally occur at the lowest SECs versus highest SECs (NIE OR 1.31, 95% CI 1.04 to 1.65). Overall, 58.9% (95% CI 52.9 to 63.7) of the total effect (OR 1.70, 95% CI 1.20 to 2.40) of SECs on risk of persistent asthma in adolescence was mediated by perinatal and environmental characteristics. CONCLUSIONS: Perinatal characteristics and the home environment in early life are more important in explaining socioeconomic inequalities in persistent asthma in British adolescents than more distal environmental exposures outside the home.

Lung function in children with cystic fibrosis in the USA and UK: a comparative longitudinal analysis of national registry data.

RATIONALE: A previous analysis found significantly higher lung function in the US paediatric cystic fibrosis (CF) population compared with the UK with this difference apparently decreasing in adolescence and adulthood. However, the cross-sectional nature of the study makes it hard to interpret these results. OBJECTIVES: To compare longitudinal trajectories of lung function in children with CF between the USA and UK and to explore reasons for any differences. METHODS: We used mixed effects regression analysis to model lung function trajectories in the study populations. Using descriptive statistics, we compared early growth and nutrition (height, weight, body mass index), infections (Pseudomonas aeruginosa, Staphylococcus aureus) and treatments (rhDnase, hypertonic saline, inhaled antibiotics). RESULTS: We included 9463 children from the USA and 3055 children from the UK with homozygous F508del genotype. Lung function was higher in the USA than in the UK when first measured at age six and remained higher throughout childhood. We did not find important differences in early growth and nutrition, or P.aeruginosa infection. Prescription of rhDNase and hypertonic saline was more common in the USA. Inhaled antibiotics were prescribed at similar levels in both countries, but Tobramycin was prescribed more in the USA and colistin in the UK. S. aureus infection was more common in the USA than the UK. CONCLUSIONS: Children with CF and homozygous F508del genotype in the USA had better lung function than UK children. These differences do not appear to be explained by early growth or nutrition, but differences in the use of early treatments need further investigation.

Projecting the impact of triple CFTR modulator therapy on intravenous antibiotic requirements in cystic fibrosis using patient registry data combined with treatment effects from randomised trials.

BACKGROUND: Cystic fibrosis (CF) is a life-threatening genetic disease, affecting around 10 500 people in the UK. Precision medicines have been developed to treat specific CF-gene mutations. The newest, elexacaftor/tezacaftor/ivacaftor (ELEX/TEZ/IVA), has been found to be highly effective in randomised controlled trials (RCTs) and became available to a large proportion of UK CF patients in 2020. Understanding the potential health economic impacts of ELEX/TEZ/IVA is vital to planning service provision. METHODS: We combined observational UK CF Registry data with RCT results to project the impact of ELEX/TEZ/IVA on total days of intravenous (IV) antibiotic treatment at a population level. Registry data from 2015 to 2017 were used to develop prediction models for IV days over a 1-year period using several predictors, and to estimate 1-year population total IV days based on standards of care pre-ELEX/TEZ/IVA. We considered two approaches to imposing the impact of ELEX/TEZ/IVA on projected outcomes using effect estimates from RCTs: approach 1 based on effect estimates on FEV1% and approach 2 based on effect estimates on exacerbation rate. RESULTS: ELEX/TEZ/IVA is expected to result in significant reductions in population-level requirements for IV antibiotics of 16.1% (~17 800 days) using approach 1 and 43.6% (~39 500 days) using approach 2. The two approaches require different assumptions. Increased understanding of the mechanisms through which ELEX/TEZ/IVA acts on these outcomes would enable further refinements to our projections. CONCLUSIONS: This work contributes to increased understanding of the changing healthcare needs of people with CF and illustrates how Registry data can be used in combination with RCT evidence to estimate population-level treatment impacts.

Mediators of socioeconomic inequalities in preterm birth: a systematic review.

