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This paper provides an overview of the INGENIOUS (UnderstandING the sourcEs, traNsformations and fates of IndOor air pollUtantS) project, aiming to better understand air pollution in homes. Although our homes are the microenvironment in which we spend most of our time, we know relatively little about the sources, transformation processes and fates of indoor air pollutants, or our exposure to them. INGENIOUS aims to address this knowledge gap by delivering: an indoor emissions inventory for UK homes; comprehensive air pollutant measurements in 310 homes in Bradford using a combination of low cost-sensors and more advanced air quality instrumentation; an analysis of the impact of indoor air pollution on outdoor air quality and vice versa using mobile measurements; insight into future indoor air quality using detailed air pollution models; identification of indoor air pollutants that warrant further toxicological study; and better understanding of the barriers and facilitators for behaviour that drives improved indoor air quality. Median daily PM 2.5 and CO 2 concentrations varied from 7.8 μg m -3 and 666 ppm in the summer, to 16.4 μg m -3 and 857 ppm in the winter respectively in our sampled homes. Peak daily PM 2.5 concentrations above 150 μg m -3 were frequently observed across all seasons, and were driven by cooking. Cooking activities also generated high concentrations of volatile organic compounds during emissions measurements, such as harmful aldehydes (up to ∼50 ppb), and alcohols (up to ∼600 ppb) from a chicken stir-fry. Our sampled homes displayed a wide variation in indoor pollutant concentrations, with a strong link to behaviour, including frequency and type of cooking activities, and use of ventilation.

Introduction: Relative to outdoor air pollution, there is little evidence examining the composition and concentrations of indoor air pollution and its associated health impacts. The INGENIOUS project aims to provide the comprehensive understanding of indoor air pollution in UK homes., Methods and Analysis: 'Real Home Assessment' is a cross-sectional, multimethod study within INGENIOUS. This study monitors indoor air pollutants over 2 weeks using low-cost sensors placed in three rooms in 300 Born in Bradford (BiB) households. Building audits are completed by researchers, and participants are asked to complete a home survey and a health and behaviour questionnaire, in addition to recording household activities and health symptoms on at least 1 weekday and 1 weekend day. A subsample of 150 households will receive more intensive measurements of volatile organic compound and particulate matter for 3 days. Qualitative interviews conducted with 30 participants will identify key barriers and enablers of effective ventilation practices. Outdoor air pollution is measured in 14 locations across Bradford to explore relationships between indoor and outdoor air quality. Data will be analysed to explore total concentrations of indoor air pollutants, how these vary with building characteristics, and whether they are related to health symptoms. Interviews will be analysed through content and thematic analysis., Ethics and Dissemination: Ethical approval has been obtained from the NHS Health Research Authority Yorkshire and the Humber (Bradford Leeds) Research Ethics Committee (22/YH/0288). We will disseminate findings using our websites, social media, publications and conferences. Data will be open access through the BiB, the Open Science Framework and the UK Data Service., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: The Born in Bradford's Better Start (BiBBS) interventional birth cohort study was designed as an innovative cohort platform for efficient evaluation of early life interventions delivered through the Better Start Bradford programme. There are a growing number of interventional cohorts being implemented internationally. This paper provides an interim analysis of BiBBS in order to share learning about the feasibility and value of this method. Methods: Recruitment began in January 2016 and will complete in December 2023 with a target sample of 5,000 pregnancies. An interim analysis was completed for all pregnancies recruited between January 2016 and November 2019 with an expected due date between 1 st April 2016 and 8 th March 2020. Descriptive statistics were completed on the data. Results: Of 4,823 eligible pregnancies, 2,626 (54%) pregnancies were recruited, resulting in 2,392 mothers and 2,501 children. The sample are representative of the pregnant population (61% Pakistani heritage; 12% White British; 8% other South Asian and 6% Central and Eastern European ethnicity). The majority of participants (84%) live in the lowest decile of the Index of Multiple Deprivation, and many live in vulnerable circumstances. A high proportion (85%) of BiBBS families have engaged in one or more of the Better Start Bradford interventions. Levels of participation varied by the characteristics of the interventions, such as the requirement for active participation and the length of commitment to a programme. Conclusions: We have demonstrated the feasibility of recruiting an interventional cohort that includes seldom heard families from ethnic minority and deprived backgrounds. The high level of uptake of interventions is encouraging for the goal of evaluating the process and outcomes of multiple early life interventions using the innovative interventional cohort approach. BiBBS covers a period before, during and after the coronavirus disease 2019 (COVID-19) pandemic which adds scientific value to the cohort., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Dickerson J et al.)

