Genetic impacts on DNA methylation help elucidate regulatory genomic processes.

BACKGROUND: Pinpointing genetic impacts on DNA methylation can improve our understanding of pathways that underlie gene regulation and disease risk. RESULTS: 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). CONCLUSIONS: 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 .

Long-term psychological distress trajectories and the COVID-19 pandemic in three British birth cohorts: A multi-cohort study.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

Age of First Overweight and Obesity, COVID-19 and Long COVID in Two British Birth Cohorts.

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/m2) and obese (> 30 kg/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). 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.

Psychological distress from early adulthood to early old age: evidence from the 1946, 1958 and 1970 British birth cohorts.

BACKGROUND: Existing 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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: Across 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.

Missing at random assumption made more plausible: evidence from the 1958 British birth cohort.

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.

Association of Early-Life Mental Health With Biomarkers in Midlife and Premature Mortality: Evidence From the 1958 British Birth Cohort.

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 < .005) such that compared with the stable-low group, differences in high-density lipoprotein and abdominal obesity were only observed in female individuals. The stable-high and teacher-identified adolescent-onset groups had elevated risk for all-cause mortality (hazard ratio, 1.878; 95% CI, 1.501-2.350 and hazard ratio, 1.412; 95% CI, 1.174-1.698). Psychopathology-associated mortality was higher in both groups but unintentional injuries-associated mortality only in the stable-high group. Conclusions and Relevance: Experiencing affective symptoms and conduct problems in childhood and adolescence is associated with less favorable levels of biomarkers 28 years later and elevated risk of premature mortality. These findings, if causal and generalizable to younger cohorts, may imply that effective interventions on early-life mental health have the potential to shift the distribution of risk and improve population health.

Parental Wealth and Children's Cognitive Ability, Mental, and Physical Health: Evidence From the UK Millennium Cohort Study.

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.

Do children's expectations about future physical activity predict their physical activity in adulthood?

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.

Living longer but not necessarily healthier: The joint progress of health and mortality in the working-age population of England.

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.

Testing Comparability Between Retrospective Life History Data and Prospective Birth Cohort Study Data.

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.

DNA Methylation Age and Physical and Cognitive Aging.

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 aging 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 = 1,388-1,685). For example, a 1-year increase in AgeAccelPheno or AgeAccelGrim was associated with a 0.01 mL (95% confidence interval [CI]: 0.01, 0.02) or 0.03 mL (95% CI: 0.01, 0.05) lower mean FEV1 respectively. 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 < .05). In a subset of NSHD participants (n = 482), there was little evidence that change in any AgeAccel measure was associated with change in performance conditional on baseline performance. CONCLUSIONS: We found little evidence to support associations between the first generation of DNAm-based biomarkers of aging and age-related physical or cognitive performance in midlife to early old age. However, there was evidence that the second generation biomarkers, AgeAccelPheno and AgeAccelGrim, could act as makers of an individual's healthspan as proposed.

Associations between body size, nutrition and socioeconomic position in early life and the epigenome: A systematic review.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Better governance, better access: practising responsible data sharing in the METADAC governance infrastructure.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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.

Association of nursery and early school attendance with later health behaviours, biomedical risk factors, and mortality: evidence from four decades of follow-up of participants in the 1958 birth cohort study.

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.

The impact of health on economic and social outcomes in the United Kingdom: A scoping literature review.

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.

Childhood socioeconomic position and adult mental wellbeing: Evidence from four British birth cohort studies.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Factors across the life course predict women's change in smoking behaviour during pregnancy and in midlife: results from the National Child Development Study.

BACKGROUND: Tobacco smoking before, during and after pregnancy remains one of the few preventable factors associated with poor health outcomes for mothers and their children. We investigate predictors across the life course for change in smoking behaviour during pregnancy and whether this change predicts smoking status in midlife. METHODS: Data were from the National Child Development Study (1958 British birth cohort). We included female cohort members who reported a first pregnancy up to age 33 years. Among 1468 women who smoked before pregnancy, we examined predictors reported in childhood (age 11 years), adolescence (age 16 years) and early adulthood (age 23 years) of change in smoking behaviour from 12 months before to during pregnancy using log-binomial regression. The association between change in smoking behaviour during pregnancy and smoking status in midlife (age 55 years) was examined while adjusting for predictors across the life course. RESULTS: Among prepregnancy smokers (39%), 26% reduced and 35% quit smoking during pregnancy. Parental smoking and lower social class during childhood, and early adulthood lower social class, depression, early smoking initiation, high smoking intensity, living with a smoker, no pregnancy planning and early motherhood were associated with lower probability of smoking reduction or cessation in pregnancy. Compared with women who smoked before and during pregnancy, women who reduced or quit were two times more likely to be non-smoker at age 55 years (95% CI 1.76 to 2.20). CONCLUSIONS: Findings from this population-based birth cohort study lend support for smoking cessation strategies that target those at risk at various stages across the life course.

Cross-Domain Symptom Development Typologies and Their Antecedents: Results From the UK Millennium Cohort Study.

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.