BACKGROUND: Rates of preterm birth are substantial with significant inequalities. Understanding the role of risk factors on the pathway from maternal socioeconomic status (SES) to preterm birth can help inform interventions and policy. This study therefore aimed to identify mediators of the relationship between maternal SES and preterm birth, assess the strength of evidence, and evaluate the quality of methods used to assess mediation. METHODS: Using Scopus, Medline OVID, "Medline In Process & Other Non-Indexed Citation", PsycINFO, and Social Science Citation Index (via Web of Science), search terms combined variations on mediation, socioeconomic status, and preterm birth. Citation and advanced Google searches supplemented this. Inclusion criteria guided screening and selection of observational studies Jan-2000 to July-2020. The metric extracted was the proportion of socioeconomic inequality in preterm birth explained by each mediator (e.g. 'proportion eliminated'). Included studies were narratively synthesised. RESULTS: Of 22 studies included, over one-half used cohort design. Most studies had potential measurement bias for mediators, and only two studies fully adjusted for key confounders. Eighteen studies found significant socioeconomic inequalities in preterm birth. Studies assessed six groups of potential mediators: maternal smoking; maternal mental health; maternal physical health (including body mass index (BMI)); maternal lifestyle (including alcohol consumption); healthcare; and working and environmental conditions. There was high confidence of smoking during pregnancy (most frequently examined mediator) and maternal physical health mediating inequalities in preterm birth. Significant residual inequalities frequently remained. Difference-of-coefficients between models was the most common mediation analysis approach, only six studies assessed exposure-mediator interaction, and only two considered causal assumptions. CONCLUSIONS: The substantial socioeconomic inequalities in preterm birth are only partly explained by six groups of mediators that have been studied, particularly maternal smoking in pregnancy. There is, however, a large residual direct effect of SES evident in most studies. Despite the mediation analysis approaches used limiting our ability to make causal inference, these findings highlight potential ways of intervening to reduce such inequalities. A focus on modifiable socioeconomic determinants, such as reducing poverty and educational inequality, is probably necessary to address inequalities in preterm birth, alongside action on mediating pathways.

Impact of newborn screening on outcomes and social inequalities in cystic fibrosis: a UK CF registry-based study.

BACKGROUND: Newborn bloodspot screening (NBS) for cystic fibrosis (CF) was introduced across the UK in 2007 but the impact on clinical outcomes and health inequalities for children with CF is unclear. METHODS: We undertook longitudinal analyses of UK CF registry data on over 3000 children with CF born between 2000 and 2015. Clinical outcomes were the trajectories of percent predicted forced expiratory volume in one second (%FEV1) from age 5, weight for age and body mass index (BMI) SD-scores from age one, and time to chronic Pseudomonas aeruginosa (cPA) infection. Using mixed effects and time-to-event models we assessed the association of NBS with outcomes and potential interactions with childhood socioeconomic conditions, while adjusting for confounders. RESULTS: NBS was associated with higher average lung function trajectory (+1.56 FEV1 percentage points 95% CI 0.1 to 3.02, n=2216), delayed onset of cPA, and higher average weight trajectory intercept at age one (+0.16 SD; 95% CI 0.07 to 0.26, n=3267) but negative rate of weight change thereafter (-0.02 SD per year; 95% CI -0.03 to -0.00). We found no significant association of NBS with BMI or rate of change of lung function. There was no clear evidence of an impact of NBS on health inequalities early in life. CONCLUSIONS: Children diagnosed with CF by NBS in the UK have better lung function and increased early weight but NBS does not appear to have narrowed early health inequalities.

Explaining the Sex Effect on Survival in Cystic Fibrosis: a Joint Modeling Study of UK Registry Data.

BACKGROUND: Male sex is associated with better lung function and survival in people with cystic fibrosis but it is unclear whether the survival benefit is solely due to the sex-effect on lung function. METHODS: This study analyzes data between 1996 and 2015 from the longitudinal registry study of the UK Cystic Fibrosis Registry. We jointly analyze repeated measurements and time-to-event outcomes to assess how much of the sex effect on lung function also explains survival. These novel methods allow examination of association between percent of forced expiratory volume in 1 second (%FEV1) and covariates such as sex and genotype, and survival, in the same modeling framework. We estimate the probability of surviving one more year with a probit model. RESULTS: The dataset includes 81,129 lung function measurements of %FEV1 on 9,741 patients seen between 1996 and 2015 and captures 1,543 deaths. Males compared with females experienced a more gradual decline in %FEV1 (difference 0.11 per year 95% confidence interval [CI] = 0.08, 0.14). After adjusting for confounders, both overall level of %FEV1 and %FEV1 rate of change are associated with the concurrent hazard for death. There was evidence of a male survival advantage (probit coefficient 0.15; 95% CI = 0.10, 0.19) which changed little after adjustment for %FEV1 using conventional approaches but was attenuated by 37% on adjustment for %FEV1 level and slope in the joint model (0.09; 95% CI = 0.06, 0.12). CONCLUSIONS: We estimate that about 37% of the association of sex on survival in cystic fibrosis is mediated through lung function.

