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Background: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. Methods: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. Results: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. Conclusion: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

RATIONALE: The identification of novel molecules associated with asthma may provide insights into mechanisms of disease and their potential clinical implications.OBJECTIVES: To conduct a screening of circulating proteins in childhood asthma and to study proteins emerged from human studies in a mouse model of asthma.METHODS: We included 2,264 children from eight birth cohorts from the MeDALL project and the Tucson TCRS Study. In cross-sectional analyses, we tested 46 circulating proteins for association with asthma in the selection stage and carried significant signals forward to a validation and replication stage. As creatine kinase (CK) was the only protein consistently associated with asthma, we also compared whole blood CK gene expression between subjects with and without asthma (n=249) and used a house dust mite (HDM) challenged mouse model to gain insights into CK lung expression and its role in resolution of asthma phenotypes.MEASUREMENTS AND MAIN RESULTS: As compared with the lowest CK tertile, children in the highest tertile had significantly lower odds for asthma in selection (adjOR: 0.31, 0.15-0.65; p=0.002), validation (0.63, 0.42-0.95; p=0.03), and replication (0.40, 0.16-0.97; p = 0.04) stages. Both cytosolic CK forms (CKM, CKB) were under-expressed in blood from asthmatics compared to controls (p=0.01 and 0.006, respectively). In the lungs of HDM-challenged mice, Ckb expression was reduced and, following HDM challenge, a CKB inhibitor blocked the resolution of airway hyperresponsiveness (AHR) and reduction of airway mucin.CONCLUSIONS: Circulating levels and gene expression of CK are inversely associated with childhood asthma. Mouse models support a possible direct involvement of CK in asthma protection via inhibition of AHR and reduction of airway mucin.

Environmental exposures are associated with children's health. Schools are often urban exposure 'hotspots' for pollution, noise, lack of green space and un-walkable built environments. The aim of this systematic review was to explore the impact of school-based interventions on the modification of indoor and outdoor stressors related to the built and natural environment on children's exposure and health. A systematic review of seven databases was performed. We included quantitative studies on children aged 5-12, which reported intervention delivered within school settings aimed at addressing key environmental exposures including air pollution, green spaces, traffic noise or active travel; and reported physical and mental health, physical activity or active travel behavior. The quality of studies was assessed and interventions were described using a standardized framework. A narrative synthesis approach was used to describe the findings. Thirty-nine papers were included on three main intervention types: improve indoor air quality by the increase of ventilation rates in classrooms; increase children's green time or greening schools, and multicomponent interventions to increase active travel to school by changes in pedestrian facilities. No eligible intervention to reduce traffic noise at school was found. Increasing ventilation rates improved short-term indoor air quality in classrooms, but the effect on cognitive performance was inconsistent. Greening schools and increasing children's green time have consistent positive effects on cognition and physical activity, but not in behavior. Multi-component interventions can increase walking and cycling after three years. Overall, the studies were rated as having poor quality owing to weak study designs. We found modest evidence that school-based built and natural environment interventions can improve children's exposure and health. This work was funded by the European Union’s Horizon 2020 research and innovation programme ATHLETE project (grant agreement 874583). This work was supported by the European Union’s Horizon 2020 research and innovation programme LifeCycle project (Grant Agreement No. 733206) and AF is supported by MCIN/AEI/10.13039/501100011033 and by European Union “NextGenerationEU/PRTR” (PCI2021-122047-2B). RM is supported by the National Institute for Health and Care Research (NIHR) applied research collaboration for Yorkshire and Humber (NIHR200166) and by the UK Prevention Research Partnership (MR/S037527/1). The authors are grateful to Iolanda Molina from ISGlobal, Maria Parras Aznar who is the librarian at Biblioteca/CRAI Universitat Pompeu Fabra, for their support of the search strategy.

Background Poor air quality is the one of the biggest causes of early death and illness across the lifespan. In the UK, 28 local authorities with illegal pollution levels have been mandated by the Government to develop plans to rapidly reduce pollution to legal limits. These plans include consideration of implementing one of four of charging 'Clean Air Zone’ (CAZ) classes in areas of high pollution which would charge older polluting vehicles a daily charge to enter. While this offers a potential to improve air quality, the extent to which CAZ might impact (for example, economically) on socio-economically deprived groups and local businesses is unclear. Aims To explore the acceptability and perceived unintended consequences of a CAZ and other initiatives to improve air quality with seldom-heard communities living in deprived, multi-ethnic areas within the city of Bradford, UK. Methods Ten semi-structured focus groups were conducted with people who live in areas of high pollution and deprivation. A total of 87 people participated from a diverse range of ethnic backgrounds with the majority of Pakistani origin. Recorded data were transcribed, coded and analysed using thematic analysis. Findings As poor air quality was not always visible it was seen as a hidden issue by many, and not prioritised over other more visible environmental issues (e.g. fly-tipping, littering). There was resistance to proposals which included charging private vehicles. Many felt that low-income families did not have the resources to purchase compliant vehicles or pay daily charges, placing a disproportionate burden on them. It was also felt that low-income taxi drivers would be disproportionately affected financially by proposals. Public transport infrastructure was felt to be inadequate. Other traffic management or emission reduction activities were also explored. Views towards these initiatives were more positive if they did not directly affect individuals financially. Conclusion Air quality initiatives such as CAZs were felt to be likely to financially disadvantage communities already living in socio-economic and environmental poverty. Policy makers need to carefully consider appropriate mitigation strategies to ensure that health and economic inequalities are not increased by implementation of CAZ. Given air quality is low priority for some groups, careful engagement and communication will be required to increase acceptance interventions such as CAZs.