Background: Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in South Asians. Foetal kidney size was smaller in South Asians in the Born in Bradford (BiB) birth cohort. As part of BiB follow up, we aimed to investigate if there were ethnic differences in kidney function and blood pressure in early childhood and whether this was different by foetal kidney size. Methods: Serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP) were analysed in blood and urine samples from those who participated in the BiB follow-up at 7-11 years. Ethnicity was categorised by parental self-report as White European and South Asian. Estimated glomerular filtration rate (eGFR) was calculated using Schwartz, and cystatin C Zappitelli and Filler equations. Linear regression was used to examine the association between ethnicity and eGFR, PCR and blood pressure. Results: 1591 children provided blood (n=1403) or urine (n=625) samples. Mean eGFR was 92 ml/min/1.73m 2 (standard deviation (SD) 9) using Schwartz (n=1156) and 94 (SD 11) using Zappitelli (n=1257). CKD prevalence was rare (1 with eGFR <60 ml/min/1.73m 2 , 14 (2.4%) had raised ACR (>2.5 mg/mmol in boys/3.5 mg/mmol in girls). Diastolic blood pressure was higher in South Asian children (difference 2.04 mmHg, 95% CI 0.99 to 3.10) but was not significant in adjusted analysis. There was no evidence of association in adjusted models between ethnicity and any eGFR or urinary measure at this age. Conclusions: There was no evidence of significant ethnic differences in kidney function at pre-pubertal age despite differences in kidney volume at birth. Longitudinal follow-up is required to track ethnic patterns in kidney function and blood pressure as children develop through puberty., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Ziauddeen N et al.)

Background: Understanding differences in sensitization profiles at the molecular allergen level is important for diagnosis, personalized treatment and prevention strategies in allergy., Methods: Immunoglobulin E (IgE) sensitization profiles were determined in more than 2800 sera from children in nine population-based cohorts in different geographical regions of Europe; north [BAMSE (Sweden), ECA (Norway)], west/central [PIAMA (the Netherlands), BiB (the United Kingdom), GINIplus (Germany)], and south [INMA Sabadell and Gipuzkoa (Spain) and ROBBIC Rome and Bologna (Italy)] using the MeDALL-allergen chip., Results: Sensitization to grass pollen allergen, Phl p 1, and to major cat allergen, Fel d 1, dominated in most European regions whereas sensitization to house dust mite allergens Der p 1, 2 and 23 varied considerably between regions and were lowest in the north. Less than half of children from Sabadell which has a hot and dry climate were sensitized to respiratory allergens, in particular house dust mite allergens as compared to Gipuzkoa nearby with a more humid climate. Peanut allergen Ara h 1 was the most frequently recognized class 1 food allergen in Northern/Western Europe, while the fruit allergens Pru p 3, Act d 1 and 2 were prominent in Southern and Western/Central Europe. Ves v 5-sensitization dominated in North and West/Central Europe., Conclusion: We show regional, exposome- and climate-dependent differences in molecular IgE-reactivity profiles in Northern, Western/Central and Southern Europe which may form a molecular basis for precision medicine-based approaches for treatment and prevention of allergy., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown., (© 2023. The Author(s).)

