Determinants of the population health distribution: an illustration examining body mass index

Most epidemiological studies examine how risk factors relate to average difference in outcomes (linear regression) or odds of a binary outcome (logistic regression); they do not explicitly examine whether risk factors are associated differentially across the distribution of the health outcome investigated. This paper documents a phenomenon found repeatedly in the minority of epidemiological studies which do this (via quantile regression); associations between a range of established risk factors and body mass index (BMI) are progressively stronger in the upper ends of the BMI distribution. In this paper, we document this finding and provide illustrative evidence of it in the 1958 British birth cohort study. Associations of low childhood socioeconomic position, high maternal weight, low childhood general cognition and adult physical inactivity with higher BMI are larger at the upper end of the BMI distribution, on both absolute and relative scales. For example, effect estimates for socioeconomic position and childhood cognition were around three times larger at the 90th compared with 10th quantile, while effect estimates for physical inactivity were increasingly larger from the 50th-90th quantiles, yet null at lower quantiles. We provide potential explanations for these findings and discuss implications. Risk factors may have larger causal effects amongst those in worse health, and these effects may not be discovered when health is only examined in average terms. In such scenarios, population-based approaches to intervention may have larger benefits than anticipated when assuming equivalent benefit across the population.. Further research is needed to understand why effect estimates differ across the BMI outcome distribution and investigate whether differential effects exist for other physical and mental health outcomes

Weakening of the cognition and height association from 1957 to 2018: Findings from four British birth cohort studies

BACKGROUND: Taller individuals have been repeatedly found to have higher scores on cognitive assessments. Recent studies have suggested that this association can be explained by genetic factors, yet this does not preclude the influence of environmental or social factors that may change over time. We thus tested whether the association changed across time using data from four British birth cohorts (born in 1946, 1958, 1970, and 2001). METHODS: In each cohort height was measured and cognition via verbal reasoning, vocabulary/comprehension, and mathematical tests; at ages 10/11 and 14/17 years (N=41,418). We examined associations between height and cognition at each age, separately in each cohort, and for each cognitive test administered. Linear and quantile regression models were used. RESULTS: Taller participants had higher mean cognitive assessment scores in childhood and adolescence, yet the associations were weaker in later (1970 and 2001) cohorts. For example, the mean difference in height comparing the highest with lowest verbal cognition scores at 10/11 years was 0.57 SD (95% CI = 0.44-0.70) in the 1946 cohort, yet 0.30 SD (0.23-0.37) in the 2001 cohort. Expressed alternatively, there was a reduction in correlation from 0.17 (0.15-0.20) to 0.08 (0.06-0.10). This pattern of change in the association was observed across all ages and cognition measures used, was robust to adjustment for social class and parental height, and modeling of plausible missing-not-at-random scenarios. Quantile regression analyses suggested that these differences were driven by differences in the lower centiles of height, where environmental influence may be greatest. CONCLUSIONS: Associations between height and cognitive assessment scores in childhood-adolescence substantially weakened from 1957-2018. These results support the notion that environmental and social change can markedly weaken associations between cognition and other traits. FUNDING: DB is supported by the Economic and Social Research Council (grant number ES/M001660/1); DB and LW by the Medical Research Council (MR/V002147/1). The Medical Research Council (MRC) and the University of Bristol support the MRC Integrative Epidemiology Unit [MC_UU_00011/1]. NMD is supported by an Norwegian Research Council Grant number 295989. VM is supported by the CLOSER Innovation Fund WP19 which is funded by the Economic and Social Research Council (award reference: ES/K000357/1) and Economic and Social Research Council (ES/M001660/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Association of childhood psychomotor coordination with survival up to 6 decades later

Importance: Poorer performance on standard tests of motor coordination in children has emerging links with sedentary behavior, obesity, and functional capacity in later life. These observations are suggestive of an untested association of coordination with health outcomes, including mortality. Objective: To examine the association of performance on a series of psychomotor coordination tests in childhood with mortality up to 6 decades later. Design, Setting, and Participants: The British National Child Development Study (1958 Birth Cohort Study) is a prospective cohort study based on a nationally representative sample of births from England, Scotland, and Wales. A total of 17 415 individuals had their gross and fine motor psychomotor coordination assessed using 9 tests at ages 11 and 16 years. Data analysis for the present study was conducted from October 2016 to December 2019. Main Outcomes and Measures: All-cause mortality as ascertained from a vital status registry and survey records. Results: In this birth cohort study of 17 415 individuals who underwent a series of psychomotor coordination tests in childhood, follow up was conducted over several decades. Of the analytical sample of 12 678 individuals, 51% were male, and 72% came from a lower social group. Mortality surveillance between ages 12 and 58 years in an analytical sample of 17 062 men and women yielded 1072 deaths (766 661 person-years at risk). In survival analyses with adjustment for sex, higher scores on 7 of the 9 childhood coordination tests were associated with a lower risk of mortality in a stepwise manner. After controlling for early-life socioeconomic, health, cognitive, and developmental factors, lower mortality was statistically significantly associated with 3 tests: ball catching at age 11 years (0-8 vs 10 catches: hazard ratio [HR], 1.57; 95% CI, 1.19-2.07), match-picking at age 11 years (>50 vs 0-36 seconds: HR, 1.33; 95% CI, 1.09-1.63), and hopping at age 16 years (very unsteady vs very steady: HR, 1.28; 95% CI, 1.01-1.63). Conclusions and Relevance: The results of this cohort study suggest that childhood motor coordination is associated with lower mortality up to middle-age; these findings require replication