Validated physical activity (PA) questionnaires are crucial for collecting information in large epidemiological studies during childhood. Thus, this study analyzed the validity of a parent-reported PA questionnaire based on the Children's Leisure Activities Study Survey by accelerometry in European children aged from 6 to 12 years old. We used data from 230 children of the Human Early-Life Exposome and Infancia y Medio Ambiente projects. Mean differences between moderate-to-vigorous PA (MVPA) reported by the questionnaire and the accelerometer were calculated (min/day), and its associated factors were explored by multiple robust linear regression. The agreement between methods was examined using a Bland-Altman plot. The concurrent validity of assessing MVPA was analyzed by cohort-adjusted Spearman's partial correlations. ROC curve analysis was also used to explore the questionnaire's capability to identify active children based on the World Health Organization guidelines. A moderate correlation was found between parent-reported and accelerometer MVPA (rho = 0.41, p < 0.001). The child's sex (girl) was statistically associated with the mean MVPA difference between methods. However, this questionnaire accurately identified physically active children (area under the curve = 83.8% and 82.7% for boys and girls, cut-points = 68.6 and 45.4 min/day in MVPA, respectively). Consequently, this questionnaire is suitable for classifying active children in order to monitor public health interventions regarding PA. This study was supported by funding from the European Community’s Seventh Framework Programme [FP7/2007–2013] under grant agreement no. 308333—the HELIX project. INMA data collections were supported by grants from the Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds; PI15/00118 incl. FEDER funds; CP16/00128 incl. FEDER funds; PI16/00118 incl. FEDER funds; PI16/00261 incl. FEDER funds; PI17/01340 incl. FEDER funds; PI18/00547 incl. FEDER funds, PI18/01237 incl. FEDER funds, PI18/00825 incl. FEDER funds); Generalitat Valenciana (GVA/2021/191); CIBERESP; and the Generalitat de Catalunya-CIRIT 1999SGR 00241; Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació La marató de TV3 (090430). ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program, Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (1262C0010; EST-2016 RF-21), EU Commission (261357, 308333, 603794 and 634453); and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). M.C. and M.G. hold Miguel Servet fellowships (CP16/00128, CPII18/00018) funded by Instituto de Salud Carlos III and co-funded by European Social Fund “Investing in your future”. R.R.C.M. received funding from the National Institute for Health Research Applied Research Collaboration for Yorkshire and Humber.

ImportanceHigher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, which of these associations are causal remains unclear.ObjectiveTo explore the relation of maternal pre-pregnancy BMI with pregnancy and perinatal outcomes by integrating evidence from three different methods (i.e. multivariable regression, Mendelian randomization, and paternal negative control analyses).DesignTriangulation of multivariable regression, Mendelian randomization and paternal negative control results from up to 14 studies in the MR-PREG collaboration.SettingEurope and North America.ParticipantsUp to 497,932 women of European ancestry.ExposureMaternal pre- or early-pregnancy BMI based on self-reported or measured weight and height.Main outcomes and MeasuresMiscarriage, stillbirth, hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, maternal anaemia, perinatal depression, pre-labour rupture of membranes, induction of labour, caesarean section, preterm birth, small- and large-for-gestational age, low and high birthweight, low Apgar score at 1 and 5 minutes, neonatal intensive care unit admission, and no initiation of breastfeeding.ResultsMultivariable regression, Mendelian randomization and paternal negative control analyses supported an association of higher maternal BMI with lower risk of small-for-gestational age and higher risk of hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, large-for-gestational age, and high birthweight. As an example, higher maternal BMI was associated with higher risk of gestational hypertension in multivariable regression (OR: 1.67; 95% CI: 1.64, 1.71 per standard unit in BMI) and Mendelian randomization (OR: 1.58; 95% CI: 1.29, 1.93), which was not seen for paternal BMI (OR: 1.02; 95% CI: 0.99, 1.05). Findings did not support a relation between maternal BMI and perinatal depression. For other outcomes, evidence was inconclusive due to inconsistencies across the applied approaches or substantial imprecision in effect estimates from Mendelian randomization.Conclusions and RelevanceOur findings support a causal role for maternal pre-/early-pregnancy BMI on a range of adverse pregnancy and perinatal outcomes. Pre-conception interventions to support women maintaining a healthy BMI may reduce the burden of obstetric and neonatal complications.KEY POINTSQuestionWhat is the effect of higher maternal pre-/early-pregnancy body mass index (BMI) on adverse pregnancy and perinatal outcomes?FindingsWe found consistent evidence that higher maternal BMI was related to higher risk of gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, and having a large-for-gestational-age baby, lower risk of having a small-for-gestational-age baby, and not related to perinatal depression.MeaningThese findings highlight the importance of supporting women to achieve/maintain a healthy pre-conception BMI to reduce the burden of obstetric and neonatal complications.