Background: Foetal and early childhood development contributes to the risk of adult non-communicable diseases such as hypertension and cardiovascular disease. We aimed to investigate whether kidney size at birth is associated with markers of kidney function at 7-11 years., Methods: Foetal kidney dimensions were measured using ultrasound scans at 34 weeks gestation and used to derive kidney volume (cm 3 ) in 1802 participants in the Born in Bradford (BiB) birth cohort. Blood and urine samples were taken from those who participated in the BiB follow-up at 7-11 years (n = 630) and analysed for serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP). Estimated glomerular filtration rate (eGFR) was calculated using Schwartz creatinine only and combined with cystatin C, and cystatin C only Zappitelli and Filler equations. Linear regression was used to examine the association between foetal kidney volume and eGFR, ACR, PCR and blood pressure, unadjusted and adjusted for confounders., Results: Kidney volume was positively associated in adjusted models with eGFR calculated using Schwartz combined (0.64 ml/min diff per unit increase in volume, 95% CI 0.25 to 1.02), Zappitelli (0.79, 95% CI 0.38 to 1.20) and Filler (2.84, 95% CI 1.40 to 4.28). There was an association with the presence of albuminuria but not with its level, or with other urinary markers or with blood pressure., Conclusion: Foetal kidney volume was associated with small increases in eGFR in mid-childhood. Longitudinal follow-up to investigate the relationship between kidney volume and markers of kidney function as children go through puberty is required., (© 2023. The Author(s).)

Bisphenol A (BPA) is a widely known endocrine disruptor (ED) found in many children's products such as toys, feeding utensils, and teething rings. Recent epidemiology association studies have shown postnatal BPA exposure resulted in developing various diseases such as diabetes, obesity, and neurodegeneration, etc., later in their lives. However, little is known about its sex-specific metabolism and consequently internal exposure. The aim of this study was to develop a sex-specific pediatric physiologically based pharmacokinetic model (PBPK) for BPA to compare their toxicokinetic differences. First, the published adult PBPK model was re-validated, and then this model was extended by interpolation to incorporate pediatric sex specific physiological and biochemical parameters. We used both the classical body weight and ontogeny-based scaling approach to interpolate the metabolic process. Then, the pharmacokinetic attributes of the models using the two-scaling approach mentioned above were compared with adult model. Further, a sex-specific PBPK model with an ontogeny scaling approach was preferred to evaluate the pharmacokinetic differences. Moreover, this model was used to reconstruct the BPA exposure from two cohorts (Helix and PBAT Cohort) from 7 EU countries. The half-life of BPA was found to be almost the same in boys and girls at the same exposure levels. Our model estimated BPA children's exposure to be about 1500 times higher than the tolerable daily intake (TDI) recently set by European Food Safety Authority (EFSA) i.e., 0.04 ng/kg BW/day. The model demonstrated feasibility of extending the adult PBPK to sex-specific pediatric, thus investigate a gender-specific health risk assessment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Children and adolescents generally experience mild COVID-19. However, those with underlying physical health conditions are at a significantly increased risk of severe disease. Here, we present a comprehensive analysis of antibody and cellular responses in adolescents with severe neuro-disabilities who received COVID-19 vaccination with either ChAdOx1 (n=6) or an mRNA vaccine (mRNA-1273, n=8, BNT162b2, n=1). Strong immune responses were observed after vaccination and antibody levels and neutralisation titres were both higher after two doses. Both measures were also higher after mRNA vaccination and were further enhanced by prior natural infection where one vaccine dose was sufficient to generate peak antibody response. Robust T-cell responses were generated after dual vaccination and were also higher following mRNA vaccination. Early T-cells were characterised by a dominant effector-memory CD4+ T-cell population with a type-1 cytokine signature with additional production of IL-10. Antibody levels were well-maintained for at least 3 months after vaccination and 3 of 4 donors showed measurable neutralisation titres against the Omicron variant. T-cell responses also remained robust, with generation of a central/stem cell memory pool and showed strong reactivity against Omicron spike. These data demonstrate that COVID-19 vaccines display strong immunogenicity in adolescents and that dual vaccination, or single vaccination following prior infection, generate higher immune responses than seen after natural infection and develop activity against Omicron. Initial evidence suggests that mRNA vaccination elicits stronger immune responses than adenoviral delivery, although the latter is also higher than seen in adult populations. COVID-19 vaccines are therefore highly immunogenic in high-risk adolescents and dual vaccination might be able to provide relative protection against the Omicron variant that is currently globally dominant., Competing Interests: MR received funding for the COV-BOOST trial under contract via University Hospital Southampton NHS Foundation Trust, Funded by the UK NIHR/Vaccine Task Force (NIHR203292). Post-marketing surveillance reports on pneumococcal and meningococcal infection have been provided to vaccine manufacturers for which a cost recovery charge was made to GSK and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dowell, Powell, Davis, Scott, Logan, Willett, Bruton, Ayodele, Jinks, Gunn, Spalkova, Sylla, Nicol, Zuo, Ireland, Okike, Baawuah, Beckmann, Ahmad, Garstang, Brent, Brent, White, Collins, Davis, Lim, Cohen, Kenny, Linley, Poh, Amirthalingam, Brown, Ramsay, Azad, Wright, Waiblinger, Moss and Ladhani.)

SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3-11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens., (© 2021. The Author(s).)

Background: Maternal iodine requirements increase during pregnancy to supply thyroid hormones critical for fetal neurodevelopment. Iodine insufficiency may result in poorer cognitive or child educational outcomes but current evidence is sparse and inconsistent., Objectives: To quantify the association between maternal iodine status and child educational outcomes., Methods: Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6971 mothers at 26-28 weeks' gestation participating in the Born in Bradford cohort. Maternal iodine status was examined in relation to child school achievement (early years foundation stage (EYFS), phonics, and Key Stage 1 (KS1)), other learning outcomes, social and behavioural difficulties, and sensorimotor control in 5745 children aged 4-7 years., Results: Median (interquartile range) UIC was 76 µg/L (46, 120), and I:Cr was 83 µg/g (59, 121). Overall, there was no strong or consistent evidence to support associations between UIC or I:Cr and neurodevelopmental outcomes. For instance, predicted EYFS and phonics scores (primary outcomes) at the 25th vs 75th I:Cr percentiles (99% confidence intervals) were similar, with no evidence of associations: EYFS scores were 32 (99% CI 31, 33) and 33 (99% CI 32, 34), and phonics scores were 34 (99% CI 33, 35) and 35 (99% CI 34, 36), respectively., Conclusions: In the largest single study of its kind, there was little evidence of detrimental neurodevelopmental outcomes in children born to pregnant women with iodine insufficiency as defined by World Health Organization-outlined thresholds. Alternative functional biomarkers for iodine status in pregnancy and focused assessment of other health outcomes may provide additional insight., (© 2020 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Iodine is essential for normal thyroid function, supporting healthy fetal and child development. Iodine requirements increase in pregnancy, but many women in regions without salt iodization have insufficient intakes. We explored associations between iodide intake and urinary iodine concentration (UIC), urinary iodine/creatinine ratio (I/Cr), thyroid stimulating hormone, thyroglobulin, free triiodothyronine, free thyroxine and palpable goiter in a region of mild-to-moderate iodine insufficiency. A total of 246 pregnant women aged 18-40 in Bradford, UK, joined the Health and Iodine in Babies (Hiba) study. They provided detailed information on diet and supplement use, urine and serum samples and were assessed for goiter at around 12, 26 and 36 weeks' gestation, and 6, 18 and 30 weeks postpartum. Dietary iodide intake from food and drink was estimated using six 24 h recalls. During pregnancy, median (IQR) dietary iodide intake was 101 µg/day (54, 142), with 42% from dairy and 9% from white fish. Including supplements, intake was 143 µg/day (94, 196), with 49% < UK reference nutrient intake (140 µg/day). Women with Pakistani heritage had 129 µg/day (87, 190) median total intake. Total intake during pregnancy was associated with 4% (95% CI: 1%, 7%) higher UIC, 5% (3%, 7%) higher I/Cr, 4% (2%, 6%) lower thyroglobulin and 21% (9%, 32%) lower odds of palpable goiter per 50 µg/day. This cohort consumed less iodide in pregnancy than UK and World Health Organization dietary recommendations. UIC, I/Cr and thyroglobulin were associated with intake. Higher intake was associated with fewer goiters. Because dairy was the dominant source of iodide, women following plant-based or low-dairy diets may be at particular risk of iodine insufficiency.