Impact of cystic fibrosis on birthweight: a population based study of children in Denmark and Wales.

BACKGROUND: Poor growth during infancy and childhood is a characteristic feature of cystic fibrosis (CF). However, the impact of CF on intrauterine growth is unclear. We studied the effect of CF on birth weight in Denmark and Wales, and assessed whether any associations are due to differences in gestational age at birth. METHODS: We conducted national registry linkage studies in two countries, using data for 2.2 million singletons born in Denmark (between 1980 and 2010) and Wales (between 1998 and 2015). We used hospital inpatient and outpatient data to identify 852 children with CF. Using causal mediation methods, we estimated the direct and indirect (via gestational age) effect of CF on birth weight after adjustment for sex, parity and socioeconomic background. We tested the robustness of our results by adjusting for additional factors such as maternal smoking during pregnancy in subpopulations where these data were available. RESULTS: Babies with CF were more likely to be born preterm and with low birth weight than babies with no CF (12.7% vs 5% and 9.4% vs 5.8% preterm; 11.9% vs 4.2% and 11% vs 5.4% low birth weight in Denmark and Wales, respectively). Using causal mediation methods, the total effect of CF on birth weight was estimated to be -178.8 g (95% CI -225.43 to -134.47 g) in the Danish population and -210.08 g (95% CI -281.97 to -141.5 g) in the Welsh population. About 40% of this effect of CF on birth weight was mediated through gestational age. CONCLUSIONS: CF significantly impacts on intrauterine growth and leads to lower birth weight in babies with CF, which is only partially explained by shorter gestation.

Use of coping strategies in MND/ALS: Association with demographic and disease-related characteristics.

OBJECTIVE: Understanding the use of coping strategies and which factors are associated with strategy utilization might help clinical staff anticipate which coping strategies individuals are more likely to utilize. In this study, we assess coping strategy use in the motor neuron disease (MND, also known as amyotrophic lateral sclerosis [ALS]) population and examine associations of demographic and disease variables with individual coping strategies. PARTICIPANTS AND METHODS: A total of 233 participants with MND/ALS were recruited into the ongoing Trajectories of Outcomes in Neurological Conditions study from MND clinics across the United Kingdom. Participants completed a questionnaire pack collecting data on demographics and a range of patient-reported measures including the Coping Orientations to Problems Experienced scale. Associations between demographic and clinical characteristics and coping strategies were examined by simple and multiple ordinal logistic regression. RESULTS: The most commonly used strategy was Acceptance, followed by Active Coping, Planning and Positive Re-interpretation and Growth. The least used strategies were Substance Use, Turning to Religion and Denial. Ten out of the fifteen strategies showed statistically significant associations with demographic and clinical characteristics. Most markedly, females were found to utilize many strategies more than males, namely Restraint, Seeking Instrumental Social Support, Seeking Emotional Social Support, Focus on and Venting of Emotions, Behavioural Disengagement and Mental Disengagement. CONCLUSION: Clinical staff should be aware that coping strategy use is associated with several demographic and disease characteristics. Targeted advice on coping may improve coping capacity and facilitate psychosocial adjustment.

Impact of Parental Mental Health and Poverty on the Health of the Next Generation: A Multi-Trajectory Analysis Using the UK Millennium Cohort Study.

