Avon Longitudinal Study Of Parents And Children Participants Research Articles

Climate change beliefs and behaviours: Data collected from 30-year-old offspring and their parents in the Avon Longitudinal Study of Parents and Children (ALSPAC)

Climate change is causing a suite of environmental and social issues. Understanding patterns of climate change beliefs and behaviours, and the factors which shape these attitudes and actions, is therefore essential. This data note describes the novel data collection of climate belief and behaviour questions embedded within the Avon Longitudinal Study of Parents and Children (ALSPAC), a longitudinal population-based birth cohort in southwest England. Two generations of ALSPAC participants completed the questionnaires containing these climate questions: the Generation-1 (G1) offspring (n=4,341), Generation-0 (G0) mothers (n=4,793), and the G0 mother’s partners (n=2,111). The questions asked about: belief in climate change; concern over climate change; whether climate change is caused by human activity; whether individual behaviours can impact climate change; the impacts of climate change in the participants’ local area; and whether participants were engaging in any of 17 pro-environmental behaviours (e.g., recycling more, reducing meat/dairy consumption) for climate change and/or other reasons. The majority of participants believed the climate was definitely changing (~80%), were somewhat or very concerned about climate change (~90%) and attributed most or all of climate change to human activity (~75%), with only small differences between the generations. On average, participants reported engaging in between 5 and 6 actions because of concerns regarding climate change (5.8 in G0 mothers; 5.2 in G1 offspring and G0 partners). Associations with sociodemographic factors (e.g., age, sex, ethnicity and socioeconomic background) were relatively weak, but positive relationships between highest level of education and greater climate change belief, concern and behaviours were evident. Increased climate belief and concern also predicted engaging in more pro-environmental actions. Responses to these climate questions were more similar within-families. This data note provides important information for future users of these data, as well as discussing some of the key strengths, limitations and considerations for data users.

An observational analysis of risk factors associated with symptomatic third molar teeth.

Third molar teeth (wisdom teeth) are a common cause of pain and infection in young adults. The study aimed to describe the prevalence of symptomatic third molar teeth and identify factors which predispose to third molar symptoms in a birth cohort. An observational study was undertaken nested in the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort based in south west England. The main outcomes were self-reported third molar pain, swelling and treatment for third molar problems, taken from questionnaires completed at age 23 years. The exposures including sex, dental history, socioeconomic status, diet, and genetic factors were obtained from earlier ALSPAC data. In total 4,222 ALSPAC participants responded to one or more questions about third molar teeth. The final sample included more female participants than male participants. The majority of participants (56.6%) reported at least one episode of pain associated with their third molars. Females had greater odds than males of reporting swelling (adjusted odds ratio (OR) 1.97; 95%confidence interval (CI) 1.56, 2.51), pain (adjusted OR=1.96; 95%CI 1.56, 2.51) and receiving both non-surgical and surgical treatment (adjusted OR=2.30; 95%CI 1.62, 3.35, adjusted OR=1.54; 95%CI 1.17, 2.06 respectively). Participants with previously filled teeth had greater odds of third molar extraction. There were no strong associations betweenindex of multiple deprivation (IMD) score or sugar intake and the third molar outcomes. There was weak evidence for a genetic contribution to third molar pain. Symptomatic third molars are common in this age group, with over half of the participants reporting pain or other symptoms. Female participants had greater odds for third molar pain, swelling and treatment.

Association between the timing of childhood adversity and epigenetic patterns across childhood and adolescence: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort

