Recently a number of metabolic biomarkers have shown a correlation with the overall mortality (Fischer et al. DOI: 10.1371/journal.pmed.1001606). The biomarker profiling can improve prediction of the short-term all factor mortality above established risk factors. This effort is part of the BBMRI Metabolomics consortium to further investigate these associations and clarify the biological mechanisms involved.

Genetic variants for multiple sclerosis (MS) have been identified. We will calculate MS genetic propensity scores for ALSPAC mothers and offspring. We will screen ALSPAC to identify phenotypes that are associated with genetic propensity to MS in individuals without the disease.

Babies born small or large are more likely to have health and development problems than those of a 'normal' size. But in reality it is difficult to know just what a small or large size is. A common measure that has been used in lots of studies is to take account of how far on the mother was in her pregnancy at the time their child was born. This allows us to tell the difference between, for example, a baby who is small because they delivered too early but might have been growing normally in the womb and one who is small because they were undernourished and did not grow properly in the womb. Similarly it allows us to tell the difference between a baby who might be large because they stayed in the womb for longer than average and one who grew too rapidly because they were overnourished. Calibrating birth size against how long a woman has been pregnant is done using growth charts, similar to those used to plot an infants growth after they are born. Until recently these charts have reflected average growth patterns for a specified population. For example if a baby today was plotted on a UK 2000 growth chart of birth weight for gestational age and they were on what was called the 50th percentile. This would indicate that their weight was the same as the average for all other babies of the same sex and who had had the same time in the womb who were born in the UK in 2000. Recently it has been suggested that instead of those total population averages 'customised growth charts' should be used to define whether a baby is too heavy or light after accounting for how long they have been in the womb. As well as time in the womb these 'customised growth charts' take account of what are assumed to be characteristics that affect fetal growth in a 'biological' (non-pathological) way: the mother's weight and height at first clinic, her ethnicity, whether this is her first, second, etc child. These charts are somewhat controversial as on the one hand they might be correctly allowing for 'biological' differences in size but on the other they might (for example) be assuming that it is normal for a particular ethnic group to always be smaller than another ethnic group which might not be the case.

When reaching their early twenties, almost 60% of the participants of the contemporary Dutch TRAILS and ALSPAC study confirm to have used cannabis at some point in their life, one in five has used ecstasy, and around one in ten young adults has used amphetamines, cocaine, or magic mushrooms. Given the adverse effects of adolescent drug use on adult outcomes, these numbers are alarming. Why do so many young people experiment with drugs? How many of them are regular users? Is the use of illicit drugs systematically linked to alcohol and tobacco use? How are temporary and chronic use reflected in psychosocial adjustment and accomplishment of normative development milestones? Perhaps most pressing, can we identify protective factors that increase the likelihood for youngsters to abstain and users to desist from using drugs before they can leave lasting damage? Answering those questions is crucial to understand drug use pathways and their antecedents and outcomes, through the life course.
Focussing on incidence and course of illegal drug use throughout adolescence and young adulthood, we aim to a) identify predictors of onset of experimental and regular use of cannabis and hard drugs, b) predict the developmental trajectories of cannabis and hard drug use, and c) identify outcomes of these trajectories. Cannabis and hard drug use are no isolated phenomena, they occur in interplay with use of other substances such as tobacco and alcohol use and are often connected to mental health problems from the internalizing and externalizing spectrum. Hence, co-developmental pattern and interactive and cumulative risks are identified.
Two major multi-reporter longitudinal cohort studies provide the data for this project: The British Avon Longitudinal Study of Parents and Children (ALSPAC, http://www.bristol.ac.uk/alspac/) is an ongoing study of 14.500 families where the first assessment took part during pregnancy and the target sample of young people has now reached the mid-twenties. Repeated measures of dDrug use have been collected xx times s been assessedon an annual or semi-annual basis from age 10 [link to questionnaires][how often] using [instrument]. Extensive contemporaneous information is available including on early life, family adversity, social position, neighbourhood, school, temperament, externalising and internalising problems, and peer drug use[covariate, risk, protective factors] are available. The Dutch TRacking Adolescents’ Individual Lives Survey (TRAILS, www.trails.nl/en/) is an ongoing study of 2261 individuals who were recruited into the study at age 11 and are now also in their mid-twenties. Drug use has been assessed [how often] using [instrument]. Extensive information on [covariate, risk, protective factors] are available. The liberal Dutch climate towards drug use, specifically the tolerance policy towards cannabis possession and production is in stark contrast to the British perspective where cannabis is criminalized. By comparing two cohorts of equal age, we are able to identify the role of the cultural context, a thus far severely under-researched aspect.

