Proposal summaries

These are research proposals that have been approved by the ALSPAC exec. The titles include a B number which identifies the proposal and the date on which the proposals received ALSPAC exec approval.

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B4411 - Exploring maternal and fetal molecular mechanisms of and risk factors for congenital anomalies - 04/10/2023

B number: 
B4411
Principal applicant name: 
Amy Taylor | University of Bristol (United Kingdom)
Co-applicants: 
Professor Deborah Lawlor, Dr Carolina Borges
Title of project: 
Exploring maternal and fetal molecular mechanisms of and risk factors for congenital anomalies
Proposal summary: 

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.

Impact of research: 
There are already several papers in progress from the initial MR-PREG analyses. This work will be important for identifying the mechanisms and causes of CAs.
Date proposal received: 
Monday, 25 September, 2023
Date proposal approved: 
Monday, 25 September, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Mendelian randomisation

B4369 - Study of Prediction model for Preeclampsia - 21/09/2023

B number: 
B4369
Principal applicant name: 
Wang Bingshun | Department of Biostatistics, Clinical Research Institute, Shanghai Jiao Tong University School of Medicine
Co-applicants: 
Wang Xiaojin, He Yunjiang
Title of project: 
Study of Prediction model for Preeclampsia
Proposal summary: 

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.

Impact of research: 
This study aims to shed light on the causes of preeclampsia and aligns with clinical practice. It will also aid in identifying women who are at a higher risk of developing preeclampsia, ultimately improving their care.
Date proposal received: 
Saturday, 5 August, 2023
Date proposal approved: 
Thursday, 21 September, 2023
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Mothers - maternal age, menopause, obstetrics

B4417 - Evaluation of polygenic risk scores and development of integrated risk tools across the life course - 25/10/2023

B number: 
B4417
Principal applicant name: 
Vincent Plagnol | Genomics plc (United Kingdom)
Co-applicants: 
Rachel Moore, Jamie Floyd, Jamie Hall, Charlie Hatcher, Edward Beard, Sophie Landon, William Tarran, Deborah Thompson, Melisa Chuong, Daniel Wells
Title of project: 
Evaluation of polygenic risk scores and development of integrated risk tools across the life course
Proposal summary: 

Polygenic risk scores (PRSs) aggregate genetic data across the genome and summarise these data into a single number that quantifies an individual’s genetically defined disease risk. PRSs can also be used to predict standard outcomes that are relevant to health, such as height or weight. Genomics plc has built a range of tools to generate the most accurate PRS library, and combine these PRSs with other non-genetic factors into integrated risk tools (IRT). However, typical PRS and IRT evaluation focuses on adulthood. As a result, we have a limited understanding of how these tools perform across the life course, especially at which age genetically driven differences become apparent. Similarly, little is known of how the combination of PRS and early life data can jointly predict adult outcomes, which is key for preventative opportunities that need to occur at an early age.
ALSPAC has generated unique data across the life course of individuals. These data provide an opportunity to understand the interplay between childhood and adult data together with genetics. We therefore are proposing to use the ALSPAC data to understand the role of PRSs in the context of an individual life’s course, with a focus not only on prediction accuracy but also on how the accuracy of these predictions varies with age and when they have the greatest utility. We will further explore whether childhood information, together with immutable genetic data, can be combined to accurately predict traits in adulthood, thus providing an effective lever for triggering health interventions that are most useful during childhood.

Impact of research: 
We anticipate that this project will enable us to better quantify our predictions of health outcomes and trait values, with and without early life information. This information will improve our understanding of the contribution of the genetic information captured by PRS to risk/trait prediction at each stage of the life course, and will hence provide clarity around the potential benefits that could be conferred by the appropriate use of PRS at different points in an individual’s life.
Date proposal received: 
Monday, 18 September, 2023
Date proposal approved: 
Thursday, 21 September, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Bone disorders - arthritis, osteoporosis, Cancer, Diabetes, Eczema, Gastrointestinal, Hypertension, Infection, Obesity, Respiratory - asthma, General quantitative traits, such as weight, BMI, height, blood pressure , GWAS, Statistical methods, Polygenic risk scores, Blood pressure, BMI, Cardiovascular, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Growth, Metabolic - metabolism, Statistical methods

B4386 - Comparison between consumers of a high free sugars diet and those of a low free sugars diet 11-07-2023 - 150900 - 21/09/2023

