Dietary patterns obtained through principal components analysis: The effect of input variable quantification

Principal components analysis (PCA) is a popular method for deriving dietary patterns. A number of decisions must be made throughout the analytic process, including how to quantify the input variables of the PCA. The present study aims to compare the effect of using different input variables on the patterns extracted using PCA on 3-d diet diary data collected from 7473 children, aged 10 years, in the Avon Longitudinal Study of Parents and Children. Four options were examined: weight consumed of each food group (g/d), energy-adjusted weight, percentage contribution to energy of each food group and binary intake (consumed/not consumed). Four separate PCA were performed, one for each intake measurement. Three or four dietary patterns were obtained from each analysis, with at least one component that described 'more healthy' and 'less healthy' diets and one component that described a diet with high consumption of meat, potatoes and vegetables. There were no obvious differences between the patterns derived using percentage energy as a measurement and adjusting weight for total energy intake, compared to those derived using gram weights. Using binary input variables yielded a component that loaded positively on reduced fat and reduced sugar foods. The present results suggest that food intakes quantified by gram weights or as binary variables both resulted in meaningful dietary patterns and each method has distinct advantages: weight takes into account the amount of each food consumed and binary intake appears to describe general food preferences, which are potentially easier to modify and useful in public health settings. © 2012 The Authors

A structured approach to hypotheses involving continuous exposures over the life course

© The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association. Background: Epidemiologists are often interested in examining different hypotheses for how exposures measured repeatedly over the life course relate to later-life outcomes. A structured approach for selecting the hypotheses most supported by theory and observed data has been developed for binary exposures. The aim of this paper is to extend this to include continuous exposures and allow for confounding and missing data. Methods: We studied two examples, the association between: (i) maternal weight during pregnancy and birthweight; and (ii) stressful family events throughout childhood and depression in adolescence. In each example we considered several plausible hypotheses including accumulation, critical periods, sensitive periods, change and effect modification. We used least angle regression to select the hypothesis that explained the most variation in the outcome, demonstrating appropriate methods for adjusting for confounders and dealing with missing data. Results: The structured approach identified a combination of sensitive periods: pre-pregnancy weight, and gestational weight gain 0-20 weeks and 20-40 weeks, as the best explanation for variation in birthweight after adjusting for maternal height. A sensitive period hypothesis best explained variation in adolescent depression, with the association strengthening with the proximity of stressful family events. For each example, these models have theoretical support at least as strong as any competing hypothesis. Conclusions: We have extended the structured approach to incorporate continuous exposures, confounding and missing data. This approach can be used in either an exploratory or a confirmatory setting. The interpretation, plausibility and consistency with causal assumptions should all be considered when proposing and choosing life course hypotheses

Population implications of cessation of IVF during the COVID-19 pandemic

Research question: Discontinuation of IVF cycles has been part of the radical transformation of healthcare provision to enable reallocation of staff and resources to deal with the COVID-19 pandemic. This study sought to estimate the impact of cessation of treatment on individual prognosis and US population live birth rates. Design: Data from 271,438 ovarian stimulation UK IVF cycles was used to model the effect of age as a continuous, yet non-linear, function on cumulative live birth rate. This model was recalibrated to cumulative live birth rates reported for the 135,673 stimulation cycles undertaken in the USA in 2016, with live birth follow-up to October 2018. The effect of a 1-month, 3-month and 6-month shutdown in IVF treatment was calculated as the effect of the equivalent increase in a woman's age, stratified by age group. Results: The average reduction in cumulative live birth rate would be 0.3% (95% confidence interval [CI] 0.3–0.3), 0.8% (95% CI 0.8–0.8) and 1.6% (95% CI 1.6–1.6) for 1-month, 3-month and 6-month shutdowns. This corresponds to a reduction of 369 (95% CI 360–378), 1098 (95% CI 1071–1123) and 2166 (95% CI 2116–2216) live births in the cohort, respectively. Th e greatest contribution to this reduction was from older mothers. Conclusions: The study demonstrated that the discontinuation of fertility treatment for even 1 month in the USA could result in 369 fewer women having a live birth, due to the increase in patients’ age during the shutdown. As a result of reductions in cumulative live birth rate, more cycles may be required to overcome infertility at individual and population levels

The mental health effects of pet death during childhood: Is it better to have loved and lost than never to have loved at all?

