A data note describing the linked data obtained by ALSPAC about the participants in ALSPAC held by AWP (Avon Wiltshire Partnership MH NHS Trust). This will describe the data available for future research.

Autism spectrum disorder (ASD) is characterised by deficits in social interaction, communication, and language, as well as stereotyped and repetitive behaviours. There is strong evidence from observational studies for comorbidity between ASD and functional incontinence in children including enuresis (bedwetting), daytime urinary incontinence (DUI), and faecal incontinence (FI).

Congenital anomalies (CAs) occur during the intrauterine life and can be identified during pregnancy, at birth or later in life. CAs can be defined as structural (e.g. limb reduction defects) or functional (metabolic disorders). In European countries, CAs affect approximately 2–3% of births. Although consequences vary depending on the type and severity of the condition, CAs are a major cause of fetal death and infant morbidity. Each year, more than 3 million children under the age of 5 die from CAs globally. In addition, many children with CAs and their families experience lifelong complications.

Whilst multiple factors have been identified as causes of CAs, approximately 50% of congenital disorders cannot be linked to a specific cause . Therefore, there is a pressing need for research to identify modifiable causes of CAs. This project aims to explore genetic and molecular mechanisms of CAs as well as risk factors such as maternal lifestyle factors, health and medication use.

Preeclampsia poses significant risks to both mothers and babies. Many prediction models for preeclampsia have emerged in recent years. Using repeated measurements along with maternal factors has proven to be more effective in screening for preeclampsia than models that only consider maternal risk factors. However, traditional methods may introduce bias due to competitive events, and there is currently no preeclampsia prediction model in ALSPAC that considers competing-risk events.

Moreover, while numerous prediction models involve complex variables or models, cost-effectiveness must be taken into consideration. It is important to customize prediction models to local populations to effectively apply them. Relying on variables that are not available in local antenatal care can restrict their usefulness. It is suggested that localization should prioritize non-invasive indicators that are easily obtainable in clinical practice. An example of this is continuous blood pressure monitoring (CBP), which was recommended by the U.S. Preventive Services Task Force in 2017 as a PE screening method until a proven one is developed. However, it is not being utilized enough.

This project aims to develop a multivariate prediction model for preeclampsia by considering competing risk events and clinically accessible repeated measurements.
Before putting the prediction model into clinical practice, it will undergo essential validation across multiple datasets externally. The project’s benefits will be two-fold: first, shedding light on preeclampsia onset determinants in line with clinical practice, and second, improving the identification of women of high risk for preeclampsia.

Despite major achievements in risk factor control (primary prevention) and clinical care (secondary prevention) over the last decades, cardiovascular disease (CVD) continue to have tremendous substantial societal impact affecting 6 million people and costing 210 billion euros each year in the European Union (EU).1 CVD has a profound negative impact on quality of life of affected individuals and has significant societal consequences including major costs and premature loss of the labor force.1 Projections are pessimistic given the global ageing population, obesity epidemic, high levels of physical inactivity and sedentary behavior, poor diet, increased health inequalities, and poor mental health. Added to this, the COVID-19 pandemic has exacerbated unhealthy behaviors, health inequalities and increased the burden of mental health especially among the young. CVD is preventable: 70 to 80% of CVD incidence has been attributed to behavioral risk factors such as smoking, poor diet and physical inactivity, that subsequently impacts weight gain, blood pressure, blood glucose and blood lipids. Therefore, preventing risk factors in the first place (i.e. primordial prevention) and promoting optimal cardiovascular health (CVH) across the life course may be a new and relevant strategy to prevent the incidence of CVD. Many CVD risk factors already occur in childhood, track into adulthood, and are predictors of fatal and non-fatal CVD events in adulthood. Furthermore, early life habits are the strongest predictors of later life habits. Taken together, programs that promote healthy habits among children and their families will likely have a lasting positive impact on adult (cardiovascular) health and therefore an important societal impact. In order for such programs to be effective, sustainable and scalable, including among socially disadvantaged groups, it is critical that a holistic and trans-disciplinary codesign approach is taken accounting for the contexts of children’s family, health literacy of the children’s family, children’s well-being, and contextual factors such as their place of residence, school environment, built environment (green space, recreational places for physical activities, food supply, noise exposure). Such programs should be designed to be responsive and easily implementable, ensuring the needs and rights of children and their families are accounted for. This can be achieved through authentic engagement with all stakeholders (beneficeries as well a service providers) in contemporary codesign in diverse contexts.

