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A sequential mixed-mode data collection, online-to-telephone, was introduced into the National Child Development Study for the first time at the study's age 55 sweep in 2013. The study included a small experiment, whereby a randomised subset of study members was allocated to a single mode, telephone-only interview, in order to test for the presence of mode effects on participation and measurement. Relative to telephone-only, the offer of the Web increased overall participation rates by 5.0 percentage points (82.8% vs. 77.8%; 95% confidence interval for difference: 2.7% to 7.3%). Differences attributable to mode of interview were detected in levels of item non-response and response values for a limited number of questions. Most notably, response by Web (relative to telephone) was found to have increased the likelihood of non-response to questions relating to pay and other financial matters, and increased the likelihood of ‘less desirable’ responses. For example, response by Web resulted in the reporting of more units of alcohol consumed, and more negative responses to subjective questions such as self-rated health, self-rated financial status and well-being. As there was evidence of mode effects, there is the potential for biases in some analyses, unless appropriate techniques are utilised to correct for these.

Schools across the UK were mostly closed from March to July 2020 due to Covid-19. Therefore, parents and children found themselves thrust into a prolonged period of home-schooling. In this study, p...

Longer exposure to obesity, and thus a longer period in an inflamed state, may increase susceptibility to infectious diseases and worsen severity. Previous cross-sectional work finds higher BMI is related to worse COVID-19 outcomes, but less is known about associations with BMI across adulthood. To examine this, we used body mass index (BMI) collected through adulthood in the 1958 National Child Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Participants were grouped by the age they were first overweight (> 25kg/m2) and obese (> 30kg/m2). Logistic regression was used to assess associations with COVID-19 (self-reported and serology-confirmed), severity (hospital admission and contact with health services) and long-COVID reported at ages 62 (NCDS) and 50 (BCS70). Longer exposure to obesity was associated with increased odds of adverse COVID-19 outcomes, but results were mixed and often underpowered. Those with early exposure to obesity were over twice as likely in NCDS (odds ratio (OR) 2.15, 95% confidence interval (CI): 1.17 to 4.00) and three times as likely in BCS70 (OR 3.01, 95% CI: 1.74 to 5.22) to have long COVID. In NCDS they were also over four times as likely to be admitted to hospital (OR 4.69, 95% CI: 1.64 to 13.39). Most associations were somewhat explained by contemporaneous BMI or reported health, diabetes or hypertension; however, the association with hospital admission in NCDS remained. An earlier age of obesity onset is related to COVID-19 outcomes in later life, providing evidence on the long-term impact of raised BMI on infectious disease outcomes in midlife.

Background: data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. Methods: in this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18–55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (0·05 for all analyses). Interpretation: in this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

BackgroundExisting evidence on profiles of psychological distress across adulthood uses cross-sectional or longitudinal studies with short observation periods. The objective of this research was to study the profile of psychological distress within the same individuals from early adulthood to early old age across three British birth cohorts.MethodsWe used data from three British birth cohorts: born in 1946 (n= 3093), 1958 (n= 13 250) and 1970 (n= 12 019). The profile of psychological distress – expressed both as probability of being a clinical case or a count of symptoms based on comparable items within and across cohorts – was modelled using the multilevel regression framework.ResultsIn both 1958 and 1970 cohorts, there was an initial drop in the probability of being a case between ages 23–26 and 33–34. Subsequently, the predicted probability of being a case increased from 12.5% at age 36 to 19.5% at age 53 in the 1946 cohort; from 8.0% at age 33 to 13.7% at age 42 in the 1958 cohort and from 15.7% at age 34 to 19.7% at age 42 in the 1970 cohort. In the 1946 cohort, there was a drop in the probability of caseness between ages 60–64 and 69 (19.5%v.15.2%). Consistent results were obtained with the continuous version of the outcome.ConclusionsAcross three post-war British birth cohorts midlife appears to be a particularly vulnerable phase for experiencing psychological distress. Understanding the reasons for this will be important for the prevention and management of mental health problems.

ImportanceMental health disorders were among the leading global contributors to years lived with disability prior to the COVID-19 pandemic onset, and growing evidence suggests that population mental health outcomes have worsened since the pandemic started. The extent that these changes have altered common age-related trends in psychological distress, where distress typically rises until mid-life and then falls in both sexes, is unknown.ObjectiveTo analyse whether long-term pre-pandemic psychological distress trajectories have altered during the pandemic, and whether these changes have been different across generations and by sex.DesignCross-cohort study with prospective data collection over a 40-year period (earliest time point: 1981; latest time point: February/March 2021).SettingPopulation-based (adult general population), Great Britain.ParticipantsMembers of three nationally representative birth cohorts which comprised all people born in Great Britain in a single week of 1946, 1958, or 1970, and who participated in at least one of the data collection waves conducted after the start of the pandemic (40.6%, 42.8%, 39.4%, respectively).Exposure(s)Time, COVID-19 pandemic.Main Outcome(s) and Measure(s)Psychological distress factor scores, as measured by validated self-reported questionnaires.Results16,389 participants (2,175 from the 1946 birth cohort, 52.8% women; 7,446 from the 1958 birth cohort, 52.4% women; and 6,768 from the 1970 birth cohort, 56.2% women) participated in the study. By September/October 2020, psychological distress levels had reached or exceeded the levels of the peak in the pre-pandemic life-course trajectories, with larger increases in younger cohorts: Standardised Mean Differences (SMD) and 95% confidence intervals (CIs) of -0.02 [-0.07, 0.04], 0.05 [0.02, 0.07], and 0.09 [0.07, 0.12] for the 1946, 1958, and 1970 birth cohorts, respectively. Increases in distress were larger among women than men, widening the pre-existing inequalities observed in the pre-pandemic peak and in the most recent pre-pandemic assessment.Conclusions and RelevancePre-existing long-term psychological distress trajectories of adults born between 1946 and 1970 were disrupted during the COVID-19 pandemic, particularly among women, who reached the highest levels ever recorded in up to 40 years of follow-up data. This may impact future trends of morbidity, disability, and mortality due to common mental health problems.