Childhood adversity is a potent determinant of health across development and is associated with altered DNA methylation signatures, which might be more common in children exposed during sensitive periods in development. However, it remains unclear whether adversity has persistent epigenetic associations across childhood and adolescence. We aimed to examine the relationship between time-varying adversity (defined through sensitive period, accumulation of risk, and recency life course hypotheses) and genome-wide DNA methylation, measured three times from birth to adolescence, using data from a prospective, longitudinal cohort study. We first investigated the relationship between the timing of exposure to childhood adversity between birth and 11 years and blood DNA methylation at age 15 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort study. Our analytic sample included ALSPAC participants with DNA methylation data and complete childhood adversity data between birth and 11 years. We analysed seven types of adversity (caregiver physical or emotional abuse, sexual or physical abuse [by anyone], maternal psychopathology, one-adult households, family instability, financial hardship, and neighbourhood disadvantage) reported by mothers five to eight times between birth and 11 years. We used the structured life course modelling approach (SLCMA) to identify time-varying associations between childhood adversity and adolescent DNA methylation. Top loci were identified using an R2 threshold of 0·035 (ie, ≥3·5% of DNA methylation variance explained by adversity). We attempted to replicate these associations using data from the Raine Study and Future of Families and Child Wellbeing Study (FFCWS). We also assessed the persistence of adversity-DNA methylation associations we previously identified from age 7 blood DNA methylation into adolescence and the influence of adversity on DNA methylation trajectories from ages 0-15 years. Of 13 988 children in the ALSPAC cohort, 609-665 children (311-337 [50-51%] boys and 298-332 [49-50%] girls) had complete data available for at least one of the seven childhood adversities and DNA methylation at 15 years. Exposure to adversity was associated with differences in DNA methylation at 15 years for 41 loci (R2 ≥0·035). Sensitive periods were the most often selected life course hypothesis by the SLCMA. 20 (49%) of 41 loci were associated with adversities occurring between age 3 and 5 years. Exposure to one-adult households was associated with differences in DNA methylation at 20 [49%] of 41 loci, exposure to financial hardship was associated with changes at nine (22%) loci, and physical or sexual abuse was associated with changes at four (10%) loci. We replicated the direction of associations for 18 (90%) of 20 loci associated with exposure to one-adult household using adolescent blood DNA methylation from the Raine Study and 18 (64%) of 28 loci using saliva DNA methylation from the FFCWS. The directions of effects for 11 one-adult household loci were replicated in both cohorts. Differences in DNA methylation at 15 years were not present at 7 years and differences identified at 7 years were no longer apparent by 15 years. We also identified six distinct DNA methylation trajectories from these patterns of stability and persistence. These findings highlight the time-varying effect of childhood adversity on DNA methylation profiles across development, which might link exposure to adversity to potential adverse health outcomes in children and adolescents. If replicated, these epigenetic signatures could ultimately serve as biological indicators or early warning signs of initiated disease processes, helping identify people at greater risk for the adverse health consequences of childhood adversity. Canadian Institutes of Health Research, Cohort and Longitudinal Studies Enhancement Resources, EU's Horizon 2020, US National Institute of Mental Health.

Evaluating future risk of NAFLD in adolescents: a prediction and decision curve analysis

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the commonest liver condition in the western world and is directly linked to obesity and the metabolic syndrome. Elevated body mass index is regarded as a major risk factor of NAFL (steatosis) and NAFLD fibrosis. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we sought to investigate whether other variables from adolescence could improve prediction of future NAFL and NAFLD fibrosis risk at 24 years, above BMI and sex.MethodsAged 24 years, 4018 ALSPAC participants had transient elastography (TE) and controlled attenuation parameter (CAP) measurement using Echosens 502 Touch. 513 participants with harmful alcohol consumption were excluded. Logistic regression models examined which variables measured at 17 years were predictive of NAFL and NAFLD fibrosis in young adults. Predictors included sex, BMI, central adiposity, lipid profile, blood pressure, liver function tests, homeostatic model assessment for insulin resistance (HOMA-IR), and ultrasound defined NAFL at 17 years (when examining fibrosis outcomes). A model including all these variables was termed “routine clinical measures”. Models were compared using area under the receiver operator curve (AUROC) and Bayesian Information Criterion (BIC), analysis, which penalises model complexity. Models were tested in all participants and those with overweight or obese standardised BMIs (BMI SDS) centiles at the 17-year time point. A decision curve analysis (DCA) was performed to evaluate the clinical utility of models in overweight and obese adolescents predicting NAFLD fibrosis at a threshold probability of 0.1.ResultsThe “routine clinical measures” model had the highest AUROC for predicting NAFL in all adolescent participants (AUROC 0.79 [SD 0.00]) and those with an overweight/obese BMI SDS centile (AUROC 0.77 [SD 0.01]). According to BIC analysis, insulin resistance was the best predictor of NAFL in all adolescents, whilst central adiposity was the best predictor in those with an overweight/obese BMI SDS centile. The “routine clinical measures” model also had the highest AUROC for predicting NAFLD fibrosis in all adolescent participants (AUROC 0.78 [SD 0.02]) and participants with an overweight/obese BMI SDS centile (AUROC 0.84 [SD 0.03]). However, following BIC analysis, BMI was the best predictor of NAFLD fibrosis in all adolescents including those with an overweight/obese BMI SDS centile. A decision curve analysis examining overweight/obese adolescent participants showed the model that had the greatest net benefit for increased NAFLD fibrosis detection, above a treat all overweight and obese adolescents’ assumption, was the “routine clinical measures” model. However, the net benefit was marginal (0.0054 [0.0034–0.0075]).ConclusionIn adolescents, routine clinical measures were not superior to central adiposity and BMI at predicting NAFL and NAFLD fibrosis respectively in young adulthood. Additional routine clinical measurements do provide incremental benefit in detecting true positive fibrosis cases, but the benefit is small. Thus, to reduce morbidity and mortality associated with NASH cirrhosis in adults, the ultimate end point of NAFLD, the focus must be on obesity management at a population level.