B number: 
B4386
Principal applicant name: 
Caroline Taylor | Bristol Medical School (UK)
Co-applicants: 
Dr Pauline Emmett
Title of project: 
Comparison between consumers of a high free sugars diet and those of a low free sugars diet (11-07-2023 - 15:09:00)
Proposal summary: 

The current recommendation is to limit intake of free sugars to below 10% of energy (calories) but very few children achieve this. We will investigate free sugars intake in the diets of ALSPAC children at 7, 10 & 13 years of age. We will identify two groups of children, those who consume 20% or more of their energy from free sugars and those who consume less that 15% of their energy from free sugars at all three ages. These two groups will be compared for differences in food group and nutrients intakes. We will investigate their background diet and social differences to determine points where intervention could be made to improve children's diets.

Impact of research: 
To inform the development of evidence-based intervention to improve children's diets and therefore long-term health.
Date proposal received: 
Thursday, 14 September, 2023
Date proposal approved: 
Wednesday, 20 September, 2023
Keywords: 
Nutrition, Obesity, Statistical methods, Nutrition - breast feeding, diet

B4414 - ICARHE Improving Childrens cARdiovascular Health in a digitalised Europe - 21/09/2023

B number: 
B4414
Principal applicant name: 
Jean-Philippe Empana | The National Institute of Health and Medical Research (INSERM) (France)
Co-applicants: 
Prof Nicholas Timpson, Prof Kate Northstone
Title of project: 
ICARHE: Improving Children’s cARdiovascular Health in (a digitalised) Europe
Proposal summary: 

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.

Impact of research: 
Potential delivery of a data educated intervention in schools.
Date proposal received: 
Thursday, 7 September, 2023
Date proposal approved: 
Tuesday, 19 September, 2023
Keywords: 
Epidemiology, Cardiometabolic, Population based data analysis and RCT, Cardiovascular

B4412 - Reproductive factors and the risk of pregnancy complications a student project linked to B4306 - 18/09/2023

B number: 
B4412
Principal applicant name: 
Fangkun Liu | Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China (China)
Co-applicants: 
Ziwei Teng M.D.
Title of project: 
Reproductive factors and the risk of pregnancy complications: a student project linked to B4306
Proposal summary: 

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.

Impact of research: 
Our research may offer more insights into the etiologies of offspring developmental failure on the central nervous system, cognition and intelligence. This may help individuals to choose a more scientific way to avoid maternal exposure to bad factors and get close to good factors, to guarantee a healthy child, or help the governments and medical institutions to establish more appropriate strategies for better maternal and child health care.
Date proposal received: 
Tuesday, 5 September, 2023
Date proposal approved: 
Monday, 18 September, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Speech/language problem, Developmental disorders - autism, Cognitive impairment, Congenital abnormalities, Diabetes, Epilepsy, Infection, Learning difficulty, Mental health, GWAS, Medical imaging, Statistical methods, Birth outcomes, Blood pressure, Environment - enviromental exposure, pollution, Genome wide association study, Intelligence - memory, Mendelian randomisation, Mothers - maternal age, menopause, obstetrics, Metabolic - metabolism, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Nutrition - breast feeding, diet, Offspring, Psychology - personality, BMI, Physical - activity, fitness, function, Speech and language, Statistical methods, Cardiovascular, Childhood - childcare, childhood adversity, Cognition - cognitive function, Communication (including non-verbal), Development, Equipment - MRI, Endocrine - endocrine disrupters

B4415 - Association of inflammation with cardiac structure in adolescents - 18/09/2023

B number: 
B4415
Principal applicant name: 
Andrew O. Agbaje | University of Eastern Finland (Finland)
Co-applicants: 
Viivi Heijari
Title of project: 
Association of inflammation with cardiac structure in adolescents
Proposal summary: 

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.

Impact of research: 
The research improves the understanding on the role of inflammation on cardiac structure in youthful life.
Date proposal received: 
Friday, 8 September, 2023
Date proposal approved: 
Monday, 18 September, 2023
Keywords: 
Epidemiology, cardiovascular disease, Medical imaging, Cardiovascular

B4416 - Pathways between neurodevelopmental conditions and Health A longitudinal examination of risk and protective factors - 18/09/2023

B number: 
B4416
Principal applicant name: 
Kirsty Samantha Lee | University of Warwick (United Kingdom)
Co-applicants: 
Ahmad Valikhani, Dr John Galvin, Prof Dieter Wolke , Dr Ayten Bilgin
Title of project: 
Pathways between neurodevelopmental conditions and Health: A longitudinal examination of risk and protective factors
Proposal summary: 