Background: Maternal iodine requirements increase during pregnancy to supply thyroid hormones essential for fetal brain development. Maternal iodine deficiency can lead to hypothyroxinemia, a reduced fetal supply of thyroid hormones which, in the first trimester, has been linked to an increased risk of autism spectrum disorder (ASD) in the child. No study to date has explored the direct link between maternal iodine deficiency and diagnosis of ASD in offspring., Methods: Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6955 mothers at 26-28 weeks gestation participating in the Born in Bradford (BiB) cohort. Maternal iodine status was examined in relation to the probability of a Read (CTV3) code for autism being present in a child's primary care records through a series of logistic regression models with restricted cubic splines., Results: Median (inter-quartile range) UIC was 76 μg/L (46, 120) and I:Cr was 83 μg/g (59, 121) indicating a deficient population according to WHO guidelines. Ninety two children (1·3%) in our cohort had received a diagnosis of ASD by the census date. Overall, there was no evidence to support an association between I:Cr or UIC and ASD risk in children aged 8-12 years (p = 0·3)., Conclusions: There was no evidence of an increased clinical ASD risk in children born to mothers with mild-to-moderate iodine deficiency at 26 weeks gestation. Alternative functional biomarkers of exposure and a wider range of conditions may provide further insight.

Background: Severe iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth outcomes. A limited number of studies have examined iodine status and birth outcomes, finding inconsistent evidence for specific outcomes., Methods: Maternal iodine status was estimated from spot urine samples collected at 26-28 weeks' gestation from 6971 mothers in the Born in Bradford birth cohort. Associations with outcomes were examined for both urinary iodine concentration (UIC) and iodine-to-creatinine ratio (I:Cr). Outcomes assessed included customised birthweight (primary outcome), birthweight, small for gestational age (SGA), low birthweight, head circumference and APGAR score., Results: There was a small positive association between I:Cr and birthweight in adjusted analyses. For a typical participant, the predicted birthweight centile at the 25th percentile of I:Cr (59 μg/g) was 2.7 percentage points lower than that at the 75th percentile of I:Cr (121 μg/g) (99% confidence interval (CI) 0.8 to 4.6), birthweight was predicted to be 41 g lower (99% CI 13 to 69) and the predicted probability of SGA was 1.9 percentage points higher (99% CI 0.0 to 3.7). There was no evidence of associations using UIC or other birth outcomes, including stillbirth, preterm birth, ultrasound growth measures or congenital anomalies., Conclusion: Lower maternal iodine status was associated with lower birthweight and greater probability of SGA. Whilst small, the effect size for lower iodine on birthweight is comparable to environmental tobacco smoke exposure. Iodine insufficiency is avoidable, and strategies to avoid deficiency in women of reproductive age should be considered., Trial Registration: ClinicalTrials.gov NCT03552341. Registered on June 11, 2018.