Project ambition
• To inform about contextual and individual determinants of CVH and the associated health outcomes in children & adolescents
Most studies in children and adolescents have evaluated the distribution of a single CVD risk factor, especially behavioral ones, at a specific age. The few studies that have addressed the distribution of multiple risk factors focused on behavior-related factors such as weight, physical activity, diet and more recently, sleep. In fact, only three small studies (n<500), conducted in the US and France, reported the distribution of the complete CVH score and examined the determinants of CVH in children. Importantly, none evaluated the possible health benefits associated with higher CVH.
SO1 has the ambition within one year , to rapidly inform the international scientific community and the relevant stakeholders from the EU member states on (i) the level of the CVH of European children and adolescents including those from socially disadvantaged backgrounds, (ii) the individual and contextual determinants of CVH, and (iii) the potential health benefit associated with higher CVH. This will be achieved by using harmonized and readily available birth cohort data from four diverse European countries already participating to the EU Child Cohort Network (n??). This will provide the first European evidence-based data to (i) inform the general public, scientific community and policy makers on the key drivers of CVH in children; (ii) estimate the long-term health and cost savings associated with higher CVH early in life and; (iii) support recommendations for primordial prevention implementation at school across Europe.
• To develop a digital solution to support the promotion of CVH in children
The widespread availability of smartphones, tablets, and computers has opened opportunities for incorporating digital health solutions into educational settings. However, few are knowledge-based and their potential to help promoting CVH in primary-school children is currently unknown.
SO3 of ICARHE has the ambition to develop a serious game to make CVH health promotion more enjoyable and engaging for children that is safe (i.e. preventing digital addiction), effective and cost-effective, generating sustained benefits, implementable, inclusive (promoting health equity) and scalable for the EU member states. An exploitable strategy for the developed serious game will be put in place in the EU market (SO5).
• To conduct a large-scale European cRCT on CVH in primary school children aged 6 to 8 years
Most randomized controlled interventions in children and adolescents have focused on behavioral outcomes including diet, weight control or physical activity. IThree cRCTs have addressed the benefit of promoting specific items of the CVH score in children. They were school-based cRCTs in pre-school children aged 3 to 5 years in specific areas in Colombia, Spain and socio-economically deprived areas in Harlem, New York City. These interventions consisted of school educational sessions for a full academic year on health knowledge and attitudes including diet, physical activity and body mass index. The feasibility, safety, and effectiveness of these interventions were demonstrated, whereby significant differences between the groups over two years of follow-up post intervention were observed.
SO 2 to 4 of ICARHE have the ambition to test the safety, and effectiveness of a a co-designed intervention to improve the CVH of primary-school children within a cRCT. The added value of this trial is as follows. Firstly, it will be conducted in four diverse European countries, making the intervention a possible scalable solution across Europe. Secondly, it will address a more comprehensive spectrum of CVH additionally considering the biological risk factors (blood pressure, glycemia and total cholesterol) together with sleep health. Thirdly, it will be co-designed with the children and their parents/guardians, teachers, and relevant stakeholders, thereby enabling the trial to be more relevant to the local needs of the target population, a key factor for effectiveness, scalability and sustainability. Fourthly,given increasing evidence on the importance of the social and psychological determinants of health, the extent to which improvement in parents’ health literacy and the children’s well-being contribute to CVH improvement will be explored.
• To provide evidence-based recommendations for primordial prevention implementation in primary-school children across Europe
EU member states have recently released national recommendations for the first 1000 days of life. These are broad recommendations addressing home environment, parent-baby interactions or maternal health during pregnancy. SO 5 of ICARHE has the ambition to provide evidence-based recommendations for the implementation of primordial prevention in primary schools that are scalable across EU member states.

