Publications by authors named "Rosemary R C McEachan"

43 Publications

Facilitators and barriers to home-based toothbrushing practices by parents of young children to reduce tooth decay: a systematic review.

Clin Oral Investig 2021 Mar 20. Epub 2021 Mar 20.

School of Dentistry, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK.

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 Electronic databases, references and unpublished literature databases were searched.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.
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http://dx.doi.org/10.1007/s00784-021-03890-zDOI Listing
March 2021

In Utero Exposure to Mercury Is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood.

Hepatology 2021 Mar 17. Epub 2021 Mar 17.

Mailman School of Public Health, Columbia University, New York, NY.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant-associated fatty liver disease. We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother-child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5-8.7) from the European Human Early-Life Exposome (HELIX) cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 μg/L; IQR, 1.1-3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation-related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNF-α). Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up-regulation of genes encoding these four cytokines and increased concentrations of IL-8 and TNF-α in the supernatants. CONCLUSION: These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.
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http://dx.doi.org/10.1002/hep.31809DOI Listing
March 2021

Experiences of lockdown during the Covid-19 pandemic: descriptive findings from a survey of families in the Born in Bradford study.

Wellcome Open Res 2020 26;5:228. Epub 2021 Feb 26.

Department of Health Sciences, University of York, Seebohm Rowntree Building, Heslington, York, YO10 5DD, UK.

: 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. : 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 30 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. : 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. : 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.
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http://dx.doi.org/10.12688/wellcomeopenres.16317.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927208.2PMC
February 2021

The Born in Bradford COVID-19 Research Study: Protocol for an adaptive mixed methods research study to gather actionable intelligence on the impact of COVID-19 on health inequalities amongst families living in Bradford.

Wellcome Open Res 2020 13;5:191. Epub 2020 Aug 13.

Department of Health Sciences, University of York, Seebohm Rowntree Building, University of York, Heslington, York, YO10 5DD, UK.

The UK COVID-19 lockdown has included restricting social movement and interaction to slow the spread of disease and reduce demand on NHS acute services. It is likely that the impacts of restrictions will hit the least advantaged disproportionately and will worsen existing structural inequalities amongst deprived and ethnic minority groups. The aim of this study is to deliver rapid intelligence to enable an effective COVID-19 response, including co-production of interventions, that address key issues in the City of Bradford, UK, and nationally. In the longer term we aim to understand the impacts of the response on health trajectories and inequalities in these. In this paper we describe our approach and protocol. We plan an adaptive longitudinal mixed methods approach embedded with Born in Bradford (BiB) birth cohorts which have rich existing data (including questionnaire, routine health and biobank). All work packages (WP) interact and are ongoing. WP1 uses co-production and engagement methods with communities, decision-makers and researchers to continuously set (changing) research priorities and will, longer-term, co-produce interventions to aid the City's recovery. In WP2 repeated quantitative surveys will be administered during lockdown (April-June 2020), with three repeat surveys until 12 months post-lockdown with an ethnically diverse pool of BiB participants (parents, children aged 9-13 years, pregnant women: total sample pool N=7,652, N=5,154, N=1,800). A range of health, social, economic and education outcomes will be assessed. In WP3 priority topics identified in WP1 and WP2 will be explored qualitatively. Initial priority topics include children's mental wellbeing, health beliefs and the peri/post-natal period. Feedback loops will ensure findings are fed directly to decision-makers and communities (via WP1) to enable co-production of acceptable interventions and identify future priority topic areas. Findings will be used to aid development of local and national policy to support recovery from the pandemic and minimise health inequalities.
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http://dx.doi.org/10.12688/wellcomeopenres.16129.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523536PMC
August 2020

Prenatal Exposure to Perfluoroalkyl Substances Associated With Increased Susceptibility to Liver Injury in Children.

Hepatology 2020 11 19;72(5):1758-1770. Epub 2020 Oct 19.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.

Background And Aims: Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been shown to have hepatotoxic effects in animal models. However, human evidence is scarce. We evaluated how prenatal exposure to PFAS associates with established serum biomarkers of liver injury and alterations in serum metabolome in children.

Approach And Results: We used data from 1,105 mothers and their children (median age, 8.2 years; interquartile range, 6.6-9.1) from the European Human Early-Life Exposome cohort (consisting of six existing population-based birth cohorts in France, Greece, Lithuania, Norway, Spain, and the United Kingdom). We measured concentrations of perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate, perfluorohexane sulfonate, and perfluoroundecanoate in maternal blood. We assessed concentrations of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in child serum. Using Bayesian kernel machine regression, we found that higher exposure to PFAS during pregnancy was associated with higher liver enzyme levels in children. We also measured child serum metabolomics through a targeted assay and found significant perturbations in amino acid and glycerophospholipid metabolism associated with prenatal PFAS. A latent variable analysis identified a profile of children at high risk of liver injury (odds ratio, 1.56; 95% confidence interval, 1.21-1.92) that was characterized by high prenatal exposure to PFAS and increased serum levels of branched-chain amino acids (valine, leucine, and isoleucine), aromatic amino acids (tryptophan and phenylalanine), and glycerophospholipids (phosphatidylcholine [PC] aa C36:1 and Lyso-PC a C18:1).

Conclusions: Developmental exposure to PFAS can contribute to pediatric liver injury.
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http://dx.doi.org/10.1002/hep.31483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723317PMC
November 2020

The LifeCycle Project-EU Child Cohort Network: a federated analysis infrastructure and harmonized data of more than 250,000 children and parents.

Eur J Epidemiol 2020 Jul 23;35(7):709-724. Epub 2020 Jul 23.

ISGlobal, Barcelona, Spain.

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.
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http://dx.doi.org/10.1007/s10654-020-00662-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387322PMC
July 2020

Stand Out in Class: restructuring the classroom environment to reduce sitting time - findings from a pilot cluster randomised controlled trial.

Int J Behav Nutr Phys Act 2020 04 29;17(1):55. Epub 2020 Apr 29.

Bradford Institute for Health Research, Bradford Teaching Hospitals Foundation Trust, Bradford, UK.

Background: Excessive sedentary behaviour (sitting) is a risk factor for poor health in children and adults. Incorporating sit-stand desks in the classroom environment has been highlighted as a potential strategy to reduce children's sitting time. The primary aim of this study was to examine the feasibility of conducting a cluster randomised controlled trial (RCT) of a sit-stand desk intervention within primary school classrooms.