This paper explores the reasons why people exit the UK labor market early and some of the barriers working against them returning. The specific focus is a qualitative exploration of three out of work individuals, approaching the age of 60, each of whom had experienced poverty and periods of worklessness during their lifetime. The fieldwork took place in 2016 and was part of a wider mixed methods study about retirement, which used data from the 1958 birth cohort study. Researchers used narrative interviews to uncover the lived experiences and realities of these three people’s lives, and applied a life course perspective to understand how the accumulation of advantages and disadvantages during their lives shapes their attitudes and expectations. The data also show the effects of money, health, and previous employment on their decision making, and how structures such as social class, gender, and poverty are represented in and through the stories they tell.

This article investigates the influence of wealth, a frequently neglected aspect of the economic circumstances of families, on children’s development. Using the UK Millennium Cohort Study, it explores whether parental wealth (net total wealth, net housing wealth, net financial wealth, and house value) is associated with children’s cognitive ability, mental, and physical health at age 11 (N = 8,645), over and above parental socioeconomic status and economic resources, in particular permanent income. Housing wealth was associated with fewer emotional and behavioral problems, independent of the full set of controls. Children’s verbal cognition and general health were more strongly associated with family permanent income and socioeconomic characteristics than with wealth. Open access funding enabled and organized by Projekt DEAL.

Duration of protection from SARS-CoV-2 infection in people with HIV (PWH) following vaccination is unclear. In a sub-study of the phase 2/3 the COV002 trial (NCT04400838), 54 HIV positive male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells >350 cells/ul) received two doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and MesoScale Discovery (MSD)), neutralisation, ACE-2 inhibition, gamma interferon ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that 6 months after vaccination the majority of measurable immune responses were greater than pre-vaccination baseline, but with evidence of a decline in both humoral and cell mediated immunity. There was, however, no significant difference compared to a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although were lower than wild type. Pre-existing cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater post-vaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the on-going policy to vaccinate PWH against SARS-CoV-2, and underpin the need for long-term monitoring of responses after vaccination.

Variation in DNA methylation (DNAm) is associated with multiple biological processes that track growth and development, ageing and age-related diseases. However, there is little understanding of what constitutes typical patterns of DNAm variation and how these patterns change across the life course. In this study, we synthesised a map of the human methylome across the life course, focussing on changes in variability and mean DNAm.Harmonizing DNAm datasets across eight longitudinal and cross-sectional UK-based studies, we meta-analysed n=13,215 blood samples from n=7,037 unique individuals from birth to 98 years of age. Changes in CpG-specific variability and means were described across the life course using a meta-regression framework. CpG-specific associations of variability or mean DNAm in relation to the likelihood of association with 100 traits linked to environmental exposures, health and disease were tested within and across ten developmental age bins across the life course.Age was linked to DNAm variability at 29,212 CpG sites. On average, we observed a 1.26 fold increase in DNAm variability per year across the life course. 33,730 CpGs displayed changes in mean DNAm, with 64% of these loci showing decreases in DNAm over time. CpG sites linked to traits were in general more variable across the life course.Our study provides, for the first time, a map of the human methylome across the life course, which is publicly accessible through a searchable online database. This resource allows researchers to query CpG-specific trajectories from birth to old age and link these to health and disease.

