The consequences of childhood obesity remain one of the biggest public health burdens in the UK. 1 in 3 children are already overweight or obese by age 10 years. This is especially problematic because obesity has been linked to many health conditions, such as diabetes, cancer and depression. There is now substantive evidence that obesity runs in families, but genetics alone cannot explain the current rise of obesity in the population. So environmental factors have been proposed to be causal for this development. It is this dual determination, that remains paradoxical:
How is it possible that obesity is explained by both genes and environments and what does this complexity mean for public health interventions?
For childhood obesity, we already know that genetic and environmental factors are
important. However, it is not known how environmental factors might be protective of genetic
liability.
The main questions are:
1. Do parental feeding practices, such as offering food to soothe, enhance or buffer the
association between genetic liability and later childhood BMI, and what could be
achieved if we changed parental feeding strategies?
2. Does the child’s physical activity mediate the association between childhood genetic
liability and later BMI, and what would happen if levels of physical activity increased?
3. Can maternal genetic risk influence the child’s body size, even though the genetic liability
are not passed on?
4. What is the association between genetic liability and the built environment of the family
home, such as access to green spaces and public transport?

Cardiovascular disease, a frontline cause of death worldwide, has some risk factors such as obesity, poor cardiorespiratory fitness (CRF), and vascular dysfunction whose primordial signs exist in childhood. Evidence suggests that excess body fat and poor CRF predict increased cardiometabolic risk and the progression of atherosclerosis. However, the mechanisms underlying vascular dysfunction with respect to predictors such as CRF, body fat, and lean mass in the young remains poorly understood.

It is unclear whether CRF in childhood and adolescence impact arterial structure and function in later life. Although several studies have assessed the influence of childhood CRF on early and or later arterial health, they are either of cross-sectional or short-term longitudinal design. Most of these studies have focused on a specific period (e.g. early or late childhood) and are restricted to a one-time measure of CRF. Moreover, inappropriate scaling measure of CRF such as not accounting for the confounding effect of body fat makes interpretation of existing evidence difficult.

Similarly, accumulation of body fat and lean mass during childhood through adolescence may significantly impact arterial health in early adulthood. But, studies that describe the physiological adaptation of vascular structure through adolescence to young adulthood in relation to increased body fat and lean mass are few. A repeated measure of CRF, body fat and lean mass is essential to determining critical periods of early life during which these factors implicate later arterial health. Evidence on suitable target ages for cardiovascular intervention, alongside unraveling the cryptic mechanisms by which CRF, body fat and lean mass relate to arterial health could be achieved. We would, therefore, assess the importance of early life exposures (e.g. CRF, body fat, lean mass, and/or endothelial function) from childhood through adolescence on vascular phenotypes between ages 9 to 24.

This proposed project is to examine whether inactive youth are more likely to have prediabetes in adolescents and young adults.

Poor mental health affects all domains of life, including work, relationships and physical health. Prevalence of mental illness in the UK is increasing, with 1 in 6 people experiencing mental health problems each week. One way of tackling this mental illness epidemic is through prevention. We can achieve this by maintaining and improving people's general mental health and wellbeing, before they reach a clinical diagnosis of mental illness. In this project we are interested in identifying behaviours in ones life that can be modified to improve mental health and wellbeing.

One possible predictor of mental health is our health behaviours. For example, our diet, how much physical activity we do, how much alcohol we consume and whether or not we smoke. While this may seem intuitive, there are many gaps in the research literature. First, it is commonly thought that these behaviours influence our mental health and wellbeing, but little research has been done to assess whether this is a causal effect rather than just a correlation. In order to identify effective intervention targets, it is critically important to ensure that these are causal. We will use complementary methods, allowing us to approach our research question through a number of different lenses. If we can draw consistent results, then we will be able to obtain the strongest and most informative evidence. Second, there is little research that has looked at the nuances of these health behaviours. For example, does the length or intensity of physical activity matter when considering its effect on mental health? We will use the wealth of secondary data available to us to untangle these specific details. Third, these health behaviours do not occur in isolation, therefore, we will investigate how they work together to affect
mental health. And finally, early intervention (i.e. in childhood) is an important aspect of prevention. We will use novel methods to understand how parental health behaviours influence the child's mental health. This can inform us about whether it is better to intervene on the parents or on the child's health behaviours.