Methods: We conducted a two-armed pilot cluster RCT involving 8 primary schools in Bradford, United Kingdom. Schools were randomised on a 1:1 basis to the intervention or usual practice control arm. All children (aged 9-10 years) in participating classes were eligible to take part. Six sit-stand desks replaced three standard desks (sitting 6 children) in the intervention classrooms for 4.5-months. Teachers were encouraged to use a rotation system to ensure all pupils were exposed to the sit-stand desks for > 1 h/day on average. Trial feasibility outcomes (assessed using quantitative and qualitative measures) included school and participant recruitment and attrition, intervention and outcome measure completion rates, acceptability, and preliminary effectiveness of the intervention for reducing sitting time. A weighted linear regression model compared changes in weekday sitting time (assessed using the activPAL accelerometer) between trial arms.

Results: School and child recruitment rates were 33% (n = 8) and 75% (n = 176). At follow-up, retention rates were 100% for schools and 97% for children. Outcome measure completion rates ranged from 63 to 97%. A preliminary estimate of intervention effectiveness revealed a mean difference in change in sitting of - 30.6 min/day (95% CI: - 56.42 to - 4.84) in favour of the intervention group, after adjusting for baseline sitting and wear time. Qualitative measures revealed the intervention and evaluation procedures were acceptable to teachers and children, except for some problems with activPAL attachment.

Conclusion: This study provides evidence of the acceptability and feasibility of a sit-stand desk intervention and evaluation methods. Preliminary evidence suggests the intervention showed potential in reducing children's weekday sitting but some adaptations to the desk rotation system are needed to maximize exposure. Lessons learnt from this trial will inform the planning of a definitive trial.

Trial Registration: ISRCTN12915848 (registered: 09/11/16).
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http://dx.doi.org/10.1186/s12966-020-00958-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189432PMC
April 2020

Home-based toothbrushing interventions for parents of young children to reduce dental caries: A systematic review.

Int J Paediatr Dent 2021 Jan 13;31(1):37-79. Epub 2020 May 13.

Faculty of Medicine and Health, School of Dentistry, University of Leeds, Leeds, UK.

Background: Dental caries is the most prevalent preventable condition in children. A key preventive home-based oral health behaviour is the adoption and maintenance of parental supervised toothbrushing until 8 years of age.

Aim: To examine interventions promoting parental supervised toothbrushing practices to reduce dental caries in young children (<8 years old).

Design: Interventions promoting parental involvement in home-based toothbrushing in children under 8 years old and their impact on caries were subjected to review. Electronic databases (MEDLINE, EMBASE, PubMed, Web of Science, PsycINFO, Scopus, and the Cochrane Library), references, and unpublished literature databases were searched for relevant literature.

Results: Of the 10 176 articles retrieved, forty-two articles were included. The Theoretical Domains Framework was used to code intervention content, with the main domains addressed being knowledge (41/42), skills (35/42), and environmental context and resources (22/42). Sufficient descriptions of the intervention development, delivery, and evaluation were lacking, with only 18 studies being underpinned by theory. Twenty-nine studies explored the impact on caries yielding mixed results.

Conclusions: There are few interventions targeting home-based oral health behaviours underpinned by theory and methodological rigour in their development and evaluation. This demonstrates a clear need for future interventions to be guided by complex intervention methodology.
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http://dx.doi.org/10.1111/ipd.12658DOI Listing
January 2021

Association of Fish Consumption and Mercury Exposure During Pregnancy With Metabolic Health and Inflammatory Biomarkers in Children.

JAMA Netw Open 2020 03 2;3(3):e201007. Epub 2020 Mar 2.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.

Importance: The balance of mercury risk and nutritional benefit from fish intake during pregnancy for the metabolic health of offspring to date is unknown.

Objective: To assess the associations of fish intake and mercury exposure during pregnancy with metabolic syndrome in children and alterations in biomarkers of inflammation in children.

Design, Setting, And Participants: This population-based prospective birth cohort study used data from studies performed in 5 European countries (France, Greece, Norway, Spain, and the UK) between April 1, 2003, and February 26, 2016, as part of the Human Early Life Exposome (HELIX) project. Mothers and their singleton offspring were followed up until the children were aged 6 to 12 years. Data were analyzed between March 1 and August 2, 2019.

Exposures: Maternal fish intake during pregnancy (measured in times per week) was assessed using validated food frequency questionnaires, and maternal mercury concentration (measured in micrograms per liter) was assessed using maternal whole blood and cord blood samples.

Main Outcomes And Measures: An aggregate metabolic syndrome score for children was calculated using the z scores of waist circumference, systolic and diastolic blood pressures, and levels of triglyceride, high-density lipoprotein cholesterol, and insulin. A higher metabolic syndrome score (score range, -4.9 to 7.5) indicated a poorer metabolic profile. Three protein panels were used to measure several cytokines and adipokines in the plasma of children.

Results: The study included 805 mothers and their singleton children. Among mothers, the mean (SD) age at cohort inclusion or delivery of their infant was 31.3 (4.6) years. A total of 400 women (49.7%) had a high educational level, and 432 women (53.7%) were multiparous. Among children, the mean (SD) age was 8.4 (1.5) years (age range, 6-12 years). A total of 453 children (56.3%) were boys, and 734 children (91.2%) were of white race/ethnicity. Fish intake consistent with health recommendations (1 to 3 times per week) during pregnancy was associated with a 1-U decrease in metabolic syndrome score in children (β = -0.96; 95% CI, -1.49 to -0.42) compared with low fish consumption (<1 time per week) after adjusting for maternal mercury levels and other covariates. No further benefit was observed with fish intake of more than 3 times per week. A higher maternal mercury concentration was independently associated with an increase in the metabolic syndrome score of their offspring (β per 2-fold increase in mercury concentration = 0.18; 95% CI, 0.01-0.34). Compared with low fish intake, moderate and high fish intake during pregnancy were associated with reduced levels of proinflammatory cytokines and adipokines in children. An integrated analysis identified a cluster of children with increased susceptibility to metabolic disease, which was characterized by low fish consumption during pregnancy, high maternal mercury levels, decreased levels of adiponectin in children, and increased levels of leptin, tumor necrosis factor α, and the cytokines interleukin 6 and interleukin 1β in children.

Conclusions And Relevance: Results of this study suggest that moderate fish intake consistent with current health recommendations during pregnancy was associated with improvements in the metabolic health of children, while high maternal mercury exposure was associated with an unfavorable metabolic profile in children.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.1007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076335PMC
March 2020

Association between the pregnancy exposome and fetal growth.

Int J Epidemiol 2020 04;49(2):572-586

Inserm, CNRS, University Grenoble Alpes, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, IAB, Grenoble, France.

Background: Several environmental contaminants were shown to possibly influence fetal growth, generally from single exposure family studies, which are prone to publication bias and confounding by co-exposures. The exposome paradigm offers perspectives to avoid selective reporting of findings and to control for confounding by co-exposures. We aimed to characterize associations of fetal growth with the pregnancy chemical and external exposomes.