Background It is reported that the longer-term outcomes for stroke survivors are poor, with a range of unmet needs identified. Objectives The aims were to develop and test a longer-term stroke care strategy focused on improving the quality of life of stroke survivors and their carers by addressing unmet needs, and maintenance and enhancement of participation (i.e. involvement in life situations). Design Five overlapping workstreams were undertaken – (1) refinement of content by semistructured interviews with stroke survivors and their carers and by a review of the literature to inform content and delivery of the care strategy; (2) exploration of service models by national survey and focus groups with purposely selected services; (3) intervention development by interaction with a reference group of stroke survivors, carers, and health and social care professionals; (4) refinement and pilot implementation of the developed intervention in three stroke services (case studies); and (5) a cluster randomised controlled feasibility trial in 10 stroke services across England and Wales. Setting The intervention development work and feasibility trial were in stroke services (inclusive of primary, secondary, community and social care provision) across England and Wales. Participants Participants were stroke survivors resident in the community and their carers, and health and social care professionals in the included stroke services. Data sources Interviews with 28 stroke survivors and their carers at least 9 months post stroke ascertained their needs and the barriers to and facilitators of addressing those needs. Additional literature reviews identified 23 needs. No evidence-based interventions to address these needs were reported; self-management was highlighted as a possible delivery mechanism. In workstream 2, a national survey revealed that the most common model of stroke service provision was care up to 12 months post stroke, reported by 46 (40%) services. Thirty-five (30%) services provided care up to 6 months post stroke and 35 (30%) provided care beyond 12 months, thus identifying 6 months post stroke as an appropriate delivery point for a new intervention. Through focus groups in a range of services, stroke survivors’ perceived unmet needs and the barriers to and enablers of service provision were identified. Intervention Using information obtained in workstreams 1 and 2 and working closely with a stakeholder reference group, we developed an intervention based on the unmet needs prioritised by stroke survivors and their carers (workstream 3). In workstream 4, action groups (clinicians, stroke survivors and researchers) were established in three stroke services that led implementation in their service and contributed to the iterative refinement of the intervention, associated training programme and implementation materials. The intervention (called New Start) was delivered at 6 months post stroke. Key components were problem-solving self-management with survivors and carers, help with obtaining usable information, and helping survivors and their carers build sustainable, flexible support networks. Results A cluster randomised feasibility trial (workstream 5) was successfully implemented in 10 stroke services across England and Wales, with associated process and health economic evaluations. Five services were randomised to provide New Start, while five continued with usual care; 269 participants were recruited. Progression criteria – in terms of our pre-determined (red, amber, green) criteria for progress to a full trial: target stroke survivor recruitment rates were achieved, on average, across sites (24.1 per site over 6 months, green); 216 (80.3%) registered stroke survivors returned follow-up questionnaires at 9 months (84.1% in the intervention arm and 75.8% in the usual care arm, green); according to data reported by sites, overall, 95.2% of registered stroke survivors were offered at least one session of the intervention (green); all five intervention sites had at least two facilitators deemed competent, delivered the New Start intervention and provided it to stroke survivors (green). However, at some sites, there were concerns regarding the number of stroke survivors being offered, accepting and receiving the intervention. Only small differences in outcomes and costs were observed between the New Start and usual care groups, and considerable uncertainty around the cost-effectiveness remains. Conclusions We report a complex programme of work that has described the longer-term needs of stroke survivors and highlighted evidence and service gaps. Working closely with stroke survivors, an intervention was developed that has been refined in three services and feasibility tested in a cluster randomised controlled trial. Further refinement of the target population and optimisation of the intervention materials is required prior to a full randomised controlled trial evaluation. Future work Optimisation of the intervention, and clearer specification of recipients, are required prior to a full trial evaluation. Trial registration Current Controlled Trials ISRCTN38920246. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 3. See the NIHR Journals Library website for further project information.

Objectives Parental supervised toothbrushing (PSB) is a collection of behaviours recommended by national guidance to improve oral health. This systematic review aimed to identify the barriers and facilitators to PSB. Materials and methods Studies investigating parental involvement in home-based toothbrushing in children under 8 years old and the impact on tooth decay were included. Electronic databases, references and unpublished literature databases were searched. The Theoretical Domains Framework (TDF) was used to code barriers/facilitators to PSB. Results Of the 10,176 articles retrieved, 68 articles were included. Barriers and facilitators were found across all 12 TDF domains. Barriers included an inadequate toothbrushing environment and resources, knowledge of what PSB entails and child behaviour management. Facilitators were increased oral health knowledge, the adaption of the social environment to facilitate PSB and positive attitudes towards oral health. When only high-quality articles were synthesized, knowledge was not a common barrier/facilitator. Conclusions There are a comprehensive range of barriers/facilitators to PSB acting across all domains and at multiple levels of influence. This review identifies the most popular domains, thus informing the focus for supporting resources to supplement oral health conversations. Clinical relevance PSB is a complex behaviour. Practitioners need to understand and be able to explore the wide range of potential barriers and have practical suggestions to enable PSB. This review provides pragmatic examples of different barriers and facilitators and emphasises the importance of listening to parents and exploring their story to identify the barriers and solutions that are relevant to each family.

Environmental exposures (EE) are increasingly recognised as important determinants of health and well-being. Understanding the influences of EE on health is critical for effective policymaking, but better-quality spatial data is needed. This article outlines the theoretical and technical foundations used for the construction of individual-level environmental exposure measurements for the population of a northern English city, Bradford. The work supports ‘Connected Bradford’, an entire population database linking health, education, social care, environmental and other local government data over a period of forty years. We argue that our current understanding of environmental effects on health outcomes is limited both by methodological shortcomings in the quantification of the environment and by a lack of consistency in the measurement of built environment features. To address these shortcomings, we measure the environmental exposure for a series of different domains including air quality, greenspace and greenness, public transport, walkability, traffic, buildings and the built form, street centrality, land-use intensity, and food environments as well as indoor dwelling qualities. We utilise general practitioners’ historical patient information to identify the precise geolocation and duration of a person’s residence. We model a person’s local neighbourhood, and the probable routes to key urban functions aggregated across the city. We outline the specific geospatial procedure used to quantify the environmental exposure for each domain and use the example of exposure to fast-food outlets to illustrate the methodological challenges in the creation of city and nationwide environmental exposure databases. The proposed EE measures will enable critical research into the relationship and causal links between the built environment and health, informing planning and policy-making.