Autism spectrum condition is a lifelong neurodevelopmental condition recognised by its heterogeneous phenotypic manifestations. This heterogeneity not only makes the condition challenging to diagnose but may also lead to misdiagnoses of psychiatric or medical disorders, which can decrease quality of life and wellbeing. Research has shown that psychiatric and medical conditions are highly comorbid with autism, but it is not known if this is due to autism per se (i.e., autism-related genetic mutations and autistic traits) or the effects of environmental risk factors or protective factors. Environmental risk factors (e.g., traumatic experiences, intimate partner violence, bullying, stressful life events) commonly contribute to poor mental and physical health in the general population, but there has been less investigation into their role among autistic individuals. It is also unknown whether protective factors in childhood and adolescence (e.g., positive relationships with parents, school enjoyment, social support) affect the association between autism and psychiatric or medical comorbidities in adolescence and adulthood. In addition to examining these association in the general population who have an autism diagnosis, we will also consider autistic traits (i.e., the broader autism phenotype; BAP) and traits of attention deficit hyperactivity disorder (ADHD), which is highly comorbid in the autistic community. As girls and women were historically neglected in neurodevelopmental research, we will also examine sex differences. The research could have clinical and policy implications for promoting health and wellbeing in the broad autism population, better recognition and earlier diagnosis, especially among girls, and the prevention/promotion of risky/protective environments.

Impact of research: 
The findings may contribute to our understanding of how phenotypic presentations of neurodevelopmental conditions relate to psychiatric, medical and social outcomes This project may identify the underlying mechanisms in the environment that amenable to intervention. Additionally, as the role of sex differences in autism have historically been ignored, our research may inform sex-specific programmes in the provision of healthcare for autistic individuals, including earlier diagnosis. In sum, the findings may have widespread clinical, policy, and research implications.
Date proposal received: 
Wednesday, 13 September, 2023
Date proposal approved: 
Monday, 18 September, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Statistical methods, Childhood - childcare, childhood adversity, Development, Environment - enviromental exposure, pollution, Sex differences, Autism, ADHD, Health, Mechanisms

B4410 - Genome-wide association study and meta-analysis of carotid intima media thickness cIMT - 03/10/2023

B number: 
B4410
Principal applicant name: 
Sonia Anand | McMaster University (Canada)
Co-applicants: 
Amel Lamri
Title of project: 
Genome-wide association study and meta-analysis of carotid intima media thickness (cIMT)
Proposal summary: 

Carotid intima media thickness is a measure of the thickness of wall of the carotid, a blood vessel located near the heart. Throughout the years, fat deposits along these walls (causing atherosclerosis) and the amount of deposits depends on multiple factors including genetic factors, poor diet quality and lack of physical activity. Larger fat deposits (and hence, thicker walls) are associated with a higher risk of cardiovascular disease.
The goals of our study are to
1- identify new genetic markers that predispose to higher levels of fat deposit and thicker carotid walls
2- investigate the age around which these genes are activated (eg. identify which ones are active at an earlier age versus the ones that are activate later in life)

Impact of research: 
Our research will help identify new associated with high cIMT at an early age that could potentially be interesting drug targets. it will also increase our understanding of the development of atherosclerosis and interplay between the genetic predisposition and time/age.
Date proposal received: 
Thursday, 31 August, 2023
Date proposal approved: 
Monday, 18 September, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), carotid intima media thickness , Statistical methods, Cardiovascular, Genetic epidemiology, Genetics, Genomics, Genome wide association study

B4408 - Assessment of Depression in Mothers of Children with Atopic Dermatitis - 13/09/2023

B number: 
B4408
Principal applicant name: 
Katrina Abuabara | University of California San Francisco
Co-applicants: 
Hannah Kang
Title of project: 
Assessment of Depression in Mothers of Children with Atopic Dermatitis
Proposal summary: 

The health impacts of caring for dependents with chronic diseases are increasingly being recognized. Atopic dermatitis is one of the most common chronic illnesses of children, therefore, we plan to use the ALSPAC cohort to understand whether caregiving for children with atopic dermatitis leads to depression in mothers and to identify those caregivers who might be at highest risk.