This is a student project linked to my current project B4306. The reproductive factors including lifestyle, disease status, infection, medication use, nutrient supplements, physical activity, and mental health are associated with pregnancy complications. The adverse outcomes of pregnancy confront the world as a major challenge, with extensive impact on individuals, families, and societies at large. This study will take advantage of the data provided by the Avon Longitudinal Study of Parents and Children to quantify the risk of possible adverse outcomes of pregnancy, and present opportunities to reduce the burden associated with congenital disorders at a population level.

Increased left ventricular mass and hypertrophy has been associated with cardiovascular morbidities and mortality in later life. Often employed as surrogate for premature heart damage in the young population, increased left ventricular mass has been associated with risk factors such as elevated blood pressure, arterial stiffness. Recent study in a large cohort of adolescents reported that inflammation may precede early vascular damage in the causal path. It remains unclear whether inflammation associates with left ventricular mass in a large population of community dwelling adolescents who are apparently healthy. This undergraduate thesis will examine the cross-sectional association between inflammation and left ventricular mass/hypertrophy in 17 year old adolescents.

Overweight and obesity are common and can have debilitating physical and mental health consequences. Overweight and obesity can start in early childhood and track throughout adolescence and adulthood. While effective treatment and prevention is still lacking, increasing our understanding of contributing factors is invaluable in designing better interventions.
Connections between mental states and obesity are well known. However, a large number of studies have focused on the role of depression in weight development while other factors that reflect vulnerabilities based on emotional symptoms have less frequently been examined. Additionally, few studies have longitudinal data that tracks participants throughout different developmental stages, including childhood, adolescence, and young adulthood.
Adolescents who are overweight are more likely to resort to unhealthy disordered eating behaviors such as skipping meals, extreme dieting, and purging through vomiting. Other disordered eating symptoms include concerns about shape and weight, weight control methods and binge eating. Disordered eating attitudes and behaviors can have detrimental effects on dietary quality, weight gain, development of obesity over an extended period, increased risk of depression, and also a higher likelihood of developing eating disorders such as anorexia nervosa, bulimia nervosa, or binge eating disorder. While there likely is a bidirectional relationship between weight development and disordered eating, the progression to development of obesity and eating disorders throughout childhood, adolescence and young adulthood is currently unknown.
This study aims to identify developmental trajectories of emotional risk factors, disordered eating, as well as body weight and examine which pathways of emotional risk factors and disordered eating are associated with later development of overweight or obesity.
Besides the focus on children’s emotional risk factors, this study also aims to examine the role of maternal psychological factors in relation to disordered eating and body weight throughout the first 3 decades of life.
This study will be fundamental in starting to understand new risk mechanisms for adolescent and
young adult overweight/obesity that can be further investigated in intervention studies following this project.

Not long ago, we learned the extent to which adverse childhood experiences (ACE) lead to long-term physical and psychological health problems (Felitti et al., 1998). In the last two-and-a-half decades, there have been continuing developments in the research of why and how adverse childhood experiences lead to death and illness in adulthood. Now, thanks to current research, we have a better understanding of why and how adverse childhood experiences increase morbidity. Inflammation is increased in those with adverse childhood experiences (Rasmussen et al., 2020). Chronic inflammation increases the risk of developing cardiovascular disease, cancer, diabetes mellitus, autoimmune, and many other health concerns (Furman et al., 2019). Although researchers have investigated this issue, the topic has not been explored in this way: Despite knowing that ACE increases health concerns through inflammation, there is very little research regarding variables that promote resiliency of immune health. Additionally, there is minimal research that confronts the specific trauma experienced by those with childhood sexual abuse (CSA). The specific research problem that will be addressed through this study is that we do not know whether and to what extent environmental factors are associated with healthier immune function among survivors of CSA.

From a psychoneuroimmunological foundation, a collection of variables among survivors will be analyzed as potential protective factors. These variables include ease to talk about problems with parents, feelings of closeness to parents, religiosity, involvement in sports or other after-school activities, religiosity, and feeling close to someone. Then, various inflammatory biomarkers will be analyzed and a relationship between factors and biomarkers will be explored.