Although the built environment (BE) is important for children’s health, there is little consensus about which features are most important due to differences in measurement and outcomes across disciplines. This meta-narrative review was undertaken by a multi-disciplinary team of researchers to summarise ways in which the BE is measured, and how this links to children’s health. A structured search of four databases across the relevant disciplines retrieved 108 relevant references. The most commonly addressed health-related outcomes were active travel, physical activity and play, and obesity. Many studies used objective (GIS and street audits) or standardised subjective (perceived) measurements of the BE. However, there was a wide variety, and sometimes inconsistency, in their definition and use. There were clear associations between the BE and children’s health. Objective physical activity and self-reported active travel, or obesity, were positively associated with higher street connectivity or walkability measures, while self-reported physical activity and play had the strongest association with reduced street connectivity, indicated by quieter, one-way streets. Despite the high heterogeneity found in BE measures and health outcomes, the meta-narrative approach enabled us to identify ten BE categories that are likely to support children’s health and be protective against some non-communicable disease risk factors. Future research should implement consistent BE measures to ensure key features are explored. A systems approach will be particularly relevant for addressing place-based health inequalities, given potential unintended health consequences of making changes to the BE.

Mental health problems are associated with lower quality of life, increased unscheduled care, high economic and social cost, and increased mortality. Nature-based interventions (NBIs) that support people to engage with nature in a structured way are asset-based solutions to improve mental health for community based adults. However, it is unclear which NBIs are most effective, or what format and dose is most efficacious. We systematically reviewed the controlled and uncontrolled evidence for outdoor NBIs. The protocol was registered at PROSPERO (CRD42020163103). Studies that included adults (aged ≥18 years) in community-based settings with or without mental and/or physical health problems were eligible for inclusion. Eligible interventions were structured outdoor activities in green and/or blue space for health and wellbeing. We searched ASSIA, CENTRAL, Embase, Greenfile, MEDLINE, PsycINFO, and Web of Science in October 2019; the search was updated in September 2020. We screened 14,321 records and included 50 studies. Sixteen studies were randomised controlled trials (RCTs); 18 were controlled studies; and 16 were uncontrolled before and after studies. Risk of bias for RCTs was low to moderate; and moderate to high for controlled and uncontrolled studies. Random effects meta-analysis of RCTs showed that NBIs were effective for improving depressive mood −0.64 (95% CI: 1.05 to −0.23), reducing anxiety −0.94 (95% CI: 0.94 to −0.01), improving positive affect 0.95 (95% CI: 0.59 to 1.31), and reducing negative affect −0.52 (95% CI: 0.77 to −0.26). Results from controlled and uncontrolled studies largely reflected findings from RCTs. There was less evidence that NBIs improved physical health. The most effective interventions were offered for between 8 and 12 weeks, and the optimal dose ranged from 20 to 90 min. NBIs, specifically gardening, green exercise and nature-based therapy, are effective for improving mental health outcomes in adults, including those with pre-existing mental health problems.

Urinary metabolic profiling is a promising powerful tool to reflect dietary intake and can help understand metabolic alterations in response to diet quality. Here, we used 1H-NMR spectroscopy in a multi-country study in European children (1147 children from 6 different cohorts) and identified a common panel of 4 urinary metabolites (hippurate, N-methylnicotinic acid, urea and sucrose) that was predictive of Mediterranean diet adherence (KIDMED) and ultra-processed food (UPF) consumption and also had higher capacity in discriminating children’s diet quality than that of established sociodemographic determinants. Further, we showed that the identified metabolite panel also reflected the associations of these diet quality indicators with C-peptide, a stable and accurate marker of insulin resistance and future risk of metabolic disease. This methodology enables objective assessment of dietary patterns in European child populations, complementary to traditional questionary methods, and can be used in future studies to evaluate diet quality. Moreover, this knowledge can provide mechanistic evidence of common biological pathways that characterize healthy and unhealthy dietary patterns, and diet-related molecular alterations that could associate to metabolic disease.