An observational analysis of risk factors associated with symptomatic third molar teeth

Background: Third molar teeth (wisdom teeth) are a common cause of pain and infection in young adults. The study aimed to describe the prevalence of symptomatic third molar teeth and identify factors which predispose to third molar symptoms in a birth cohort. Methods: An observational study was undertaken nested in the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort based in south west England. The main outcomes were self-reported third molar pain, swelling and treatment for third molar problems, taken from questionnaires completed at age 23 years. The exposures including sex, dental history, socioeconomic status, diet, and genetic factors were obtained from earlier ALSPAC data. Results: In total 4,222 ALSPAC participants responded to one or more questions about third molar teeth. The final sample included more female participants than male participants. The majority of participants (56.6%) reported at least one episode of pain associated with their third molars. Females had greater odds than males of reporting swelling (adjusted odds ratio (OR) 1.97; 95%confidence interval (CI) 1.56, 2.51), pain (adjusted OR=1.96; 95%CI 1.56, 2.51) and receiving both non-surgical and surgical treatment (adjusted OR=2.30; 95%CI 1.62, 3.35, adjusted OR=1.54; 95%CI 1.17, 2.06 respectively). Participants with previously filled teeth had greater odds of third molar extraction. There were no strong associations between index of multiple deprivation (IMD) score or sugar intake and the third molar outcomes. There was weak evidence for a genetic contribution to third molar pain. Conclusions: Symptomatic third molars are common in this age group, with over half of the participants reporting pain or other symptoms. Female participants had greater odds for third molar pain, swelling and treatment.

The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Antibody testing results, April - June 2021.

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort which recruited pregnant women in 1990-1992 and has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. The study reacted rapidly and repeatedly to the coronavirus disease 2019 (COVID-19) pandemic, deploying multiple online questionnaires and a previous home-based antibody test in October 2020. A second antibody test, in collaboration with ten other longitudinal population studies, was completed by 4,622 ALSPAC participants between April and June 2021. Of 4,241 participants with a valid spike protein antibody test result (8.2% were void), indicating antibody response to either COVID-19 vaccination or natural infection, 3,172 were positive (74.8%). Generational differences were substantial, with 2,463/2,555 G0 participants classified positive (96.4%) compared to 709/1,686 G1 participants (42.1%). Of 4,199 participants with a valid nucleocapsid antibody test result (9.2% were void), suggesting potential and recent natural infection, 493 were positive (11.7%); 248/2,526 G0 participants (9.8%) and 245/1,673 G1 participants (14.6%) tested positive, respectively. We also compare results for this round of testing to that undertaken in October 2020. Future work will combine these test results with additional sources of data to identify participants' COVID-19 infection and vaccination status. These ALSPAC COVID-19 serology data are being complemented with linkage to health records and Public Health England pillar testing results as they become available, in addition to four previous questionnaire waves and a prior antibody test. Data have been released as an update to the previous COVID-19 datasets. These comprise: 1) a standard dataset containing all participant responses to all four previous questionnaires with key sociodemographic factors; and 2) individual participant-specific release files enabling bespoke research across all areas supported by the study. This data note describes the second ALSPAC antibody test and the data obtained from it.

The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Antibody testing results, April - June 2021.

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort which recruited pregnant women in 1990-1992 and has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. The study reacted rapidly and repeatedly to the coronavirus disease 2019 (COVID-19) pandemic, deploying multiple online questionnaires and a previous home-based antibody test in October 2020. A second antibody test, in collaboration with ten other longitudinal population studies, was completed by 4,622 ALSPAC participants between April and June 2021. Of participants with a valid spike protein antibody test result (4,241; 8.2% void), indicating antibody response to either COVID-19 vaccination or natural infection, 3,172 were positive (74.8%). Generational differences were substantial, with 2,463/2,555 G0 participants classified positive (96.4%) compared to 709/1,686 G1 participants (42.1%). Of participants with a valid nucleocapsid antibody test result (4,199; 9.2% void), suggesting potential and recent natural infection, 493 were positive (11.7%); with 248/2,526 G0 participants (9.8%) and 245/1,673 G1 participants (14.6%) testing positive, respectively. We also compare results for this round of testing to that undertaken in October 2020. Future work will combine these test results with additional sources of data to identify participants' COVID-19 infection and vaccination status. These ALSPAC COVID-19 serology data are being complemented with linkage to health records and Public Health England pillar testing results as they become available, in addition to four previous questionnaire waves and a prior antibody test. Data have been released as an update to the previous COVID-19 datasets. These comprise: 1) a standard dataset containing all participant responses to all four previous questionnaires with key sociodemographic factors; and 2) individual participant-specific release files enabling bespoke research across all areas supported by the study. This data note describes the second ALSPAC antibody test and the data obtained from it.

