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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B593 - The assessment of gene loci confirmed to alter adult height in longitudinal growth in children - 11/12/2007

B number: 
B593
Principal applicant name: 
Dr Michael N Weedon (Peninsula Medical School, University of Plymouth, UK)
Co-applicants: 
Prof Tim Frayling (Not used 0, Not used 0)
Title of project: 
The assessment of gene loci confirmed to alter adult height in longitudinal growth in children
Proposal summary: 

The assessment of gene loci confirmed to alter adult height in longitudinal growth in children.

In summary we plan to use genome wide data from 43,000 to 50,000 individuals from at least 12 different studies to identify in the region of 50 new loci that alter adult height. We will not know the exact number of loci until we have followed up ~200 SNPs in 55,000 samples from the HUNT study but our QQ plots and False discovery rate calculations suggest this is a realistic number. These will be in addition to the current 20 loci we have identified and typed in the ALSPAC children recently (results pending).

We propose to genotype, using Kbiosciences, the 50 SNPs representing these loci, in the 10,000+ ALSPAC children. This will enable us to test the hypothesis that common gene variants known to alter adult height alter birth length, and childhood growth at different ages. We will colloborate with Bruna Galobardes who has expertise in using the ALSPAC growth longitudinal data.

Statistics

We will use within study and within sex Z scores and the same genetic model (additive, dominant, recessive) that fits the adult data. We will initially perform cross sectional analysis at each age point from birth to the maximum age available. We will then collaborate with Bruna to model the longitudinal data.

Table of data needed (form does not allow tables!):

Children

Birth - length, weightChildhood, ages 2 months to 15 years, all measures of length/height, sex, puberty data

Mothers

Adult height, age

Date proposal received: 
Tuesday, 11 December, 2007
Date proposal approved: 
Tuesday, 11 December, 2007
Keywords: 
Genetics
Primary keyword: 

B595 - Neighbourhood variations in child physical activity The role of area definition - 11/12/2007

B number: 
B595
Principal applicant name: 
Dr Andy Jones (University of East Anglia, UK)
Co-applicants: 
Esther van Sluijis (Not used 0, Not used 0), Richard Haynes (Not used 0, Not used 0), Richard Reading (Not used 0, Not used 0), Prof Andy Ness (University of Bristol, UK)
Title of project: 
Neighbourhood variations in child physical activity: The role of area definition
Proposal summary: 

Although "neighbourhood effects" on health have been recognised in many studies1 very little is known about the underlying mechanisms and very little experimentation has been done to find out what kind of neighbourhoods might have the greatest influence on health. While researchers have been challenged to consider the geographical scales at which processes might operate and to compare alternative neighbourhood sets, few studies so far have done this. By analyzing health variations within a single set of neighbourhoods, almost all published studies have been blind to whether alternative definitions of neighbourhoods might produce different results. The question is important for two reasons. Firstly, knowledge of the characteristics of the set of neighbourhoods that produce the strongest relationship with health might help to identify any processes involved. Secondly, policy-makers advocating interventions that focus on disadvantaged areas to improve individual health need to be better informed about how to identify the areas most amenable to treatment.

We (Jones and colleagues) have recently examined the importance of alternative neighbourhood definitions on the strength of area effects on accident rates to preschool children in the ALSPAC cohort2. Alternative sets of subjective and automated zone design neighbourhoods which incorporated different boundaries and different scales were used.Neighbourhoods based on different criteria produced similar area effect sizes as did neighbourhoods at different scales, but slightly stronger effects were observed in areas with populations less than 4,000.Most of the characteristics of children and mothers associated with accident risk were themselves associated with neighbourhoods, and particularly with the neighbourhoods of smallest size.

Another health related outcome where it is of interest to investigate the possible existence of neighbourhood effects is that of physical activity. In his report At least five a week, the Chief Medical Officer notes that the scientific evidence for the health benefits of physical activity are compelling. Nevertheless, the majority of adults and children fail to meet government guidelines for activity. Reviews of the evidence of the effects of individual level interventions indicate that while positive changes in physical activity can be achieved, the effects are small and short term3. In children and adolescents there is no evidence for the effect of individual-based educational interventions4. Larger, more sustainable changes in physical activity are more likely to be achieved by a multi-level strategy combining environmental and individual level interventions4. In recent years the research focus has moved from individuals to the environment. It is hypothesised that the environment is strongly associated with physical activity yet its actual relationship with physical activity in adults and children is relatively unknown within a UK context5.