PURPOSE: Exposure to parental mental ill-health and poverty in childhood impact health across the lifecourse. Both maternal and paternal mental health may be important influences, but few studies have unpicked the complex interrelationships between these exposures and family poverty for later health. METHODS: We used longitudinal data on 10,500 children from the nationally representative UK millennium cohort study. Trajectories of poverty, maternal mental health, and secondary caregiver mental health were constructed from child age of 9 months through to 14 years. We assessed the associations of these trajectories with mental health outcomes at the age of 17 years. Population-attributable fractions were calculated to quantify the contribution of caregivers' mental health problems and poverty to adverse outcomes at the country level. RESULTS: We identified five distinct trajectories. Compared with children with low poverty and good parental mental health, those who experienced poverty and poor primary or secondary caregiver mental health (53%) had worse outcomes. Children exposed to both persistent poverty and poor caregiver mental health were at markedly increased risk of socioemotional behavioural problems (aOR 4.2; 95% CI 2.7-6.7), mental health problems (aOR 2.5; CI 1.6-3.9), and cognitive disability (aOR 1.7; CI 1.1-2.5). We estimate that 40% of socioemotional behavioural problems at the age of 17 were attributable to persistent parental caregivers' mental health problems and poverty. DISCUSSION: More than half of children growing up in the UK are persistently exposed to either one or both of poor caregiver mental health and family poverty. The combination of these exposures is strongly associated with adverse health outcomes in the next generation.

Sharing decisions on reproductive goals: A mixed-methods study of the views of women who have cystic fibrosis.

BACKGROUND: There are complex medical, psychological, social and economic aspects to becoming a parent with Cystic Fibrosis (CF). A shared decision-making (SDM) approach could help women with CF make informed decisions about their reproductive goals that are sensitive to their individual values and preferences. This study investigated capability, opportunity, and motivation to participate in SDM from the perspective of women with CF. METHODS: Mixed-methods design. An international online survey was completed by 182 women with CF, to investigate participation in SDM in relation to reproductive goals, and measures of capability (information needs), opportunity (social environment) and motivation (SDM attitudes and self-efficacy) to engage in SDM. Twenty-one women were interviewed using a visual timelines method to explore their SDM experiences and preferences. Qualitative data were analysed thematically. RESULTS: Women with higher decision self-efficacy reported better experiences of SDM relating to their reproductive goals. Decision self-efficacy was positively associated with social support, age, and level of education, highlighting inequalities. Interviews indicated that women were highly motivated to engage in SDM, but their capability was compromised by lack of information, perception of insufficient opportunities for focused discussions about SDM. CONCLUSIONS: Women with CF are keen to engage in SDM about reproductive health, but currently lack sufficient information and support to do so. Interventions at patient, clinician and system levels are needed to support capability, opportunity and motivation to engage equitably in SDM in relation to their reproductive goals.

Computational modeling of single-cell migration: the leading role of extracellular matrix fibers.

Cell migration is vitally important in a wide variety of biological contexts ranging from embryonic development and wound healing to malignant diseases such as cancer. It is a very complex process that is controlled by intracellular signaling pathways as well as the cell's microenvironment. Due to its importance and complexity, it has been studied for many years in the biomedical sciences, and in the last 30 years it also received an increasing amount of interest from theoretical scientists and mathematical modelers. Here we propose a force-based, individual-based modeling framework that links single-cell migration with matrix fibers and cell-matrix interactions through contact guidance and matrix remodelling. With this approach, we can highlight the effect of the cell's environment on its migration. We investigate the influence of matrix stiffness, matrix architecture, and cell speed on migration using quantitative measures that allow us to compare the results to experiments.

Educational achievements of children aged 10-11 years with cystic fibrosis. A data linkage study in Wales.

Introduction: As people with cystic fibrosis (CF) lead longer, healthier lives, educational qualifications and employment prospects are increasingly important. However, little is known about the social consequences of CF, in particular, any impact on educational achievements and the support children with CF receive in schools. Objectives: To assess the educational achievements of children with CF in Wales compared to the general Welsh population, and the additional learning support children with CF receive in schools. Methods: We conducted a population-scale data linkage study of all children born in Wales using the Secure Anonymised Information Linkage (SAIL) Databank. We used anonymised individual-level population-scale health and administrative data sources to identify children with CF born between 2000 - 2015, linked to educational attainment records. We calculated the percentage of children that reached expected levels in statutory assessment at age 10-11, Key Stage 2 (KS2), and compared this to educational outcomes in the general population. We also assessed the percentage of children with CF that received extra learning support. Results: Out of 150 eligible children, 119 had KS2 results. 77% (95% CI: 69%-84%) of children achieved expected levels in English, 81% (95% CI: 73% -87%) in Mathematics and 82% (95% CI: 75% - 88%) in Science. In the comparable general Welsh population, 83.4% to 91.1% achieved the expected level in English, 84.9% to 91.6% in Maths, and 87.1% to 92.2% in Science across the years of the study. 70% of children with CF received extra learning support. Conclusions: Children with CF in Wales may have worse educational achievements than the general population. More research is needed to inform policies and interventions to better support children with CF to reach their full educational potential and employment opportunities.