Impact of research: 
A peer-reviewed scientific article; more generally increased awareness of caregiver burden, and support for caregivers
Date proposal received: 
Wednesday, 30 August, 2023
Date proposal approved: 
Wednesday, 13 September, 2023
Keywords: 
Epidemiology, Allergy, Mental health, Statistical methods, Dermatology

B4397 - Mendelian randomization analyses of maternal iron deficiency anaemia during pregnancy and offspring congenital heart disease - 11/09/2023

B number: 
B4397
Principal applicant name: 
Manisha Nair | University of Oxford (United Kingdom)
Co-applicants: 
Dr Tuck Seng Cheng
Title of project: 
Mendelian randomization analyses of maternal iron deficiency anaemia during pregnancy and offspring congenital heart disease
Proposal summary: 

Our ongoing observational analyses in the UK population have shown an association between maternal anaemia and congenital heart defects in children. We therefore aim to conduct a two-sample Mendelian randomization analysis to examine evidence of a potential causal association.
This proposed research will analyse data on maternal and offspring genotypes, maternal iron status (such as haemoglobin and ferritin concentrations) during pregnancy and offspring congenital heart defects in ALSPAC. The resulting summary statistics on the maternal genetic effects on iron status during pregnancy, the maternal genetic and offspring effects on congenital heart defects will be separately compared and meta-analysed with summary statistics from other genome-wide association studies among European ancestry.

Impact of research: 
This research will inform the potential causal effect of maternal iron haemostasis parameters on offspring congenital heart defects leading on to a follow-on trial.
Date proposal received: 
Monday, 28 August, 2023
Date proposal approved: 
Monday, 11 September, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Congenital abnormalities, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Statistical methods, Cardiovascular, Mendelian randomisation

B4413 - Building blocks of cognition The co-development of brain function and cognition across the first 5 years of life - 13/02/2024

B number: 
B4413
Principal applicant name: 
Karla Holmboe | University of Bristol (United Kingdom)
Co-applicants: 
Prof. Mara Cercignani, Dr. Zsofia Nemoda
Title of project: 
Building blocks of cognition: The co-development of brain function and cognition across the first 5 years of life
Proposal summary: 

The first 5 years of life is a key period of development – not only do children grow at the fastest rate in their lifetime, they also develop a vast range of new skills and abilities. In this study, we are interested in some of the most important skills that children develop during this period, including language skills, the ability to quickly understand and react to new information, and the ability to concentrate and adjust behaviour in everyday life. Alongside this, we are interested in how the brain develops and allows children to learn all these new things, and, in turn, how new experiences may lead to changes in the brain. To do this, we will see the same children in the lab for assessments at multiple time points between 6 months and 5 years. Participating families will be recruited from the ALSPAC sample, meaning that the study children’s parents (i.e., the ‘Children of the 90s’) will already have participated in many assessments themselves (since their own childhood). This gives us useful information about the parents and their background, which will help us understand more about how their children develop. At the final time point (when children are 5 years old), we will look at how development of the brain and the key cognitive skills prepare children to start school, with the ultimate aim of understanding more about why some children struggle in school, either academically and/or socially.

Impact of research: 
The over-arching aim of my research is to understand the early developmental pathways (at both the biological/neural and behavioural levels) that lead to some children struggling in school. I have taken the approach of investigating this question in typically developing children (instead of ‘at risk’ children) because even in this group there is a full spectrum of outcomes – from children who easily transition and thrive in school to children who really struggle. It seems likely that the development of key skills and abilities before the school years play a significant role preparing the child for the requirements of school (e.g., ability to pick up new information, concentration skills, language skills). Unfortunately, we know that children who struggle in the early years often continue to struggle throughout the school years and into adulthood. Therefore, in the long term, knowing the factors that lead to difficulties at school start may allow us to better support children at the earliest possible age, which I hope will lead to better outcomes during the school years and beyond.
Date proposal received: 
Wednesday, 6 September, 2023
Date proposal approved: 
Monday, 11 September, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Learning difficulty, Mental health, Speech/language problem, Cognitive development across the typical and atypical spectrum; Struggling in school, Medical imaging, Microarrays, Statistical methods, Neuroimaging, physiological measures, behavioural testing, executive functions, language skills, cognitive development

B4406 - Factors that Predict Immune Function Resilience of Adult Survivors of Childhood Sexual Abuse - 11/09/2023

B number: 
B4406
Principal applicant name: 
Sandra Rasmusssen | Walden University: College of Psychology & Community Services (United States)
Co-applicants: 
Samantha Colombo, Mrs.
Title of project: 
Factors that Predict Immune Function Resilience of Adult Survivors of Childhood Sexual Abuse
Proposal summary: 

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.