One of the unanswered research questions concerns the role which the neighbourhood might play in determining the activity levels of the children living within it. It could be, for example, that certain neighbourhoods are more conducive to activity than others. Such effects could be ascribed to their physical characteristics, or may be associated with shared norms and behaviours amongst residents. Understanding how activity levels vary between different types of neighbourhoods will guide further studies of the more detailed environmental determinants of physical activity in children. The aim of this preliminary study is to compare the strength of neighbourhood effects on physical activity levels in children aged 11 years in the ALSPAC cohort, using alternative, contrasting sets of neighbourhoods.

Methods:

Based on our previous research we will divide the ALSPAC study area into thirteen different sets of neighbourhoods. One set are enumeration districts, the smallest units in the 1991 population census. The other twelve sets all use enumeration districts as building blocks and group them into larger units at three spatial scales. Some of these neighbourhoods are based on "communities" defined by planners in Bristol whilst others have been generated by the automated zone design program "A2Z". A more detailed description and maps showing examples of the zones within Bristol are given elsewhere.6

Date proposal received: 
Tuesday, 11 December, 2007
Date proposal approved: 
Tuesday, 11 December, 2007
Keywords: 
Physical Activity, Physical Fitness, Exercise & Fitness
Primary keyword: 

B594 - Investigation of associations between diet and blood pressure in CIF at 5 and 7 years - 11/12/2007

B number: 
B594
Principal applicant name: 
Dr Imogen Rogers (University of Brighton, Brighton)
Co-applicants: 
Title of project: 
Investigation of associations between diet and blood pressure in CIF at 5 and 7 years
Proposal summary: 

Aim

The aim of this project is to investigate the associations between diet and blood pressure, measured at 5 years and 7 years in the CIF sample.

Background

Cardiovascular disease is the leading cause of death in industrialised countries, and raised blood pressure is a major risk factor(1). Geographical variations in childhood blood pressure in the UK coincide with geographical variations in adult cardiovascular mortality, and are likely to be related to childhood environment(2). Blood pressure level in childhood has also been shown to track through to adulthood(3). Diet has been shown to relate to blood pressure(4) in childhood and there is evidence that dietary changes in very early life may have persistent effects on blood pressure(5). This suggests that dietary interventions aiming to lower blood pressure in childhood could have an impact on adult cardiovascular mortality. However, data on the associations between diet and blood pressure in childhood are limited. The aim of this study is to investigate the cross-sectional and longitudinal associations between dietary intakes and blood pressure levels measured in the CIF sample at ages 5 and 7 years, taking account of potential confounding variables. Key dietary variables considered will include intakes of sodium, potassium

, magnesium, calcium, fat, protein, wholegrains, fish, fruit and vegetables. These results will be of use in formulating dietary recommendations for children.

References

1. Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic and cardiovascular risk factors: US population data. Archives of Internal Medicine. 1993;153:598-615.

2. Whincup PH, Cook DG, Adshead F, Taylor S, Papacosta O, Walker M, Wilson V. Cardiovascular risk factors in British children from towns with widely differing adult cardiovascular mortality. BMJ 1996;313:79-84.

3. Kivimaki M et al. Early socioeconomic position and blood pressure in childhood and adulthood: the Cardiovascular Risk in Young Finns Study. Hypertension 2006;47:39-44.

4. Simons-Morton DG et al. Nutrient intake and blood pressure in the Dietary Intervention Study in Children. Hypertension 1997;29:930-936.

5. Geleijnse JM, Hofman A, Witteman JCM et al., Long-term effects of neonatal sodium retention on blood pressure, Hypertension 1996; 29, pp. 913-917.