High Insulin in Early Childhood Is Associated with Subsequent Asthma Risk Independent of Body Mass Index

Asthma and obesity are major, interconnected public health challenges that usually have their origins in childhood, and for which the relationship is strengthened among those with insulin resistance. To determine whether high insulin in early life confers increased longitudinal risk for asthma independent of body mass index. The study used data from the Tucson Children's Respiratory Study (TCRS) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Nonfasting insulin was measured in TCRS participants at age 6 years and fasting insulin in ALSPAC participants at age 8 years. Physician-diagnosed active asthma was determined at baseline and at subsequent assessments up to age 36 years in TCRS and 17 years in ALSPAC. In TCRS, high insulin (upper quartile) at age 6 years was associated with increased odds of having active asthma from ages 8 to 36 years compared with low insulin (odds ratio,1.98; 95% CI, 1.28-3.05; P= .002). Similarly, in ALSPAC, high insulin was associated with a significantly higher risk of active asthma from ages 11 to 17 years compared with low insulin (odds ratio, 1.59; 95% CI, 1.12-2.27; P= .009). These findings were independent of baseline body mass index in both cohorts, and were not related to other demographic and asthma risk factors nor other tested markers of systemic inflammation and metabolic syndrome. In 2 separate birth cohorts, higher blood insulin level in early childhood was associated with increased risk of active asthma through adolescence and adulthood, independent of body mass index. High insulin indicates a novel mechanism for asthma development, which may be a target for intervention.

Gambling by Young Adults in the UK During COVID-19 Lockdown

Gambling is a common activity amongst young adults in the UK, and was a behavior of interest during the early mitigation against COVID-19 (first lockdown). The Avon Longitudinal Study of Parents and Children (ALSPAC) was used to investigate attitudes, moods and behavior during lockdown in England. ALSPAC participants were invited to complete online questionnaires in May 2020, including a set of questions about frequency of gambling and gambling activities which had been asked three years previously. Mental health and wellbeing data and alcohol use were also collected as part of lockdown questionnaires. Gambling questions were completed by 2632 young adults, 71% female, with a mean age of 27.8 years. Overall, gambling frequency reduced during lockdown for both males and females, but more males engaged in regular (weekly) gambling. Gambling activities became more restricted compared to previous reports, but online gambling (e.g. online poker, bingo, casino games) was more frequent. Previous gambling behaviour predicted gambling frequency during lockdown. No associations were apparent between gambling frequency and measures of mental health and well-being. Heavy alcohol use was strongly linked with regular gambling during lockdown. Gamblers were more than twice as likely as non-gamblers to have experienced financial difficulties pre-COVID, but gambling frequency was not related to employment status during lockdown. Online gambling increased during lockdown, whilst offline gambling activities decreased in frequency. A small minority of regular weekly gamblers, who tended to be male and heavy users of alcohol, participated in a wide range of online and offline gambling activities.

Development of Proteomic Prediction Models for Transition to Psychotic Disorder in the Clinical High-Risk State and Psychotic Experiences in Adolescence

Biomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies. To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population. This diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC). EU-GEI is an international multisite prospective study of participants at CHR referred from local mental health services. ALSPAC is a United Kingdom-based general population birth cohort. Included were EU-GEI participants who met CHR criteria at baseline and ALSPAC participants who did not report PEs at age 12 years. Data were analyzed from September 2018 to April 2020. In EU-GEI, transition status was assessed by the Comprehensive Assessment of At-Risk Mental States or contact with clinical services. In ALSPAC, PEs at age 18 years were assessed using the Psychosis-Like Symptoms Interview. Proteomic data were obtained from mass spectrometry of baseline plasma samples in EU-GEI and plasma samples at age 12 years in ALSPAC. Support vector machine learning algorithms were used to develop predictive models. The EU-GEI subsample (133 participants at CHR (mean [SD] age, 22.6 [4.5] years; 68 [51.1%] male) comprised 49 (36.8%) who developed psychosis and 84 (63.2%) who did not. A model based on baseline clinical and proteomic data demonstrated excellent performance for prediction of transition outcome (area under the receiver operating characteristic curve [AUC], 0.95; positive predictive value [PPV], 75.0%; and negative predictive value [NPV], 98.6%). Functional analysis of differentially expressed proteins implicated the complement and coagulation cascade. A model based on the 10 most predictive proteins accurately predicted transition status in training (AUC, 0.99; PPV, 76.9%; and NPV, 100%) and test (AUC, 0.92; PPV, 81.8%; and NPV, 96.8%) data. The ALSPAC subsample (121 participants from the general population with plasma samples available at age 12 years (61 [50.4%] male) comprised 55 participants (45.5%) with PEs at age 18 years and 61 (50.4%) without PEs at age 18 years. A model using proteomic data at age 12 years predicted PEs at age 18 years, with an AUC of 0.74 (PPV, 67.8%; and NPV, 75.8%). In individuals at risk of psychosis, proteomic biomarkers may contribute to individualized prognosis and stratification strategies. These findings implicate early dysregulation of the complement and coagulation cascade in the development of psychosis outcomes.

