It is well established that cardiovascular disease (CVD) begins in childhood. Impairments in vascular function occur before the structural changes of CVD present in the arteries and the progression of CVD is related to CVD risk factors, such as cardiorespiratory fitness, physical activity, body composition and blood markers, in youth. Therefore, there is great interest in understanding how exposure to early lifestyle factors could be related to CVD risk in children and adolescents. Our current project utilising the ALSPAC data (B3455) is investigating the associations between early exposure to cardiorespiratory fitness and body composition with measures of arterial structure and function. However, physical activity and sedentary time are additional important markers of health, and warrant exploration for their potential associations with arterial structure and function at an early age.

Existing paediatric data examining associations between physical activity and/or sedentary time with measures of arterial structure and function are limited by small sample sizes and a subjective assessment of physical activity. Therefore, the current models are unable to account for a suitable number of confounding variables. Also, most studies have used cross-sectional design, and those which are longitudinal have a maximum follow up period of two years. Moreover, independent relationships of physical activity and sedentary time with arterial structure and function, may be altered by an existing interaction between physical activity and/or sedentary time.

Recent experimental data in prepubertal children has shown that the decline in arterial function during prolonged sitting can be prevented by performing 10 minutes of moderate intensity exercise each hour. There is evidence on the interaction between physical activity and/or sedentary time and traditional CVD risk factors, such as body composition and blood markers, in children and adolescents. However, there is a scarcity of data at a population level that examines how sedentary time and physical activity interact in children and how this relates to direct measures of vascular function and structure. Therefore, this project aims to examine the cross-sectional and longitudinal relationships between the early life exposure to physical activity and sedentary time with vascular function and structure from childhood to adulthood, while controlling for traditional CVD risk factors and cardiorespiratory fitness.

Adverse Childhood Experiences (ACEs) are stressful events that occur during childhood and adolescence, and include child maltreatment (i.e. emotional, physical, and sexual abuse and neglect) as well as measures of family dysfunction (e.g. parental divorce/separation, intimate partner violence, substance misuse, mental illness, and imprisonment). People who experience ACEs are less likely to do well in school, more likely to become unemployed, and more likely to have poor health. Furthermore, since people who live in socioeconomic deprivation are more at risk of experiencing ACEs, and also more at risk of poor health, ACEs are one mechanism that could drive socioeconomic inequalities in health. However, most of the research to date has looked at ACEs as a whole, and not asked whether experiencing ACEs at different points during infancy, childhood and adolescence might have different impacts. This is important, because it affects decisions about how we best support people who experience ACEs. If ACEs in infancy have the biggest effect on later outcomes, then focusing support on the early years will be most beneficial. Whereas if ACEs at older ages also cause problems, potentially ‘derailing’ people from their previous educational level for example, that would imply that continued support across the whole of childhood and adolescence is important. At a time when local government budgets are severely stretched, generating evidence to help support the justification and prioritisation of interventions is crucial. At present, our ability to carry out high-quality cost-effectiveness analysis of interventions to mitigate the effects of ACEs is limited by a lack of good evidence on the effects of ACEs on key economic outcomes, and how these effects differ across the life course. In this project, we will plug this gap, using extremely detailed data about experiences of ACEs across the life course, linked with detailed family and socioeconomic data, and repeated measures of educational attainment, employment, and health. We will explore the links between ACEs and education and employment, whether these are affected by the timing, duration and recency of ACE exposure, and the mechanisms underlying the associations.
The 2020 SARS-Cov-2 pandemic is likely to have severe implications for children experiencing ACEs and adults who have experienced ACEs. The ‘lockdown’ measures are likely to lead to increased occurrence of ACEs. Missed schooling is likely to be more detrimental for already vulnerable children, and many children who were entitled to continue attending school during lockdown did not do so. Job losses and reductions in income have been concentrated in the already disadvantaged, and the uncertain job market going forwards will pose a greater risk to young adults without the cushioning of a stable family environment and educational success. Using new data collected during the pandemic, we will assess whether young adults who have experienced ACEs are more vulnerable to the economic consequences of the pandemic, e.g. reduced income, furlough, or job loss. This evidence could provide support to the continued and increased need for the provision of services for people experiencing ACEs at this time.
We will work with key academic and non-academic collaborators to ensure that the results from this project are used to support the case for services designed to support people who have experienced ACEs, including with our results being used directly to improve the quality of cost-effectiveness analyses for interventions.