Pet ownership is common. Growing evidence suggests children form deep emotional attachments to their pets. Yet, little is known about children’s emotional reactions to a pet’s death. The goal of this study was to describe the relationship between experiences of pet death and risk of childhood psychopathology and determine if it was “better to have loved and lost than never to have loved at all”. Data came from the Avon Longitudinal Study of Parents and Children, a UK-based prospective birth cohort (n = 6260). Children were characterized based on their exposure to pet ownership and pet death from birth to age 7 (never loved;loved without loss; loved with loss). Psychopathology symptoms at age 8 were compared across groups using multivariable linear regression. Psychopathology symptoms were higher among children who had loved with loss compared to those who had loved without loss (β = 0.35, p = 0.013; 95% CI = 0.07, 0.63), even after adjustment for other adversities. This group effect was more pronounced in males than in females. There was no difference in psychopathology symptoms between children who had loved with loss and those who had never loved (β = 0.20, p = 0.31, 95% CI = −0.18–0.58). The developmental timing, recency, or accumulation of pet death was unassociated with psychopathology symptoms. Pet death may be traumatic for children and associated with subsequent mental health difficulties. Where childhood pet ownership and pet bereavement is concerned, Tennyson’s pronouncement may not apply to children’s grief responses: it may not be “better to have loved and lost than never to have loved at all”

Exposure to early childhood maltreatment and its effect over time on social cognition

Social cognitive deficits can have many negative consequences, spanning social withdrawal to psychopathology. Prior work has shown that child maltreatment may associate with poorer social cognitive skills in later life. However, no studies have examined this association from early childhood into adolescence. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4,438), we examined the association between maltreatment (caregiver physical or emotional abuse; sexual or physical abuse), assessed repeatedly (every 1-3 years) from birth to age 9, and social cognitive skills at ages 7.5, 10.5, and 14 years. We evaluated the role of both the developmental timing (defined by age at exposure) and accumulation of maltreatment (defined as the number of occasions exposed) using a least angle regression variable selection procedure, followed by structural equation modeling. Among females, accumulation of maltreatment explained the most variation in social cognitive skills. For males, no significant associations were found. These findings underscore the importance of early intervention to minimize the accumulation of maltreatment and showcase the importance of prospective studies to understand the development of social cognition over time

What life course theoretical models best explain the relationship between exposure to childhood adversity and psychopathology symptoms: Recency, accumulation, or sensitive periods?

Copyright © Cambridge University Press 2018Â. Background Although childhood adversity is a potent determinant of psychopathology, relatively little is known about how the characteristics of adversity exposure, including its developmental timing or duration, influence subsequent mental health outcomes. This study compared three models from life course theory (recency, accumulation, sensitive period) to determine which one(s) best explained this relationship.Methods Prospective data came from the Avon Longitudinal Study of Parents and Children (n = 7476). Four adversities commonly linked to psychopathology (caregiver physical/emotional abuse; sexual/physical abuse; financial stress; parent legal problems) were measured repeatedly from birth to age 8. Using a statistical modeling approach grounded in least angle regression, we determined the theoretical model(s) explaining the most variability (r2) in psychopathology symptoms measured at age 8 using the Strengths and Difficulties Questionnaire and evaluated the magnitude of each association.Results Recency was the best fitting theoretical model for the effect of physical/sexual abuse (girls r2 = 2.35%; boys r2 = 1.68%). Both recency (girls r2 = 1.55%) and accumulation (boys r2 = 1.71%) were the best fitting models for caregiver physical/emotional abuse. Sensitive period models were chosen alone (parent legal problems in boys r2 = 0.29%) and with accumulation (financial stress in girls r2 = 3.08%) more rarely. Substantial effect sizes were observed (standardized mean differences = 0.22-1.18).Conclusions Child psychopathology symptoms are primarily explained by recency and accumulation models. Evidence for sensitive periods did not emerge strongly in these data. These findings underscore the need to measure the characteristics of adversity, which can aid in understanding disease mechanisms and determining how best to reduce the consequences of exposure to adversity

Programming of adiposity in childhood and adolescence: Associations with birth weight and cord blood adipokines