Background In England, the onset of COVID-19 and a rapidly increasing infection rate resulted in a lockdown (March-June 2020) which placed strict restrictions on movement of the public, including children. Using data collected from children living in a multi-ethnic city with high levels of deprivation, this study aimed to: (1) report children’s self-reported physical activity (PA) during the first COVID-19 UK lockdown and identify associated factors; (2) examine changes of children’s self-reported PA prior to and during the first UK lockdown. Methods This study is part of the Born in Bradford (BiB) COVID-19 Research Study. PA (amended Youth Activity Profile), sleep, sedentary behaviours, daily frequency/time/destination/activity when leaving the home, were self-reported by 949 children (9–13 years). A sub-sample (n = 634) also self-reported PA (Physical Activity Questionnaire for Children) pre-pandemic (2017-February 2020). Univariate analysis assessed differences in PA between sex and ethnicity groups; multivariable logistic regression identified factors associated with children’s PA. Differences in children's levels of being sufficiently active prior to and during the lockdown were examined using the McNemar test; and multivariable logistic regression was used to identify factors explaining change. Results During the pandemic, White British (WB) children were more sufficiently active (34.1%) compared to Pakistani Heritage children (PH) (22.8%) or ‘Other’ ethnicity children (O) (22.8%). WB children reported leaving the home more frequently and for longer periods than PH and O children. Modifiable variables related to being sufficiently active were frequency, duration, type of activity, and destination away from the home environment. There was a large reduction in children being sufficiently active during the first COVID-19 lockdown (28.9%) compared to pre-pandemic (69.4%). Conclusions Promoting safe extended periods of PA everyday outdoors is important for all children, in particular for children from ethnic minority groups. Children’s PA during the first COVID-19 UK lockdown has drastically reduced from before. Policy and decision makers, and practitioners should consider the findings in order to begin to understand the impact and consequences that COVID-19 has had upon children’s PA which is a key and vital behaviour for health and development.

Background Understanding the effect of occupational exposure to endocrine disrupting chemicals (EDC) during pregnancy on inadequate fetal growth as measured by small-for-gestational age (SGA) and as measured by percentage of optimal birth weight (POBW) is not well understood. Methods We studied 4142 pregnant women who were in paid employment during pregnancy and participated in a population-based, prospective 2007–2011 birth cohort study, the Born in Bradford Study, with an estimated participation of 80%. Job titles were coded at 26–28 weeks' gestation at a 4-digit level according to 353 unit groups in the 2000 UK Standard Occupational Classification. They were then linked to expert judgment on exposure to each of ten EDC groups as assessed through a job exposure matrix. A modified Poisson regression was used to assess the risk of POBW and SGA associated with an increased risk of chemical exposures. Results The frequency of POBW Conclusion Maternal occupational exposure to estimated concentrations of pesticides and phthalates is associated with impaired fetal growth. Key messages The POBW is useful in measuring inadequate fetal growth in study of occupational chemical exposures.

This study aims to understand the experience and impact of the initial COVID-19 lockdown in young families with children aged below 4 years. Free text questions were administered to participants in the ORIGINS (Australia) and Born in Bradford (UK) cohort studies to collect qualitative information on worries, concerns and enjoyable experiences during the pandemic. A total of 903 (400 for ORIGINS and 503 for BiB) participants completed the two surveys during April 2020. Despite varying in geography, levels of socio-economic disadvantage and their situational context during the pandemic, respondents from both cohorts reported similar worries and challenges during the lockdown period, including: employment/finances, health anxiety, mental health and social isolation, caring for children and child development. Families across the globe experienced both positive and negative immediate impacts of COVID-19. Population-based data can be used to inform the development of support services, public health campaigns and universal interventions to assist families in future health crises.

BACKGROUND AND AIM: Mixtures analysis methods are increasingly being applied in environmental epidemiology, but current methods are often limited by either only providing a group effect or independ...

BACKGROUND AND AIM: Exposure to Endocrine Disrupting Chemicals (EDC) may increase liver injury, but few studies have examined these associations in children and most focused on a single chemical gr...

BACKGROUND AND AIM: Urban environmental exposures have been investigated separately in relation to growth and childhood obesity. In this study we aim to determine which prenatal and postnatal outdo...

The impact of long COVID is increasingly recognised, but risk factors are poorly characterised. We analysed questionnaire data on symptom duration from 10 longitudinal study (LS) samples and electronic healthcare records (EHR) to investigate sociodemographic and health risk factors associated with long COVID, as part of the UK National Core Study for Longitudinal Health and Wellbeing.MethodsAnalysis was conducted on 6,899 adults self-reporting COVID-19 from 45,096 participants of the UK LS, and on 3,327 cases assigned a long COVID code in primary care EHR out of 1,199,812 adults diagnosed with acute COVID-19. In LS, we derived two outcomes: symptoms lasting 4+ weeks and symptoms lasting 12+ weeks. Associations of potential risk factors (age, sex, ethnicity, socioeconomic factors, smoking, general and mental health, overweight/obesity, diabetes, hypertension, hypercholesterolaemia, and asthma) with these two outcomes were assessed, using logistic regression, with meta-analyses of findings presented alongside equivalent results from EHR analyses.ResultsFunctionally limiting long COVID for 12+ weeks affected between 1.2% (age 20), and 4.8% (age 63) of people reporting COVID-19 in LS. The proportion reporting symptoms overall for 12+ weeks ranged from 7.8 (mean age 28) to 17% (mean age 58) and for 4+ weeks 4.2% (age 20) to 33.1% (age 56). Age was associated with a linear increase in long COVID between age 20-70. Being female (LS: OR=1.49; 95%CI:1.24-1.79; EHR: OR=1.51 [1.41-1.61]), poor pre-pandemic mental health (LS: OR=1.46 [1.17-1.83]; EHR: OR=1.57 [1.47-1.68]) and poor general health (LS: OR=1.62 [1.25-2.09]; EHR: OR=1.26; [1.18-1.35]) were associated with higher risk of long COVID. Individuals with asthma also had higher risk (LS: OR=1.32 [1.07-1.62]; EHR: OR=1.56 [1.46-1.67]), as did those categorised as overweight or obese (LS: OR=1.25 [1.01-1.55]; EHR: OR=1.31 [1.21-1.42]) though associations for symptoms lasting 12+ weeks were less pronounced. Non-white ethnic minority groups had lower 4+ week symptom risk (LS: OR=0.32 [0.22-0.47]), a finding consistent in EHR. Associations were not observed for other risk factors. Few participants in the studies had been admitted to hospital (0.8-5.2%).ConclusionsLong COVID is clearly distributed differentially according to several sociodemographic and pre-existing health factors. Establishing which of these risk factors are causal and predisposing is necessary to further inform strategies for preventing and treating long COVID.