Previous studies have demonstrated that maternal thyroid dysfunction is associated with a number of neurodevelopmental disorders, such as attention deficit hyperactivity disorder and epilepsy. However, the association between maternal thyroid dysfunction and other health outcomes in offspring were either investigated in single study, or not examined. One single study conducted in 998 maternal-child pairs in Canada demonstrated that maternal hypothyroidism was associated with increased risk of congenital heart disease (CHD) in offspring (OR=1.68; 95% CI: 1.02-2.78). Another retrospective cohort study showed that children born to mothers with hypothyroidism have increased risk of hypoglycemia (RR=2.9; 95% CI: 1.4-6.2) and total endocrine morbidity (RR=2.1; 95% CI: 1.2-3.8). It was also observed that offspring of mothers with subclinical hypothyroid during the third trimester of pregnancy had higher systolic blood pressure. It remains unclear if the above associations exist in other populations. Whereas, inconsistent findings were observed for the risk of diabetes in children born to mothers with various thyroid diseases. It is known that thyroid dysfunction in adults may affect a number of cardiometabolic traits. This project aims to evaluate the observational and causal association between maternal thyroid dysfunction and various cardiometabolic traits in offspring.

Stark inequalities in health already exist in the UK, with people from lower socioeconomic backgrounds suffering from greater levels of ill health across multiple domains. The covid-19 pandemic potentially threatens to worsen these health inequalities. The ‘lockdown’ changed people’s behaviour radically, but the socioeconomic differences in these experiences are not well understood. Some groups of society may have increased health-promoting behaviours – for example, engaging in more physical activity and preparing more food within the home. Other groups may have experienced adverse changes in health-related behaviours – for example, smoking more or consuming more alcohol in response to the stress and anxiety induced by the pandemic. It is possible these differences are socioeconomically patterned, and could therefore worsen pre-existing inequalities. Another key factor likely to influence patterns of behaviour change during the pandemic is household/family structure. For example, parents with children and individuals shielding or living with a household member who was shielding may have been less able to engage with health-promoting behaviours.

Data from the Office for National Statistics demonstrate that between 23rd March and 5th April 2020, 27% of the UK workforce were furloughed due to the COVID-19 lockdown. Many others lost jobs, or had working hours and income reduced. The adverse financial and employment consequences of the covid-19 lockdown are concentrated in already vulnerable groups of society – they are more likely to be experienced by people in insecure or low-paid jobs. The young adults in ALSPAC are in the age groups most likely to have been affected by furlough, job losses, and loss of pay or hours (https://www.resolutionfoundation.org/publications/young-workers-in-the-c...). Detailed pre-pandemic data from the ALSPAC cohort offers the opportunity to better understand which groups of society were more likely to be impacted financially by the lockdown. We will explore whether SEP, adverse childhood experiences, pre-existing mental health problems, obesity, smoking, alcohol use, shielding or living with a household member who was shielding, and family structure are associated with greater likelihood of adverse financial changes during covid-19, and hence whether the lockdown is likely to exacerbate health challenges for these groups.

New-onset hypertension during pregnancy occurs in up to 10% of women. People born to pregnancies complicated by hypertension (i.e. gestational hypertension and preeclampsia) are at increased risk for cardiovascular disorders, including hypertension and stroke, in later life. The underlying disease process is identifiable in the first decades of life with evidence of emerging damage to their hearts and blood vessels. Phenotypic changes that have been observed in early postnatal life and as they reach young adulthood include higher blood pressure, altered heart structure and function, as well as a reduced number, size, and function of small blood vessels. However, to date, longitudinal data in the same individuals, as well as a multi-systems, deep phenotyping approach to characterizing cardiovascular physiology in offspring of hypertensive pregnancies, remains limited. By using ALSPAC, we will be able to make use of the previously collected demographic, anthropometric, and phenotypic data collected. We will also design a new study in 200 young adults, of which 100 will be born to hypertensive pregnancies and 100 born to normotensive pregnancies. These participants will be invited by the ALSPAC team to travel to Oxford for a 3 hour study visit, including blood sample collection, exercise stress testing, blood pressure and imaging of the small blood vessels in the eye, brain MRI, as well heart scans using both MRI and echocardiography at rest and during exercise. By studying and tracking changes both temporally and spatially across multiple organs, we will be able to better describe and quantify the multi-dimensional landscape of hypertensive disease progression.

