George David Batty

Background: The consequences of prolonged exposure to obesity on biomarkers of myocardial stress and injury remain unclear. We examined associations of duration and cumulative severity of obesity from childhood to later adulthood with concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I (hs-cTnI), and growth differentiation factor-15 (GDF-15) at age 62 years. Methods: The sample comprised 4,901 participants in the 1958 National Child Development Study who had measurements of NT-proBNP, hs-cTnI, or GDF-15 at age 62 years and at least four BMI assessments between 7 and 62 years of age. Individual BMI trajectories were modelled, from which total duration of obesity and mean excess BMI (area between the trajectory and the age-specific obesity threshold divided by duration) were derived. Associations of ever versus never having been obese, obesity duration, and mean excess BMI with biomarker concentrations were examined using general linear regression models with progressive adjustment for early-life characteristics; contemporaneous cardiometabolic factors; and health behaviours, socioeconomic position, and psychosocial factors. Nonlinear associations of obesity duration were estimated using restricted cubic splines and subsequently approximated using linear splines. Results: Overall, 26.3% of participants had ever experienced obesity. There was no evidence of an association between ever versus never having been obese and NT-proBNP. Among men, ever having been obese was associated with 11.00% (95% CI, 4.62–17.37) higher hs-cTnI in the fully adjusted model, whereas there was no evidence of an association among women. Ever having been obese was associated with higher GDF-15, although the association attenuated substantially after adjustment for contemporaneous cardiometabolic factors. Longer obesity duration was associated with higher concentrations of all three biomarkers in fully adjusted models, but the pattern differed by biomarker: hs-cTnI increased approximately linearly with duration, whereas NT-proBNP and GDF-15 remained relatively stable up to approximately 25 years of obesity before increasing with longer duration. In fully adjusted models, each additional year of obesity beyond 25 years was associated with 1.80% (95% CI, 0.54–3.06) higher NT-proBNP and 0.81% (95% CI, 0.25–1.36) higher GDF-15, while each additional year across the full range of obesity duration was associated with 0.41% (95% CI, 0.07–0.76) higher hs-cTnI. Among participants who had ever experienced obesity, each 1 kg/m² higher mean excess BMI was associated with 4.02% (95% CI, 1.79–6.24) higher NT-proBNP and 2.00% (95% CI, 0.49–3.51) higher hs-cTnI in fully adjusted models; there was no evidence of an association with GDF-15. Conclusions: Longer duration of obesity was associated with higher concentrations of biomarkers reflecting myocardial stress, injury, and cellular stress at age 62 years, with associations particularly evident after approximately 25 years of obesity for NT-proBNP and GDF-15. These findings suggest that duration of obesity may provide clinically relevant information beyond current obesity status, supporting its consideration as an additional dimension of cumulative obesity burden in cardiovascular risk assessment.

Background: The association between homelessness and the type of homeless experience with all-cause and cause-specific mortality is uncertain. Methods: Published studies were retrieved through a systematic search of MEDLINE, Embase PsycINFO, and Scopus from inception to December 2024. Unpublished data were identified from open-access data archives. We used random-effects meta-analysis to combine the effect estimates from published and unpublished data from 116 studies comprising 2 563 633 homeless people and 129 292 553 population controls. This review is registered at PROSPERO (CRD42023430984). Results: The risk of all-cause mortality was increased in people exposed to homelessness compared with those unexposed [relative risk (RR) 2.21, 95% confidence interval (CI) 1.91–2.57, P < .001, I2 = 99.7], with risks similar in men (RR 4.04, 95% CI 2.87–5.21) and women (RR 3.58, 95% CI 2.35–4.82). Risks were higher in people who had slept rough (RR 7.63, 95% CI 3.29–11.97) than in those who had slept in homeless hostels/shelters (RR 3.44, 95% CI 2.10–4.77) and also elevated for people staying in low-cost hotels (RR 5.18, 95% CI 1.14–9.23). Summary RR estimates were elevated for 33 of the 36 (92%) causes of death. The highest risk of death was apparent for psychoactive-substance-use disorder (RR 21.38, 95% CI 14.44–31.67), accidental injuries (RR 13.15, 95% CI 5.46–31.69), and drug overdose (RR 11.65, 95% CI 6.97–19.48). Around half of the studies (57%) were of high quality. No studies were found in low-income countries. There was no evidence of publication bias. Conclusion: Compared with the general population, homeless people experience an increased risk of premature mortality. The most extreme inequalities were from deaths through psychoactive-substance-use disorder, accidents, and drug overdose. There are evidence-based treatments for psychoactive substance use and drug overdose, suggesting that some of these deaths are avoidable.