Methods: Within the Human Early-Life Exposome project, 131 prenatal exposures were assessed using biomarkers and environmental models in 1287 mother-child pairs from six European cohorts. We investigated their associations with fetal growth using a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering each exposure independently. We corrected for exposure measurement error and tested for exposure-exposure and sex-exposure interactions.

Results: The DSA model identified lead blood level, which was associated with a 97 g birth weight decrease for each doubling in lead concentration. No exposure passed the multiple testing-corrected significance threshold of ExWAS; without multiple testing correction, this model was in favour of negative associations of lead, fine particulate matter concentration and absorbance with birth weight, and of a positive sex-specific association of parabens with birth weight in boys. No two-way interaction between exposure variables was identified.

Conclusions: This first large-scale exposome study of fetal growth simultaneously considered >100 environmental exposures. Compared with single exposure studies, our approach allowed making all tests (usually reported in successive publications) explicit. Lead exposure is still a health concern in Europe and parabens health effects warrant further investigation.
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http://dx.doi.org/10.1093/ije/dyaa017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266545PMC
April 2020

Associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth: Findings from Mendelian randomization and parental negative control studies.

PLoS Med 2019 11 13;16(11):e1002972. Epub 2019 Nov 13.

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.

Background: Maternal smoking during pregnancy is an established risk factor for low infant birth weight, but evidence on critical exposure windows and timing of fetal growth restriction is limited. Here we investigate the associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth by triangulating evidence from 3 analytical approaches to strengthen causal inference.

Methods And Findings: We analysed data from 8,621 European liveborn singletons in 2 population-based pregnancy cohorts (the Generation R Study, the Netherlands 2002-2006 [n = 4,682]) and the Born in Bradford study, United Kingdom 2007-2010 [n = 3,939]) with fetal ultrasound and birth anthropometric measures, parental smoking during pregnancy, and maternal genetic data. Associations with trajectories of estimated fetal weight (EFW) and individual fetal parameters (head circumference, femur length [FL], and abdominal circumference [AC]) from 12-16 to 40 weeks' gestation were analysed using multilevel fractional polynomial models. We compared results from (1) confounder-adjusted multivariable analyses, (2) a Mendelian randomization (MR) analysis using maternal rs1051730 genotype as an instrument for smoking quantity and ease of quitting, and (3) a negative control analysis comparing maternal and mother's partner's smoking associations. In multivariable analyses, women who continued smoking during pregnancy had a smaller fetal size than non-smokers from early gestation (16-20 weeks) through to birth (p-value for each parameter < 0.001). Fetal size reductions in continuing smokers followed a dose-dependent pattern (compared to non-smokers, difference in mean EFW [95% CI] at 40 weeks' gestation was -144 g [-182 to -106], -215 g [-248 to -182], and -290 g [-334 to -247] for light, moderate, and heavy smoking, respectively). Overall, fetal size reductions were most pronounced for FL. The fetal growth trajectory in women who quit smoking in early pregnancy was similar to that of non-smokers, except for a shorter FL and greater AC around 36-40 weeks' gestation. In MR analyses, each genetically determined 1-cigarette-per-day increase was associated with a smaller EFW from 20 weeks' gestation to birth in smokers (p = 0.01, difference in mean EFW at 40 weeks = -45 g [95% CI -81 to -10]) and a greater EFW from 32 weeks' gestation onwards in non-smokers (p = 0.03, difference in mean EFW at 40 weeks = 26 g [95% CI 5 to 47]). There was no evidence that partner smoking was associated with fetal growth. Study limitations include measurement error due to maternal self-report of smoking and the modest sample size for MR analyses resulting in unconfounded estimates being less precise. The apparent positive association of the genetic instrument with fetal growth in non-smokers suggests that genetic pleiotropy may have masked a stronger association in smokers.

Conclusions: A consistent linear dose-dependent association of maternal smoking with fetal growth was observed from the early second trimester onwards, while no major growth deficit was found in women who quit smoking early in pregnancy except for a shorter FL during late gestation. These findings reinforce the importance of smoking cessation advice in preconception and antenatal care and show that smoking reduction can lower the risk of impaired fetal growth in women who struggle to quit.
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http://dx.doi.org/10.1371/journal.pmed.1002972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853297PMC
November 2019

Diet as a Source of Exposure to Environmental Contaminants for Pregnant Women and Children from Six European Countries.

Environ Health Perspect 2019 10 16;127(10):107005. Epub 2019 Oct 16.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA.

Background: Pregnant women and children are especially vulnerable to exposures to food contaminants, and a balanced diet during these periods is critical for optimal nutritional status.

Objectives: Our objective was to study the association between diet and measured blood and urinary levels of environmental contaminants in mother-child pairs from six European birth cohorts ( mothers and 1,288 children).

Methods: We assessed the consumption of seven food groups and the blood levels of organochlorine pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and heavy metals and urinary levels of phthalate metabolites, phenolic compounds, and organophosphate pesticide (OP) metabolites. Organic food consumption during childhood was also studied. We applied multivariable linear regressions and targeted maximum likelihood based estimation (TMLE).

Results: Maternal high () versus low () fish consumption was associated with 15% higher PCBs [geometric mean (GM) ; 95% confidence interval (CI): 1.02, 1.29], 42% higher perfluoroundecanoate (PFUnDA) (; 95% CI: 1.20, 1.68), 89% higher mercury (Hg) (; 95% CI: 1.47, 2.41) and a 487% increase in arsenic (As) (; 95% CI: 2.57, 9.23) levels. In children, high () versus low () fish consumption was associated with 23% higher perfluorononanoate (PFNA) (; 95% CI: 1.08, 1.40), 36% higher PFUnDA (; 95% CI: 1.12, 1.64), 37% higher perfluorooctane sulfonate (PFOS) (; 95% CI: 1.22, 1.54), and higher Hg and As [ (95% CI: 1.91, 4.31) and (95% CI: 2.23, 3.21)] concentrations. Using TMLE analysis, we estimated that fish consumption within the recommended 2-3 times/week resulted in lower PFAS, Hg, and As compared with higher consumption. Fruit consumption was positively associated with OP metabolites. Organic food consumption was negatively associated with OP metabolites.

Discussion: Fish consumption is related to higher PFAS, Hg, and As exposures. In addition, fruit consumption is a source of exposure to OPs. https://doi.org/10.1289/EHP5324.
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http://dx.doi.org/10.1289/EHP5324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867312PMC
October 2019

Implementation evaluation of multiple complex early years interventions: an evaluation framework and study protocol.

BMJ Paediatr Open 2019 20;3(1):e000479. Epub 2019 Jun 20.

University of Leeds, Leeds, UK.