Prevalence of steatosis and fibrosis in young adults in the UK: a population-based study

SummaryBackgroundThe estimated worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) in adults is 25%; however, prevalence in young adults remains unclear. We aimed to identify the prevalence of steatosis and fibrosis in young adults in a sample of participants recruited through the Avon Longitudinal Study of Parents and Children (ALSPAC), based on transient elastography and controlled attenuation parameter (CAP) score.MethodsIn this population-based study, we invited active participants of the ALSPAC cohort to our Focus@24+ clinic at the University of Bristol (Bristol, UK) between June 5, 2015, and Oct 31, 2017, for assessment by transient elastography with FibroScan, to determine the prevalence of steatosis and fibrosis. FibroScan data were collected on histologically equivalent fibrosis stage (F0-F4) and steatosis grade (S0-S3); results with an IQR to median ratio of 30% or greater were excluded for median fibrosis results greater than 7·1 kPa, and CAP scores for steatosis were excluded if less than ten valid readings could be obtained. Results were collated with data on serology (including alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transferase) and exposures of interest: alcohol consumption (via the Alcohol Use Disorder Identification Test for Consumption [AUDIT-C] and the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for alcohol use disorder), body-mass index (BMI), waist-to-height ratio, socioeconomic status (based on predefined ALSPAC markers), and sex. We used logistic regression models to calculate odds ratios (ORs) for the effect of exposures of interest on risk of steatosis and fibrosis, after dichotomising the prevalences of fibrosis and steatosis and adjusting for covariates (excessive alcohol intake [hazardous drinking, AUDIT-C score ≥5; or harmful drinking, evidence of alcohol use disorder], social class, smoking, and BMI).Findings10 018 active ALSPAC participants were invited to our Focus@24+ clinic, and 4021 attended (1507 men and 2514 women), with a mean age of 24·0 years (IQR 23·0–25·0). 3768 CAP scores were eligible for analysis. 780 (20·7% [95% CI 19·4–22·0]) participants had suspected steatosis (S1–S3; ≥248 dB/m), with 377 (10·0%) presenting with S3 (severe) steatosis (≥280 dB/m). A BMI in the overweight or obese range was positively associated with steatosis when adjusted for excessive alcohol consumption, social class, and smoking (overweight BMI: OR 5·17 [95% CI 4·11–6·50], p<0·0001; obese BMI: 27·27 [20·54–36·19], p<0·0001). 3600 participants had valid transient elastography results for fibrosis analysis. 96 participants (2·7% [95% CI 2·2–3·2]) had transient elastography values equivalent to suspected fibrosis (F2–F4; ≥7·9 kPa), nine of whom had values equivalent to F4 fibrosis (≥11·7 kPa). Individuals with alcohol use disorder and steatosis had an increased risk of fibrosis when adjusted for smoking and social class (4·02 [1·24–13·02]; p=0·02).InterpretationOne in five young people had steatosis and one in 40 had fibrosis around the age of 24 years. The risk of fibrosis appears to be greatest in young adults who have harmful drinking patterns and steatosis. A holistic approach to the UK obesity epidemic and excessive drinking patterns is required to prevent an increasing health-care burden of adults with advanced liver disease in later life.FundingMedical Research Council UK, Alcohol Change UK, David Telling Charitable Trust.

Early life adversity, contact with children’s social care services and educational outcomes at age 16 years: UK birth cohort study with linkage to national administrative records

ObjectivesTo use record linkage of birth cohort and administrative data to study educational outcomes of children who are looked-after (in public care) and in need (social services involvement), and examine...

Association Between Repeated Episodes of Gastroenteritis and Mental Health Problems in Childhood and Adolescence.

The Avon Longitudinal Study of Parents and Children (ALSPAC) and Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohorts were used to determine whether repeated exposure to gastroenteritis in early life could predict risk for psychiatric problems in childhood and in ALSPAC adolescents. We determined whether inflammatory biomarkers moderated the association between repeated gastroenteritis and mental health in adolescents from ALSPAC. Episodes of gastroenteritis from birth to 30 and 36 months were reported by mothers. Psychological problems were assessed using the total difficulties and subscale scores on the Revised Rutter Parent Scale for Preschool Children at 42 months and the Strengths and Difficulties Questionnaire (SDQ) at 81 months in ALSPAC. Presence of psychiatric disorders at 15.5 years was assessed using the Development and Well-Being Assessment (DAWBA) in ALSPAC. In the MAVAN replication cohort, total difficulties were assessed on the SDQ at 60 and 72 months. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) at 9.5 years and CRP at 15.5 years were measured in ALSPAC participants. Repeated gastroenteritis associated with the total difficulties score in ALSPAC and MAVAN children. The β values were small, indicating that the clinical relevance of these findings requires further investigation. Repeated gastroenteritis was significantly associated with an increased prevalence of externalizing disorders at age 15.5 years, but odds ratios were small. CRP or IL-6 at 9.5 years or CRP at 15.5 years did not significantly moderate the association between repeated gastroenteritis and prevalence of psychiatric disorders. Identifying factors associated with vulnerability to psychopathology is key to early identification of individuals at risk.

