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.
Abstract
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 <40 years) and early menopause (FMP 40–44 years), a risk that is amplified for nulliparous women.
WHAT IS KNOWN ALREADY
Women with either premature or early menopause face an increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, failure to adjust for confounding factors and inadequate statistical power.
STUDY DESIGN, SIZE, DURATION
This pooled study comprises 51 450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Age at menarche (categorized as ≤11, 12, 13, 14 and 15 or more years) and parity (categorized as no children, one child and two or more children) were exposures of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorized as premature menopause (FMP before age 40), early menopause (FMP 40–44 years), 45–49 years, 50–51 years, 52–53 years and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% CI for associations between menarche, parity and age at FMP adjusting for within-study correlation.
MAIN RESULTS AND THE ROLE OF CHANCE
The median age at FMP was 50 years (interquartile range 48–53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12–13 years) were at higher risk of premature menopause (RRR 1.80, 95% CI 1.53–2.12) and early menopause (1.31, 1.19–1.44). Nulliparity was associated with increased risk of premature menopause (2.26, 1.84–2.77) and early menopause (1.32, 1.09–1.59). Women having early menarche and nulliparity were at over 5-fold increased risk of premature menopause (5.64, 4.04–7.87) and 2-fold increased risk of early menopause (2.16, 1.48–3.15) compared with women who had menarche at ≥12 years and two or more children.
LIMITATIONS, REASONS FOR CAUTION
Most of the studies (except the birth cohorts) relied on retrospectively reported age at menarche, which may have led to some degree of recall bias.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with early menopause.
STUDY FUNDING/COMPETING INTEREST(S)
InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). G.D.M. is supported by Australian Research Council Future Fellowship (FT120100812). There are no competing interests.
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 midlife and then falls after midlife in both sexes, is unknown. We aimed to analyse whether long-term pre-pandemic psychological distress trajectories were disrupted during the pandemic, and whether these changes have been different across cohorts and by sex.
We used data from three nationally representative birth cohorts comprising all people born in Great Britain in a single week of 1946 (National Survey of Health and Development, NSHD), 1958 (National Child Development Study, NCDS), or 1970 (British Cohort Study, BCS70). The follow-up data used spanned 39 years in NSHD (1982 to 2021), 40 years in NCDS (1981 to 2001), and 25 years in BCS70 (1996 to 2021). We used psychological distress factor scores, as measured by validated self-reported questionnaires (NSHD: Present State Examination, Psychiatric Symptoms Frequency, and 28- and 12-item versions of General Health Questionnaire; NCDS and BCS70: Malaise Inventory; all: 2-item versions of Generalized Anxiety Disorder scale and Patient Health Questionnaire). We used a multilevel growth curve modelling approach to model the trajectories of distress across cohorts and sexes and obtained estimates of the differences between the distress levels observed during the pandemic and those observed at the most recent pre-pandemic assessment and at the peak in the cohort-specific pre-pandemic distress trajectory, located at midlife. We further analysed whether pre-existing cohort and sex inequalities had changed with the pandemic onset using a difference-in-differences (DiD) approach. The analytic sample included 16,389 participants. By September/October 2020, 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 of SMDNSHD,pre-peak = -0.02 -0.07, 0.04, SMDNCDS,pre-peak = 0.05 0.02, 0.07, and SMDBCS70,pre-peak = 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 pre-existing sex inequalities (DiD and 95% confidence intervals of DiDNSHD,sex,pre-peak = 0.17 0.06, 0.28, DiDNCDS,sex,pre-peak = 0.11 0.07, 0.16, and DiDBCS70,sex,pre-peak = 0.11 0.05, 0.16 when comparing sex inequalities in the pre-pandemic peak in midlife to those observed by September/October 2020). As expected in cohort designs, our study suffered from high proportions of attrition with respect to the original samples. Although we used non-response weights to restore sample representativeness to the target populations (those born in the United Kingdom in 1946, 1958, and 1970, alive and residing in the UK), results may not be generalisable to other sections within the UK population (e.g., migrants and ethnic minority groups) and countries different than the UK.