Background DNA methylation (DNAm) age acceleration (AgeAccel) has been shown to be predictive of all-cause mortality but it is unclear what functional aspect/s of ageing it captures. We examine associations between four measures of AgeAccel in adults aged 45-87 years and physical and cognitive performance and their age-related decline. Methods AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno and AgeAccelGrim were calculated in the Medical Research Council National Survey of Health and Development (NSHD), National Child Development Study (NCDS) and TwinsUK. Three measures of physical (grip strength, chair rise speed and forced expiratory volume in one second[FEV1]) and two measures of cognitive (episodic memory and mental speed) performance were assessed. Results AgeAccelPheno and AgeAccelGrim, but not AgeAccelHannum and AgeAccelHorvath were related to performance in random effects meta-analyses (n=1388-1685). For example, a one year increase in AgeAccelPheno/AgeAccelGrim was associated with a 0.01ml[95%CI:0.01,0.02]/0.03ml[95%CI:0.01,0.05] lower mean FEV1. In NSHD, AgeAccelPheno and AgeAccelGrim at 53 years were associated with age-related decline in performance between 53 and 69 years as tested by linear mixed models (p, This work was supported by the Economic and Social Research Council/Biotechnology and Biological Sciences Research Council [ES/N000404/1] and the UK Medical Research Council (MC_UU_12015/2).The UK Medical Research Council also provides core funding for the MRC National Survey of Health and Development and support for AW, RC, DK and RH [MC_UU_12019/1, MC_UU_12019/2, MC_UU_12019/4]. JM is supported by CLOSER through the Economic and Social Research Council [547821 GA3 ESRC]. The TwinsUK study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007–2013); National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London

Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers. A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989-1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA). Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results. This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk. This study was supported by the Economic and Social Research Council (ESRC, Grant Number ES/N000404/1 to J.T.B). Data governance for access to UK birth cohort data was provided by the METADAC data access committee, funded by ESRC, Wellcome and MRC (2015–2018: Grant Number MR/N01104X/1 2018–2020: Grant Number ES/S008349/1). This work made use of data and samples generated by the 1958 Birth Cohort (NCDS), which is managed by the Centre for Longitudinal Studies at the UCL Institute of Education, funded by the ESRC (Grant Number ES/M001660/1); blood sample collection was funded by MRC (Grant G0000934). Access to these resources was enabled via the Wellcome Trust and MRC: 58FORWARDS Grant (108439/Z/15/Z). Before 2015 biomedical resources were maintained under the Wellcome Trust and Medical Research Council 58READIE Project (Grant Numbers WT095219MA and G1001799). Work undertaken at Great Ormond Street Hospital/University College London, Institute of Child Health, is in part supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The UK Medical Research Council also provided core funding for the MRC National Survey of Health and Development (Grant MC_UU_00019/1). The TwinsUK study is supported by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007–2013); the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility. The SHS study received support from the National Heart, Lung, and Blood Institute (NHLBI) of the USA (under contract numbers 75N92019D00027, 75N92019D00028, 75N92019D00029 and 75N92019D00030) and previous Grants (R01HL090863, R01HL109315, R01HL109301, R01HL109284, R01HL109282 and R01HL109319 and Cooperative Agreements: U01HL41642, U01HL41652, U01HL41654, U01HL65520 and U01HL65521), from the National Institutes of Health Sciences of the USA (R01ES021367, R01ES025216, P42ES010349, P30ES009089) and from “la Caixa” Foundation (ID 100010434) (fellowship code “LCF/BQ/DR19/11740016”). The GENOA study received funding from U01HL054457, RC1HL100185, R01HL119443, R01HL133221, R01HL141292. Sí

Objective Non-response is unavoidable in longitudinal surveys. The consequences are lower statistical power and the potential for bias. We implemented a systematic data-driven approach to identify predictors of non-response in the National Child Development Study (NCDS; 1958 British birth cohort). Such variables can help make the missing at random assumption more plausible, which has implications for the handling of missing data Study Design and Setting We identified predictors of non-response using data from the 11 sweeps (birth to age 55) of the NCDS (n = 17,415), employing parametric regressions and the LASSO for variable selection. Results Disadvantaged socio-economic background in childhood, worse mental health and lower cognitive ability in early life, and lack of civic and social participation in adulthood were consistently associated with non-response. Using this information, along with other data from NCDS, we were able to replicate the “population distribution” of educational attainment and marital status (derived from external data), and the original distributions of key early life characteristics. Conclusion The identified predictors of non-response have the potential to improve the plausibility of the missing at random assumption. They can be straightforwardly used as “auxiliary variables” in analyses with principled methods to reduce bias due to missing data.

Background: The Pfizer-BioNTech (BNT162b2) and the Oxford/AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in Phase III trials. Here we report results from a real world setting on the two most administered vaccines in the UK. Methods: We investigated self-reported systemic and local effects within eight days of vaccination in 387,471 individuals from the COVID Symptom Study app who received one (n=209,251) or two (n=13,478) doses of the BNT162b2 vaccine, or one dose of ChAdOx1 nCoV-19 vaccine (n=178,220) between December 8 and February 15 2021. A subset of individuals subsequently tested for SARS-CoV-2 were studied for infection rates from PCR or lateral flow test results post-vaccination (59,639 vaccinated vs 277,599 controls). Findings: Systemic side effects were reported in 11.8% of participants after the first BNT162b2 dose, 20.3% after the second BNT162b2 dose, and 29.4% after the first ChAdOx1 nCoV-19 dose. Systemic effects were more prevalent among individuals with pre-existing COVID-19 infection (BNT162b2:34.1%; ChAdOx1 nCoV-19:51.6%) than among individuals without known prior infection (BNT162b2:10.6%; ChAdOx1 nCoV-19:28.6%) and among those aged 55 years (BNT162b2:9.2%, ChAdOx1 nCoV-19: 26.9%). We observed significant reduction in infection risk 12-21 days after the first dose (BNT162b2:-57% [-71%, -38%], ChAdOx1 nCoV-19:-42% [-71%, -17%]). Interpretation: This phase IV-type study assessing both BNT162b2 and ChAdOx1 nCoV-19 vaccines identifies mild systemic side effects affecting 11-30% of individuals post-vaccination, lower than in published Phase III trials. Our data on infection post-vaccine were also reassuring. Funding: Zoe, NIHR, CDRF, NIH, MRC Declaration of Interests: TDS and AMV are consultants to Zoe Global Ltd (“Zoe”). JW, AM, LP and JC are employees of Zoe Global Limited. ALG is a regional PI on the COV002 trial and the Novavax COVID-19 vaccine trial and as such her organisation has received grants from Novavax. Other authors have no conflict of interest to declare. Ethics Approval Statement: Ethical approval for use of the app for research purposes in the UK was obtained from King’s College London Ethics Committee (review reference LRS-19/20-18210), and all users provided consent for non-commercial use.

Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine is immunogenic and protects against COVID-19. However, data on vaccine immunogenicity are needed for the 40 million people living with HIV (PWH), who may have less functional immunity and more associated co-morbidities than the general population. Methods: Between the 5th and 24th November 2020, 54 adults with HIV, aged 18-55 years, were enrolled into a single arm open label vaccination study within the protocol of the larger phase 2/3 COV002 trial. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses (5 × 1010 vp) was given 4-6 weeks apart. All participants were on antiretroviral therapy (ART) with undetectable plasma HIV viral loads and CD4+ T cell counts >350 cells/µl at enrolment. Data were captured on adverse events. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo interferon-γ enzyme-linked immunospot assay (ELISpot) and T cell proliferation. All outcomes were compared with a HIV uninfected group from the main COV002 study. Findings: 54 participants with HIV (median age 42.5 years (IQR 37.2-49.8)) received two doses of ChAdOx1 nCoV-19. Median CD4+ T cell count at enrolment was 694 cells/µl (IQR 562-864). Results are reported for 56 days of follow-up. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (49%), fatigue (47%), headache (47%), malaise (34%), chills (23%), and muscle or (36%) joint pain (9%), the frequencies of which were similar to the HIV-negative participants. There were no serious adverse events. Anti-spike IgG responses by ELISA peaked at Day 42 (median 1440 ELISA units, IQR 704-2728) and were sustained out to Day 56. There was no correlation with CD4+ T cell count or age and the magnitude of the anti-spike IgG response at Day 56 (P>0.05 for both). ELISpot and T cell proliferative responses peaked between Day 14 and 28 after prime and were sustained through to Day 56. When compared to participants without HIV there was no statistical difference in magnitude or persistence of SARS-CoV-2 spike-specific humoral or cellular responses (P>0.05 for all analyses). Interpretation: In this study of PWH, vaccination with ChAdOx1 nCoV-19 was well tolerated and there was no difference in humoral and cell-mediated immune responses compared to an adult cohort without HIV who received the same vaccination regime. Trial Registration: Trial Registration number is NCT04400838. Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Declaration of Interest: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19 (AZD1222). AstraZeneca reviewed the data from the study and the final manuscript before 474 submission, but the authors retained editorial control. SCG is cofounder of Vaccitech (a collaborator in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was consultant to Vaccitech. PMF is a consultant to Vaccitech. AJP is Chair of the UK Department of Health and Social Care’s JCVI, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AVSH is a cofounder of and consultant to Vaccitech and is named as an inventor on a patent covering design and use of ChAdOx1-vectored vaccines (PCT/GB2012/000467). Ethical Approval: Written informed consent was obtained from all participants, and the trial was done in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. This study was approved in the UK by the Medicines and Healthcare products Regulatory Agency (reference 21584/0424/001-0001) and the South Central Berkshire Research Ethics Committee (reference 20/SC/0145). Vaccine use was authorised by Genetically Modified Organisms Safety Committees at each participating site.

This paper uses a life course perspective to explore and understand how an individual’s experiences over their lifetime contribute to the formation of a growing consciousness about their impending retirement. The fieldwork took place in 2016 and was part of a wider mixed methods study about retirement in the UK, which used data from the 1958 birth cohort study (also known as the National Child Development Study). The paper focuses on the qualitative dimension of the study and uses in-depth case studies of four people approaching 60 to consider, in particular, the effects of health, financial resources and employment history on their views on retiring, including the anticipated timing of their exit from the labour market. All four were purposively chosen because they had experienced low pay or poverty during their lifetime and were employed in relatively low paid jobs. State Pension Ages (SPAs) are on the rise in many countries, including the UK, and the authors maintain that it is important to study the working poor, who, even though are more likely to continue working until SPA, are more prone to suffer from poor health, and less likely to be able to put savings aside for their retirement.