Young people’s views about consenting to data linkage: Findings from the PEARL qualitative study

ABSTRACT&#x0D; BackgroundElectronic administrative data exist in several domains which, if linked, are potentially useful for research. However, benefits from data linkage should be considered alongside risks such as the threat to privacy. Avon Longitudinal Study of Parents and Children (ALSPAC) is a birth cohort study. The Project to Enhance ALSPAC through Record Linkage (PEARL) was established to enrich the ALSPAC resource through linkage between ALSPAC participants and routine sources of health and social data. Qualitative research was incorporated in the PEARL study to examine participants’ views about data linkage and inform approaches to information. This paper focusses on issues of consent.&#x0D; MethodsDigitally recorded interviews were conducted with 55 participants aged 17-19 years. Terms and processes relating to consent, anonymization and data linkage were explained to interviewees. Scenarios were used to prompt consideration of linking different sources of data, and whether consent should be requested. Interview recordings were fully transcribed. Thematic analysis was undertaken using the Framework approach.&#x0D; ResultsParticipant views on data linkage appeared to be most influenced by: considerations around the social sensitivity of the research question, and; the possibility of tangible health benefits in the public interest. Some participants appeared unsure about the effectiveness of anonymization, or did not always view effective anonymization as making consent unnecessary. This was related to notions of ownership of personal information and etiquette around asking permission for secondary use. Despite different consent procedures being explained, participants tended to equate consent with ‘opt-in’ consent through which participants are ‘asked’ if their data can be used for a specific study. Participants raising similar concerns came to differing conclusions about whether consent was needed. Views changed when presented with different scenarios, and were sometimes inconsistent.&#x0D; ConclusionsFindings from this study question the validity of ‘informed consent’ as a cornerstone of good governance, and the extent to which potential research participants understand different types of consent and what they are consenting, or not consenting, to. Pragmatic, imaginative and flexible approaches are needed if research using data linkage is to successfully realise its potential for public good without undermining public trust in the research process.

Young people's views about the purpose and composition of research ethics committees: findings from the PEARL qualitative study.

BackgroundAvon Longitudinal Study of Parents and Children (ALSPAC) is a birth cohort study within which the Project to Enhance ALSPAC through Record Linkage (PEARL) was established to enrich the ALSPAC resource through linkage between ALSPAC participants and routine sources of health and social data. PEARL incorporated qualitative research to seek the views of young people about data linkage, including their opinions about appropriate safeguards and research governance. In this paper we focus on views expressed about the purpose and composition of research ethics committees.MethodsDigitally recorded interviews were conducted with 48 participants aged 17–19 years. Participants were asked about whether medical research should be monitored and controlled, their knowledge of research ethics committees, who should sit on these committees and what their role should be. Interview recordings were fully transcribed and anonymised. Thematic analysis was undertaken, assisted by the Framework approach to data management.ResultsThe majority of interviewees had little or no specific knowledge of ethics committees. Once given basic information about research ethics committees, only three respondents suggested there was no need for such bodies to scrutinise research. The key tasks of ethics committees were identified as monitoring the research process and protecting research participants. The difficulty of balancing the potential to inhibit research against the need to protect research participants was acknowledged. The importance of relevant research and professional expertise was identified but it was also considered important to represent wider public opinion, and to counter the bias potentially associated with self-selection possibly through a selection process similar to ‘jury duty’.ConclusionsThere is a need for more education and public awareness about the role and composition of research ethics committees. Despite an initial lack of knowledge, interviewees were able to contribute their ideas and balance the rights of individuals with the wider benefits from research. The suggestion that public opinion should be represented through random selection similar to jury duty may be worth pursuing in the light of the need to ensure diversity of opinion and establish trust amongst the general public about the use of ‘big data’ for the wider public good.

Phenotypic Manifestation of Genetic Risk for Schizophrenia During Adolescence in the General Population.