Pre-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.
There 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.
The 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.
More 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.
Socioeconomic 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.
This is the first review of the evidence, based on longitudinal studies in the United Kingdom, on the association of ill health at any life stage and later social and economic outcomes. The review ...included a wide range of physical and mental health exposures, both self-reported and objectively measured, as well as social (e.g. life satisfaction) and economic (e.g. employment) outcomes. We searched the Web of Science, key longitudinal datasets based in the UK, major economic journals, Google Scholar and reference lists of relevant publications. The review includes 80 studies. There was strong evidence for the association between early mental health, mainly attention deficit hyperactivity disorder, and lifetime educational, occupational and various social outcomes. Also, both poor physical and mental health in early and middle adulthood, tended to be associated with unemployment and lower socioeconomic status. Among older adults, the evidence quite consistently indicated an association between mental health, chronic conditions, disability/functional limitations, self-rated general health and quality of life, life satisfaction and early retirement. Overall, mental health was consistently found to be associated with a range of social and economic outcomes throughout the lifespan. The evidence for the association between physical health and later outcomes is more inconsistent. A number of methodological challenges need to be addressed, particularly related to causal inference, to produce robust evidence with potential to inform public health policy.
Pinpointing genetic impacts on DNA methylation can improve our understanding of pathways that underlie gene regulation and disease risk.
We report heritability and methylation quantitative trait ...locus (meQTL) analysis at 724,499 CpGs profiled with the Illumina Infinium MethylationEPIC array in 2358 blood samples from three UK cohorts. Methylation levels at 34.2% of CpGs are affected by SNPs, and 98% of effects are cis-acting or within 1 Mbp of the tested CpG. Our results are consistent with meQTL analyses based on the former Illumina Infinium HumanMethylation450 array. Both SNPs and CpGs with meQTLs are overrepresented in enhancers, which have improved coverage on this platform compared to previous approaches. Co-localisation analyses across genetic effects on DNA methylation and 56 human traits identify 1520 co-localisations across 1325 unique CpGs and 34 phenotypes, including in disease-relevant genes, such as USP1 and DOCK7 (total cholesterol levels), and ICOSLG (inflammatory bowel disease). Enrichment analysis of meQTLs and integration with expression QTLs give insights into mechanisms underlying cis-meQTLs (e.g. through disruption of transcription factor binding sites for CTCF and SMC3) and trans-meQTLs (e.g. through regulating the expression of ACD and SENP7 which can modulate DNA methylation at distal sites).
Our findings improve the characterisation of the mechanisms underlying DNA methylation variability and are informative for prioritisation of GWAS variants for functional follow-ups. The MeQTL EPIC Database and viewer are available online at https://epicmeqtl.kcl.ac.uk .
Body size, nutrition and socioeconomic position (SEP) in early life have been associated with a wide range of long-term health effects. Epigenetics is one possible mechanism through which these early ...life exposures can impact later life health. We conducted a systematic review examining the observational evidence for the impact of body size, nutrition and SEP in early life on the epigenome in humans.
This systematic review is registered with the PROSPERO database (registration number: CRD42016050193). Three datasets were simultaneously searched using Ovid and the resulting studies were evaluated by at least two independent reviewers. Studies measuring epigenetic markers either at the same time as, or after, the early life exposure and have a measure of body size, nutrition or SEP in early life (up to 12 years), written in English and from a community-dwelling participants were included.
We identified 90 eligible studies. Seventeen of these papers examined more than one early life exposure of interest. Fifty six papers examined body size, 37 nutrition and 17 SEP. All of the included papers examined DNA methylation (DNAm) as the epigenetic marker. Overall there was no strong evidence for a consistent association between these early life variables in DNAm which may be due to the heterogeneous study designs, data collection methods and statistical analyses.
