[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

Association between prenatal maternal infection and disordered eating behaviours in adolescence: A UK population-based prospective birth cohort study

Background Prenatal infections have been proposed as a putative risk factor for a number of psychiatric outcomes across a continuum of severity. Evidence on eating disorders is scarce. We investigated whether exposure to prenatal maternal infections is associated with an increased risk of disordered eating and weight and shape concerns in adolescence in a large UK birth cohort.Methods We used data from the Avon Longitudinal Study of Parents and Children. The primary exposure was maternal experience of infections at any time in pregnancy. Study outcomes were presence of any, monthly or weekly disordered eating at 14 and 16 years of age, and weight and shape concerns at 14 years. We defined the causal effect of the exposure on these outcomes using a counterfactual framework adjusting our analyses for a number of hypothesised confounders, and imputing missing confounder data using multiple imputation.Results In total, 4884 children had complete exposure and outcome data at age 14 years, and 4124 at 16 years. Exposed children had a greater risk of reporting weekly disordered eating at both age 14 [risk difference (RD) 0.9%, 95% confidence interval (CI)-0.01 to 1.9, p = 0.08] and 16 (RD 2.3%, 95% CI 0.6-3.9, p < 0.01), though evidence of an association was weak at age 14 years. Exposed children also had greater weight and shape concerns at age 14 years (mean difference 0.15, 95% CI 0.05-0.26, p < 0.01).Conclusions Exposure to prenatal maternal infection is associated with greater risk of disordered eating in adolescence. This association could be explained by in utero processes leading to impaired neurodevelopment or altered immunological profiles. Residual confounding cannot be excluded

Associations between blood metabolic profile at 7 years old and eating disorders in adolescence: Findings from the avon longitudinal study of parents and children

Eating disorders are severe illnesses characterized by both psychiatric and metabolic factors. We explored the prospective role of metabolic risk in eating disorders in a UK cohort (n = 2929 participants), measuring 158 metabolic traits in non-fasting EDTA-plasma by nuclear magnetic resonance. We associated metabolic markers at 7 years (exposure) with risk for anorexia nervosa and binge-eating disorder (outcomes) at 14, 16, and 18 years using logistic regression adjusted for maternal education, child's sex, age, body mass index, and calorie intake at 7 years. Elevated very low-density lipoproteins, triglycerides, apolipoprotein-B/A, and monounsaturated fatty acids ratio were associated with lower odds of anorexia nervosa at age 18, while elevated high-density lipoproteins, docosahexaenoic acid and polyunsaturated fatty acids ratio, and fatty acid unsaturation were associated with higher risk for anorexia nervosa at 18 years. Elevated linoleic acid and n-6 fatty acid ratios were associated with lower odds of binge-eating disorder at 16 years, while elevated saturated fatty acid ratio was associated with higher odds of binge-eating disorder. Most associations had large confidence intervals and showed, for anorexia nervosa, different directions across time points. Overall, our results show some evidence for a role of metabolic factors in eating disorders development in adolescence

Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: developmental and validation in two general population cohorts

Study questionCan routine antenatal blood pressure measurements between 20 and 36 weeks’ gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes?MethodsThis study used repeated antenatal measurements of blood pressure from 12?996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women’s Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks.Study answer and limitationsThe addition of blood pressure measurements from 28 weeks onwards improved prediction models compared with use of early pregnancy risk factors alone, but they contributed little to the prediction of preterm birth or small for gestational age. Though multiple imputation of missing data was used to increase the sample size and minimise selection bias, the validation sample might have been slightly underpowered as the number of cases of pre-eclampsia was just below the recommended 100. Several risk factors were self reported, potentially introducing measurement error, but this reflects how information would be obtained in clinical practice.What this study adds The addition of routinely collected blood pressure measurements from 28 weeks onwards improves predictive models for pre-eclampsia based on blood pressure in early pregnancy and other characteristics, facilitating a reduction in scheduled antenatal care.Funding, competing interests, data sharingUK Wellcome Trust, US National Institutes of Health, and UK Medical Research Council. Other funding sources for authors are detailed in the full online paper. With the exceptions of CM-W, HMI, and KMG there were no competing interests

Mortality from cancer and other causes in commercial airline crews: A joint analysis of cohorts from 10 countries

Background: Commercial airline crew is one of the occupational groups with the highest exposures to ionising radiation. Crew members are also exposed to other physical risk factors and subject to potential disruption of circadian rhythms. Methods: This study analyses mortality in a pooled cohort of 93 771 crew members from 10 countries. The cohort was followed for a mean of 21.7 years (2.0 million person-years), during which 5508 deaths occurred. Results: The overall mortality was strongly reduced in male cockpit (SMR 0.56) and female cabin crews (SMR 0.73). The mortality from radiation-related cancers was also reduced in male cockpit crew (SMR 0.73), but not in female or male cabin crews (SMR 1.01 and 1.00, respectively). The mortality from female breast cancer (SMR 1.06), leukaemia and brain cancer was similar to that of the general population. The mortality from malignant melanoma was elevated, and significantly so in male cockpit crew (SMR 1.57). The mortality from cardiovascular diseases was strongly reduced (SMR 0.46). On the other hand, the mortality from aircraft accidents was exceedingly high (SMR 33.9), as was that from AIDS in male cabin crew (SMR 14.0). Conclusions: This large study with highly complete follow-up shows a reduced overall mortality in male cockpit and female cabin crews, an increased mortality of aircraft accidents and an increased mortality in malignant skin melanoma in cockpit crew. Further analysis after longer follow-up is recommended