Schizophrenia is a highly heritable, polygenic condition characterized by a relatively diverse phenotype and frequent comorbid conditions, such as anxiety and depression. At present, limited evidence explains how genetic risk for schizophrenia is manifest in the general population. To investigate the extent to which genetic risk for schizophrenia is associated with different phenotypes during adolescence in a population-based birth cohort. This cohort study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Of 14,062 children in the birth cohort, genetic data were available for 9912 adolescents. Data were collected periodically from September 6, 1990, and collection is ongoing. Data were analyzed from March 4 to August 13, 2015. Polygenic risk scores (PRSs) for schizophrenia generated for individuals in the ALSPAC cohort using results of the second Psychiatric Genomics Consortium Schizophrenia genome-wide association study as a training set. Logistic regression was used to assess associations between the schizophrenia PRS and (1) psychotic experiences (Psychosis-Like Symptom Interview at 12 and 18 years of age), (2) negative symptoms (Community Assessment of Psychic Experiences at 16.5 years of age), (3) depressive disorder (Development and Well-Being Assessment at 15.5 years of age), and (4) anxiety disorder (Development and Well-Being Assessment at 15.5 years of age) in adolescence. Of the 8230 ALSPAC participants whose genetic data passed quality control checks (51.2% male, 48.8% female), 3676 to 5444 participated in assessments from 12 to 18 years of age. The PRSs created using single-nucleotide polymorphisms with a training-set P ≤ .05 threshold were associated with negative symptoms (odds ratio [OR] per SD increase in PRS, 1.21; 95% CI, 1.08-1.36; R(2) = 0.007) and anxiety disorder (OR per SD increase in PRS, 1.17; 95% CI, 1.06- 1.29; R(2) = 0.005). No evidence was found of an association between schizophrenia PRS and psychotic experiences (OR per SD increase in PRS, 1.08; 95% CI, 0.98-1.19; R(2) = 0.001) or depressive disorder (OR per SD increase in PRS, 1.02; 95% CI, 0.91-1.13; R(2) = 0.00005). Results were mostly consistent across different training-set P value thresholds and using different cutoffs and measures of the psychopathological outcomes. This study demonstrates polygenic overlaps between common genetic polymorphisms associated with schizophrenia and negative symptoms and anxiety disorder but not with psychotic experiences or depression. Because the genetic risk for schizophrenia appears to be manifest as anxiety and negative symptoms during adolescence, a greater focus on these phenotypes rather than on psychotic experiences might be required for prediction of transition in at-risk samples.

LB03.02

Objective: To investigate the association between paternal circulatory health in middle age and offspring blood pressure across childhood and adolescence in order to examine the importance of inter-generational influences on blood pressure trajectories and the potential development of hypertension in later adult life. Design and method: We used data from 1,969 paternal-offspring pairs recruited as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Paternal pressures and arterial stiffness (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse wave velocity (PWV) and augmentation index (AI)) were measured at the Focus on Fathers clinic between 2011 to 2013. This was linked to 6 prior measures of offspring SBP and DBP taken at research clinics when the ALSPAC participants were approximately 7, 9, 10, 11, 15 and 17 years old. We used both multivariable linear regression and 2 level linear-spline models to model the associations between a one standard deviation increase (z-score) in paternal circulatory measures and offspring SBP and DBP at each time point as well as the intercept (BP at age 7) and rate of blood pressure change from linear slopes between ages 7–11, 11–15 and 15–17 from our multi-level model. Results: A positive association was found between paternal SBP and male offspring systolic and diastolic blood pressures in simple and adiposity adjusted analyses (SBP +1.48 mmHg; CI 0.82 - 2.14 mmHg, p < 0.0001 at age 7 for 1 z-score increase in paternal SBP). These associations remained similar throughout adolescence. No associations were seen with paternal PWV or AI and male offspring pressures. Far weaker or null associations were seen for female blood pressures (p-value for gender interaction=0.01 at 7 years). Conclusions: This study demonstrates sexual dimorphism for associations between paternal and offspring blood pressures which require replication from other studies. The associations were strongest in the pre-pubertal period and, if anything, weakened with adolescence suggesting other environmental factors may be more important in determining age-related increases in blood pressure. Future follow-up is required to test whether associations reappear in later life.

P02 Outcome of mild traumatic brain injury (tbi) in children- results from a prospective uk cohort study

Aim To use prospectively collected data to investigate the outcomes up to 16 years of TBI in childhood. Methods Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were analysed. Background demographics and developmental and behavioural profile of the children were derived from questionnaires completed by the mother in pregnancy, at 6 weeks and at 18 and 42 months. Injury data were derived from questionnaires completed by the child’s carer at 4½ 5½ 6½ 8 ½ and 11½ years of age. Outcomes were collected when the child was 11–16 years old, from ALSPAC questionnaires and research clinics, and from linked educational data. TBI cases (n = 410), defined as any head injury resulting in loss of consciousness and/or a skull fracture before the age of 11, were compared with children of the same age (n = 1819) who suffered traumatic orthopaedic injuries (fractures- excluding skull fractures). Controls (n = 8770) were all children with available injury data who did not have a TBI or orthopaedic injury. Results 410 ALSPAC participants (59% male) had a TBI before 11; 154 (38%) had a fractured skull, and 36 (9%) had multiple TBIs. Orthopaedic injuries were reported for 1819 participants (52% male) before 11. Compared to controls, children who had a TBI came from families living in adversity, with mothers with lower educational qualifications and a history of depression. The children who suffered a TBI had higher hyperactivity and conduct scores age 42 months, but no differences were apparent for those who later suffered orthopaedic injuries. Outcomes at 13–16 which remained associated with TBI after adjustment were the total behavioural problems score, the hyperactivity score and the conduct problems score of the SDQ, and high levels of anxiety and depression. Adjustment for pre-injury SDQ scores attenuated the associations with the SDQ scores but these remained significantly different from controls. Weak associations were also observed between orthopaedic injuries and later conduct problems. Conclusions TBI in childhood was associated with increased behavioural problems up to 16 years, and increased hyperactivity and conduct problems which were not explained by pre-injury characteristics. Depression and anxiety were also more common in TBI survivors.