Despite these inconclusive results, the hypothesis that the early life environment can impact DNAm, potentially persisting into adult life, was supported by some studies and warrants further investigation. We provide recommendations for future studies.
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 (> 25 kg/m
2
) and obese (> 30 kg/m
2
). 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). An earlier age of obesity and overweight, compared to those who never became obese or overweight, 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) 1.17–4.00) and three times as likely in BCS70 (OR 3.01, 95% CI 1.74–5.22) to have long COVID. In NCDS they were also over four times as likely to be admitted to hospital (OR 4.69, 95% CI 1.64–13.39). 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 of the long-term impact of raised BMI on infectious disease outcomes in midlife.
ObjectivesDevelop administrative linkages within a national Trusted Research Environment (TRE) that hosts Longitudinal Population Study (LPS) data for over 20 LPS. We will describe the methodological ...development carried out to enable linkage to administrative datasets. These linked administrative data will support research for public good, informing policy and practice.
MethodsThe first sets of administrative data under consideration in this Feasibility Study are from the Department of Work and Pensions (DWP), the Department for Education (DfE) and HM Revenue and Customs (HMRC). Working with UK Government departments through a Task & Finish group we have gathered input from DWP, HMRC and DfE and Office for National Statistics (ONS) data sharing experts. The Task & Finish group identified three pragmatic data linkage and data sharing models, that would enable data to be linked via a newly designed secure data pipeline in a legal, secure, and trustworthy manner for all stakeholders.
ResultsTo encourage sustainability and acceptability, a model designed to be maintained over a long period is based on the re-use of Departmental Personal Identifiable Information (PII) – i.e., name, date of birth, gender, National Insurance number - and attribute data already deposited by the Departments into ONS. ONS will develop for the linkage and extraction of ONS Data into the TRE a system which conducts, and quality assesses the linkage; minimises the Departmental data to participants within the TRE only and the variables specified in the agreements; and, de-identifies the data to their DEA processing standards. The minimised and functionally anonymous data extract will be securely transferred for ingest and integration into the TRE enabling researchers to address a wider range of questions for public benefit.
ConclusionThis is a model for efficient and low-burden linkages to inform cross cutting research. It will form part of a responsive UK data science capability which can inform government research needs and be used to meet future crisis e.g. new pandemics, the impacts of climate change or economic shocks.
Genomic and biosocial research data about individuals is rapidly proliferating, bringing the potential for novel opportunities for data integration and use. The scale, pace and novelty of these ...applications raise a number of urgent sociotechnical, ethical and legal questions, including optimal methods of data storage, management and access. Although the open science movement advocates unfettered access to research data, many of the UK's longitudinal cohort studies operate systems of managed data access, in which access is governed by legal and ethical agreements between stewards of research datasets and researchers wishing to make use of them. Amongst other things, these agreements aim to respect the reasonable expectations of the research participants who provided data and samples, as expressed in the consent process. Arguably, responsible data management and governance of data and sample use are foundational to the consent process in longitudinal studies and are an important source of trustworthiness in the eyes of those who contribute data to genomic and biosocial research.
This paper presents an ethnographic case study exploring the foundational principles of a governance infrastructure for Managing Ethico-social, Technical and Administrative issues in Data ACcess (METADAC), which are operationalised through a committee known as the METADAC Access Committee. METADAC governs access to phenotype, genotype and 'omic' data and samples from five UK longitudinal studies.
Using the example of METADAC, we argue that three key structural features are foundational for practising responsible data sharing: independence and transparency; interdisciplinarity; and participant-centric decision-making. We observe that the international research community is proactively working towards optimising the use of research data, integrating/linking these data with routine data generated by health and social care services and other administrative data services to improve the analysis, interpretation and utility of these data. The governance of these new complex data assemblages will require a range of expertise from across a number of domains and disciplines, including that of study participants. Human-mediated decision-making bodies will be central to ensuring achievable, reasoned and responsible decisions about the use of these data; the METADAC model described in this paper provides an example of how this could be realised.
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