Child poverty and children entering care in England, 2015-20: a longitudinal ecological study at the local area level.

BACKGROUND: Children in care face adverse health outcomes throughout their life course compared with their peers. In England, over the past decade, the stark rise in the number of cared-for children has coincided with rising child poverty, a key risk factor for children entering care. We aimed to assess the contribution of recent trends in child poverty to trends in care entry. METHODS: In this longitudinal, ecological study of 147 local authorities in England, we linked data from the Department for Work and Pensions and HM Revenue & Customs on the proportion of children younger than 16 years living in families with income less than 60% of the contemporary national median income, before housing costs, with Department for Education data on rates of children younger than 16 years entering care. Using within-between regression models, and controlling for employment trends, we estimated the association of changing child poverty rates with changing care entry rates within different areas. Our primary outcome was the annual rate of children younger than 16 years starting to be looked after by local authorities in England. FINDINGS: Between 2015 and 2020, controlling for employment rates, a 1 percentage point increase in child poverty was associated with an additional five children entering care per 100 000 children (95% CI 2-8). We estimate that, over the study period, 8·1% of the total number of children under the age of 16 entering care (5·0-11·3) were linked to rising child poverty, equivalent to 10 351 (6447-14 567) additional children. INTERPRETATION: We report evidence that rising child poverty rates might be contributing to an increase in children entering care. Children's exposure to poverty creates and compounds adversity, driving poor health and social outcomes in later life. National anti-poverty policies are key to tackling adverse trends in children's care entry in England. FUNDING: National Institute for Health Research (NIHR) School for Public Health Research, NIHR Public Health Policy Research Unit, Swedish Research Council, Wellcome Trust, Medical Research Council, and NIHR Applied Research Collaboration North West Coast.

Impact of poverty and family adversity on adolescent health: a multi-trajectory analysis using the UK Millennium Cohort Study.

BACKGROUND: Children exposed to poverty and family adversities including domestic violence, parental mental ill health and parental alcohol misuse may experience poor outcomes across the life course. However, the complex interrelationships between these exposures in childhood are unclear. We therefore assessed the clustering of trajectories of household poverty and family adversities and their impacts on adolescent health outcomes. METHODS: We used longitudinal data from the UK Millennium Cohort study on 11564 children followed to age 14 years. Family adversities included parent reported domestic violence and abuse, poor mental health and frequent alcohol use. We used a group-based multi-trajectory cluster model to identify trajectories of poverty and family adversity for children. We assessed associations of these trajectories with child physical, mental and behavioural outcomes at age 14 years using multivariable logistic regression, adjusting for confounders. FINDINGS: Six trajectories were identified: low poverty and family adversity (43·2%), persistent parental alcohol use (7·7%), persistent domestic violence and abuse (3·4%), persistent poor parental mental health (11·9%), persistent poverty (22·6%) and persistent poverty and poor parental mental health (11·1%). Compared with children exposed to low poverty and adversity, children in the persistent adversity trajectory groups experienced worse outcomes; those exposed to persistent poor parental mental health and poverty were particularly at increased risk of socioemotional behavioural problems (adjusted odds ratio 6·4; 95% CI 5·0 - 8·3), cognitive disability (aOR 2·1; CI 1·5 - 2·8), drug experimentation (aOR 2·8; CI 1·8 - 4·2) and obesity (aOR 1·8; CI 1·3 - 2·5). INTERPRETATION: In a contemporary UK cohort, persistent poverty and/or persistent poor parental mental health affects over four in ten children. The combination of both affects one in ten children and is strongly associated with adverse child outcomes, particularly poor child mental health. FUNDING: The National Institute for Health Research (NIHR) Policy Research Programme, NIHR Applied Research Collaboration South London (ARC South London) at King's College Hospital NHS Foundation Trust and the Medical Research Council (MRC).

A comparison of characteristics, developmental disorders and motor progression between children with and without developmental coordination disorder.