© 2017 by the Endocrine Society. Context: Exposure to maternal adiposity during pregnancy is associated with higher offspring birth weight and greater adiposity through childhood and adult life. As birth weight reflects the summation of lean and fat mass, the extent to which fat mass at birth tracks into later life is unknown. Objective: To determine whether fat mass at birth is associated with child and adolescent adiposity. Design, Setting, and Participants: UK birth cohort with markers of neonatal fat mass; cord blood leptin, adiponectin, and birth weight and adiposity outcomes at age 9 (n = 2775) and 17 years (n = 2138). Main Outcomes: Offspring body mass index (BMI), waist circumference, dual-energy X-ray absorptiometry-determined fat mass, and obesity at age 9 and 17 years. Results: Higher cord blood leptin was associated with higher z scores of fat mass [difference in mean per 10 pg/mL: 0.03 standard deviation (SD); 95% confidence interval (CI), 0.00 to 0.06], waist circumference (0.04 SD; 95% CI, 0.00 to 0.07), and BMI (0.04 SD; 95% CI, 0.00 to 0.08) at age 9. However, by age 17 the adjusted results were attenuated to the null. Cord blood adiponectin was not associated with measures of adiposity at age 9. At age 17, cord blood adiponectin was positively associated with fat mass (0.02 SD per 10 mg/mL; 95% CI, 0.02 to 0.03) and waist circumference (0.04 SD per 10 mg/mL; 95% CI, 0.03 to 0.05). Birth weight was positively associated with waist circumference (0.03 SD per 100 g; 95% CI, 0.02 to 0.04) and BMI (0.02 SD per 100 μg; 95% CI, 0.00 to 0.03), but not fat mass or odds of obesity. Cord blood leptin and adiponectin were not associated with obesity at either age. Conclusions: Increased cord blood leptin and adiponectin, known surrogates of fetal fat mass, were weakly associated with increased fat mass in late childhood and adolescence, respectively

Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: Findings from the Avon Longitudinal Study of Parents and Children (ALSPAC)

© The Author 2014. Maternal smoking during pregnancy has been found to influence newborn DNA methylation in genes involved in fundamental developmental processes. It is pertinent to understand the degree to which the offspring methylomeis sensitive to the intensity and duration of prenatal smoking. An investigation of the persistence of offspring methylation associated with maternal smoking and the relative roles of the intrauterine and postnatal environment is alsowarranted. In the Avon Longitudinal Study of Parents and Children, we investigated associations between prenatal exposure to maternal smoking and offspring DNA methylation at multiple time points in approximately 800 mother-offspring pairs. In cord blood, methylation at 15 CpG sites in seven gene regions (AHRR, MYO1G, GFI1, CYP1A1, CNTNAP2, KLF13 and ATP9A) was associated with maternal smoking, and a dose-dependent response was observed in relation to smoking duration and intensity. Longitudinal analysis of blood DNA methylation in serial samples at birth, age 7 and 17 years demonstrated that some CpG sites showed reversibility of methylation (GFI1, KLF13 and ATP9A), whereas others showed persistently perturbed patterns (AHRR, MYO1G, CYP1A1 and CNTNAP2). Of those showing persistence, we explored the effect of postnatal smoke exposure and found that the major contribution to altered methylation was attributed to a critical window of in utero exposure. A comparison of paternal and maternal smoking and offspring methylation showed consistently stronger maternal associations, providing further evidence for causal intrauterine mechanisms. These findings emphasize the sensitivity of the methylome to maternal smoking during early development and the long-term impact of such exposure

Updates to data versions and analytic methods influence the reproducibility of results from epigenome-wide association studies

Biomedical research has grown increasingly cooperative through the sharing of consortia-level epigenetic data. Since consortia preprocess data prior to distribution, new processing pipelines can lead to different versions of the same dataset. Similarly, analytic frameworks evolve to incorporate cutting-edge methods and best practices. However, it remains unknown how different data and analytic versions alter the results of epigenome-wide analyses, which could influence the replicability of epigenetic associations. Thus, we assessed the impact of these changes using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. We analysed DNA methylation from two data versions, processed using separate preprocessing and analytic pipelines, examining associations between seven childhood adversities or prenatal smoking exposure and DNA methylation at age 7. We performed two sets of analyses: (1) epigenome-wide association studies (EWAS); (2) Structured Life Course Modelling Approach (SLCMA), a two-stage method that models time-dependent effects. SLCMA results were also compared across two analytic versions. Data version changes impacted both EWAS and SLCMA analyses, yielding different associations at conventional p-value thresholds. However, the magnitude and direction of associations was generally consistent between data versions, regardless of p-values. Differences were especially apparent in analyses of childhood adversity, while smoking associations were more consistent using significance thresholds. SLCMA analytic versions similarly altered top associations, but time-dependent effects remained concordant. Alterations to data and analytic versions influenced the results of epigenome-wide analyses. Our findings highlight that magnitude and direction are better measures for replication and stability than p-value thresholds.</p