The project will explore how being born as part of a twin birth or being born premature affects school readiness (performance on entry assessments) and academic outcomes during the early primary school years (Key Stage 1).

There is evidence that twins have poorer academic outcomes during early adulthood relative to singletons (Tsou, Tsou, Wu, & Liu, 2008). It is possible that this is actually a consequence of the increased probability of twins being born preterm or small for gestational age.
In addition, this finding is not consistently observed; a large scale Danish study found no significant differenes in adolescents’ academic outcomes between twins and singletons (Christensen, Petersen, Skytthe, & Hersking, 2006). We aim to explore whether being born as a twin affects school readiness and early academic outcomes relative to being an only child or having one older non-twin sibling and if so, whether this effect persists after controlling for factors known to affect academic outcomes (e.g. birth weight, maternal education).

The second research question aims to examine whether the birth order of twins affects academic outcomes. There is some evidence that first born twins weigh more than second born twins (Yokoyama et al., 2016). Whilst first born twins can be delivered in much the same way as a singleton, there are many more opportunities for obstetric complications (and therefore perinatal compromise) for second born twins, particularly if delivered vaginally. Intrapartum monitoring of the second twin can be challenging, there may be a malpresentation of the second twin requiring internal cephalic version and breech delivery; if these manouveres fail an emergency caesarean section may be required (Leung 2002, Leung 2004). The analysis will therefore explore whether first born twins perform better academically during the primary school years, and whether this effect differs depending on the mode of delivery. Also of interest is whether any effects are reduced or eliminated once controlling for factors such as birth weight and gestational age.

A final analysis will be completed to explore whether children born preterm have worse academic performace relative to their term born siblings. Pettinger et al. (2019) found that gestational age was a significant predictor of whether a child attained a good level of development on the early years foundation stage profile (EYFSP) (e.g. Pettinger et al., 2019). The EYFSP is a mandatory assessment carried out in all state-funded schools at the end of reception year, and is seen as a measure of ‘school readiness’.
However, it is possible that this effect may be (in part) explained by the home environment. Although Pettinger et al. (2019) controlled for factors such as maternal education and receipt of means tested benefits, there may be other unknown environmental factors that affect school readiness. Comparing preterm children to term born siblings would allow us to control for these factors. There is published evidence from Scandinavian studies using sibling matching, which shows that extreme prematurity (<27 weeks gestation) is associated with increased mortality, autism and low educational attainment (D’Onofrio BM, 2013; Risnes KR, 2016). Our work could add significantly more than this, since this study only reported on ‘years in education’ and ‘failing’ education.

These analyses have been completed on the Born in Bradford data already (approval code: SP335). However, the number of children in each analysis is small, limiting the conclusions that can be drawn. We are therefore seeking to replicate our findings using the ALSPAC database, as this would allow us to strengthen our conclusions if the outcomes are replicated. If possible, we also plan to run a set of analyses on a combined dataset, which would allow us to increase the statistical power.

Prenatal depression has been reported to have associations with adverse pregnancy/ birth outcomes in previous observational studies. However, due to residual confounding, the causal effect of prenatal depression on these outcomes still remain unclear. Mendelian randomisation works well as a novel causal inference approach with utilising genetic variants as instrument variables. This aim of this project is to conduct genome wide association studies (GWAS) of prenatal depression to facilitate Mendelian randomisation studies in perinatal epidemiology area.

Placental size directly correlates with its ability to provide developing feotues with the nutrients needed for growth while in the womb, differing placenta size has been linked with health issues both during pregnancy and for both the child and the mother later in life. In this project we propose to study the effect of placenta size on health outcomes of the child and mother both post pregnancy and throughout their lifespans.