Long-term trends in BMI: are contemporary childhood BMI growth references appropriate when looking at historical datasets?

Background Body mass index (BMI) is the most widely used surrogate measure of adiposity, and BMI z-scores are often calculated when comparing childhood BMI between populations and population sub-groups. Several growth references are currently used as the basis for calculation of such z-scores, for both contemporary cohorts as well as cohorts born decades ago. Due to the widely acknowledged increases in childhood obesity over recent years it is generally assumed that older birth cohorts would have lower BMIs relative to the current standards. However, this reasonable assumption has not been formally tested.   Methods Two growth references (1990 UK and 2000 CDC) are used to calculate BMI z-scores in three historical British national birth cohorts (National Survey of Health and Development (1958), National Child Development Study (1958) and British Cohort Study (1970)). BMI z-scores are obtained for each child at each follow-up age using the lambda-mu-sigma (LMS) method, and their distributions examined.   Results Across all three cohorts, median BMI z-score at each follow-up age is observed to be positive in early childhood. This is contrary to what might have been expected given the assumed temporal increase in childhood BMI. However, z-scores then decrease and become negative during adolescence, before increasing once more.   Conclusions The differences in BMI distribution between the historical cohorts and the contemporary growth references appear systematic and similar across the cohorts. This might be explained by contemporary reference data describing a faster tempo of weight increase relative to height than observed in older birth cohorts. Comparisons using z-scores over extended periods of time should therefore be interpreted with caution

The combined influence of parental education and preterm birth on school performance.

BACKGROUND: Social background and birth characteristics are generally found to be independently associated with school achievements but the underlying mechanisms are not fully understood. This study aimed to explore how parental education and shorter gestational age jointly influence school performance in a cohort of Swedish children. METHODS: 10,835 children born between 1973 and 1981 were studied, the third generation of the register-based Uppsala Multigenerational Birth Cohort. Ordinal logistic regression models were fitted to estimate OR of achieving middle and high grades in Swedish language at age 16 years, relative to low grade, by parental education and own gestational age, adjusting for potential confounders. RESULTS: In children from families with lower parental education, the adjusted OR of receiving a higher grade was 0.54 (95% CI 0.41 to 0.71) for preterm (<37 completed weeks) compared with full-term births. This estimate did not change when adjusted for several potential confounders (0.59; CI 0.44 to 0.79). When different cut-points were selected to define preterm birth, the estimated OR for those with low parental education decreased linearly from 0.83 (CI 0.72 to 0.96) using less than 39 weeks as the cut-point, to 0.52 (CI 0.30 to 0.90) using less than 35 weeks. There was no evidence of significant effects of shorter gestational age for children with parents from other educational groups. CONCLUSIONS: The disadvantage of shorter gestational age on the chance of achieving higher grades in Swedish language was confined to children from families in which none of the parents had higher education. This suggests that the detrimental influence of shorter gestational age on school performance in language may be avoidable

Estimating cluster-level local average treatment effects in cluster randomised trials with non-adherence

Non-adherence to assigned treatment is a common issue in cluster randomised trials (CRTs). In these settings, the efficacy estimand may be also of interest. Many methodological contributions in recent years have advocated using instrumental variables to identify and estimate the local average treatment effect (LATE). However, the clustered nature of randomisation in CRTs adds to the complexity of such analyses. In this paper, we show that under certain assumptions, the LATE can be estimated via two-stage least squares (TSLS) using cluster-level summaries of outcomes and treatment received. Implementation needs to account for this, as well as the possible heteroscedasticity, to obtain valid inferences. We use simulations to assess the performance of TSLS of cluster-level summaries under cluster-level or individual-level non-adherence, with and without weighting and robust standard errors. We also explore the impact of adjusting for cluster-level covariates and of appropriate degrees of freedom correction for inference. We find that TSLS estimation using cluster-level summaries provides estimates with small to negligible bias and coverage close to nominal level, provided small sample degrees of freedom correction is used for inference, with appropriate use of robust standard errors. We illustrate the methods by re-analysing a CRT in UK primary health settings.Comment: 21 pages, 6 Figure

Birth size and breast cancer risk: Re-analysis of individual participant data from 32 studied

Background Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size–breast cancer association. Methods and Findings Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02–1.09) and parental recall when the participants were children (1.02; 95% CI 0.99–1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95–1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000–3.499 kg, the risk was 0.96 (CI 0.80–1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00–1.25) in those who weighed ≥ 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03–1.10] and 1.09 [95% CI 1.03–1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. Conclusions This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood

[Accepted Manuscript] Detecting bias arising from delayed recording of time

Sometimes in studies of the dependence of survival time on explanatory variables the natural time origin for defining entry into study cannot be observed and a delayed time origin is used instead. For example, diagnosis of disease may in some patients be made only at death. The effect of such delays is investigated both theoretically and in the context of the England and Wales National Cancer Register

Years of sunlight exposure and cataract: a case-control study in a Mediterranean population.

BACKGROUND: We aimed to investigate the relation between sunlight exposure and risk of cataract. METHODS: We carried out a frequency-matched case-control study of 343 cases and 334 controls attending an ophthalmology outpatient clinic at a primary health-care center in a small town near Valencia, Spain. All cases were diagnosed as having a cataract in at least one eye based on the Lens Opacification Classification system (LOCS II). Controls had no opacities in either eye. All cases and controls were interviewed for information on outdoor exposure, "usual" diet, history of severe episodes of diarrhea illness, life-style factors and medical and socio-demographic variables. Blood antioxidant vitamin levels were also analyzed. We used logistic regression models to estimate sex and age-adjusted odds ratios (ORs) by quintiles of years of occupational outdoor exposure, adjusting for potential confounders such as smoking, alcohol consumption, serum antioxidants and education. RESULTS: No association was found between years of outdoor exposure and risk of cataract. However, exploratory analyses suggested a positive association between years of outdoor exposure at younger ages and risk of nuclear cataract later in life. CONCLUSION: Our study does not support an association with cataract and sunlight exposure over adult life