Background: The prevalence of allergic diseases has increased in recent decades, but the causes remain unclear. Changes in the epidemiology of childhood infections could have contributed, but the current evidence is inconclusive. This study aims to investigate whether age at cytomegalovirus (CMV), Epstein-Barr virus (EBV) or varicella zoster virus (VZV) infection is associated with the development of atopy., Methods: A total of 2559 children were enrolled in the Born in Bradford Allergy and Infection Study. Serum samples collected at 12 and 24 months were tested for CMV-IgG, EBV-IgG and VZV-IgG for 1000 children to establish age at infection. Skin prick testing (SPT) was conducted at age 4 years., Results: Serology and SPT results were available for 740 children. Of these, 135 (18%) were atopic. In girls, there was a strong association of CMV infection in the second year with increased odds of atopy (adjusted OR 4.38, 95% CI 1.87-10.29) but this was not observed in boys. Age at EBV or VZV infection was not associated with risk of atopy in unadjusted analysis, but there was effect modification by sex; girls infected with VZV in the second year of life had increased odds of atopy (adjusted OR 2.85, 95% CI 1.29-6.30)., Conclusions: Our results highlight potential sex-specific effects of age at CMV infection and age at VZV infection on risk of atopy, which provide insight into the mechanisms involved in the development of atopy., (© 2019 The Authors. Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.)

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.

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 (PM 2.5 ), 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 PM 2.5 levels higher than recommended (≥25μg/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 < 0.30). The levels of personal external exposures in both pregnant women and children are above the health recommendations, and there is little correlation between the different exposures. The assessment of the personal external exposome is feasible but sampling requires from one day to more than one year depending on exposure due to high variability between and within cities and participants., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Exposome studies are challenged by exposure misclassification for non-persistent chemicals, whose temporal variability contributes to bias in dose-response functions., Objectives: We evaluated the variability of urinary concentrations of 24 non-persistent chemicals: 10 phthalate metabolites, 7 phenols, 6 organophosphate (OP) pesticide metabolites, and cotinine, between weeks from different pregnancy trimesters in pregnant women, and between days and between seasons in children., Methods: 154 pregnant women and 152 children from six European countries were enrolled in 2014-2015. Pregnant women provided three urine samples over a day (morning, midday, and night), for one week in the 2nd and 3rd pregnancy trimesters. Children provided two urines a day (morning and night), over two one-week periods, six months apart. We pooled all samples for a given subject that were collected within a week. In children, we also made four daily pools (combining morning and night voids) during the last four days of the first follow-up week. Pools were analyzed for all 24 metabolites of interest. We calculated intraclass-correlation coefficients (ICC) and estimated the number of pools needed to obtain an ICC above 0.80., Results: All phthalate metabolites and phenols were detected in >90% of pools whereas certain OP pesticide metabolites and cotinine were detected in <43% of pools. We observed fair (ICC = 0.40-0.59) to good (0.60-0.74) between-day reliability of the pools of two samples in children for all chemicals. Reliability was poor (<0.40) to fair between trimesters in pregnant women and between seasons in children. For most chemicals, three daily pools of two urines each (for weekly exposure windows) and four weekly pools of 15-20 urines each would be necessary to obtain an ICC above 0.80., Conclusions: This quantification of the variability of biomarker measurements of many non-persistent chemicals during several time windows shows that for many of these compounds a few dozen samples are required to accurately assess exposure over periods encompassing several trimesters or months., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations., Participants: The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6-11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level)., Findings to Date: Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6-11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder., Future Plans: HELIX study results will inform on the early life exposome and its association with molecular omics signatures and child health outcomes. Cohort data are accessible for future research involving researchers external to the project., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cytomegalovirus (CMV), Epstein Barr virus (EBV) and varicella-zoster virus (VZV) are common herpesviruses frequently acquired in childhood, which establish persistent, latent infection and are likely to impact the developing immune system. Little is known about the epidemiology of CMV and EBV infections in contemporary UK paediatric populations, particularly whether age at infection differs by ethnic group., Methods: Children enrolled in the Born in Bradford Allergy and Infection Study had a blood sample taken and a questionnaire completed at 12 and 24 months of age. Ordered logistic regression quantified associations between ethnicity and other risk factors and age at CMV/EBV/VZV infection (<12 months, 12-24 months, uninfected at 24 months)., Results: Pakistani children (n = 472) were more likely to be infected with CMV and EBV at a younger age than White British children (n = 391) (CMV: adjusted odds ratio (OR) 2.53, 95% confidence interval (CI) 1.47-4.33; EBV: adjusted OR 2.16, 95% CI 1.43-3.26). Conversely, Pakistani children had lower odds of being VZV infected in the second year than White British children (adjusted OR 0.57, 95% CI 0.33-0.97). There was a strong association between increasing birth order and later CMV infection in Pakistani children., Conclusions: We report large differences in CMV and EBV incidence in the first 2 years between Pakistani and White British children born in Bradford, which cannot be explained by differences in risk factors for infection. Our data will inform the optimum schedule for future CMV and EBV vaccination programmes.