BACKGROUND AND AIM: Children with Developmental Coordination Disorder (DCD) have difficulty in the development of motor coordination and with learning new motor skills. Studies demonstrate that children with DCD differ in terms of the nature and severity of their motor difficulties, the incidence of co occurring conditions and family background. However, little is known whether these profiles may relate to motor progression over time. The aim of this study was to describe the profiles of children with and without DCD and track motor progression over time. METHOD: The characteristics of thirty-four 7-14 year old children (M = 10.07, 85.3% boys) with and without DCD were compared and their motor progression monitored over a two academic years. DCD was identified using DSM5 criteria. The Movement Assessment Battery for Children-2 (MABC-2) was used to classify children as TD (≥25th percentile), having moderate motor coordination difficulties (6-16th percentile) or severe motor coordination difficulties (≤ 5th percentile). The Kaufman Brief Intelligence Test - 2 (KBIT-2) was used to measure full scale IQ. Parent questionnaires were used to gather information on socio economic status and co occurrence of other developmental disorders. We used ANOVA to assess whether there were differences in characteristics between the TD children, children with severe motor coordination difficulties and children with moderate motor coordination difficulties. Linear mixed effect modelling was used to estimate any change in motor performance over time and whether this differed between the three groups of children. RESULTS: Children with severe motor coordination difficulties had distinct profiles in motor and non-motor domains, lower IQ and a greater likelihood of having associated characteristics of 2 or more developmental disorders. We found significant differences between the poor motor performance of the severe group compared to the other two groups. Longitudinal analyses revealed stable, persistent and lower motor competence for the severe group. The rate of change in motor proficiency for the typical and severe groups was similar. However, the group with moderate motor difficulties gained on average more points per week compared to the typical group and achieved motor scores in the typically developing range over time. CONCLUSIONS: This is one of the first studies to compare the characteristics and rate of motor progression of children with and without DCD using different motor proficiency cut off scores. The children with severe motor coordination difficulties progressed at the same rate as typically developing peers but remained in the severe group over time, whereas the children with moderate motor coordination difficulties caught up to TDC. The results indicate that different intervention may be required according to the nature and severity of the characteristics in both the motor and non-motor domains of children with DCD.

Trends in inequalities in Children Looked After in England between 2004 and 2019: a local area ecological analysis.

OBJECTIVE: To assess trends in inequalities in Children Looked After (CLA) in England between 2004 and 2019, after controlling for unemployment, a marker of recession and risk factor for child maltreatment. DESIGN: Longitudinal local area ecological analysis. SETTING: 150 English upper-tier local authorities. PARTICIPANTS: Children under the age of 18 years. PRIMARY OUTCOME MEASURE: The annual age-standardised rate of children starting to be looked after (CLA rate) across English local authorities, grouped into quintiles based on their level of income deprivation. Slope indices of inequality were estimated using longitudinal segmented mixed-effects models, controlling for unemployment. RESULTS: Since 2008, there has been a precipitous rise in CLA rates and a marked widening of inequalities. Unemployment was associated with rising CLA rates: for each percentage point increase in unemployment rate, an estimated additional 9 children per 100 000 per year (95% CI 6 to 11) became looked after the following year. However, inequalities increased independently of the effect of unemployment. Between 2007 and 2019, after controlling for unemployment, the gap between the most and least deprived areas increased by 15 children per 100 000 per year (95% CI 4 to 26) relative to the 2004-2006 trend. CONCLUSIONS: The dramatic increase in the rate of children starting to be looked after has been greater in poorer areas and in areas more deeply affected by recession. But trends in unemployment do not explain the decade-long rise in inequalities, suggesting that other socioeconomic factors, including rising child poverty and reduced spending on children's services, may be fuelling inequalities. Policies to safely reduce the CLA rate should urgently address the social determinants of child health and well-being.

Understanding pathways to inequalities in child mental health: a counterfactual mediation analysis in two national birth cohorts in the UK and Denmark.