Impact of research: 
This study is significant in that there are many mental and physical health concerns increased in those who survived childhood sexual abuse and experience chronic stress from the trauma. The significance of this study is to find factors that aid in mitigating these concerns through immune function resilience. Inflammation is the specific aspect of immune function considered, which is important for many physical and mental health concerns. Finding factors to implement, embrace, and encourage those who experienced abuse could aid in reducing these health concerns. Understanding these factors can help inform treatment plans of children who have experienced CSA and inform their parents of factors that help mitigate the adverse health effects, thus promoting positive social change.
Date proposal received: 
Sunday, 10 September, 2023
Date proposal approved: 
Monday, 11 September, 2023
Keywords: 
Immunology

B4407 - Prospective relationship between emotional risk factors and development of overweight/obesity in adolescents and young adults - 11/09/2023

B number: 
B4407
Principal applicant name: 
Nadia Micali | Eating Disorders research unit, Psychiatric Center Ballerup (Denmark)
Co-applicants: 
Fernando Fernández-Aranda, Elena Jansen, Anna Victoria Brieva-Toloza, Bilal Hassan Ashraf
Title of project: 
Prospective relationship between emotional risk factors and development of overweight/obesity in adolescents and young adults
Proposal summary: 

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.

Impact of research: 
This study will bring together a focus on a range of potential predictors of the development of overweight and obesity throughout the first 3 decades of life. These included emotional risk factors and disordered eating behaviors in the child but also comprise psychological risk factors of the mother. As such, the findings will provide a unique understanding of prospective relationships across the individual and family level.
Date proposal received: 
Tuesday, 29 August, 2023
Date proposal approved: 
Monday, 11 September, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Eating disorders - anorexia, bulimia, Mental health, Obesity, Statistical methods, BMI, Development, Growth, Psychology - personality

B4409 - Cooperative childrearing in middle childhood and biosocial pathways to adolescent wellbeing - 11/09/2023

B number: 
B4409
Principal applicant name: 
Emily Emmott | University College London (United Kingdom)
Co-applicants: 
Title of project: 
Cooperative childrearing in middle childhood and biosocial pathways to adolescent wellbeing
Proposal summary: 

Are non-parental caregivers important for children and young people’s wellbeing, even in societies with strong nuclear family and intensive parenting norms? This mixed-method project uses the “Children of the 90s” cohort study to investigate the role of alloparents (non-parental caregivers) in England, examining the biosocial pathways between different forms of local childrearing systems and adolescent outcomes.

CONTEXT: Western family structures are often described as nuclear, and in the UK, this is coupled with intensive parenting norms. Childrearing is seen as a private matter, and parents (particularly mothers) are predominantly viewed as being responsible for raising children. From an evolutionary anthropological perspective, this way of raising children is highly unusual: anthropological studies from across populations show that non-parental caregivers (alloparents) are ubiquitous and crucial contributors to childcare, although who helps and how they help vary. Humans have therefore been hypothesised to have evolved a unique system of “cooperative childrearing,” co-evolving with an extended period of dependence through childhood and adolescence. In essence, it takes a village to raise a child.

CURRENT CHALLENGE: Despite intensive parenting norms, families in the UK exist within varied and complex systems of support. However, while evolutionary theory points to the importance of non-parental caregivers, much of our knowledge around raising children centre on parenting with particular focus on early years. There is limited focus on alloparenting, and few studies investigate the impact of alloparental care in middle childhood despite the reliance on continued after-school/weekend childcare for many families. It is therefore unclear how families exist within local systems of childrearing, and how these systems impact children and young people’s health and wellbeing. A comprehensive understanding of the wider childrearing system is crucial to design effective policy and practice impacting parents, children, and young people.

PROJECT AIMS: This project extends the focus of childrearing from parenting to incorporate alloparenting, building a comprehensive understanding of childrearing systems in middle childhood and their pathways to adolescent wellbeing in England (UK).
Specifically, this project aims to (1) identify and classify the different typologies of childrearing systems beyond parenting within England, and (2) investigate the biosocial pathways between alloparenting, markers of stress, and adolescent outcomes including affect (anxiety/depression), socio-emotional development, and health-related risky behaviours. We use data from Avon Longitudinal Study of Parents and Children (“Children of the 90s”) which uniquely holds detailed data on alloparenting during middle childhood (age 6-12), together with biomarkers of stress/inflammation (cortisol, c-reactive protein, interleukin-6). We apply an innovative combination of quantitative and qualitative methods by quantitatively identifying typologies of caregiving (latent class analysis), deepening our understanding of these typologies by using the longitudinal data to constructing life history case studies, then test the hypothesised causal pathways through structural equation modelling.

