Meeting physical activity, sleep and sedentary behavior guidelines is associated with better cardiometabolic health and adiposity outcomes among children and youth. Unfortunately, recent estimates suggest that only 25.4% of adolescents in the US meet sleep guidelines, 26.1% meet physical activity guidelines, and only 5% meet guidelines for sleep, physical activity and sedentary behavior. Although some evidence indicates that there is a positive association between physical activity levels and sleep duration, findings among children and adolescents are not consistent and are limited by a predominantly cross-sectional study design. Although low income and minority youth are at a higher risk of not meeting both sleep and physical activity recommendations, it is unclear whether the sleep and physical activity relationship varies by racial, ethnic or socioeconomic group. Furthermore, exercise intensity appears to have a strong, positive relationship with sleep, although more research is needed to determine whether exercise at a light or moderate intensities can lead to improvements in sleep outcomes. This study aims to examine the association between physical activity and sedentary behavior, measured objectively at 11, 13 and 15 years of age, with subjectively-measured sleep at age 15. Furthermore, this study aims to understand whether the sleep and physical activity relationship varies by demographic characteristics and measures of adiposity.

Maternal life style factors during pregnancy has been related to child neurodevelopment and behavioral problems. However, there is a need to further study them in combination as a general score and perform the analyses in a consortium of several European cohorts. The harmonization of mental health problems in several population-based birth cohorts will allow us to perform trajectory analyses with specific mental health domains. In this study, we will study the association of a maternal lifestyle score during pregnancy and the trajectories of internalizing and externalizing problems. These are the main domains in child neurobehavioral development. The creation of the lifestyle score will be based on different lifestyle variables reported during pregnancy: Smoking, Alcohol consumption, DASH diet, folic acid supplement, pre-pregnancy weight/height, sleep duration, physical activity and tv watching. We will create a maternal healthy lifestyle score (CHLS) using the dichotomous variables. The final summation of these variables will be used as the main exposure variable.

Eating disorders (ED) such as anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) are common psychiatric disorders with life-long health impacts. Additionally, current treatment options have limited effectiveness, highlighted by the observation that only 30% of adult patients with AN fully recover. The development of EDs is highly complex and driven by environmental and genetic factors. Previous research has suggested that EDs run in families, but the specific genetic variants associated with risk for EDs are not well understood. Twin studies have shown that the heritability for EDs ranges from 40%-70%. Similarly, to other psychiatric disorders, such as depression or schizophrenia, many genetic variants with relatively small effect underlie the overall genetic risk for EDs. Due to the nature of these effects, extremely large sample sizes are necessary which can only be amassed by international efforts. For AN previous large scale genetic studies, comparing patients with healthy controls, have been successful in pinpointing genetic variants associated with the illness (Duncan et al., 2017). However, no such attempts have been made regarding BN or BED and the field of EDs is lacking behind the genomic discovery of other psychiatric disorders. The success of these studies, which search across the entire genome to find associated genetic markers, is highly dependent on the number of patients and controls included in the research because the sample sizes defines the statistical power to detect significant associations. Thus, worldwide joint forces are necessary to combine datasets to boost sample sizes. Therefore, we propose to include ALSPAC participants in the international approach: Using the rich database of ALSPAC to identify patients diagnosed with AN, BN or BED and add them to international cohorts examining the genetic architecture of EDs. The findings may provide a better understanding of the development of EDs and may help to identify or new treatment strategies including potential targets for pharmaceutical treatment.

There is mounting pressure on the government to close nurseries in the current COVID lockdown. There is little data available to assist policy makers in making this decision. ALSPAC is a unique position with our second generation of children, many of whom will be of pre-school age. In the first instance this project will determine whether COVID cases are more or less likely in the parents of children of nursery age. Depending on the results we may approach parents to complete a brief questionnaire on whether their children are currently attending nursery and what the consequences might be if their current provieer were to close.

Experiences of childhood maltreatment is suggested as an important risk factor for the development of delinquent behaviour. Heightened sensation-seeking is related to the development of delinquency. Moreover, sensation-seeking, or biological correlates of sensation-seeking, are suggested as factors linking childhood maltreatment to delinquency. More specifically, it is hypothesized that epigenetic correlates of sensation-seeking might function as a mechanism for translating environmental signals into biological changes that may subsequently lead to maladaptive behavior development. In this study we will try to identify the epigenetic correlates of sensation-seeking in children and investigate whether these epigenetic correlates are influenced by earlier experiences of childhood maltreatment and may impact subsequent development of delinquency in early adolescence.

Molar-incisor Hypomineralisation (MIH) is a tooth condition specifically affecting the enamel (outer layer of the tooth) of one or more of the child’s first adult molars (back teeth) and in some cases the incisors (front teeth). MIH affected teeth appear discoloured, and vary in presentation; cream, yellow or brown. Teeth are commonly very sensitive, painful and in severe cases crumbly. Furthermore, affected teeth often have a poor prognosis and are more susceptible to dental decay meaning the teeth are often extracted before adulthood. It is usually diagnosed when the adult molars and incisors erupt in the mouth at around 6-7 years of age. In some cases, it can also affect the primary teeth, which is known as hypominersalised second primary molars (HSPM) and is seen around 2-3 years of age.