Introduction: Implementation evaluations are integral to understanding whether, how and why interventions work. However, unpicking the mechanisms of complex interventions is often challenging in usual service settings where multiple services are delivered concurrently. Furthermore, many locally developed and/or adapted interventions have not undergone any evaluation, thus limiting the evidence base available. Born in Bradford's Better Start cohort is evaluating the impact of multiple early life interventions being delivered as part of the Big Lottery Fund's 'A Better Start' programme to improve the health and well-being of children living in one of the most socially and ethnically diverse areas of the UK. In this paper, we outline our evaluation framework and protocol for embedding pragmatic implementation evaluation across multiple early years interventions and services.

Methods And Analysis: The evaluation framework is based on a modified version of The Conceptual Framework for Implementation Fidelity. Using qualitative and quantitative methods, our evaluation framework incorporates semistructured interviews, focus groups, routinely collected data and questionnaires. We will explore factors related to content, delivery and reach of interventions at both individual and wider community levels. Potential moderating factors impacting intervention success such as participants' satisfaction, strategies to facilitate implementation, quality of delivery and context will also be examined. Interview and focus guides will be based on the Theoretical Domains Framework to further explore the barriers and facilitators of implementation. Descriptive statistics will be employed to analyse the routinely collected quantitative data and thematic analysis will be used to analyse qualitative data.

Ethics And Dissemination: The Health Research Authority (HRA) has confirmed our implementation evaluations do not require review by an NHS Research Ethics Committee (HRA decision 60/88/81). Findings will be shared widely to aid commissioning decisions and will also be disseminated through peer-reviewed journals, summary reports, conferences and community newsletters.
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http://dx.doi.org/10.1136/bmjpo-2019-000479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598556PMC
June 2019

Growing up in Bradford: protocol for the age 7-11 follow up of the Born in Bradford birth cohort.

BMC Public Health 2019 Jul 12;19(1):939. Epub 2019 Jul 12.

Born in Bradford, Bradford Institute for Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford Royal Infirmary, Duckworth Lane, Bradford, BD9 6RJ, UK.

Background: Born in Bradford (BiB) is a prospective multi-ethnic pregnancy and birth cohort study that was established to examine determinants of health and development during childhood and, subsequently, adult life in a deprived multi-ethnic population in the north of England. Between 2007 and 2010, the BiB cohort recruited 12,453 women who experienced 13,776 pregnancies and 13,858 births, along with 3353 of their partners. Forty five percent of the cohort are of Pakistani origin. Now that children are at primary school, the first full follow-up of the cohort is taking place. The aims of the follow-up are to investigate the determinants of children's pre-pubertal health and development, including through understanding parents' health and wellbeing, and to obtain data on exposures in childhood that might influence future health.

Methods: We are employing a multi-method approach across three data collection arms (community-based family visits, school based physical assessment, and whole classroom cognitive, motor function and wellbeing measures) to follow-up over 9000 BiB children aged 7-11 years and their families between 2017 and 2021. We are collecting detailed parent and child questionnaires, cognitive and sensorimotor assessments, blood pressure, anthropometry and blood samples from parents and children. Dual x-ray absorptiometry body scans, accelerometry and urine samples are collected on subsamples. Informed consent is collected for continued routine data linkage to health, social care and education records. A range of engagement activities are being used to raise the profile of BiB and to disseminate findings.

Discussion: Our multi-method approach to recruitment and assessment provides an efficient method of collecting rich data on all family members. Data collected will enhance BiB as a resource for the international research community to study the interplay between ethnicity, socioeconomic circumstances and biology in relation to cardiometabolic health, mental health, education, cognitive and sensorimotor development and wellbeing.
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http://dx.doi.org/10.1186/s12889-019-7222-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626420PMC
July 2019

Integrating research and system-wide practice in public health: lessons learnt from Better Start Bradford.

BMC Public Health 2019 Mar 4;19(1):260. Epub 2019 Mar 4.

Born in Bradford, Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, England.

Many interventions that are delivered within public health services have little evidence of effect. Evaluating interventions that are being delivered as a part of usual practice offers opportunities to improve the evidence base of public health. However, such evaluation is challenging and requires the integration of research into system-wide practice. The Born in Bradford's Better Start experimental birth cohort offers an opportunity to efficiently evaluate multiple complex community interventions to improve the health, wellbeing and development of children aged 0-3 years. Based on the learning from this programme, this paper offers a pragmatic and practical guide to researchers, public health commissioners and service providers to enable them to integrate research into their everyday practice, thus enabling relevant and robust evaluations within a complex and changing system.Using the principles of co-production the key challenges of integrating research and practice were identified, and appropriate strategies to overcome these, developed across five key stages: 1) Community and stakeholder engagement; 2) Intervention design; 3) Optimising routinely collected data; 4) Monitoring implementation; and 5) Evaluation. As a result of our learning we have developed comprehensive toolkits ( https://borninbradford.nhs.uk/what-we-do/pregnancy-early-years/toolkit/ ) including: an operational guide through the service design process; an implementation and monitoring guide; and an evaluation framework. The evaluation framework incorporates implementation evaluations to enable understanding of intervention performance in practice, and quasi experimental approaches to infer causal effects in a timely manner. We also offer strategies to harness routinely collected data to enhance the efficiency and affordability of evaluations that are directly relevant to policy and practice.These strategies and tools will help researchers, commissioners and service providers to work together to evaluate interventions delivered in real-life settings. More importantly, however, we hope that they will support the development of a connected system that empowers practitioners and commissioners to embed innovation and improvement into their own practice, thus enabling them to learn, evaluate and improve their own services.
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http://dx.doi.org/10.1186/s12889-019-6554-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399808PMC
March 2019

Not a level playing field: A qualitative study exploring structural, community and individual determinants of greenspace use amongst low-income multi-ethnic families.

Health Place 2019 03 5;56:118-126. Epub 2019 Feb 5.

Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford Royal Infirmary, Duckworth Lane, Bradford BD9 6RJ, United Kingdom. Electronic address:

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.
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http://dx.doi.org/10.1016/j.healthplace.2019.01.018DOI Listing
March 2019

Not All Green Space Is Created Equal: Biodiversity Predicts Psychological Restorative Benefits From Urban Green Space.

Front Psychol 2018 27;9:2320. Epub 2018 Nov 27.

School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.