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.

Background: Using a multi-methods approach we aimed to explore the relative prediction of demographic, socioeconomic and modifiable predictors from the Theory of Planned behaviour (TPB) in explaining feeding intentions amongst a multi-ethnic sample., Methods: 476 women completed a questionnaire at 28 weeks gestation. They were grouped into breastfeeding (N = 258), mixed-feeding (N = 50), bottle-feeding (N = 88) intenders, or a no clear intention (N = 88). Multinomial adjusted regressions explored the influence of modifiable TPB factors, along with ethnicity and socioeconomic status in predicting group membership. Free-text responses allowed women to elaborate on reasons behind their intention., Results: TPB factors were significant predictors of feeding intention. Women with high intention to breastfeed were less likely to report high attitudes in any other feeding alternative. Bottle-feeding intenders reported poorer self-efficacy regarding breastfeeding compared to breastfeeding intenders (prevalence rate ratio, PRR = 0.10). Mixed and bottle-feeding intenders reported greater self-efficacy for mixed-feeding (PRR = 1.80, 5.50 respectively). Descriptive norms for mixed (PRR = 13.77) and bottle-feeding (PRR = 10.68) were predictive of mixed-feeding intention. Reasons for breastfeeding intentions related to health considerations, whilst bottle-feeding reasons related to convenience. Mixed-feeding intenders reported both breast and bottle-related factors., Conclusions: Understanding modifiable predictors related to feeding intentions like TPB factors can help professionals target appropriate interventions to encourage breastfeeding.

Background: Numerous birth cohorts have been initiated in the world over the past 30 years using heterogeneous methods to assess the incidence, course and risk factors of asthma and allergies. The aim of the present work is to provide the stepwise proceedings of the development and current version of the harmonized MeDALL-Core Questionnaire (MeDALL-CQ) used prospectively in 11 European birth cohorts., Methods: The harmonization of questions was accomplished in 4 steps: (i) collection of variables from 14 birth cohorts, (ii) consensus on questionnaire items, (iii) translation and back-translation of the harmonized English MeDALL-CQ into 8 other languages and (iv) implementation of the harmonized follow-up., Results: Three harmonized MeDALL-CQs (2 for parents of children aged 4-9 and 14-18, 1 for adolescents aged 14-18) were developed and used for a harmonized follow-up assessment of 11 European birth cohorts on asthma and allergies with over 13,000 children., Conclusions: The harmonized MeDALL follow-up produced more comparable data across different cohorts and countries in Europe and will offer the possibility to verify results of former cohort analyses. Thus, MeDALL can become the starting point to stringently plan, conduct and support future common asthma and allergy research initiatives in Europe., (© 2014 S. Karger AG, Basel.)