OBJECTIVES: We assessed social inequalities in child mental health problems (MHPs) and how they are mediated by perinatal factors, childhood illness and maternal mental health in two national birth cohorts. DESIGN: Longitudinal cohort study SETTING: We used data from the UK Millennium Cohort Study and the Danish National Birth Cohort. PRIMARY AND SECONDARY OUTCOME MEASURES: We applied causal mediation analysis to longitudinal cohort data. Socioeconomic conditions (SECs) at birth were measured by maternal education. Our outcome was child MHPs measured by the Strength and Difficulty Questionnaire at age 11. We estimated natural direct, indirect and total effects (TEs) of SECs on MHPs. We calculated the proportion mediated (PM) via three blocks of mediators-perinatal factors (smoking/alcohol use during pregnancy, birth weight and gestational age), childhood illness and maternal mental health. RESULTS: At age 11 years, 9% of children in the UK and 3.8% in Denmark had MHPs. Compared with high SECs, children in low SECs had a higher risk of MHPs (relative risk (RR)=4.3, 95% CI 3.3 to 5.5 in the UK, n=13 112; and RR=6.2, 95% CI 4.9 to 7.8 in Denmark, n=35 764). In the UK, perinatal factors mediated 10.2% (95% CI 4.5 to 15.9) of the TE, and adding maternal mental health tripled the PM to 32.2% (95% CI 25.4 to 39.1). In Denmark, perinatal factors mediated 16.5% (95% CI 11.9 to 21.1) of the TE, and including maternal mental health increased the PM to 16.9% (95% CI 11.2 to 22.6). Adding childhood illness made little difference in either country. CONCLUSION: Social inequalities in child mental health are partially explained by perinatal factors in the UK and Denmark. Maternal mental health partially explained inequalities in the UK but not in Denmark.

Seasonal fluctuation of lung function in cystic fibrosis: A national register-based study in two northern European populations.

BACKGROUND: Many risk factors for lung disease in cystic fibrosis (CF) display a seasonal pattern yet it is unclear whether this is reflected in seasonal fluctuations in lung function. METHODS: We conducted a longitudinal study using CF registries in Denmark and the UK. 471 individuals with a median of 104 FEV1 measurements per person and 7586 individuals with a median of nine FEV1 measures per person were included from Denmark and the UK respectively. We estimated the effect of seasonality on percent predicted FEV1 trajectories using mixed effects models whilst adjusting for clinically important covariates. RESULTS: We found no significant cyclical seasonal variation in lung function in either country. The maximum variation in percent predicted FEV1 around the yearly average was estimated to be 0.1 percentage points (95%CI 0 to 0.21) and 0.14 percentage points (95%CI 0 to 0.29) in Denmark and the UK, respectively. When considering possible step-like changes between the four seasons, we found that lung function was higher in spring compared to winter in the UK (0.34 percentage points, 95%CI 0.1 to 0.59) though the difference was not of clinical significance. CONCLUSION: In both the UK and Denmark there may be small seasonal changes in lung function but this effect is not of clinical importance.

Use of acoustic emission to identify novel candidate biomarkers for knee osteoarthritis (OA).

Our objective was to determine the efficacy and feasibility of a new approach for identifying candidate biomarkers for knee osteoarthritis (OA), based on selecting promising candidates from a range of high-frequency acoustic emission (AE) measurements generated during weight-bearing knee movement. Candidate AE biomarkers identified by this approach could then be validated in larger studies for use in future clinical trials and stratified medicine applications for this common health condition. A population cohort of participants with knee pain and a Kellgren-Lawrence (KL) score between 1-4 were recruited from local NHS primary and secondary care sites. Focusing on participants' self-identified worse knee, and using our established movement protocol, sources of variation in AE measurement and associations of AE markers with other markers were explored. Using this approach we identified 4 initial candidate AE biomarkers, of which "number of hits" showed the best reproducibility, in terms of within-session, day to day, week to week, between-practitioner, and between-machine variation, at 2 different machine upper frequency settings. "Number of hits" was higher in knees with KL scores of 2 than in KL1, and also showed significant associations with pain in the contralateral knee, and with body weight. "Hits" occurred predominantly in 2 of 4 defined movement quadrants. The protocol was feasible and acceptable to all participants and professionals involved. This study demonstrates how AE measurement during simple sit-stand-sit movements can be used to generate novel candidate knee OA biomarkers. AE measurements probably reflect a composite of structural changes and joint loading factors. Refinement of the method and increasing understanding of factors contributing to AE will enable this approach to be used to generate further candidate biomarkers for validation and potential use in clinical trials.