Contemporary epidemiological methods testing the associations between green space and psychological well-being treat all vegetation cover as equal. However, there is very good reason to expect that variations in ecological "quality" (number of species, integrity of ecological processes) may influence the link between access to green space and benefits to human health and well-being. We test the relationship between green space quality and restorative benefit in an inner city urban population in Bradford, United Kingdom. We selected 12 urban parks for study where we carried out botanical and faunal surveys to quantify biodiversity and assessed the site facilities of the green space (cleanliness, provision of amenities). We also conducted 128 surveys with park users to quantify psychological restoration based on four self-reported measure of general restoration, attention-grabbing distractions, being away from everyday life, and site preference. We present three key results. First, there is a positive association between site facilities and biodiversity. Second, restorative benefit is predicted by biodiversity, which explained 43% of the variance in restorative benefit across the parks, with minimal input from other variables. Third, the benefits accrued through access to green space were unrelated to age, gender, and ethnic background. The results add to a small but growing body of evidence that emphasize the role of nature in contributing to the well-being of urban populations and, hence, the need to consider biodiversity in the design of landscapes that enhance multiple ecosystem services.
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http://dx.doi.org/10.3389/fpsyg.2018.02320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277587PMC
November 2018

The early-life exposome: Description and patterns in six European countries.

Environ Int 2019 02 6;123:189-200. Epub 2018 Dec 6.

Team of Environmental Epidemiology, IAB, Institute for Advanced Biosciences, Inserm, CNRS, CHU-Grenoble-Alpes, University Grenoble-Alpes, Grenoble, France.

Characterization of the "exposome", the set of all environmental factors that one is exposed to from conception onwards, has been advocated to better understand the role of environmental factors on chronic diseases. Here, we aimed to describe the early-life exposome. Specifically, we focused on the correlations between multiple environmental exposures, their patterns and their variability across European regions and across time (pregnancy and childhood periods). We relied on the Human Early-Life Exposome (HELIX) project, in which 87 environmental exposures during pregnancy and 122 during the childhood period (grouped in 19 exposure groups) were assessed in 1301 pregnant mothers and their children at 6-11 years in 6 European birth cohorts. Some correlations between exposures in the same exposure group reached high values above 0.8. The median correlation within exposure groups was >0.3 for many exposure groups, reaching 0.69 for water disinfection by products in pregnancy and 0.67 for the meteorological group in childhood. Median correlations between different exposure groups rarely reached 0.3. Some correlations were driven by cohort-level associations (e.g. air pollution and chemicals). Ten principal components explained 45% and 39% of the total variance in the pregnancy and childhood exposome, respectively, while 65 and 90 components were required to explain 95% of the exposome variability. Correlations between maternal (pregnancy) and childhood exposures were high (>0.6) for most exposures modeled at the residential address (e.g. air pollution), but were much lower and even close to zero for some chemical exposures. In conclusion, the early life exposome was high dimensional, meaning that it cannot easily be measured by or reduced to fewer components. Correlations between exposures from different exposure groups were much lower than within exposure groups, which have important implications for co-exposure confounding in multiple exposure studies. Also, we observed the early life exposome to be variable over time and to vary by cohort, so measurements at one time point or one place will not capture its complexities.
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http://dx.doi.org/10.1016/j.envint.2018.11.067DOI Listing
February 2019

Determinants of the urinary and serum metabolome in children from six European populations.

BMC Med 2018 11 8;16(1):202. Epub 2018 Nov 8.

Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, SW7 2AZ, UK.

Background: Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment-health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project ( http://www.projecthelix.eu ).

Methods: Metabolic phenotypes of matched urine and serum samples from 1192 children (aged 6-11) recruited from birth cohorts in six European countries were measured using high-throughput H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit).

Results: We identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythreonic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r > 0.18) between urine and serum.

Conclusions: We have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children.
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http://dx.doi.org/10.1186/s12916-018-1190-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223046PMC
November 2018

Socioeconomic inequalities in urban and transport planning related exposures and mortality: A health impact assessment study for Bradford, UK.

Environ Int 2018 12 20;121(Pt 1):931-941. Epub 2018 Oct 20.

ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Electronic address:

Background: Cities have unique geographic, environmental and sociocultural characteristics that influence the health status of their citizens. Identification and modification of these characteristics may help to promote healthier cities.

Objective: We estimated premature mortality impacts of breaching international exposure guidelines for physical activity (PA), air pollution, noise and access to green space for Bradford (UK) adult residents (n = 393,091).

Methods: We applied the Urban and TranspOrt Planning Health Impact Assessment (UTOPHIA) methodology and estimated mortality, life expectancy (LE) and economic impacts of non-compliance with recommended exposure levels. We also investigated the distribution of the mortality burden among the population, focusing on socioeconomic position (SEP) as defined by deprivation status and ethnicity.

Results: We estimated that annually almost 10% of premature mortality (i.e. 375 deaths, 95% CI: 276-474) in Bradford is attributable to non-compliance with recommended exposure levels. Non-compliance was also estimated to result in over 300 days of LE lost (95% CI: 238-432), which translated in economic losses of over £50,000 per person (95% CI: 38,518-69,991). 90% of the premature mortality impact resulted from insufficient PA performance. Air and noise pollution and the lack of green space had smaller impacts (i.e. 48 deaths). Residents of lower SEP neighborhoods had the highest risks for adverse exposure and premature death. A larger number of deaths (i.e. 253 and 145, respectively) could be prevented by reducing air and noise pollution levels well below the guidelines.

Discussion: Current urban and transport planning related exposures result in a considerable health burden that is unequally distributed among the Bradford population. Improvements in urban and transport planning practices including the reduction of motor traffic and the promotion of active transport together with greening of the district, particularly in areas of lower SEP, are promising strategies to increase PA performance and reduce harmful environmental exposures.
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http://dx.doi.org/10.1016/j.envint.2018.10.017DOI Listing
December 2018

Availability, use of, and satisfaction with green space, and children's mental wellbeing at age 4 years in a multicultural, deprived, urban area: results from the Born in Bradford cohort study.

Lancet Planet Health 2018 06;2(6):e244-e254

ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Background: It is unknown whether the quantity or quality of green space is more important for mental wellbeing. We aimed to explore associations between availability of, satisfaction with, and use of green space and mental wellbeing among children aged 4 years in a multi-ethnic sample.

Methods: We did a 4-year follow-up assessment of participants in the Born in Bradford longitudinal cohort study, which recruited children and mothers at the city's main maternity unit from 2007 to 2011. The primary outcome was parent-reported mental wellbeing for children aged 4 years, assessed with the standardised Strengths and Difficulties Questionnaire. Total, internalising, and externalising behavioural difficulties and prosocial behaviour scales were computed (with higher scores indicating greater difficulties or more prosocial behaviour). Residential green space around participants' home addresses and distance to major green spaces were computed with the normalised difference vegetation index (NDVI). A subsample of participants completed additional questionnaires on measures of satisfaction with, and use of, local green spaces. Multiple regressions examined associations between green space and children's mental wellbeing and explored moderation by ethnicity (white British vs south Asian) and socioeconomic status.