The human exposome affects child development and health later in life, but its personal external levels, variability, and correlations are largely unknown. We characterized the personal external exposome of pregnant women and children in eight European cities. Panel studies included 167 pregnant women and 183 children (aged 6-11 years). A personal exposure monitoring kit composed of smartphone, accelerometer, ultraviolet (UV) dosimeter, and two air pollution monitors were used to monitor physical activity (PA), fine particulate matter (PM2.5), black carbon, traffic-related noise, UV-B radiation, and natural outdoor environments (NOE). 77% of women performed the adult recommendation of >= 150 min/week of moderate to vigorous PA (MVPA), while only 3% of children achieved the childhood recommendation of >= 60 min/day MVPA. 11% of women and 17% of children were exposed to daily PM2.5 levels higher than recommended >= 25 mu g/m(3)). Mean exposure to noise ranged from Lden 51.1 dB in Kaunas to Lden 65.2 dB in Barcelona. 4% of women and 23% of children exceeded the recommended maximum of 2 Standard-Erythemal-Dose of UV-B at least once a week. 33% of women and 43% of children never reached the minimum NOE contact recommendation of >= 30 min/week. The variations in air and noise pollution exposure were dominated by between-city variability, while most of the variation observed for NOE contact and PA was between-participants. The correlations between all personal exposures ranged from very low to low (Rho

Objective: To investigate the impact of premature extraction of primary teeth (PEPT) on orthodontic treatment need in a cohort of children participating in the Born in Bradford (BiB) longitudinal birth cohort. Design: Observational, cross-sectional cohort. Participants: We aim to recruit 1000 children aged 7–11 years: 500 with a history of PEPT and 500 matched non-PEPT controls. Methods: After informed consent/assent, orthodontic records will be collected, including extra and intra-oral photographs and alginate impressions for study models. Participants will also complete a measure of oral health-related quality of life (COHIP-SF 19). The records will be used to quantify space loss, identify other occlusal anomalies and assess orthodontic treatment need using the Index of Orthodontic Treatment Need. For each outcome, summary statistics will be calculated and the data for children with and without PEPT compared. The records of the children identified to be in need of orthodontic treatment will be examined by an expert orthodontic panel to judge if this treatment should be undertaken at the time of the records or delayed until the early permanent dentition. Collecting robust records in the mixed dentition provides the clinical basis to link each stage of the causal chain and enable the impact of PEPT on orthodontic need to be characterised. This study is the first to provide the foundations for future longitudinal data collection allowing the long-term impact of PEPT to be studied.

Greenspace is important for physical and mental health. Low-income, multi-ethnic populations in deprived urban areas experience several barriers to using greenspace. This may exacerbate health inequalities. The current study explored structural and individual determinants of greenspace use amongst parents of young children in an urban, deprived, multi-cultural area situated in the North of England, UK. Semi-structured in-depth interviews and focus group discussions were conducted with 30 parents of children aged 0-3 between December 2016 and May 2017 from a range of ethnic groups. Thematic analyses were informed by the Human Health Habitat Map and the Theoretical Domains Framework. The results show that whilst all families recognised the benefits of greenspaces, use was bounded by a variety of structural, community, and individual determinants. Individual determinants preventing use included lack of knowledge about where to go, or how to get there and confidence in managing young children whilst outdoors. Fear of crime, antisocial behaviour and accidents were the overriding barriers to use, even in high quality spaces. Social and community influences both positively encouraged use (for example, positive social interactions, and practical support by others) and prevented use (antisocial or inappropriate behaviours experienced in greenspace). The built environment was a key barrier to use. Problems related to unsuitable or unsafe playgrounds, no gardens or safe areas for children's play, poor accessibility, and lack of toilets were identified. However, the value that parents and children placed on natural blue and green features was an enabler to use. Contextual influences included external time pressures, difficulties of transporting and caring for young children and poor weather. Multi-sectoral efforts are needed to tackle the uneven playing field experienced by multi-ethnic, urban, deprived communities. Initiatives to increase use should tackle structural quality issues, addressing fears about safety, whilst simultaneously encouraging communities to reclaim their local greenspaces.

Street-level built environment factors, for example, walking infrastructure, building density, availability of public transport, and proliferation of fast-food outlets can impact on health by influencing our ability to engage in healthy behaviour. Unhealthy environments are often clustered in deprived areas, thus interventions to improve the built environments may improve health and reduce inequalities. The aim of this review was to identify whether street-level built environment interventions can improve children’s health in high income countries. A secondary aim was to describe key built environment elements targeted in interventions and research gaps. A systematic review of published literature was conducted by a multi-disciplinary team. Ten intervention papers were included. Physical activity or play was the only health outcome assessed. Most interventions described temporary changes including closure of streets to traffic (N = 6), which were mainly located in deprived neighbourhoods, or the addition of technology to ‘gamify’ active travel to school (N = 2). Two studies reported permanent changes to street design. There was limited evidence that closing streets to traffic was associated with increases in activity or play and inconclusive evidence with changes to street design and using technology to gamify active travel. Our ability to draw conclusions was hampered by inadequate study designs. Description of interventions was poor. Rigorous evaluation of built environment interventions remains challenging. We recommend a multi-disciplinary approach to evaluation, explicit reporting of built environment indicators targeted in interventions and offer solutions to others working in this area.

