Childhood Maltreatment and BMI Trajectories to Mid-Adult Life: Follow-Up to Age 50y in a British Birth Cohort.

Childhood maltreatment including abuse and neglect has been associated with adult obesity, but evidence on life-course development of obesity or BMI gain is unclear. We aim to establish whether childhood maltreatments are related to obesity or BMI at different life-stages 7y-50y and to identify possible explanations for associations

Child maltreatment, early life socioeconomic disadvantage and all-cause mortality in mid-adulthood: findings from a prospective British birth cohort

Objectives: Early-life adversities (ELAs) such as child maltreatment (neglect and abuse) and socioeconomic disadvantage have been associated with adult mortality. However, evidence is sparse for specific types of ELA. We aimed to establish whether specific ELAs (ie, different types of child maltreatment and socioeconomic disadvantage) were associated independently with all-cause mortality in mid-adulthood and to examine potential intermediary pathways. / Design: Prospective cohort study. / Setting: 1958 British birth cohort: a longitudinal, population-based sample of individuals born in Great Britain during a single week in March 1958. / Participants: 9310 males and females with data on child maltreatment and mortality (44/45–58 years). / Outcome measures: Mortality follow-up from 2002/2003 to 2016 when participants were aged 44/45–58 years. Death was ascertained via the NHS Central Register (N=296) or cohort maintenance activities (N=16). / Results: Prevalence of ELAs ranged from 1.6% (sexual abuse) to 11% (psychological abuse). Several, but not all, ELAs were associated with increased risk of premature death, independent of covariates and other adversities; adjusted HRs were 2.64 (95% CI 1.52 to 4.59) for sexual abuse, 1.93 (95% CI 1.45 to 2.58) for socioeconomic disadvantage, 1.73 (95% CI 1.11 to 2.71) for physical abuse and 1.43 (95% CI 1.03 to 1.98) for neglect. After adjustment for covariates and other adversities, no associations with mortality were observed for psychological and witnessing abuse. Regarding potential intermediaries (including adult socioeconomic factors, behaviours, adiposity, mental health and cardiometabolic markers), most associations attenuated after accounting for adult health behaviours (particularly smoking). In addition, early-life socioeconomic disadvantage and neglect associations attenuated after accounting for adult socioeconomic factors. The association for sexual abuse and premature mortality was largely unaffected by potential intermediaries. / Conclusions: Associations with premature mortality varied by type of ELA: associations for sexual and physical abuse, neglect and socioeconomic disadvantage were independent of each other. Different types of ELAs could influence premature mortality via different pathways; this requires further research

Obesity and risk factors for cardiovascular disease and type 2 diabetes: Investigating the role of physical activity and sedentary behaviour in mid-life in the 1958 British cohort.

A key public health priority is to minimise obesity-related health consequences. We aim to establish whether physical activity (PA) or less sedentary behaviour ameliorate associations of obesity with biomarkers for cardiovascular disease (CVD) and type 2 diabetes

Combined early and adult life risk factor associations for mid-life obesity in a prospective birth cohort: assessing potential public health impact.

OBJECTIVE: The combined effect of life-course influences on obesity development and thus their potential public health impact is unclear. We evaluated combined associations and predicted probabilities for early and adult life risk factors with central and general obesity in mid-adulthood. SETTING: 1958 British birth cohort. PARTICIPANTS: 4629 males and 4670 females with data on waist circumference. OUTCOME MEASURES: 45 year obesity measured via waist circumference, waist-hip ratio (WHR) and BMI. RESULTS: At 45 years, approximately a third of the population were centrally obese and a quarter were generally obese. Three factors (parental overweight, maternal smoking during pregnancy and adult inactivity) were consistently associated with central and general obesity. Predicted probabilities for waist obesity increased from those with none to all three risk factors (0.15-0.33 in men; 0.19-0.39 in women (ptrend<0.001)), with a similar trend for general obesity. Additional factors (adult smoking, low fibre and heavy alcohol consumption) were associated with WHR obesity, although varying by gender. Prevalence of risk factors was higher in manual than non-manual groups: for example, in men 38% versus 25%, respectively, had ≥2 risk factors for waist and general obesity. CONCLUSIONS: Early-life and adult factors that are amenable to change are highly prevalent and accumulate in association with central and general obesity in mid-adulthood. The increase in probabilities for mid-adult obesity associated with cumulative levels of risk factors suggests the potential for public health impact

Change in health and social factors in mid-adulthood and corresponding changes in leisure-time physical inactivity in a prospective cohort

BACKGROUND: To identify whether changes in adult health and social factors are associated with simultaneous changes in inactivity. METHODS: Health, social factors and leisure-time inactivity (activity frequency < 1/week) were self-reported at 33y and 50y in the 1958 British birth cohort (N = 12,271). Baseline (33y) health and social factors and also patterns of change in factors 33y-to-50y were related to inactivity 33y-to-50y (never inactive, persistently inactive, deteriorating to inactivity, or improving from inactivity) using multinomial logistic regression. RESULTS: Approximately 31% were inactive at 33y and 50y; 35% changed status 33y-to-50y (17% deteriorating to inactivity, 18% improving from inactivity). Baseline poor health and obesity were associated with subsequent (33y-to-50y) inactivity; e.g. for poor health, relative risk ratios (RRRs) for deteriorating to inactivity (vs never inactive) and improving from inactivity (vs persistently inactive) were 1.38(1.16,1.64) and 0.77(0.63,0.94) respectively. Adverse changes in health and weight were associated with simultaneous adverse changes in inactivity; e.g. worsening health (vs always good/excellent health) was associated with higher risk of deteriorating to inactivity (RRR:2.20(1.85,2.62)) and lower risk of improving from inactivity (RRR:0.61(0.49,0.77)). However, improving health and weight loss were not associated with improving from inactivity. Worsening self-efficacy 33y-to-50y was associated with lower risk of improving from inactivity; there was no association between improving self-efficacy and inactivity change. Downward social mobility was not associated with deteriorating to or improving from inactivity. Changes in depression symptom level, marriage/co-habitation or parenthood 33y-to-50y were not associated with inactivity changes. No associations were observed for employment. CONCLUSIONS: Associated changes in mid-life health factors with deleterious inactivity changes, highlight the importance of maintaining health, weight and self-efficacy across adulthood to deter inactivity