Findings: Between Oct 1, 2012, and June 30, 2015, 2594 mothers attended a follow-up appointment during which they completed a detailed questionnaire assessing the health of their child. 1519 (58%) participants were of south Asian origin, 740 (29%) of white British origin, and 333 (13%) of another ethnicity. Data on ethnicity were missing for two participants. 832 (32%) of 2594 participants completed additional questionnaires. Ethnicity moderated associations between residential green space and mental wellbeing (p<0·05 for total and internalising difficulties). After adjusting for all relevant variables, more green space was associated with fewer internalising behavioural difficulties (mean NDVI 100 m: β -2·35 [95% CI -4·20 to -0·50]; 300 m: -3·15 [-5·18 to -1·13]; 500 m: -2·85 [-4·91 to -0·80]) and with fewer total behavioural difficulties (100 m: -4·27 [-7·65 to -0·90]; 300 m: -5·22 [-8·91 to -1·54]; 500 m: -4·82 [-8·57 to -1·07]) only for south Asian children across all three buffer zones. In the subsample of participants, the effect of NDVI on wellbeing was rendered non-significant after controlling for satisfaction with, and use of, green space. Among south Asian children, satisfaction with green space was significantly associated with fewer total behavioural difficulties across all three buffer zones (β -0·59 [95% CI -1·11 to -0·07]), fewer internalising behavioural difficulties within 100 m (-0·28 [95% CI -0·56 to -0·003]) and 300 m buffer zones (-0·28 [-0·56 to -0·002]), and greater prosocial behaviour across all three buffer zones (0·20 [0·02 to 0·38]); no such associations were observed among white British children.

Interpretation: Positive effects of green space on wellbeing differ by ethnicity. Satisfaction with the quality of green space appears to be a more important predictor of wellbeing than does quantity of green space. Public health professionals and urban planners need to focus on both quality and quantity of urban green spaces to promote health, particularly among ethnic minority groups.

Funding: European Community's Seventh Framework Programme.
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http://dx.doi.org/10.1016/S2542-5196(18)30119-0DOI Listing
June 2018

Role of patient and public involvement in implementation research: a consensus study.

BMJ Qual Saf 2018 10 17;27(10):858-864. Epub 2018 Apr 17.

Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, BD9 6RJ., Bradford, UK.

Background: Patient and public involvement (PPI) is often an essential requirement for research funding. Distinctions can be drawn between clinical research, which generally focuses on patients, and implementation research, which generally focuses on health professional behaviour. There is uncertainty about the role of PPI in this latter field. We explored and defined the roles of PPI in implementation research to inform relevant good practice guidance.

Methods: We used a structured consensus process using a convenience sample panel of nine experienced PPI and two researcher members. We drew on available literature to identify 21 PPI research roles. The panel rated their agreement with roles independently online in relation to both implementation and clinical research. Disagreements were discussed at a face-to-face meeting prior to a second online rating of all roles. Median scores were calculated and a final meeting held to review findings and consider recommendations.

Results: Ten panellists completed the consensus process. For clinical research, there was strong support and consensus for the role of PPI throughout most of the research process. For implementation research, there were eight roles with consensus and strong support, seven roles with consensus but weaker support and six roles with no consensus. There were more disagreements relating to PPI roles in implementation research compared with clinical research. PPI was rated as contributing less to the design and management of implementation research than for clinical research.

Conclusions: The roles of PPI need to be tailored according to the nature of research to ensure authentic and appropriate involvement. We provide a framework to guide the planning, conduct and reporting of PPI in implementation research, and encourage further research to evaluate its use.
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http://dx.doi.org/10.1136/bmjqs-2017-006954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166593PMC
October 2018

DNA methylation in childhood asthma: an epigenome-wide meta-analysis.

Lancet Respir Med 2018 05 26;6(5):379-388. Epub 2018 Feb 26.

ISGlobal, Centre for Research in Environmental Epidemiology, the Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma.

Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4-16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2-56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1-79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting.

Findings: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p<1·14 × 10) after meta-analysis. Consistently lower methylation levels were observed at all associated loci across childhood from age 4 to 16 years in participants with asthma, but not in cord blood at birth. All 14 CpG sites were significantly associated with asthma in the second replication study using whole-blood DNA, and were strongly associated with asthma in purified eosinophils. Whole-blood transcriptional signatures associated with these CpG sites indicated increased activation of eosinophils, effector and memory CD8 T cells and natural killer cells, and reduced number of naive T cells. Five of the 14 CpG sites were associated with asthma in respiratory epithelial cells, indicating cross-tissue epigenetic effects.

Interpretation: Reduced whole-blood DNA methylation at 14 CpG sites acquired after birth was strongly associated with childhood asthma. These CpG sites and their associated transcriptional profiles indicate activation of eosinophils and cytotoxic T cells in childhood asthma. Our findings merit further investigations of the role of epigenetics in a clinical context.

Funding: EU and the Seventh Framework Programme (the MeDALL project).
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http://dx.doi.org/10.1016/S2213-2600(18)30052-3DOI Listing
May 2018

To what extent can behaviour change techniques be identified within an adaptable implementation package for primary care? A prospective directed content analysis.

Implement Sci 2018 02 17;13(1):32. Epub 2018 Feb 17.

Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.

Background: Interpreting evaluations of complex interventions can be difficult without sufficient description of key intervention content. We aimed to develop an implementation package for primary care which could be delivered using typically available resources and could be adapted to target determinants of behaviour for each of four quality indicators: diabetes control, blood pressure control, anticoagulation for atrial fibrillation and risky prescribing. We describe the development and prospective verification of behaviour change techniques (BCTs) embedded within the adaptable implementation packages.

Methods: We used an over-lapping multi-staged process. We identified evidence-based, candidate delivery mechanisms-mainly audit and feedback, educational outreach and computerised prompts and reminders. We drew upon interviews with primary care professionals using the Theoretical Domains Framework to explore likely determinants of adherence to quality indicators. We linked determinants to candidate BCTs. With input from stakeholder panels, we prioritised likely determinants and intervention content prior to piloting the implementation packages. Our content analysis assessed the extent to which embedded BCTs could be identified within the packages and compared them across the delivery mechanisms and four quality indicators.

Results: Each implementation package included at least 27 out of 30 potentially applicable BCTs representing 15 of 16 BCT categories. Whilst 23 BCTs were shared across all four implementation packages (e.g. BCTs relating to feedback and comparing behaviour), some BCTs were unique to certain delivery mechanisms (e.g. 'graded tasks' and 'problem solving' for educational outreach). BCTs addressing the determinants 'environmental context' and 'social and professional roles' (e.g. 'restructuring the social and 'physical environment' and 'adding objects to the environment') were indicator specific. We found it challenging to operationalise BCTs targeting 'environmental context', 'social influences' and 'social and professional roles' within our chosen delivery mechanisms.