Behavioural studies suggest atypical or delayed development of “theory of mind” (ToM; our ability to reason about others’ mental states) following preterm birth. Using pre-registered analyses of behavioural and movie-viewing functional magnetic resonance imaging (fMRI) metrics of ToM, we tested for a domain-specific impact of preterm birth (24-32 weeks’ gestational age) on theory of mind development at age five years. Preterm-born children (n=52) scored lower than term-born comparators (n=58) on a linguistic behavioural ToM task, but this difference was primarily driven by differences in receptive language. Neurally, preterm-born children (n=30) had qualitatively similar responses in brain regions that support ToM reasoning to a short movie to term-born comparators (n=46), as characterised by four neural metrics; responses to one scene differed as a function of gestational age. Using intersubject correlation analyses, we found that preterm-born children’s ToM network responses were more heterogenous than term-born children’s responses; however individual preterm-born children’s responses most resembled those observed in same-age term-born children, relative to younger children or other preterm-born children. Taken together, preterm birth does not appear to preclude broadly similar functional development in ToM brain regions by age five years.

Whereas attention-deficit/hyperactive disorder (ADHD) has consistently been shown to be correlated with later risk of depression, anxiety, and substance misuse, the relationship with other adverse health endpoints, particularly somatic conditions, is uncertain. In a full-nation birth cohort study, we used a phenotype-wide approach to explore the influence, if any, of a ADHD diagnosis in childhood/adolescence on later disease and injury. Comprising 52594 children (25463 females) born in a single year with non-missing data, the 1987 Finnish Birth Cohort was generated from linkage of routinely collected data. ADHD diagnosis was captured from in- and out-patient hospital records up to age 18 years and study members continued to be surveilled for other diagnoses until 2020 (aged 33). Pre-adulthood, 0.43% ( N = 228) of study members were diagnosed with ADHD. In people with ADHD, relative to population controls, there was a heightened risk of developing all of the 17 health endpoints examined. Of these associations, however, eleven were statistically significant after adjustment for age and sex, and five after further control for birth weight, family socioeconomic circumstances, study members’ educational performance, and multiple testing (odds ratio; 99.7%): neurotic disorders (2.11; 1.25, 3.41); substance abuse disorder (2.26; 1.27, 3.79); poisoning (2.30; 1.02, 4.52); mood disorders (2.45; 1.49, 3.88); and epilepsy (4.55; 1.82, 9.55). Repeating the main analyses following data imputation ( N = 54045) confirmed these associations with the emergence of a connection between psychotic disorders and antecedent ADHD (2.63; 1.34, 5.18). Overall, young people with ADHD in the present cohort experienced an increased future burden of psychiatric and neurological conditions but seemingly not somatic disorders.

Preterm birth is closely associated with immune dysregulation in early life and subsequent learning and psychiatric disorders, but methods for stratifying infants at risk remain elusive. Protein epigenetic Scores (EpiScores) are DNA methylation (DNAm)-based proxies of circulating proteins and can capture health-related exposures such as chronic inflammation. EpiScore of C-reactive protein (DNAm CRP) is associated with inflammatory burden in early life, atypical brain development following preterm birth and adult cognitive ability. To evaluate the utility of neonatal protein EpiScores for predicting childhood cognition, we examined associations of DNAm CRP and 42 other saliva-based EpiScores enriched for inflammatory proteins correlated with low gestational age, with cognition in a cohort of 231 children, including 154 preterm children assessed at 2 years and 127 preterm and term-born children assessed at 5 years. DNAm CRP was negatively associated with 5-year Mullen Scales of Early Learning Composite (ELC) (β = −0.273, p = 0.002). Association magnitudes were larger for children born earlier (DNAm CRP x gestational age, β _interaction = 0.181). DNAm CD209 was positively associated with 5-year ELC (β = 0.267, adjusted p < 0.005). Fourteen other EpiScores were nominally associated with either 2-year Bayley-III Cognitive composite or 5-year ELC (absolute β range 0.180 to 0.245, p < 0.05). For preterm children, associations of DNAm CCL18 with 2-year cognition (β = 0.182, p = 0.039) and of DNAm CRP (β = −0.318, p = 0.021) and DNAm CRTAM (β = −0.307, p = 0.008) with 5-year cognition remained significant after adjustment for inflammatory exposures. We demonstrate associations between a range of neonatal salivary EpiScores and childhood cognition, suggesting the clinical value of EpiScores as early life markers of cognitive ability in children at risk of impairment warrants further investigation.