PROJECT BENEFITS: By extending the focus of caregiving to incorporate alloparents and taking an innovative mixed-method approach, this project contributes to an in-depth understanding of middle-childhood caregiving systems and their impact on young people within a parent-focused culture; and, in doing so, we improve our understanding of human childrearing systems more broadly. Overall, this project will: improve cross-disciplinary knowledge around optimal childrearing practices in middle childhood; contribute to methodological development by applying a novel combination of mixed methods to longitudinal cohort data; and contribute knowledge towards effective policy and practice development for children and families in England and beyond.

Impact of research: 
Impact 1: Address cross-disciplinary conflict around optimal childrearing practices in middle childhood. Much of the literature on caregiving and childhood development is informed by Bowlby and Ainsworth’s Attachment Theory from developmental psychology, which assumes the importance of responsive parenting by a primary caregiver (usually the mother). While Attachment Theory as originally proposed concerned caregiving in infancy, it has increasingly been applied to later life stages, bringing with it the assumption that high levels of alloparenting (and less parenting) may lead to negative consequences for children and young people. This directly conflicts with recent developments in evolutionary anthropology where cooperative childrearing is acknowledged as extended and ubiquitous in humans, and lack of alloparents are predicted to lead to poorer child outcomes under most circumstances. By testing the impact of alloparents on adolescent outcomes, this project contributes knowledge to address this conflict, with potential for cross-disciplinary impact. Impact 2: Contribute to methodological development by applying a novel combination of mixed methods to longitudinal cohort data. This project offers a novel combination of established methods, latent class analysis to quantitatively identify clusters of different childrearing systems in the data, and narrative life history case construction/analysis44 to better-understand what the different childrearing systems mean in terms of life experiences. This will be followed by careful hypothesis generation of causal pathways via directed acyclic graphs, followed by testing of these hypotheses through Bayesian structural equation modelling. The combination of these methods will maximise the validity of our findings through robust data analysis, while offering a deeper understanding of the causal pathways/mechanisms. By incorporating a qualitative element, this project will reveal the value of longitudinal cohort data beyond the traditional quantitative approach. Through knowledge-sharing, this project will help build the skills and capacity of mixed-methods researchers in the UK. Impact 3: Contribute knowledge towards effective policy and practice development in England and beyond. Aspects of current policy and practice impacting parents, children, and young people in England are not always effective or optimal. Increasingly, researchers have raised issues around designing policy and practice around Western middle-class assumptions of care which conflict with lived-experiences of families, including recent calls to "close the gap between official guidelines and reality". Thus, by detailing local childrearing systems in England, and by detailing the biosocial causal pathways between caregiving and adolescent wellbeing outcomes, this project contributes crucial information which is required for effective policy and practice development and implementation.
Date proposal received: 
Wednesday, 30 August, 2023
Date proposal approved: 
Monday, 11 September, 2023
Keywords: 
Anthropology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Qualitative study, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Childhood - childcare, childhood adversity, Parenting

B4404 - Desistance from violent and non-violent crime - exploring the snaring role of substance use - 19/09/2023

B number: 
B4404
Principal applicant name: 
Gemma Hammerton | Population Health Sciences, University of Bristol (UK)
Co-applicants: 
Dr Jon Heron, Professor Matthew Hickman
Title of project: 
Desistance from violent and non-violent crime - exploring the snaring role of substance use
Proposal summary: 

Criminal behaviour peaks in mid- to late adolescence, and then declines throughout early adulthood. However, there are
individual differences in the course of criminal behaviour across this time period, with a small proportion of young people continuing to commit crimes beyond the peak age for criminal offending. Desistance is defined as “the process by which criminality, or the individual risk for antisocial conduct, declines over the life course, generally after adolescence”. Life-course theories of desistance suggest that certain ‘snares’ (such as substance use) may prohibit desistance.