Conclusion: We have demonstrated a transparent process for selecting, operationalising and verifying the BCT content in implementation packages adapted to target four quality indicators in primary care. There was considerable overlap in BCTs identified across the four indicators suggesting core BCTs can be embedded and verified within delivery mechanisms commonly available to primary care. Whilst feedback reports can include a wide range of BCTs, computerised prompts can deliver BCTs at the time of decision making, and educational outreach can allow for flexibility and individual tailoring in delivery.
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http://dx.doi.org/10.1186/s13012-017-0704-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816358PMC
February 2018

Physical Activity, Sedentary Time, and Fatness in a Biethnic Sample of Young Children.

Med Sci Sports Exerc 2017 05;49(5):930-938

1Bradford Institute for Health Research, Bradford NHS Foundation Trust, Bradford, UNITED KINGDOM; 2MRC Epidemiology Unit, University of Cambridge, Cambridge, UNITED KINGDOM; 3School of Sport, Exercise and Health Sciences, Loughborough University, Leicestershire, UNITED KINGDOM; and 4UKCRC Centre for Diet and Activity Research (CEDAR), School of Clinical Medicine, University of Cambridge, Cambridge, UNITED KINGDOM.

Purpose: This study aimed to investigate associations of objectively measured physical activity (PA) and sedentary time with adiposity in a predominantly biethnic (South Asian and White British) sample of young children.

Methods: The sample included 333 children age 11 months to 5 yr who provided 526 cross-sectional observations for PA and body composition. Total PA volume (vector magnitude counts per minute), daily time at multiple intensity levels (the cumulative time in activity >500, >1000, >1500, …, >6000 counts per minute), and time spent sedentary (<820 counts per minute), in light PA (820-3907 counts per minute) and in moderate-to-vigorous PA (≥3908 counts per minute) were estimated with triaxial accelerometry. Indicators of adiposity included body mass index, waist circumference, and the sum of subscapular and triceps skinfold thicknesses. Statistical analyses were performed using multilevel regression and isotemporal substitution models adjusted for confounders. Effect modification by ethnicity was examined.

Results: There was no evidence for effect modification by ethnicity (P interaction ≥ 0.13). In the whole sample, the accumulated time spent above 3500 counts per minute (i.e., high light-intensity PA) was inversely associated with the sum of skinfolds (β = -0.60 mm, 95% confidence interval [CI] = -1.19 to -0.021, per 20 min·d), and the magnitude of association increased dose dependently with PA intensity (peaking for time spent >6000 counts per minute = -1.57 mm, 95% CI = -3.01 to -0.12, per 20 min·d). The substitution of 20 min·d of sedentary time with moderate-to-vigorous PA was associated with a lower sum of skinfolds (-0.77 mm, 95% CI = -1.46 to -0.084).

Conclusions: High light-intensity PA appears to be beneficial for body composition in young South Asian and White British children, but higher-intensity PA is more advantageous.
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http://dx.doi.org/10.1249/MSS.0000000000001180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392414PMC
May 2017

Using the Theoretical Domains Framework (TDF) to understand adherence to multiple evidence-based indicators in primary care: a qualitative study.

Implement Sci 2016 Aug 8;11:113. Epub 2016 Aug 8.

Leeds Institute of Health Sciences, University of Leeds, Charles Thackrah Building, 101 Clarendon Road, Leeds, LS2 9LJ, UK.

Background: There are recognised gaps between evidence and practice in general practice, a setting posing particular implementation challenges. We earlier screened clinical guideline recommendations to derive a set of 'high-impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. Here, we explore health professionals' perceived determinants of adherence to these indicators, examining the degree to which determinants were indicator-specific or potentially generalisable across indicators.

Methods: We interviewed 60 general practitioners, practice nurses and practice managers in West Yorkshire, the UK, about adherence to four indicators: avoidance of risky prescribing; treatment targets in type 2 diabetes; blood pressure targets in treated hypertension; and anticoagulation in atrial fibrillation. Interview questions drew upon the Theoretical Domains Framework (TDF). Data were analysed using framework analysis.

Results: Professional role and identity and environmental context and resources featured prominently across all indicators whilst the importance of other domains, for example, beliefs about consequences, social influences and knowledge varied across indicators. We identified five meta-themes representing more general organisational and contextual factors common to all indicators.

Conclusions: The TDF helped elicit a wide range of reported determinants of adherence to 'high-impact' indicators in primary care. It was more difficult to pinpoint which determinants, if targeted by an implementation strategy, would maximise change. The meta-themes broadly underline the need to align the design of interventions targeting general practices with higher level supports and broader contextual considerations. However, our findings suggest that it is feasible to develop interventions to promote the uptake of different evidence-based indicators which share common features whilst also including content-specific adaptations.
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http://dx.doi.org/10.1186/s13012-016-0479-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977705PMC
August 2016

The HAPPY (Healthy and Active Parenting Programmme for early Years) feasibility randomised control trial: acceptability and feasibility of an intervention to reduce infant obesity.

BMC Public Health 2016 Mar 1;16:211. Epub 2016 Mar 1.

Bradford Institute for Health Research, Bradford Teaching Hospital NHS Foundation Trust, Bradford Royal Infirmary, Duckworth Lane, Bradford, BD9 6RJ, UK.

Background: The prevalence of infant obesity is increasing, but there is a lack of evidence-based approaches to prevent obesity at this age. This study tested the acceptability and feasibility of evaluating a theory-based intervention aimed at reducing risk of obesity in infants of overweight/obese women during and after pregnancy: the Healthy and Active Parenting Programme for Early Years (HAPPY).

Methods: A feasibility randomised controlled trial was conducted in Bradford, England. One hundred twenty overweight/obese pregnant women (Body Mass Index [BMI] ≥25 kg/m(2)) were recruited between 10-26 weeks gestation. Consenting women were randomly allocated to HAPPY (6 antenatal, 6 postnatal sessions: N = 59) or usual care (N = 61). Appropriate outcome measures for a full trial were explored, including: infant's length and weight, woman's BMI, physical activity and dietary intake of the women and infants. Health economic data were collected. Measurement occurred before randomisation and when the infant was aged 6 months and 12 months. Feasibility outcomes were: recruitment/attrition rates, and acceptability of: randomisation, measurement, and intervention. Intra-class correlations for infant weight were calculated. Fidelity was assessed through observations and facilitator feedback. Focus groups and semi-structured interviews explored acceptability of methods, implementation, and intervention content.

Results: Recruitment targets were met (~20 women/month) with a recruitment rate of 30 % of eligible women (120/396). There was 30 % attrition at 12 months; 66 % of recruited women failed to attend intervention sessions, but those who attended the first session were likely to continue to attend (mean 9.4/12 sessions, range 1-12). Reaction to intervention content was positive, and fidelity was high. Group clustering was minimal; an adjusted effect size of -0.25 standard deviation scores for infant weight at 12 months (95 % CI: -0.16-0.65) favouring the intervention was observed using intention to treat analyses. No adverse events were reported.