Background: Lockdown measures implemented to contain the Covid-19 virus have increased health inequalities, with families from deprived and ethnically diverse backgrounds most likely to be adversely affected. This paper describes the experiences of families living in the multi-ethnic and deprived city of Bradford, England. Methods: A wave of survey data collection using a combination of email, text and phone with postal follow-up during the first Covid-19 UK lockdown (10th April to 30th June 2020) with parents participating in two longitudinal studies. Cross tabulations explored variation by ethnicity and financial insecurity. Text from open questions was analysed using thematic analysis. Results: Of 7,652 families invited, 2,144 (28%) participated. The results presented are based on the 2,043 (95%) mothers’ responses: 957 (47%) of whom were of Pakistani heritage, 715 (35%) White British and 356 (18%) other ethnicity 971 (46%) lived in the most deprived decile of material deprivation in England. and 738 (37%) were financially insecure. Many families lived in poor quality (N=574, 28%), overcrowded (N=364, 19%) housing. Food (N=396, 20%), employment (N=728, 37%) and housing (N=204, 10%) insecurities were common, particularly in those who were furloughed, self-employed not working or unemployed. Clinically important depression and anxiety were reported by 372 (19%) and 318 (16%) mothers. Ethnic minority and financially insecure families had a worse experience during the lockdown across all domains, with the exception of mental health which appeared worse in White British mothers. Open text responses corroborated these findings and highlighted high levels of anxiety and fear about Covid-19. Conclusions: There is a need for policy makers and commissioners to better support vulnerable families during and after the pandemic. Future work will use longitudinal data from before the pandemic, and from future surveys during the pandemic, to describe trajectories and the long-term consequences of the pandemic on vulnerable populations.

ObjectiveTo describe the prevalence of factors related to well-being among primary school children in a deprived multiethnic community in the UK.Design and participantsCross-sectional survey of 15 641 children aged 7–10 years in Born in Bradford’s Primary School Years study: whole-classroom samples in 89 Bradford primary schools between 2016 and 2019.Main outcome measuresPrevalence estimates by ethnicity (%, 95% CI) of single and multiple vulnerabilities in child well-being within and across four domains (Home, Family, Relationships; Material Resources; Friends and School; Subjective Well-being).ResultsOnly 10% of children had no vulnerabilities in any domain of well-being; 10% had one or more vulnerabilities in all four domains. The highest prevalence estimates were for being bullied some or all of the time (52.7%, 95% CI: 51.9% to 53.4%), keeping worries to oneself (31.2%, 95% CI: 30.5% to 31.9%), having no park near home (30.8%, 95% CI: 30.1% to 31.5%) and worrying all the time about how much money their family has (26.3%, 95% CI: 25.6% to 27%). Boys were consistently significantly more likely than girls to report all of the vulnerabilities in the Home, Family and Family Relationships domain, and the majority of indicators in the other domains, and in all domains except Friends and School, boys were significantly more likely to have at least one vulnerability. Girls were significantly more likely to report not having many friends (16.7%, 95% CI: 15.9% to 17.6% vs 12.5%, 95% CI: 11.8% to 13.2%), being bullied some or all of the time (55.8%, 95% CI: 54.7% to 56.9% vs 49.7%, 95% CI: 48.6% to 50.8%) and feeling left out all the time (12.1%, 95% CI: 11.4% to 12.8%) versus (10.3%, 95% CI: 9.7% to 11.0%). Variations in vulnerabilities by ethnicity were complex, with children in black, Asian and minority ethnic groups sometimes reporting more vulnerabilities and sometimes fewer than white British children. For example, compared with children of Pakistani heritage, white British children were more likely to say that their family never gets along well (6.3%, 95% CI: 5.6% to 7.1% vs 4.1%, 95% CI: 3.6% to 4.6%) and to have no access to the internet at home (22.3%, 95% CI: 21% to 23.6% vs 18%, 95% CI: 17% to 18.9%). Children with Pakistani heritage were more likely than white British children to say they had no park near their home where they can play with friends (32.7%, 95% CI: 31.6% to 33.9% vs 29.9%, 95% CI: 28.6% to 31.3%), to report not having three meals a day (17.9%, 95% CI: 16.9% to 18.8% vs 11.9%, 95% CI: 10.9% to 12.9%) and to worry all the time about how much money their families have (29.3%, 95% CI: 28.2% to 30.3%) vs (21.6%, 95% CI: 20.4% to 22.9%). Gypsy/Irish Traveller children were less likely than white British children to say they were bullied some or all of the time (42.2%, 95% CI: 35.4% to 49.4% vs 53.8%, 95% CI: 52.3% to 55.3%), but more likely to say they were mean to others all the time (9.9%, 95% CI: 6.3% to 15.2% vs 4%, 95% CI: 3.5% to 4.7%) and can never work out what to do when things are hard (15.2%, 95% CI: 10.6% to 21.2% vs 9%, 95% CI: 8.2% to 9.9%). We considered six vulnerabilities to be of particular concern during the COVID-19 pandemic and associated national and local lockdowns: family never gets along well together; no garden where child can play; no nearby park where they can play; not having three meals a day; no internet at home; worried about money all the time. Pre-pandemic, 37.4% (95% CI: 36.6% to 38.3%) of Bradford children had one of these vulnerabilities and a further 29.6% (95% CI: 28.9% to 30.4%) had more than one.ConclusionsAlthough most primary school children aged 7–10 in our study had good levels of well-being on most indicators across multiple domains, fewer than 10% had no vulnerabilities at all, a worrying 10% had at least one vulnerability in all the four domains we studied and two-thirds had vulnerabilities of particular concern during the COVID-19 lockdowns.