Impact of research: 
This project will contribute new knowledge on robust targets for crime prevention and strategies to support desistance. The goal is to identify the obstacles faced in maintaining long term desistance, who is most at risk of encountering ‘snares’, and when.
Date proposal received: 
Thursday, 24 August, 2023
Date proposal approved: 
Monday, 4 September, 2023
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Statistical methods

B4401 - Making sense of the varying methylome and varying disease patterns - 11/09/2023

B number: 
B4401
Principal applicant name: 
Josine Min | MRC IEU
Co-applicants: 
Gibran Hemani, Johann Hawe, Yueying Li
Title of project: 
Making sense of the varying methylome and varying disease patterns
Proposal summary: 

DNA methylation (DNAm) plays a central role in gene regulation. However, it is unknown how DNAm patterns change. For example, through genetic factors or physiological states.
Longitudinal birth cohort studies such as ALSPAC provide an unique opportunity to study DNAm patterns over time and to link it to varying physiological states. Quantitative traits comprising your physiological state (such as BMI, glucose and inflammation levels) have varying patterns over time. Similarly eczema and asthma have varying disease patterns over time. Identifying changes in DNAm preceding a change in physiological state or a disease status may lead to identification of a marker that predicts disease outcome.(1)
Multiple studies have identified genetic variants associated with DNAm (mQTL: methylation quantitative trait locus) by combining genome wide genotype information with DNAm levels.(2) The Genetics of DNA methylation Consortium brought together a large number of cohorts to identify mQTLs in blood and investigated whether the mQTLs play a role in disease etiology.(3) Modelling DNAm trajectories with genetic variation could improve our understanding of biological mechanisms.

1. Chen R, Xia L, Tu K, Duan M, Kukurba K, Li-Pook-Than J, et al. Longitudinal personal DNA methylome dynamics in a human with a chronic condition. Nat Med. 2018;24(12):1930-9.
2. Gaunt TR, Shihab HA, Hemani G, Min JL, Woodward G, Lyttleton O, et al. Systematic identification of genetic influences on methylation across the human life course. Genome Biol. 2016;17:61.
3. Min JL, Hemani G, Hannon E, Dekkers KF, Castillo-Fernandez J, Luijk R, et al. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation. Nat Genet. 2021;53(9):1311-21.

Impact of research: 
Date proposal received: 
Wednesday, 23 August, 2023
Date proposal approved: 
Monday, 4 September, 2023
Keywords: 
Molecular genetics and genomics, eczema, asthma, glucose, BMI, inflammation markers, GWAS of DNA methylation, mendelian randomization, colocalization, longitudinal modelling, machine learning, Epigenetics

B4402 - Health Economic Model for Evaluating Interventions for Children of Parents with Mental Illness - 18/09/2023

B number: 
B4402
Principal applicant name: 
Ben Wijnen | Trimbos Institute (the Netherlands)
Co-applicants: 
dr. Frederick Thielen
Title of project: 
Health Economic Model for Evaluating Interventions for Children of Parents with Mental Illness
Proposal summary: 

Children of parents with mental illness (COPMI) face a heightened risk of developing mental disorders themselves. While the literature underscores the importance of early interventions, there is a scarcity of studies investigating the economic implications of such interventions. This project seeks to bridge this gap by constructing a health economic model that synthesizes both clinical and economic data, enabling a comprehensive analysis of the potential benefits and costs associated with different intervention approaches.
Hence, in this project, we will develop a health economic simulation model to examine the cost-effectiveness of interventions targeting these children/families. The ultimate goal is to demonstrate the added value of these interventions for children, their parents, and society as a whole.
Upon completion, the health economic model will provide a quantifiable assessment of the economic value of various interventions for children of parents with mental illness. It will enable decision-makers to compare the costs and benefits of different strategies, facilitating resource allocation based on a comprehensive understanding of both short-term and long-term outcomes. Sensitivity analyses will be conducted to assess the robustness of the model to variations in input parameters, and scenario analyses will explore the impact of different assumptions and policies.

Impact of research: 
The implications of this research are substantial, as they have the potential to guide policy recommendations and inform clinical practices. By quantifying the economic consequences of interventions for children of parents with mental illness, this study addresses a critical gap in the literature and contributes to the broader field of health economics. The results will aid in prioritizing interventions that maximize both health outcomes and efficient resource utilization, thereby improving the well-being of a vulnerable population while optimizing healthcare spending. At Trimbos, we have a team dedicated at improving health for children with parents who are addicted to alcohol or drugs or who are mentally ill. We run a program to increase awareness of associated risks among professionals who work with children such as teachers. We provide facts and figures, guides and tools, training and events. Moreover, professionals can participate in the national platform specifically directed to this issue that gathers annually.
Date proposal received: 
Wednesday, 23 August, 2023
Date proposal approved: 
Monday, 4 September, 2023
Keywords: 
Health Economics, Mental health, Statistical methods, Childhood - childcare, childhood adversity, Psychology - personality