Early adulthood determinants of mid-life leisure-time physical inactivity stability and change: Findings from a prospective birth cohort

OBJECTIVES: Physical inactivity is highly prevalent. Knowledge is needed of influences on inactive lifestyles. We aimed to establish whether early adult factors predict subsequent inactivity patterns in mid-adulthood. DESIGN: Leisure-time inactivity (activity frequency<1/week) was assessed at 33y and 50y in the 1958 British Birth cohort (N=12,271). METHODS: We assessed associations of early adult (23-33y) physical status, mental function, social, family and neighbourhood circumstances with four 33-50y patterns (never inactive, persistently inactive, deteriorating or improving) using multinomial logistic regression with and without adjustment for childhood factors (e.g. social class). RESULTS: Inactivity prevalence was similar at 33y and 50y (∼31%), but 17% deteriorated and 18% improved with age. Factors associated with persistent vs never inactive were: limiting illness (relative risk ratio (RRR):1.21(1.04,1.42) per number of ages exposed (0,1 or 2 times across ages 23y and 33y), obesity (1.33(1.16,1.54) per number of ages exposed), height (0.93(0.89,0.98) per 5cm), depression (1.32(1.19,1.47) per number of ages exposed); education (1.28(1.20,1.38) per decrease on 5-point scale) and neighbourhood (1.59(1.37,1.86) in 'industrial/local authority housing areas' and 1.33(1.12,1.58) in 'growth/metropolitan inner areas' vs 'suburbs, service, rural or seaside areas'). Associations were broadly similar for inactivity deterioration. Industrial/local authority housing areas (0.75(0.61,0.91)) and longer obesity exposure (0.78(0.64,0.95)) were associated with lower RRRs for improvement. Number of children was associated with improvement, although associations varied by age. Associations remained after adjustment for childhood factors. CONCLUSIONS: Several early adult factors are associated with inactivity persistence and deterioration; fewer with improvement. Obesity duration and neighbourhood lived in during young adulthood had long-lasting associations with inactivity patterns in mid-life

Childhood maltreatment and biomarkers for cardiometabolic disease in mid-adulthood in a prospective British birth cohort: associations and potential explanations

OBJECTIVES: Research on associations between childhood maltreatment and adult cardiometabolic disease risk is sparse. We aimed to investigate associations between different forms of child maltreatment and mid-adult cardiometabolic markers and whether potential intermediaries could account for the associations observed. SETTING: 1958 British birth cohort. PARTICIPANTS: Approximately 9000 cohort members with data on cardiometabolic markers. OUTCOMES: Adult (45y) cardiometabolic markers (blood pressure, lipids and glycated haemoglobin [HbA1c]). RESULTS: Seventeen per cent of participants were identified as neglected; 6.1%, 1.6% and 10.0% were identified as experiencing physical, sexual and psychological abuse, respectively. Childhood neglect and physical abuse were associated with high body mass index (BMI) and large waist circumference when adjusting for early-life covariates. For neglect, the adjusted odds ratio (AOR) was 1.16 (95% CI: 1.02 to 1.32) and 1.15 (1.02 to 1.30) for general and central obesity, respectively, and for physical abuse, the respective AOR was 1.36 (1.13 to 1.64) and 1.38 (1.16 to 1.65). Neglect was also associated with raised triglycerides by 3.9 (0.3 to 7.5)% and HbA1c by 1.2 (0.4 to 2.0)%, and among females, lower high-density lipoprotein cholesterol (HDL-c) by 0.05 (0.01 to 0.08)mmol/L after adjustment. For physical abuse, the AOR was 1.25 (1.00 to 1.56) for high low-density lipoprotein cholesterol, HbA1c was raised by 2.5 (0.7 to 4.3)% (in males) and HDL-c was lower by 0.06 (0.01 to 0.12)mmol/L (in females). Associations for sexual abuse were similar to those for physical abuse but 95% CIs were wide. For psychological abuse, the AOR for elevated triglycerides was 1.21 (1.02 to 1.44) and HDL-c was lower by 0.04 (0.01 to 0.07)mmol/L. Maltreatments were not associated with raised blood pressure. In analyses of potential intermediary factors, several associations attenuated after adjustment for adult lifestyles (mainly smoking and alcohol consumption rather than physical activity) and child-to-adult BMI. CONCLUSIONS: Childhood maltreatments, particularly neglect and physical abuse, were associated with greater adiposity and poorer lipid and HbA1c profiles decades later in adulthood. Associations were modest but independent of early-life factors linked to these outcomes. Findings implicate adult lifestyles as an important intermediary between child maltreatment and outcomes

Repeated exposure to socioeconomic disadvantage and health selection as life course pathways to mid-life depressive and anxiety disorders

The biomedical examination was funded by Medical Research Council [G0000934], awarded under the Health of the Public initiative. Charlotte Clark is supported by an Engineering and Physical Sciences Research Fellowship. Bryan Rodgers is supported by Research Fellowships Nos 148948 and 366758 and by Program Grant No. 179805 from the National Health and Medical Research Council of Australia. Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)