Supported by the National Institute of Environmental Health Sciences (R21ES029681; R01ES030691, R01ES029944, R01ES030364, R21ES028903, and P30ES007048, to L.C.; R01ES030691, R01ES030364, R21ES028903, and P30ES007048, to R.M.; R01ES030691, R01ES029944, R01ES030364, and P30ES007048, to D.V.C.; R01ES030691, R01ES029944, R01ES030364, and R21ES028903, to D.V.; R01ES030364, to N.S.; and P30ES007048, to E.G), the National Institutes of Health (P01CA196569 and R01CA140561, to D.V.C.; P30DK048522, to N.S.), the Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128, to M.C.), and the Juan de la Cierva-Incorporacion fellowship (IJC2018-035394-I, to L.M.), awarded by the Spanish Ministerio de Economia, Industria y Competitividad. The Human Early Life Exposome project was supported by the European Community’s Seventh Framework Programme (FP7/2007-2013, under grant 30833). INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. The KANC cohort was supported by the Lithuanian Agency for Science Innovation and Technology (31V-77). For a full list of funding that supported the EDEN cohort, see https://doi.org/10.1093/ije/dyv151. The Norwegian Mother, Father and Child Cohort Study was supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The Rhea cohort was supported by European projects; the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece), 2011-2014; and Rhea Plus: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-2015. The BiB cohort was supported by a Wellcome Trust infrastructure grant (WT101597MA). R.R.C.M. and J.W. received funding from the National Institute for Health Research Applied Research Collaboration for Yorkshire and Humber. The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and a member of the ProteoRed PRB3 consortium, which is supported by grant PT17/0019 of the PE I + D+i 2013-2016 from the Instituto de Salud Carlos III and European Regional Development Fund. This study was further supported by grants from the Spanish Ministry of Science, Innovation and Universities, Centro de Excelencia Severo Ochoa 2013-2017 (SEV-2012-0208), and Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (2017SGR595).

Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoroalkyl substances (PFAS), a group of endocrine disrupting chemicals. We hypothesized that early life exposure to PFASs is associated with poor metabolic health in children. We studied the association between prenatal and postnatal PFASs mixture exposure and cardiometabolic health in children, and the role of inflammatory proteins. In 1,101 mothers-child pairs from the Human Early Life Exposome project, we measured the concentrations of PFAS in blood collected in pregnancy and at 8 years (range = 6-12 years). We applied Bayesian Kernel Machine regression (BKMR) to estimate the associations between exposure to PFAS mixture and the cardiometabolic factors as age and sex- specific z-scores of waist circumference (WC), systolic and diastolic blood pressures (BP), and concentrations of triglycerides (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. We measured thirty six inflammatory biomarkers in child plasma and examined the underlying role of inflammatory status for the exposure-outcome association by integrating the three panels into a network. Exposure to the PFAS mixture was positively associated with HDL-C and systolic BP, and negatively associated with WC, LDL-C and TG. When we examined the independent effects of the individual chemicals in the mixture, prenatal PFHxS was negatively associated with HDL-C and prenatal PFNA was positively associated with WC and these were opposing directions from the overall mixture. Further, the network consisted of five distinct communities connected with positive and negative correlations. The selected inflammatory biomarkers were positively, while the postnatal PFAS were negatively related with the included cardiometabolic factors, and only prenatal PFOA was positively related with the pro-inflammatory cytokine IL-1beta and WC. Our study supports that prenatal, rather than postnatal, PFAS exposure might contribute to an unfavorable lipidemic profile and adiposity in childhood. This work was supported by the Norwegian Research Council under the MILJØFORSK-Miljøforskning for en grønn samfunnsomstilling call (project No. 268465-short name: "CATCHUP project"). The HELIX project is funded by the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no 308,333 – the HELIX project. The HELIX program is built on six existing cohorts that received previous funding. The Born in Bradford (BiB) study presents independent research commissioned by the National Institute for Health Research Collaboration for Applied Health Research and Care (NIHR CLAHRC) and the Programme Grants for Applied Research funding scheme (RP-PG-0407–10044). INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6–04-2014_31V-66). Dr. Maribel Casas received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128). Dr. Leda Chatzi was supported by NIH/NIHES R01 ES029944, R01ES030691, R01ES030364, R21 ES029681, R21 ES028903, and P30 ES007048-23. Dr. David Conti was supported by P01CA196569, R01CA140561, R01 ES016813, R01 ES029944, R01ES030691, R01ES030364. Dr. Nikos Stratakis was supported by NIH/NIHES R21 ES029681 and P30 ES007048-23, and NIH/NIDDK P30 DK048522-24. The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I + D + i 2013–2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. ISGlobal affiliated researchers acknowledge support from the Spanish Ministry of Science, Innovation and Universities, “Centro de Excelencia Severo Ochoa 2013–2017”, SEV-2012–0208, and “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595)