Data requested

1. Food and nutrient intakes assessed by dietary diary at 5 years and 7 years in the CIF sample

2. Blood pressure measured in the Focus@7 clinic in the CIF sample

3. Blood pressure measured at 5 year clinic in the CIF sample

4. Birthweight, measured or abstracted from medical records

5. Gestational age abstracted from medical records

6. Height and weight and waist circumference at 5 years measured in the CIF clinic

7. Height and weight and waist circumference measured in the Focus@7 clinic in the CIF sample

7. Physical fitness measured at 5 year clinic in the CIF sample

8. Measures of maternal educational level and paternal occupational class by questionnaire

9. Maternal smoking in pregnancy measured by questionnaire

10. Duration of breast-feeding assessed by questionnaire

11. Age of introduction of solids assessed by questionnaire

Date proposal received: 
Tuesday, 11 December, 2007
Date proposal approved: 
Tuesday, 11 December, 2007
Keywords: 
Diet, Eating disorders
Primary keyword: 

B588 - Alspac maths data - 30/11/2007

B number: 
B588
Principal applicant name: 
Deborah Wilson (Dept of Children Families & Schools, Sheffield, UK)
Co-applicants: 
Title of project: 
Alspac maths data
Proposal summary: 

We want to us ALSPAC maths data as we feel that information on maths and maths teachers is particularly strong. Young people's attitudes to maths have been examined at different stages in their lives, and their ability has been tested through independent tests in years 4, 6 and 8 (covering specific domains of maths). In addition, there have been surveys of maths teachers' experience and attitudes in the main ALSPAC schools (in KS3) which could be linked to individual pupil data. None of this data has yet been analysed. Our understanding is that the data for assessments at Year 4 and Year 6 are now available, but Year 8 needs additional funding to clean and release the data, as does the data from the maths teacher questionnaires in 2002/3 and 2004/5, and the linking of questionnaires from teachers to children.

Once this data is available we intend to commission a separate analysis project. This will be competively tendered. The successful tenderer will require access to the data.

There are three possible areas for analysis:

* Young people's experience - using the questionnaires and independent assessments to examine how the young people have developed capability and confidence in maths, either looking at evidence throughout their lives (up to 14 or 16) or just at change between Y4-Y8.

* Teachers' experience - using the teachers' questionnaires to look at teacher attitudes and relating these to their school circumstances, stress and confidence

* Linking teacher and child experience - how teacher experience and attitudes link to child enjoyment, engagement and ability.

Funding may be available this financial year to make this data available. Please advise on timetable and costs.

Date proposal received: 
Friday, 30 November, 2007
Date proposal approved: 
Friday, 30 November, 2007
Keywords: 
Education
Primary keyword: 

B591 - Identifying psychosocial risk factors associated with the developmental outcomes of children with and without autism - 29/11/2007

B number: 
B591
Principal applicant name: 
Dr Elizabeth Pellicano (University of Bristol, UK)
Co-applicants: 
Prof Alan Emond (University of Bristol, UK)
Title of project: 
Identifying psychosocial risk factors associated with the developmental outcomes of children with and without autism
Proposal summary: 

The overarching aim of this study is to assess the extent to which individual differences in a variety of early psychosocial measures taken in the ALSPAC cohort predict individual differences in outcome 10 to 15 years later. To achieve this aim, this study will use a case-control design, where a group of individuals with autism (cases) will be compared with a group of individuals without autism (controls). Nonautistic adolescents matched for childhood IQ, sex, birth order, and parental social class will be selected as control individuals. To begin, we will determine the developmental outcomes of case and control individuals, including current autistic symptomatology, social and communicative competence, cognitive functioning, academic attainment, and mental health status. We will then examine whether early psychosocial predictors are independently associated with multiple outcomes, and whether the same variables are predictive of outcomes (and to the same extent) for adolescents with and without autism.