Background Biomarkers of ageing based on DNA methylation (DNAm) have recently been developed. The first (Hannum and Horvath) and second generation (Levine and GrimAge) DNAm biomarkers predict survival, age-related disease and functional capabilities better than chronological age alone; with second generation biomarkers showing more consistent and stronger associations. In the first study of its kind, we examine the association between growth in early life, pubertal timing and DNAm age biomarkers in mid-life. Methods Participants from the Medical Research Council (MRC) National Survey of Health and Development who had information on DNAm were analysed (NSHD, n=1,376). Four DNAm age acceleration (AgeAccel) biomarkers were calculated when participants were aged 53 years: AgeAccelHannum, AgeAccelHorvath, AgeAccelLevine and AgeAccelGrim. Birthweight and weight and height across infancy, childhood and adolescence were measured. Pubertal timing was established using age at menarche (girls) and pubertal stage at 14–15 years (boys). The relationship between weight and height change in infancy (2–4), childhood (4–7) and adolescence (7–15) and AgeAccel was investigated using regression with conditional growth measures; sex-specific residuals from a regression of current size on previous size. Linear regression models examined associations between pubertal timing and AgeAccel. We replicated analyses using height and weight from late childhood (7 y) to adolescence (16 y) and pubertal timing among 240 participants at 45 years from The National Child and Development Study (NCDS). Results A one standard deviation (SD) increase in weight gain between 7 and 15 years was associated with 0.50 years (95% CI: 0.21, 0.80) higher AgeAccelGrim and, with 0.22 years (95% CI: -0.11, 0.55) higher AgeAccelLevine. This was replicated in NCDS. For linear growth, there was some evidence that more rapid growth between 2 and 4 years was associated with lower AgeAccelLevine (-0.39 years [95% CI: -0.74, -0.050) and AgeAccelGrim (-0.24 years [95% CI: -0.54, 0.06]). There was no evidence that relative weight gain and linear growth during childhood was associated with any other AgeAccel biomarker. There was no relationship between pubertal timing in men and any of the AgeAccel biomarkers at 53 years. Women who reached menarche ≥12 years had 1.20 years (95% CI: 0.15, 2.24) higher AgeAccelGrim on average than women who reached menarche Conclusion Our findings support the use of the second generation DNAm age biomarkers as markers of ageing and reinforces the idea that faster gains in weight during adolescence has lasting implications for healthy ageing.

Background Much of the population fails to meet recommended physical activity (PA) levels, but there remains considerable individual variation. By understanding drivers of different trajectories, interventions can be better targeted and more effective. One such driver may be a person’s physical activity identity (PAI)—the extent to which a person perceives PA as central to who they are. Methods Using survey information and a unique body of essays written at age 11 from the National Child Development Study (N = 10 500), essays mentioning PA were automatically identified using the machine learning technique support vector classification and PA trajectories were estimated using latent class analysis. Analyses tested the extent to which childhood PAI correlated with activity levels from age 23 through 55 and with trajectories across adulthood. Results 42.2% of males and 33.5% of females mentioned PA in their essays, describing active and/or passive engagement. Active PAI in childhood was correlated with higher levels of activity for men but not women, and was correlated with consistently active PA trajectories for both genders. Passive PAI was not related to PA for either gender. Conclusions This study offers a novel approach for analysing large qualitative datasets to assess identity and behaviours. Findings suggest that at as young as 11 years old, the way a young person conceptualizes activity as part of their identity has a lasting association with behaviour. Still, an active identity may require a supportive sociocultural context to manifest in subsequent behaviour.

Despite improvements in life expectancy, there is uncertainty on whether the increase in years of healthy life expectancy has kept pace. In this paper we explore whether there is empirical support for the expansion of morbidity hypothesis in the population aged 25-64 living in England. Nationally representative cohorts born between 1945 and 1980 are constructed from repeated annual cross-sections of the Health Survey for England, 1991-2014. Later-born cohorts at a given age have the same or higher prevalence of self-reported bad general health and long-term illness, self-reported high blood pressure (in men), self-reported and objectively-measured diabetes, circulatory illnesses, clinical hypertension, and overweight BMI. We also find that healthy life expectancies (in the sense of absence of each of these problems) at age 25 have increased at a slower pace than life expectancy between 1993 and 2013. Our findings lend support to the expansion of morbidity hypothesis and point to increased future demand for specific healthcare services at younger ages.

Objectives To determine whether comparable prospective and retrospective data present the same association between childhood and life course exposures and mid-life wellbeing. Method Prospective data is taken from the 1958 UK National Child Development Study at age 50 in 2008 and earlier sweeps (n = 8,033). Retrospective data is taken from the English Longitudinal Study of Ageing at ages 50–55 from a life history interview in 2007 (n = 921). Results There is a high degree of similarity in the direction of association between childhood exposures that have been prospectively collected in National Child Development Study and retrospectively collected in English Longitudinal Study of Ageing and wellbeing outcomes in mid-life. However, the magnitude of these associations is attenuated substantially by the inclusion of measurements, which are difficult or impossible to capture retrospectively, and are only available in prospective data, such as childhood poverty, cognitive ability, and indices of social and emotional adjustment. Discussion The findings on the one hand provide some reassurance to the growing literature using life history data to determine life course associations with later life wellbeing. On the other hand, the findings show an overestimation in the retrospective data, in part, arising from the absence in life history data of childhood measures that are not well suited to retrospective collection.