Background. Nascent findings suggest that people with attention-deficit/hyperactivity disorder (ADHD) experience higher rates of mortality. To date, study samples have been insufficiently well-characterized to examine the mechanisms via which this neurodevelopmental condition elevates mortality risk. Methods. We used data from the 2007 and 2011 waves of the US National Health Interview Survey, a general population-based cohort study comprising 52097 adults (28675 women) aged 18 years or older at baseline. ADHD diagnosis and an array of demographic, socioeconomic, lifestyle, and co-morbidity (somatic and psychiatric) covariates were self-reported.Findings. At baseline, compared with unaffected individuals, participants with ADHD were more likely to be socioeconomically disadvantaged, smoke cigarettes, consume alcohol, and report symptoms of psychological distress. A median 7.75 years of mortality surveillance (range: 7.25-12.25) gave rise to 6597 deaths from all-causes. After adjustment for age, sex, ethnicity, and survey year, ADHD was associated with a markedly elevated risk of death (hazard ratio [95% confidence interval]: 1.58 [1.20-2.09]). Statistical adjustment for socioeconomic circumstances (11% attenuation), physical co-morbidities (15%), and lifestyle factors (17%) had only a modest impact on the ADHD–death gradient, with the greatest explanatory power apparent for symptoms of depression and anxiety (58%). The magnitude of the association of ADHD with mortality was commensurate to that for several well-established risk factors such as poverty (1.66 [1.55-1.78]), hypertension (1.41 [1.32-1.51]), and diabetes (1.71 [1.59-1.85]) but somewhat lower than cigarette smoking (2.51 [2.29-2.76]) after controlling for age, sex, ethnicity, and survey year. Associations between ADHD and cause-specific mortality from cardiovascular disease, cancer, and chronic respiratory disease were inconclusive. Interpretation. In the present study, the influence of ADHD on total mortality appears to be largely embodied via a series of malleable characteristics, particularly mental illness. If confirmed elsewhere, these results raise the possibility that risk factor modification via standard pharmacological and behavioral interventions could help reduce rates of premature mortality in this patient group.

Summary: Background: Nascent findings suggest that people with attention-deficit/hyperactivity disorder (ADHD) experience higher rates of mortality. To date, study samples have been insufficiently well-characterized to examine the mechanisms via which this neurodevelopmental condition elevates mortality risk. Methods: We used data from the 2007 and 2011 waves of the US National Health Interview Survey, a general population-based cohort study comprising 52097 adults (28675 women) aged 18 years or older at baseline. ADHD diagnosis and an array of demographic, socioeconomic, lifestyle, and co-morbidity (somatic and psychiatric) covariates were self-reported. Findings: At baseline, compared with unaffected individuals, participants with ADHD were more likely to be socioeconomically disadvantaged, smoke cigarettes, consume alcohol, and report symptoms of psychological distress. A median 7.75 years of mortality surveillance (range: 7.25-12.25) gave rise to 6597 deaths from all-causes. After adjustment for age, sex, ethnicity, and survey year, ADHD was associated with a markedly elevated risk of death (hazard ratio [95% confidence interval]: 1.58 [1.20-2.09]). Statistical adjustment for socioeconomic circumstances (11% attenuation), physical co-morbidities (15%), and lifestyle factors (17%) had only a modest impact on the ADHD–death gradient, with the greatest explanatory power apparent for symptoms of depression and anxiety (58%). The magnitude of the association of ADHD with mortality was commensurate to that for several well-established risk factors such as poverty (1.66 [1.55-1.78]), hypertension (1.41 [1.32-1.51]), and diabetes (1.71 [1.59-1.85]) but somewhat lower than cigarette smoking (2.51 [2.29-2.76]) after controlling for age, sex, ethnicity, and survey year. Associations between ADHD and cause-specific mortality from cardiovascular disease, cancer, and chronic respiratory disease were inconclusive. Interpretation: In the present study, the influence of ADHD on total mortality appears to be largely embodied via a series of malleable characteristics, particularly mental illness. If confirmed elsewhere, these results raise the possibility that risk factor modification via standard pharmacological and behavioral interventions could help reduce rates of premature mortality in this patient group. Funding: This paper received no direct funding. GDB is supported by the UK Medical Research Council (MR/P023444/1) and the US National Institute on Aging (1R56AG052519-01, 1R01AG052519-01A1). Research in context: Evidence before this study: We searched the PubMed database (January 1947 to June 2026) using the terms ‘attention-deficit/hyperactivity disorder ‘, ‘ADHD’, ‘mortality’, and ‘death’ with no language or date restrictions. We considered individual studies, systematic reviews, and meta-analyses. The most recent systematic review was published in 2022 and the majority of the eight non-overlapping studies found that ADHD was associated with a raised risk of mortality. Included cohort studies were typically generated from linked administrative health records and therefore insufficiently well characterized to comprehensively test how ADHD was embodied in order to elevate death rates. There was some suggestion of a role for mediation via socioeconomic position and mental illness but lifestyle factors such as obesity, smoking, physical inactivity, and alcohol intake had not been considered. A side-by-side comparison of the magnitude of the relationship of ADHD with conventional risk factors for mortality was also lacking. Added value of this study: This is the first prospective cohort study to systematically and comprehensively test the mechanisms via which ADHD elevates mortality and to contextualize the strength of this relationship against well-established risk factors. Socioeconomic circumstances, physical co-morbidities, and lifestyle factors mediated less than one fifth of the ADHD–death gradient, with the greatest explanatory power apparent for depression and anxiety. The impact of ADHD on mortality risk was commensurate to that apparent for several well-established risk factors for mortality such as poverty, hypertension, and diabetes but somewhat lower than estimates for cigarette smoking and physical inactivity. Implications of all the available evidence: While supporting evidence is required, our findings point to the possibility that modification of physical co-morbidities, lifestyle factors, and mental illness via pharmacological treatment and behavioral intervention may have utility in the avoidance of premature mortality in people with ADHD.