Conclusions: The HAPPY intervention appeared feasible and acceptable to participants who attended and those delivering it, however attendance was low; adaptations to increase initial attendance are recommended. Whilst the study was not powered to detect a definitive effect, our results suggest a potential to reduce risk of infant obesity. The evidence reported provides valuable lessons to inform progression to a definitive trial.

Trial Registration: Current Controlled Trials ISRCTN56735429.
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http://dx.doi.org/10.1186/s12889-016-2861-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774160PMC
March 2016

Action to Support Practices Implement Research Evidence (ASPIRE): protocol for a cluster-randomised evaluation of adaptable implementation packages targeting 'high impact' clinical practice recommendations in general practice.

Implement Sci 2016 Feb 29;11:25. Epub 2016 Feb 29.

Leeds Institute of Health Sciences, University of Leeds, Leeds, LS2 9JT, UK.

Background: There are recognised gaps between evidence and practice in general practice, a setting which provides particular challenges for implementation. We earlier screened clinical guideline recommendations to derive a set of 'high impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. We aim to evaluate the effectiveness and cost-effectiveness of a multifaceted, adaptable intervention package to implement four targeted, high impact recommendations in general practice.

Methods/design: The research programme Action to Support Practice Implement Research Evidence (ASPIRE) includes a pair of pragmatic cluster-randomised trials which use a balanced incomplete block design. Clusters are general practices in West Yorkshire, United Kingdom (UK), recruited using an 'opt-out' recruitment process. The intervention package adapted to each recommendation includes combinations of audit and feedback, educational outreach visits and computerised prompts with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. In trial 1, practices are randomised to adapted interventions targeting either diabetes control or risky prescribing and those in trial 2 to adapted interventions targeting either blood pressure control in patients at risk of cardiovascular events or anticoagulation in atrial fibrillation. The respective primary endpoints comprise achievement of all recommended target levels of haemoglobin A1c (HbA1c), blood pressure and cholesterol in patients with type 2 diabetes, a composite indicator of risky prescribing, achievement of recommended blood pressure targets for specific patient groups and anticoagulation prescribing in patients with atrial fibrillation. We are also randomising practices to a fifth, non-intervention control group to further assess Hawthorne effects. Outcomes will be assessed using routinely collected data extracted 1 year after randomisation. Economic modelling will estimate intervention cost-effectiveness. A process evaluation involving eight non-trial practices will examine intervention delivery, mechanisms of action and unintended consequences.

Discussion: ASPIRE will provide 'real-world' evidence about the effects, cost-effectiveness and delivery of adapted intervention packages targeting high impact recommendations. By implementing our adaptable intervention package across four distinct clinical topics, and using 'opt-out' recruitment, our findings will provide evidence of wider generalisability.

Trial Registration: ISRCTN91989345.
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http://dx.doi.org/10.1186/s13012-016-0387-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770678PMC
February 2016

Born in Bradford's Better Start: an experimental birth cohort study to evaluate the impact of early life interventions.

BMC Public Health 2016 08 4;15:711. Epub 2016 Aug 4.

Born in Bradford, Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, BD9 6RJ, UK.

Background: Early interventions are recognised as key to improving life chances for children and reducing inequalities in health and well-being, however there is a paucity of high quality research into the effectiveness of interventions to address childhood health and development outcomes. Planning and implementing standalone RCTs for multiple, individual interventions would be slow, cumbersome and expensive. This paper describes the protocol for an innovative experimental birth cohort: Born in Bradford's Better Start (BiBBS) that will simultaneously evaluate the impact of multiple early life interventions using efficient study designs. Better Start Bradford (BSB) has been allocated £49 million from the Big Lottery Fund to implement 22 interventions to improve outcomes for children aged 0-3 in three key areas: social and emotional development; communication and language development; and nutrition and obesity. The interventions will be implemented in three deprived and ethnically diverse inner city areas of Bradford.

Method: The BiBBS study aims to recruit 5000 babies, their mothers and their mothers' partners over 5 years from January 2016-December 2020. Demographic and socioeconomic information, physical and mental health, lifestyle factors and biological samples will be collected during pregnancy. Parents and children will be linked to their routine health and local authority (including education) data throughout the children's lives. Their participation in BSB interventions will also be tracked. BiBBS will test interventions using the Trials within Cohorts (TwiCs) approach and other quasi-experimental designs where TwiCs are neither feasible nor ethical, to evaluate these early life interventions. The effects of single interventions, and the cumulative effects of stacked (multiple) interventions on health and social outcomes during the critical early years will be measured.

Discussion: The focus of the BiBBS cohort is on intervention impact rather than observation. As far as we are aware BiBBS is the world's first such experimental birth cohort study. While some risk factors for adverse health and social outcomes are increasingly well described, the solutions to tackling them remain elusive. The novel design of BiBBS can contribute much needed evidence to inform policy makers and practitioners about effective approaches to improve health and well-being for future generations.
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http://dx.doi.org/10.1186/s12889-016-3318-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996273PMC
August 2016

Inequality, green spaces, and pregnant women: roles of ethnicity and individual and neighbourhood socioeconomic status.

Environ Int 2014 Oct 3;71:101-8. Epub 2014 Jul 3.

Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.

Evidence of the impact of green spaces on pregnancy outcomes is limited with no report on how this impact might vary by ethnicity. We investigated the association between residential surrounding greenness and proximity to green spaces and birth weight and explored the modification of this association by ethnicity and indicators of individual (maternal education) and neighbourhood (Index of Multiple Deprivation) socioeconomic status. Our study was based on 10,780 singleton live-births from the Born in Bradford cohort, UK (2007-2010). We defined residential surrounding greenness as average of satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 50 m, 100 m, 250 m, 500 m and 1000 m around each maternal home address. Residential proximity to green spaces was defined as living within 300 m of a green space with an area of ≥ 5000 m(2). We utilized mixed effects models to estimate adjusted change in birth weight associated with residential surrounding greenness as well as proximity to green spaces. We found a positive association between birth weight and residential surrounding greenness. Furthermore, we observed an interaction between ethnicity and residential surrounding greenness in that for White British participants there was a positive association between birth weight and residential surrounding greenness whereas for participants of Pakistani origin there was no such an association. For surrounding greenness in larger buffers (500 m and 1000 m) there were some indications of stronger associations for participants with lower education and those living in more deprived neighbourhoods which were not replicated for surrounding greenness in smaller buffer sizes (i.e. 50 m, 100 m, and 250 m). The findings for residential proximity to a green space were not conclusive. Our study showed that residential surrounding greenness is associated with better foetal growth and this association could vary between different ethnic and socioeconomic groups.
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http://dx.doi.org/10.1016/j.envint.2014.06.010DOI Listing
October 2014