Which children and young people are excluded from school? Findings from the Avon Longitudinal Study of Parents and Children (ALSPAC)

BackgroundSchool exclusion is a disciplinary method used to remove a child from the school environment. It is known to affect certain groups disproportionately, including boys, some ethnic minorities, children in care, children in poverty, and children with special educational needs. Population-based studies on wider characteristics of excluded pupils are scarce. The aim of this study was to describe factors associated with school exclusion in the Avon Longitudinal Study of Parents and Children (ALSPAC), focussing on neurodevelopment and mental health. MethodsALSPAC is a prospective population-based British birth cohort study, with the initial sample consisting of 14 541 pregnancies. The study has data for whether a child has been permanently excluded from school up to the age of 8 years as reported by parents and also permanent and fixed period exclusions in the preceding 12 months as reported by parents and young people at age 16 years. Upstream risk factors were assessed for associations with exclusion on univariable analysis. The association with social communication difficulties was investigated with multivariable logistic regression. FindingsData for exclusions up to the age of 8 years were available for 8245 ALSPAC participants and 4482 participants for exclusion at age 16 years. 53 pupils (0·6%) were excluded from school by age 8 years, and 390 (8·7%) at age 16 years. The odds of exclusion by 8 years and at 16 years were increased with male sex (p=0·001 and p<0·0001, respectively), low family income (p=0·014 and p<0·0001), family adversity (p<0·0001 for both), maternal psychopathology (p=0·013 and p=0·004), low intelligence quotient (p=0·041 and p<0·0001), mental health difficulties (p<0·0001 for both), psychiatric disorder (p<0·0001 for both), social communication difficulties (p<0·0001 for both), antisocial activities (p=0·004 and p<0·0001), bullying or being bullied (p=0·005 and p<0·0001), low educational attainment (p<0·0001 for both), and increased special educational needs (p<0·0001 for both). On multivariable analysis, having social communication difficulties above a clinical threshold on the Social Communication Disorders Checklist was strongly associated with exclusion by 8 years (odds ratio 7·4, 95% CI 3·6–15·4) and at 16 years (2·3, 1·5–3·5), after adjustment for relevant confounders. InterpretationAlthough cohort attrition and small numbers of exclusions at 8 years are limitations, this study suggests that school exclusion is associated with numerous risk factors identifiable at or before primary school entry. Child health professionals have an important role in the holistic assessment of children who are excluded, or who are at risk of school exclusion. There is particular need to ensure that mental health and neurodevelopmental difficulties are appropriately recognised and supported. FundingNational Institute for Health Research Academic Clinical Fellowship.

Identifying Scoliosis in Population-Based Cohorts: Development and Validation of a Novel Method Based on Total-Body Dual-Energy X-Ray Absorptiometric Scans

The purpose of this study was to develop and validate a novel method of identifying scoliosis on total-body dual energy X-ray absorptiometric (DXA) scans. Scoliosis was identified on total-body DXA scans by triaging to distinguish true curves from positioning errors, followed by a modified Ferguson method to measure angles. Precision was assessed on 174 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), who underwent repeat DXA scans at age 15, 2-6weeks apart. In addition, precision of angle estimation was evaluated on 20 scans measured five times. To evaluate accuracy, angle size was compared to spinal radiographs in 13 individuals with known scoliosis. Subsequently, this method was applied to estimate scoliosis prevalence rates and curve patterns from DXA scans previously obtained in 7,298 ALSPAC participants at age 9 and 5,122 at age 15. There was substantial agreement in identifying those with scoliosis on repeat DXA scans taken 2-6weeks apart (kappa 0.74, 95% CI 0.59-0.89). Of repeat angle measures, 95% were within 5°. Angle size was underestimated by approximately 40%. Prevalence of scoliosis ≥10° in the ALSPAC was 0.3% at age 9 and 3.5% at age 15 and was higher in girls at both time points. The mean±SD curve size was 12±4° at age 9years and 15±7° at age 15. We have developed and validated a novel method for identifying scoliosis from DXA scans. Comparison with prevalence data using more established techniques suggests our method provides valid estimates of scoliosis prevalence in population-based cohorts.