Background: While the greater burden of cardiovascular disease (CVD) in Black Americans relative to White has persisted for four decades, the potential to mitigate this disparity via clinical and non-clinical approaches is largely untested. We examined the relative impact on these race/ethnic differentials in CVD of membership of low risk groups based on conventional risk factors (e.g., diabetes) and the social determinants of health (e.g., education).Methods: In this multicohort study, we used baseline ethnicity and risk factor data from the US National Health and Nutrition Examination Survey (NHANES, 10 cohorts initiated 1999-2018) with participant linkage to national registries for cause-specific mortality. Low risk was denoted by individual risk factors and their combination. Cox proportional hazard regression models were used to summarise the association of race/ethnicity with CVD mortality.Findings: An analytical sample of 50,065 individuals (25,934 women; mean baseline age 53) contributed 473,949 person-years at risk (mean follow-up 9.5 yr), giving rise to 9118 deaths (2908 from CVD). In age- and sex-adjusted analyses, as anticipated, relative to White individuals, Black Americans had a markedly higher burden of CVD (hazard ratio; 95% confidence interval: 1.51; 1.30, 1.77) and other major causes of mortality. Black Americans classified as low-risk based on individual clinical risk indices (e.g., normotensives: 1.58; 1.22, 2.04) and the Framingham algorithm (2.94; 2.04, 4.25) continued to experience higher rates of CVD relative to White individuals. A marked reduction in this disparity was, however, apparent in Black versus White Americans who had one (1.09; 0.78, 1.51), two (0.99; 0.67, 1.48), and three or more (1.31; 0.81, 2.12) favourable social determinants. A similar pattern of results was evident for total mortality. Interpretation: While disparities in CVD continued to be apparent in Black Americans who were in the low risk category based on targets for clinical and lifestyle factors, those in favourable social circumstances had disease rates similar to White people with the same characteristics.