MIH has a high prevalence; approximately 13.1% globally (95% CI 11.8-14.5%) and 15.9% in the UK (95% CI 14.5-17.1%). The literature suggests MIH is caused by disturbances during tooth development. This is influenced by genetics and environmental factors, particularly during pregnancy, time of birth and in the first few years of life. Some of the environmental factors investigated include breastfeeding, environmental toxins (dioxins and Bisphenol A), problems occurring at birth and childhood illnesses. However, the literature concludes that the aetiology of MIH is unclear. Currently, there is little research on maternal factors and MIH, particularly the common environmental risk factors; maternal smoking (7 studies – the most recent suggesting a significant association) and alcohol consumption (2 studies), both in which the strength of evidence is weak and conflicting. Furthermore, much of the research conducted is retrospective and therefore prone common biases such as recall bias. There is a need for high-quality prospective studies. Other studies suggest that maternal smoking and alcohol consumption are associated with offspring HSPM. The embryological development of the second primary molars and first permanent molars are similar, and therefore may share the same environmental influences.

We propose to conduct a prospective study looking at the association between common maternal pregnancy characteristics and MIH. These include maternal smoking, alcohol consumption and body mass index (BMI). We will assess for the presence of residual confounding by including a negative parental exposure control. This involves comparing the confounder adjusted associations of maternal pregnancy exposures with the offspring outcome of interest to similarly adjusted associations of the same characteristics (negative controls) in the father. Similarly, we will use offspring dental trauma as a negative control outcome. Triangulating results from conventional multivariable regression, negative exposure controls and negative outcome controls provides scope to improve causal understanding.

Substantial differences exist between the immune reponses made by males and females that critically impact health and survival. Typically, females make stronger immune responses to vaccines and infections and achieve superior outcomes throughout life. For example, females achieve the same levels of neutralizing antibodies from half the dose of influenza vaccine as males from the full dose. However, this more exuberant immune response leads to greater susceptibility to immunopathology and autoimmune diseases and more adverse events from immunizations. To complicate matters, there are exceptions; as fetuses, females have a 2-fold greater susceptibility to mother-to-child transmission of both HIV and HCV infection, and to IFN-I-resistant viruses. To better understand the mechanisms responsible for these complex observations, we propose to compare the epigenetic and hormonal responses in males and females to immunization and vaccination in early life. We hypothesize that life-long immune sex differences are established early through the interplay of host genetics, sex-specific steroid biosynthesis, epigenetics and the environment, and that early-life epigenetic changes in response to sex-specific steroid modulation and infection and immunization play a dominant role in this process.

Reducing inequalities in child mental health is a public health priority, yet the pathways that link social conditions to mental health outcomes in the early years are unclear. Few studies have compared the social distribution and prevalence of mental health problems across countries, or have compared pathways to any inequalities. Understanding these pathways is critical in order to guide public policy to improve child health and reduce inequalities. In Life Cycle cohort families we aim to assess how early years risk factors mediate the relationship between childhood SECs and subsequent inequalities in child mental health and cognitive development.

Puberty is a time of sweeping biological and social change. Boys and girls who experience early and/or rapid puberty are at elevated risk for psychiatric and physical health problems, including substance use disorders, suicide, polycystic ovary syndrome (in females), and cardiovascular disease. Psychiatric disorders like major depressive disorder also become much more prevalent at puberty and may impede cognitive skill development . Considering the many negative implications of departures from the normal pubertal development, understanding the genetic and environmental regulators of puberty has become a topic of increasing urgency. Our research aims to identify specific and potentially modifiable environmental factors that influence pubertal timing and examine its association with children’s cognitive development and mental health, and we view genetic and epigenetic data as essential tools for accomplishing that goal.

Scientific progress on understanding genetic influences and epigenetic changes (including DNA methylation) at puberty has moved slowly. Previous studies looking at changes in DNA methylation across puberty have been conducted in very small samples; nevertheless, this previous work support the potential to develop an epigenetic clock for pubertal age, analogous to epigenetic clocks that exist for aging. However, generating a clock that is highly accurate and robust requires longitudinal DNA methylation data spanning the pubertal transition. We will substantially improve the rigor and reproducibility of previous research on the epigenetics of pubertal age by using a discovery sample that is substantially better-powered (the Texas Twin project) and by replicating results in an independent sample (ALSPAC). We can then examine potential environmental (e.g., family socioeconomic background) and genetic predictors (e.g., polygenic scores of reproductive phenotypes) of our epigenetic clock for pubertal age, as well as the cognitive and mental health sequelae of advanced epigenetic pubertal age.