Autism is a lifelong condition characterised by difficulties with social interaction, social communication and repetitive behaviours. In recent decades, the number of children and adults diagnosed with autism has increased. As autism is heritable, genetic risk may explain why there are some individuals with mild autistic traits but they may not meet the criteria for an autism diagnosis and subsequent treatment or other support requirements. As more children with autism and mild autistic traits reach adulthood, the need for support from health and other services will likely increase. However, few large, population based longitudinal studies involving adults with autism/autistic traits exist, representing a research gap.

During this phase of my PhD project, I will study how autism and autism traits, including genetic risk for autism, may be associated with BMI and disordered eating behaviours in adulthood. Children with autism often having sensory issues and unusual eating preferences, which could have an effect on growth and health in adult life. It has been reported that social communication difficulties may increase the risk of disordered eating patterns in adolescence. This implies that maintaining a healthy BMI may be challenging during this period and that there is a possible increased risk of disordered eating behaviours and eating disorders in adulthood for those with social communication difficulties. This phase of my PhD project is focussed on whether autistic individuals are more likely to have high BMI and disordered eating behaviours in adulthood. Changes in growth during late childhood into late adolescence will also be studied to assess whether there are critical periods that are suitable for intervention.

The obesity epidemic is one of the most important health challenges of the 21st century.
Identifying genetic factors predisposing to weight gain is crucial for identifying biological processes important for weight-control and help identify individuals already at young age that might benefit from health interventions and thereby reducing their risk for disorders such as type 2 diabetes that follow in its footpath.

While there is great progress deciphering the genetic factors influencing weight in in adulthood, and at birth, there is a huge knowledge gap on the role of the genomes of the child and its parents in infancy and childhood into puberty. This is very unfortunate, as it is firmly established that the BMI-development during the first 6 years of life are strong predictors of obesity in adolescence . Results from our own ongoing work in the Norwegian Mother, Father and Child and work of others show that it is possible to find novel genetic variants with specific and substantial effect on weight development during infancy with high quality data and large GWAS sample sizes.

Cardiovascular diseases (CVDs) are a significant public health concern and are a leading cause of mortality, representing 31% of all global deaths in 2017. These diseases often have their origins in childhood. Ample evidence suggests that exposure to childhood adversity, such as experiences of violence, parent imprisonment, household mental illness or substance use, has harmful effects on cardiovascular and other non-communicable diseases. Experiencing two or more adversities is associated with higher risk of cardiovascular disease in Europe and North America, respectively, corresponding to US$150 and US$164 billion in associated costs. Whilst there is evidence that adverse childhood experiences are associated with higher cardiovascular risk, whether socioeconomic inequalities in cardiovascular risk might be explained by childhood adversities. Understanding the extent to which adverse experiences in childhood could potentially explain socioeconomic inequities in CVD risk would help to inform the targeting of resources.

Further, the milieu of the family environment includes not just adverse experiences, however, but also positive experiences, which have been understudied. Positive experiences do not simply reflect the absence of risk factors, but instead are independent attributes or assets that enhance health and resilience over time. For example, the absence of abuse in the household does not necessary imply optimal parenting. The Health Outcomes from Positive Experiences (HOPE) is a complimentary framework to childhood adversity that organises positive childhood experiences into four broad categories: Being in nurturing, supportive relationships; Living, developing, playing, and learning in safe, stable, protective, and equitable environments; Having opportunities for constructive social engagement and to develop a sense of connectedness; and Learning social and emotional competencies.

Emerging evidence suggests that positive childhood experiences – variably defined – are associated with better adult cardiovascular health. These studies are suggestive that positive experiences in childhood also have relevance for cardiovascular health. To fully understand children’s experiences in the early years and how environments can be optimised to promote cardiovascular health in later life, however, we need to capture both adverse and positive experiences in childhood; otherwise, we just look at half the picture. For example, no previous studies have examined whether the effect of positive experiences was evident over and above that of adverse experiences in childhood. While adverse and positive experiences are not the inverse of one another, they are negatively correlated. Do positive experiences actually matter for cardiovascular health, or are they just a proxy indicator for the absence of adverse experiences? If they do matter, can they help to promote resilience in the presence of childhood adversity; that is, good health despite the presence of adversity?