IMPORTANCE: Early-life mental health is known to be associated with socioeconomic adversity and psychological distress in adulthood, but less is known about potential associations with biomarkers and mortality. OBJECTIVE: To investigate the association between early-life mental health trajectories with biomarkers in midlife and premature mortality. DESIGN, SETTING, AND PARTICIPANTS: This study used data from the British National Child Development Study, a population-based birth cohort. The initial sample of 17 415 individuals consisted of all infants born in Great Britain in a single week in 1958. Analysis began Feburary 2017 and ended May 2020. MAIN OUTCOMES AND MEASURES: Biomarkers collected at age 44 to 45 years were fibrinogen, C-reactive protein, glycated hemoglobin, high- and low-density lipoprotein cholesterol, forced expiratory volume, blood pressure, and waist-to-hip ratio. Information on all-cause mortality was available up to age 58 years and cause-specific mortality up to age 50 years. RESULTS: Biomarkers were analyzed from 9377 participants (age, 44-45 years, 4712 female [50.3%]) and mortality data from 15 067 participants (age, 58 years; 7379 female [49.0%]). A 4-group longitudinal typology of early-life conduct problems and affective symptoms was identified: (1) stable low, (2) teacher-identified adolescent onset, (3) moderate, and (4) stable high. Compared with the stable-low group, the stable-high (B, 2.308; 95% CI, 0.213-4.404) and teacher-identified adolescent-onset (B, 2.114; 95% CI, 0.725-3.503) groups had less favorable levels of fibrinogen in middle age. Effect modification was observed by sex (P

BackgroundThis paper addresses the levels of psychological distress experienced at age 42 years by men and women born in 1958 and 1970. Comparing these cohorts born 12 years apart, we ask whether psychological distress has increased, and, if so, whether this increase can be explained by differences in their childhood conditions.MethodData were utilized from two well-known population-based birth cohorts, the National Child Development Study and the 1970 British Cohort Study. Latent variable models and causal mediation methods were employed.ResultsAfter establishing the measurement equivalence of psychological distress in the two cohorts we found that men and women born in 1970 reported higher levels of psychological distress compared with those born in 1958. These differences were more pronounced in men (b = 0.314, 95% confidence interval 0.252–0.375), with the magnitude of the effect being twice as strong compared with women (b = 0.147, 95% confidence interval 0.076–0.218). The effect of all hypothesized early-life mediators in explaining these differences was modest.ConclusionsOur findings have implications for public health policy, indicating a higher average level of psychological distress among a cohort born in 1970 compared with a generation born 12 years earlier. Due to increases in life expectancy, more recently born cohorts are expected to live longer, which implies – if such differences persist – that they are likely to spend more years with mental health-related morbidity compared with earlier-born cohorts.

Background Although early life education for improved long-term health and the amelioration of socioeconomically generated inequalities in chronic disease is advocated in influential policy statements, the evidence base is very modest. Aims To address this dearth of evidence using data from a representative UK national birth cohort study. Methods The analytical sample comprised men and women in the 1958 birth cohort study with prospectively gathered data on attendance at nursery or primary school before the age of 5 years who had gone on to participate in social survey at 42 years (n=11 374), or a biomedical survey at 44/5 years of age (n=9210), or had data on vital status from 18 to 55 years (n=17 657). Results Relative to study members who had not attended nursery, in those who had, there was in fact a higher prevalence of smoking and high alcohol intake in middle age. Conversely, nursery attenders had more favourable levels of lung function and systolic blood pressure in middle age. This apparent association between nursery attendance and lower systolic blood pressure was confined to study members from more deprived social backgrounds of origin (P value for interaction 0.030). There was no apparent link between early school attendance and any behavioural or biological risk factor. Neither nursery nor early school attendance was clearly related to mortality risk. Conclusions We found no clear evidence for an association of either attendance at nursery or primary school before the age of 5 years and health outcomes around four decades later.

We describe the shared task for the CLPsych 2018 workshop, which focused on predicting current and future psychological health from an essay authored in childhood. Language-based predictions of a person’s current health have the potential to supplement traditional psychological assessment such as questionnaires, improving intake risk measurement and monitoring. Predictions of future psychological health can aid with both early detection and the development of preventative care. Research into the mental health trajectory of people, beginning from their childhood, has thus far been an area of little work within the NLP community. This shared task represents one of the first attempts to evaluate the use of early language to predict future health; this has the potential to support a wide variety of clinical health care tasks, from early assessment of lifetime risk for mental health problems, to optimal timing for targeted interventions aimed at both prevention and treatment.