Background: Initiation of breast feeding and duration of any breast feeding are known to differ by ethnic group, but there are limited data on differences in exclusive breast feeding. This study aimed to determine if there are ethnic differences in the initiation and duration of any and exclusive breast feeding., Methods: Breast-feeding data were obtained from a subsample of 1365 women recruited to a multi-ethnic cohort study (Born in Bradford) between August 2008 and March 2009. Poisson regression was used to investigate the impact of socio-economic, life style and birth factors on ethnic differences in the prevalence of breast feeding., Results: Compared with white British mothers, initiation of breast feeding was significantly higher in all ethnic groups and this persisted after adjustment for socio-economic, life style and birth factors [Pakistani: prevalence rate ratio (PRR) = 1.19 (95% confidence interval 1.10, 1.29); Other South Asian: PRR = 1.29 (1.18, 1.42); Other ethnicities: PRR = 1.33 (1.21, 1.46)]. There were no differences in exclusive breast feeding at 4 months [Pakistani: PRR = 0.77 (0.54, 1.09); Other South Asian: PRR = 1.55 (0.99, 2.43); Other ethnicities: PRR = 1.50 (0.88, 2.56)]. Any breast feeding at 4 months was significantly higher in mothers of all non-white British ethnicities [Pakistani: PRR = 1.27 (1.02, 1.58); Other South Asian: PRR = 1.99 (1.52, 2.62); Other ethnicities: 2.45 (1.86, 3.21)]., Conclusions: Whilst women of ethnic minority groups were significantly more likely to initiate breast feeding and continue any breast feeding for 4 months compared with white British women, the rates of exclusive breast feeding at 4 months were not significantly different once socio-economic, life style and birth factors were accounted for., (© 2013 John Wiley & Sons Ltd.)

Background: Despite reported differences in breastfeeding rates amongst women of different ethnic groups, little research has investigated whether the thoughts and feelings (social cognitions) of women from these different groups during pregnancy influence their later breastfeeding behaviour., Objective: This study investigates the extent to which social cognitions (based on the Theory of Planned Behaviour; TPB) predict differences in breastfeeding intentions, initiation, and maintenance between White British (WB) and South Asian (SA) women., Design and Methods: Two hundred and fifty women (predominantly WB or SA) in the last trimester of pregnancy completed a questionnaire based on the TPB. The women were followed up 6 months later and their breastfeeding during the previous 6 months was recorded., Results: The TPB predicted significant variance in breastfeeding across the sample and was able to account for differences between SA and WB women. Affective attitudes (emotional reactions to breastfeeding) and moral norms (reactions about whether breastfeeding is right or wrong) were the strongest predictors of intentions. Intentions and affective attitudes were predictive of breastfeeding initiation, whilst only affective attitudes were predictive of breastfeeding maintenance., Conclusion: Stronger intentions to breastfeed led to higher rates of breastfeeding amongst SA women. In turn, intentions were predicted by emotional and moral beliefs about breastfeeding, beliefs that were less positive amongst a WB sample. This suggests that those tasked with encouraging breastfeeding may need to have a different conversation with women about breastfeeding that goes beyond a focus on costs and benefits., (©2012 The British Psychological Society.)

Assessing neonatal size reliably is important for research and clinical practice. The aim of this study was to examine the reliability of routine clinical measurements of neonatal circumferences and of skinfold thicknesses assessed for research purposes. All measurements were undertaken on the same population of neonates born in a large maternity unit in Bradford, UK. Technical error of measurement (TEM), relative TEM and the coefficient of reliability are reported. Intra-observer TEMs for routine circumference measurements were all below 0.4 cm and were generally within ± 2-times the mean. Inter-observer TEM ranged from 0.20 to 0.36 cm for head circumference, 0.19 to 0.39 cm for mid upper arm circumference and from 0.39 to 0.77 cm for abdominal circumference. Intra and inter-observer TEM for triceps skinfold thickness ranged from 0.22 to 0.35 mm and 0.15 to 0.54 mm, respectively. Subscapular skinfold thickness TEM values were 0.14 to 0.25 mm for intra-observer measurements and 0.17 to 0.63 mm for inter-observer measurements. Relative TEM values for routine circumferences were all below 4.00% but varied between 2.88% and 14.23% for research skinfold measurements. Reliability was mostly between 80% and 99% for routine circumference measurements and ≥ 70% for most research skinfold measurements. Routine clinical measurements of neonatal circumferences are reliably assessed in Bradford. Assessing skinfolds in neonates has variable reliability, but on the whole is good. The greater intra-observer, compared with inter-observer, reliability for both sets of measurements highlights the importance of having a minimal number of assessors whenever possible., (© 2011 Blackwell Publishing Ltd.)