B4391 - Resilience development and child health outcomes - 24/08/2023

B number: 
B4391
Principal applicant name: 
Rosa Wong | The Education University of Hong Kong
Co-applicants: 
Dr Frederick Ho, Dr Patrick Ip, Dr Keith Tung
Title of project: 
Resilience development and child health outcomes
Proposal summary: 

Resilience is known to be the process and outcome of successfully adapting to difficult or challenging life experiences. Promoting resilience is helpful to minimizing the detrimental impact of life stressors which may be unavoidable at times. While interventions aiming to enhance resilience are increasing among different age groups, there remains gaps in our understanding of how and when resilience manifest, as well as the role of negative and positive emotions in this process. This project aims to use intergenerational data from ALSPAC to investigate predictors of the trajectories of resilient behavior, and connections between maternal resilience and offspring resilience from the prenatal stages through childhood years. This includes identifying time and environmental predictors that can be useful in designing future interventions to assist individuals who are at risk in coping with stress and difficult situations.

Impact of research: 
The proposed study aims to generate new knowledge about the connection between maternal mental health and offspring development. It will make a significant contribution to academic and policy debates about individual vulnerability to psychopathology because of their genetic susceptibility, family medical history, and other person-specific factors during pregnancy and in early life. This will increase recognition of the immediate and long-term impacts that mental health problems before and during pregnancy can have on the development of offspring's abilities to overcome difficulties, as well as the various environmental factors after birth that can either worsen or promote the child's developmental adaptation.
Date proposal received: 
Tuesday, 15 August, 2023
Date proposal approved: 
Thursday, 24 August, 2023
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Development

B4398 - Impact of paternal obesity on cognitive function of offspring - 24/08/2023

B number: 
B4398
Principal applicant name: 
Cheryl Hawkes | Lancaster University (UK)
Co-applicants: 
Dr Neil Dawson, Dr Xiaowen Lin, Prof. Rebecca Hardy, Prof. Keith Godfrey, Dr. Sheila Barton, Prof. Katie Lunnon
Title of project: 
Impact of paternal obesity on cognitive function of offspring
Proposal summary: 

Parental health during pregnancy is a key driver of long-term brain health of offspring. Evidence suggests that children born to obese mothers have lower IQ and poorer memory compared to children of lean mothers. However, much less is known about the impact of paternal obesity on the brain function and mental health of their children. This project will analyse the cognitive function, memory performance and mental health of infants, children and adolescents born to obese and overweight vs lean fathers. We will also investigate the impact of paternal BMI on the brain structure of their children. In addition, we will evaluate the potential additive effect of maternal and paternal obesity on these outcomes. Where possible, we will include relevant genetic information in the analyses to ensure that conclusions about parent-child outcomes are not simply due to gene inheritance. Results from this project will generate important information about whether parental obesity influences the long-term brain health of offspring and the risk of developing neurodevelopmental disorders. The impact on long-term brain health up to young adulthood, as characterised in this study, may also have consequences for the future risk developing neurodegenerative disorders given the primary role of cognitive reserve in protecting against these age-related disorders. This study will play a key role in providing novel insight and new targets for interventional strategies to ensure brain health across the lifespan in the context of an increasing, global at-risk population.

Impact of research: 
More than 60% of adults in England are currently overweight or obese, with men making up a disproportionate percentage. However, little is known about the impact of paternal obesity on offspring health, particularly in terms of offspring brain health across development. Results from this project will generate key information about whether parental obesity influences brain development and maturation across infancy and into early adulthood. Moreover, any interactive effects with maternal obesity will able to be determined. Emerging evidence suggests that parental obesity is an important factor in the development of neurodevelopmental disorders, but this is under researched. In addition, as increasing evidence suggests that neurodegenerative diseases may begin in mid-life, these findings may have consequences for future risk of age-related brain disorders. Results from this project will provide new insight into novel aetiologically-relevant mechanisms that disrupt brain development and increase the risk of poor mental health, and will also provide novel insight into the value of new interventional strategies to ensure brain health across the lifespan.
Date proposal received: 
Wednesday, 16 August, 2023
Date proposal approved: 
Thursday, 24 August, 2023
Keywords: 
Neurology, Developmental disorders - autism, Cognitive impairment, Learning difficulty, Obesity, Statistical methods, BMI, Cognition - cognitive function, Communication (including non-verbal), Development, Intelligence - memory, Neurology, Offspring, Sex differences, Speech and language

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