BackgroundThere is much evidence showing that childhood socioeconomic position is associated with physical health in adulthood; however existing evidence on how early life disadvantage is associated with adult mental wellbeing is inconsistent. This paper investigated whether childhood socioeconomic position (SEP) is associated with adult mental wellbeing and to what extent any association is explained by adult SEP using harmonised data from four British birth cohort studies.MethodsThe sample comprised 20,717 participants with mental wellbeing data in the Hertfordshire Cohort Study (HCS), the MRC National Survey of Health and Development (NSHD), the National Child Development Study (NCDS), and the British Cohort Study (BCS70). Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) scores at age 73 (HCS), 60–64 (NSHD), 50 (NCDS), or 42 (BCS70) were used. Harmonised socioeconomic position (Registrar General’s Social Classification) was ascertained in childhood (age 10/11) and adulthood (age 42/43). Associations between childhood SEP, adult SEP, and wellbeing were tested using linear regression and multi-group structural equation models.ResultsMore advantaged father’s social class was associated with better adult mental wellbeing in the BCS70 and the NCDS. This association was independent of adult SEP in the BCS70 but fully mediated by adult SEP in the NCDS. There was no evidence of an association between father’s social class and adult mental wellbeing in the HCS or the NSHD.ConclusionsSocioeconomic conditions in childhood are directly and indirectly, through adult socioeconomic pathways, associated with adult mental wellbeing, but findings from these harmonised data suggest this association may depend on cohort or age.

Objective Typologies of symptom development have been used to identify individuals with different symptom development in the externalizing and internalizing domains of child psychopathology separately despite the domains’ high comorbidity and shared common etiologic risk. This study identified typologies of development jointly across the 2 symptom domains in childhood and investigated their associated antecedents with a specific focus on the comparisons between overall severity of symptoms and symptom expression in one or the other domain. Method Latent class analysis identified groups based on emotional and behavioral symptoms assessed at 3, 5, 7, and 11 years in the UK Millennium Cohort Study (N = 15,439). Different sociodemographic, family structure and environment, birth, infancy, and early childhood antecedents were examined. Results Five groups were identified: 1. low symptoms (57%), 2. moderate behavioral (21%), 3. moderate emotional (12.5%), 4. high emotional and moderate behavioral (5.5%), and 5. high behavioral and moderate emotional (4%). Higher symptoms were predicted by larger numbers of antecedents and risk factors compared with the low symptom group and compared with moderate and high levels of symptoms in either domain (groups 5 versus 2 and 4 versus 3). Comparisons of groups with similar overall symptom levels but different dominant symptom domain (groups 2 versus 3 and 4 versus 5) indicated that apart from gender and ethnicity, there were few unique antecedents of whether children mainly internalize or externalize their symptoms. Conclusion It is possible and useful to define groupings or typologies jointly across externalizing and internalizing symptom development in childhood. Although numerous antecedents predict the experience of symptoms, there are few unique antecedents that differentiate individuals with similarly high levels of psychopathology expressed mainly as internalizing or externalizing symptoms. Identification of at-risk children and delivery of early intervention might benefit from a decreased focus on symptom domain with possible downstream effects through the life course for most common psychiatric disorders.

Using data from the British Millennium Cohort Study (MCS), an ongoing longitudinal study of a cohort of 18,827 children born in the UK in 2000–2001, we investigate important correlates of mental health issues during childhood. MCS respondents were sampled at birth, at age 9 months, and then when they were 3, 5, 7 and 11 years old. Each sweep contains detailed information on the family’s SES, parenting activities, developmental indicators, parental relationship status, and indicators of parental mental health. The Strengths and Difficulties Questionnaire (SDQ) and the related Rutter scale were used to identify behavioral and emotional problems in children. In this paper, childhood problems are separated into four domains: hyperactivity, emotional symptoms, conduct problems, and peer problems. We focus on two aspects of this relationship at ages 5 and 11 – the role of temporary and persistent poverty and the role of temporary and persistent mental health problems of mothers and fathers. At ages 11 and 5, without other controls in the model, persistent and transitory poverty have strong estimated associations with all four domains, with somewhat stronger estimated effects for persistent poverty. After a set of controls are added, we document that both persistent levels of poverty and transitions into poverty are strongly associated with levels of and transitions into childhood mental health problems. Similarly, sustained levels and transitions into mothers’ mental health problems are strongly associated with levels and transitions into children’s mental health problems. This is much less so for fathers.

STUDY QUESTION Are parity and the timing of menarche associated with premature and early natural menopause? SUMMARY ANSWER Early menarche (≤11 years) is a risk factor for both premature menopause (final menstrual period, FMP

The British Birth Cohort Studies are multi-purpose, multi-disciplinary longitudinal studies with a host of potential applications, separately or in comparison with each other and with cohort studies in other countries. This chapter illustrates how the data they collect prospectively on social and emotional skills in childhood can be linked to educational attainment at a range of stages, and how these relationships can be analysed in the context of other features of a child’s family background.