Polygenic and socioeconomic risk for high body mass index:69 years of follow-up across life

Genetic influences on body mass index (BMI) appear to markedly differ across life, yet existing research is equivocal and limited by a paucity of life course data. We thus used a birth cohort study to investigate differences in association and explained variance in polygenic risk for high BMI across infancy to old age (2-69 years). A secondary aim was to investigate how the association between BMI and a key purported environmental determinant (childhood socioeconomic position) differed across life, and whether this operated independently and/or multiplicatively of genetic influences. Data were from up to 2677 participants in the MRC National Survey of Health and Development, with measured BMI at 12 timepoints from 2-69 years. We used multiple polygenic indices from GWAS of adult and childhood BMI, and investigated their associations with BMI at each age. For polygenic liability to higher adult BMI, the trajectories of effect size (β) and explained variance (R2) diverged: explained variance peaked in early adulthood and plateaued thereafter, while absolute effect sizes increased throughout adulthood. For polygenic liability to higher childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller in absolute terms from adolescence to adulthood. All polygenic indices were related to higher variation in BMI; quantile regression analyses showed that effect sizes were sizably larger at the upper end of the BMI distribution. Socioeconomic and polygenic risk for higher BMI across life appear to operate additively; we found little evidence of interaction. Our findings highlight the likely independent influences of polygenic and socioeconomic factors on BMI across life. Despite sizable associations, the BMI variance explained by each plateaued or declined across adulthood while BMI variance itself increased. This is suggestive of the increasing importance of chance ('non-shared') environmental influences on BMI across life

Socioeconomic inequalities in childhood-to-adulthood BMI tracking in three British birth cohorts

Background: Body mass index (BMI) tracks from childhood to adulthood, but the extent to which this relationship varies across the distribution and according to socio-economic position (SEP) is unknown. We aimed to address this using data from three British cohort studies. Methods: We used data from: 1946 National Survey of Health and Development (NSHD, n=2,470); 1958 National Child Development Study (NCDS, n=7,747); 1970 British Cohort Study (BCS, n=5,323). BMI tracking between 11 and 42 years was estimated using quantile regression, with estimates reflecting correlation coefficients. SEP disparities in tracking were investigated using a derived SEP variable based on parental education reported in childhood. This SEP variable was then interacted with the 11-year BMI z-score. Results: In each cohort and sex, tracking was stronger at the upper end of the distribution of BMI at 42 years. For example, for men in the 1946 NSHD, the tracking estimate at the 10th quantile was 0.31 (0.20, 0.41), increasing to 0.71 (0.61, 0.82) at the 90th quantile. We observed no strong evidence of SEP inequalities in tracking in men in the 1946 and 1958 cohorts. In the 1970 cohort, however, we observed tentative evidence of stronger tracking in low SEP groups, particularly in women and at the higher end of the BMI distribution. For example, women in the 1970 cohort from low SEP backgrounds had tracking coefficients at the 50th, 70th, and 90th quantiles which were 0.05 (-0.04; 0.15), 0.19 (0.06; 0.31), and 0.22 (0.02; 0.43) units higher, respectively, than children from high SEP groups. Conclusion: Tracking was consistently stronger at the higher quantiles of the BMI distribution. We observed suggestive evidence for a pattern of greater BMI tracking in lower (compared to higher) SEP groups in the more recently born cohort, particularly in women and at the higher end of the BMI distribution

Associations of childcare type, age at start, and intensity with body mass index trajectories from 10 to 42 years of age in the 1970 British Cohort Study.

BACKGROUND: Attending childcare is related to greater childhood obesity risk, but there are few long-term follow-up studies. We aimed to examine the associations of childcare type, age at start, and intensity with body mass index body mass index (BMI) trajectories from ages 10 to 42 years. METHODS: The sample comprised 8234 individuals in the 1970 British Cohort Study, who had data on childcare attendance (no, yes), type (formal, informal), age at start (4-5, 3-3.99, 0-2.99 years old), and intensity (1, 2, 3, 4-5 days/week) reported at age 5 years and 32 563 BMI observations. Multilevel linear spline models were used to estimate the association of each exposure with the sample-average BMI trajectory, with covariate adjustment. A combined age at start and intensity exposure was also examined. RESULTS: Attending vs not attending and the type of childcare (none vs formal/informal) were not strongly related to BMI trajectories. Among participants who attended childcare 1 to 2 days a week, those who started when 3 to 3.99 years old had a 0.197 (-0.004, 0.399) kg/m2 higher BMI at age 10 years than those who started when 4 to 5 years old, and those who started when 0 to 2.99 years old had a 0.289 (0.049, 0.529) kg/m2 higher BMI. A similar dose-response pattern for intensity was observed when holding age at start constant. By age 42 years, individuals who started childcare at age 0 to 2.99 years and attended 3 to 5 days/week had a 1.356 kg/m2 (0.637, 2.075) higher BMI than individuals who started at age 4 to 5 years and attended 1 to 2 days/week. CONCLUSIONS: Children who start childcare earlier and/or attend more frequently may have greater long-term obesity risk.WJ is supported by the UK Medical Research Council (New Investigator Research Grant: MR/P023347/1) and acknowledges support from the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University, and the University of Leicester. JA is funded by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence which is funded by the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust (MRC administered grant MR/K023187/1)

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