Background: Higher childhood (pre-morbid) cognitive function (IQ) appears to confer a lower risk of cardiovascular disease (CVD) episodes in adulthood, however, the underpinning mechanisms are uncertain. We tested the association between childhood cognitive ability and later CVD risk factors that may underpin this gradient. Methods: We used data from two well-characterized prospective birth cohort studies initiated in the United Kingdom in 1958 (N=10870) and 1970 (N=9278). Cognitive function was quantified using validated written tests at around 10 years of age. A total of 16 biological, psychosocial, and behavioral risk factors were collected at 46-48 (1970 cohort) and 61-65 (1958 cohort) years of age in both studies. Associations were summarized using linear and logistic regression. Results: After pooling the data and controlling for early life confounding factors, higher childhood cognitive ability was related to more favorable levels of 4/4 psychosocial, 3/3 behavioral, and 6/9 biological risk factors in middle/older age. The magnitude of these relationships increased from biological, to behavioral then psychosocial risk factors. For example, a one standard deviation higher cognitive test score was related to protective levels of body mass index (beta coefficient [95% confidence interval]: -0.58 [-0.70, -0.45]; p-value <0.001), triglycerides (-0.03 [-0.04, -0.01]; <0.001), cigarette smoking (odds ratio [95% confidence interval]: 0.72 [0.67, 0.76] <0.001), depressive symptoms (0.79 [0.74, 0.84]; <0.001), and a high prestige occupation (2.27 [2.21, 2.35]; <0.001). There was some evidence of mediation via educational attainment. Conclusions: The present correlations implicate a series of mechanistic pathways which may connect cognition with subsequent CVD events. The greater burden of unfavorable risk factors at the lower end of the cognition spectrum suggests that compliance with preventive health advice may be sub-optimal. Clinical Perspective What is new?: This is the most comprehensive examination of cardiovascular disease risk factors in relation to antecedent (pre-morbid) cognitive function (IQ) Pooling data from two large cohort studies of births from 1958 and 1970 in the UK, children with high cognitive function experienced the most favorable levels of a range of psychosocial, behavioral, and biological CVD risk factors up to six decades later. What are the clinical implications?: These IQ–risk factor correlations implicate a series of mechanistic pathways connecting cognition with future CVD events. It also seems likely that preventive health advice from clinicians, including lifestyle modification and drug treatments, may be associated with low levels of compliance and/or initiation in people at the lower end of the cognition spectrum.

Background: Preterm birth (PTB) is a leading cause of atypical brain development and cognitive impairment, however, there are sparse data on its impact on statutory educational assessments. We aimed to describe school readiness at 5 years and educational attainment at 6–7 years of children born preterm in England and identify the early life factors that associate with attainment. Methods: We created a novel record linkage between the National Neonatal Research Database and the National Pupil Database for all babies born st , 2015, to October 1 ^st , 2025, with no language restrictions for publications using the terms ((“preterm” OR “premature” OR “gestational age”) AND “socioeconomic” AND (“school” OR “education”)) in the title/ Our search identified 20 relevant peer-reviewed studies, including one narrative systematic review that examined how socioeconomic inequalities and preterm birth interact to modify health and education outcomes. Three studies were conducted in the UK and used linked data to investigate educational outcomes for preterm-born children. The remainder were conducted in Scandinavian countries, Canada, Australia, and the Netherlands. Collectively, these studies have consistently shown that children born preterm have lower educational attainment compared with those born at term: a well-established dose-response relationship exists between gestational age and educational outcomes, with lower gestational age associated with progressively poorer attainment across all stages of education. However, most existing linkage studies did not capture the clinical heterogeneity of the preterm-born population underlying this gradient, as these data are rarely available in population-level datasets linked to education records. Whilst some studies included measures of socioeconomic status as a covariate, their independent effects have seldom been investigated, particularly relative to neonatal risk factors. Added value of this study: The present study addresses these gaps through a novel linkage of population-level neonatal clinical data with national statutory educational assessments. We describe the high prevalence of low attainment among very preterm children (<32 weeks’ gestation) at ages 5 through 7 years in England. The linkage enables a granular characterisation of how maternal and neonatal conditions, exposures and treatments, and neighbourhood-and family-level measures of social disadvantage explain educational performance of children born <32 weeks’ gestation. The findings show a dose effect of low GA on low attainment and that the adverse effects of socioeconomic deprivation at birth persist through early school age. The effect of family-level deprivation at the start of school age is comparable in magnitude to that of severe neonatal brain injury, however, impacts a greater proportion of the population. As such, this study provides a more holistic understanding of the pathways underlying educational risk in this population. Implications of all the available evidence: Improving the educational attainment of very preterm children is likely to require a reduction in social inequalities in pregnancy and early childhood, alongside care practices and research to minimise comorbidities of preterm birth. Furthermore, the identification of modifiable exposures, including maternal non-smoking, antenatal or postnatal corticosteroid exposure, breastfeeding, and deferred school entry or targeted additional support for very preterm children born in the summer months, offers practical targets for parents, clinicians, teachers and school leaders and educators, that could facilitate long-term educational attainment for children born preterm.