This paper investigates the financial implications of the higher education funding regime to be introduced in English universities in September 2012. The analysis is based on simulated lifetime earnings profiles among graduates, linked to imputed information on parental incomes and institution and course choices. We find that, on average, total gross tuition fees will increase by over £15,000 as a result of the reforms; nevertheless, students will be significantly better off while they study due to the increased generosity of student support. The average graduate will be roughly £8,850 worse off over their lifetime, while universities will, on average, be better off as they are more than able to make up for the loss of substantial amounts of

The introduction of top-up fees for home-domiciled undergraduate tuition in England from 2006–07 – and their planned increase in 2012–13 – raises important issues for university funding in Scotland, since it abolished tuition fees for Scottish and EU students in 2000–01. This paper focuses on what the increase in resources directed at English universities arising from top-up fees means for the relative funding of English and Scottish undergraduates. Widely-used funding-per-head figures do not provide an accurate picture of home- and EU-domiciled undergraduate funding, as they include funding for research, postgraduate degrees and overseas students. The empirical work of this paper focuses on creating a consistent series of funding per full-time equivalent undergraduate over time for England and for Scotland, stripping out funding for research, non-EU students and postgraduate degrees to create a more accurate picture of the funding gap between the two countries. It also takes into account the different composition of undergraduate degree subjects taken in England and Scotland. The findings indicate that the apparent historical advantage in funding per head in Scottish institutions compared with English ones has been largely driven by compositional differences: Scotland has a high proportion of medical, science and engineering undergraduates – subjects that command greater funding due to their relative complexity to teach. The top-up fee introduced in 2006–07 brought funding per head in England to a level similar to that experienced in Scotland, and the future increase will result in funding per head in England outstripping that in Scotland by some magnitude. This suggests that the funding of Scottish students will fall significantly behind that of English students unless additional new sources of public or private funding for Scottish universities are found.

In this article we assess and compare long-term adult socioeconomic status impacts from having experienced psychological and physical health problems in childhood. To do so, we use unique prospective data from the British National Child Development Study, a continuing panel study of a cohort of 17,634 children born in Great Britain during a single week in March 1958. To date there have been nine waves for this birth cohort to monitor their physical, educational, and social development, during childhood (at birth and 7, 11, and 16 y) and adulthood (age 23, 33, 42, 46, and 50 y). Excellent contemporaneous information exists throughout childhood on physical and psychological health, captured by doctor and nurse-led medical examinations and detailed parental and teacher questionnaires. This information is combined with a wealth of contemporaneous information on adult health and economic experiences collected from cohort members. Information includes their economic circumstances (earnings, labor supply, and other sources of family income), physical and psychological health, and relationship status. Large effects are found due to childhood psychological problems on the ability of affected children to work and earn as adults and on intergenerational and within-generation social mobility. Adult family incomes are reduced by 28% by age 50 y, with sustained impacts on labor supply, marriage stability, and the conscientiousness and agreeableness components of the “Big Five” personality traits. Effects of psychological health disorders during childhood are far more important over a lifetime than physical health problems.

We use unique workplace and employee-level data to evaluate a major UK government pilot program to increase qualification-based, employer-provided training for low-qualified employees. We evaluate the program’s effect using a difference-in-differences approach. Using data on eligible employers and workers we find noevidence of a statistically significant effect on the take-up of training in the first 3 years of the program. Our results suggest that the program involved a high level of deadweight and that improving the additionality of the subsequent national program is crucial if it is to make a significant contribution toward government targets to increase qualification levels.

This paper undertakes a quantitative analysis of substantial reforms to the system of higher education (HE) finance first announced in 2004 and then revised again in July 2007. The reforms introduced deferred fees for HE, payable by graduates through the tax system in the form of income-contingent repayments on loans subsidised by the government. Lifetime earnings that have been simulated by the authors using innovative methods, are used to analyse the likely distributional consequences of the reforms for graduates. It is shown that graduates with low lifetime earnings will pay less for their HE than graduates higher up the lifetime earnings distribution compared to the system operating before the reforms. Taxpayers will bear substantial costs due to the interest rate and debt write-off subsidies. The extent to which the reforms are likely to shift the balance of funding for HE between the public and private sector is also analysed, as well as the likely distributional consequences of a number of variations to the system such as removing the interest subsidy from the loans.

We evaluate the effects of undergoing any early schooling (before the compulsory starting age of 5) and of pre-school on a cohort of British children born in 1958. In contrast to most available studies, we are able to assess whether any effects on cognition and socialisation are long-lasting, as well as to estimate their net impact on subsequent educational attainment and labour market performance. Controlling for a particularly rich set of child, parental, family and neighbourhood characteristics, we find some positive and long-lasting effects from early education. Specifically, pre-compulsory education (pre-school or school entry prior to age 5) was found to yield large improvements in cognitive tests at age 7, which, though diminished in size, remained significant throughout the schooling years, up to age 16. By contrast, attendance of pre-school (nursery or playgroup) was found to yield a positive but short-lived impact on test scores. The effects on socialisation appear to be more mixed, with adverse behavioural effects from parental reports at age 7 persisting, for pre-school participants, up to age 11. In adulthood, pre-compulsory schooling was found to increase the probability of obtaining qualifications and to be employed at 33. For both pre-compulsory education and pre-school per se we found evidence of a marginally significant 3-4% wage gain at 33.