Recent studies on humans and animal models indicate that stress in parents alters both parenting behaviors and parental epigenetics, which can be inherited. As a consequence, stressors in parents can transmit to the offspring, causing depression-like behavior in the descendants of stressed parents or grandparents. In turn, depression-like behavior results in decreased goal-directed activity, and depression associates with unemployment, poverty, and other adverse socioeconomic outcomes in humans. Because poverty can be stressful, and indeed depression rates are higher for the impoverished, this intergenerational transfer of the effects of stress might be an important mechanism impeding intergenerational mobility. In the language of economics, parents provide their children with a type of human capital—which I term ‘affective capital’—through their genetic and epigenetic bequests and through their parenting investments. The children carry this capital with them into adulthood, where it protects children from anxiety and depression, influencing their educational and labor market choices as well as their own parenting behavior, propagating through multiple generations.

My project aims to elucidate the roll of epigenetics, genetics, and parenting behavior in the intergenerational transmission of affective capital as well as the impact of this transmission on intergenerational mobility.

Despite advances in maternal medicine, pre-eclampsia continues to be a major contributor to maternal, fetal and neonatal mortality and morbidity. Pre-eclampsia is not a single disorder but a syndrome. The early onset disease is more severe, and is considered to have different pathophysiology than the late onset disease. It is unlikely that one single model will accurately predict both early and late onset disease. A brief by the HTA calls for a systematic review on the predictive accuracy of markers, separately and in combination for predicting pre-eclampsia, especially early onset disease. We have identified 59 systematic reviews on clinical characteristics, biomarkers and ultrasound in the prediction of pre-eclampsia, including our HTA report (HTA No. 12060), and 69 prediction models for pre-eclampsia.

However, clinical applicability of the aggregate meta-analyses is limited due to the observed heterogeneity in population, test characteristics including timing and cut off, and outcomes. Furthermore, they often do not account for multiple predictors, and are mainly focussed on any pre-eclampsia than early onset. An Individual Patient Data (IPD) meta-analysis will allow us to assess the differential accuracy of the tests in various subgroups according to the risk status. It will provide us with sufficient sample size to develop and validate a multivariable prediction model, for the clinically important outcome of early onset pre-eclampsia. Furthermore, by taking into account the clustering within studies, the developed model will avoid the model performance deterioration encountered in aggregate meta-analysis, when the individual’s baseline risk is different from the average estimated during model development.

Prior to use of prediction models in clinical practice, there is a need to successfully validate the model in multiple datasets external to the model development phase. This often takes many years to accomplish. None of the prediction models have robustly undertaken external validation to assess model performance in relevant population. Our International Prediction of Pre-eclampsia IPD Collaborative Network (IPPIC) of global researchers has provided access to the IPD from existing studies and large databases, thereby allowing us to both develop and validate the risk prediction models simultaneously, within an IPD meta-analysis framework. Our collaborative approach encourages consensus towards a single, well developed, and validated prognostic model, rather than a number of competing and non-validated models for the same clinical question.

The development of cardiovascular diseases can start at an early age, although the clinical manifestations commonly appear in adulthood. Previous studies have reported that the adherence to an overall healthy dietary pattern is associated with a lower risk of cardiovascular events and cardiovascular mortality among adults. However, there are few reports on the association of dietary patterns with cardiometabolic risk factors and cardiovascular structure and function before the clinical manifestations of cardiovascular diseases among adolescents.

The objective of this study is to assess the association of dietary patterns at the age of 7, 10 and 13 years with cardiometabolic risk factors and cardiovascular structure and function at the age of 17 years.

The study population will be 2 121 adolescents participating in the ALSPAC, a 50 % subsample of clinic attendees at the age of 17 years. Measures of cardiometabolic risk factors include fasting concentrations of glucose, insulin, triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol, systolic and diastolic blood pressure, and a cardiometabolic risk score. Measures of cardiovascular structure and function included carotid intima-media thickness, artery stiffness and endothelial function. Dietary intake was assessed by 3-day food records at the age of 7, 10 and 13 years. Dietary patterns were extracted using principal component analysis. The associations of dietary patterns with cardiometabolic risk factors and cardiovascular structure and function will be analyzed using multiple linear regression models adjusted for potential confounding factors.

The proposed study will be conducted in 2016.

To explore genetic, biomedical and environmental predictors of and consequence of alcohol use and misuse.

BACKGROUND: Picky/selective eating is a common behaviour in children, that can range from being a normal phase in child development to a severe problem that causes negative physical and psychological consequences for the child and greatly impacts families. We still know very little about which children with picky/selective eating require assessment and treatment.
Picky/selective eating is one of the most common eating problem reported by parents, and a common reason for seeking medical help by parents, however very little research is available on its manifestations in the general population. This sub-study is part of a larger study focusing on understanding picky/selective eating in clinical and population-based samples.
OBJECTIVES: This study will focus on picky/selective eating, its psychopathological correlates (anxiety, depression, ASD traits, and other psychopathology), its relationship with parental anxiety and depression and its outcomes in terms of disordered eating in adolescence.