Suitable families will be contacted and invited to take part in the follow-up study. Only families who have not actively declined participation previously will be eligible for participation in this study. The extent of attrition is expected to be reasonably high given the amount of time for which the longitudinal study has been running; therefore, we expect to see approximately 40-50 individuals with autism and 40-50 matched controls. Initially, we will interview case and control parents via telephone to obtain information about developmental history (Social Communication Questionnaire; Rutter et ao., 2003) and basic demographic factors. The interviewer(s) will be blind to the case/control status of the participants. We will then invite participants and their primary caregiver to come in to the University for interviews and assessments. Outcome measures will include (1) extent and nature of autistic symptomatology (as indexed by the Autism Diagnostic Interview - Revised [Lord et al., 1994] and the Autism Diagnostic Observation Schedules [Lord et al., 2000]); (2) specific cognitive skills (as measured by a battery of tasks tapping social cognition, executive function, and visuospatial ability); (3) social adaptation (as measured by the subject and informant versions of the Socio-emotional Functioning Intervew; Rutter et al., 1988); (4) IQ (as assessed by the full form of the Wechsler Adult Scales of Intelligence - Third Edition; Wechsler, 1999); (5) academic functioning (as indexed by measures of maths, reading, and phonological skills); and (6) psychiatric functioning (particularly anxiety and depression). Outcome variables will be assessed blind to predictor variables.

Initial analyses will be performed by comparing cases and controls on key outcome variables. Data will be linked with retrospective data on key psychosocial variables (deprivation, family size, temperament, attachment behaviour, parenting style, behaviour/emotions, social relationships) as well as other child variables (autistic symptoms, childhood IQ, language ability) for individual participants. Multiple regression models will be used to predict outcome, with 'caseness' (i.e., autism, nonautism) entered as an additional independent variable. For each outcome variable, we will determine (1) the amount of total variance explained, (2) the independent and separate contributions of each predictor variable, (3) and the interaction term (caseness by predictor variable). If the interaction term turns out to be significant, then this would suggest that the link between the predictor and outcome variable differs according to whether or not the individual has an autism spectrum condition.

This study should advance our knowledge of the sorts of factors predictive of individual children's developmental outcomes. This knowledge is not only critical for achieving a complete aetiological understanding of the condition, but also will highlight which factors play a role in maximise children's potential as they 'move on up' into adulthood (National Autistic Society, 2007).

A list of specific ALSPAC variables is attached.

Date proposal received: 
Thursday, 29 November, 2007
Date proposal approved: 
Thursday, 29 November, 2007
Keywords: 
Depression, Mental Health
Primary keyword: 

B590 - The intergenerational transmission of violence and pro-violence attitudes in the ALSPAC cohort - 28/11/2007

B number: 
B590
Principal applicant name: 
Dr Erica Bowen (University of Crete, Greece, Europe)
Co-applicants: 
Title of project: 
The intergenerational transmission of violence and pro-violence attitudes in the ALSPAC cohort
Proposal summary: 

This study will examine the nature of dating violence as reported by male and female adolescents and determine the applicability of the intergenerational hypothesis in each case. In addition, the study will examine the relationship between early socialization and the development of pro-violence attitudes.

There are three aims of this project:

1.The first is to provide a descriptive analysis of the incidence of dating violence within the ALSPAC cohort. This will include a gender based analysis of the use and receipt of violence within dating relationships as well as the young people's understanding of these behaviours and help seeking behaviours associated with the experience of these behaviours.

2. The second aim is to determine the extent to which the experience of violence within dating relationships (as both perpetrator and victim) reflects an intergenerational pattern. This will be examined in relation to the young person's possible exposure to inter-parental violence, harsh parental discipline and parental maltreatment, controlling for additional family adversity exposure and previous involvement in bullying and antisocial behaviour. Should the data permit, a gender based analysis of these issues will be conducted.

3. The final aim is to determine the extent to which pro-violence attitudes reflect earlier exposure to inter-parental violence, harsh parental discipline, parental maltreatment, after controlling for additional family adversity exposure and previous involvement in bullying, antisocial behaviour and dating violence.

As a consequence of this investigation at least three manuscripts will be written for submission in international peer reviewed journals. In addition, these preliminary investigations will provide the basis of continued research funding applications that will focus on examining potential mediators and moderators of any intergenerational effects wtihin a risk and resilience framework.

In order to fulfil these project aims, the following data is required:

Family Adversity Index (FAI) data with the maternal victimization variables isolated for separate analyses

Child Maltreatment Index - this will be derived from variables relating to maternal parenting practices.

Maternal reports of victimization

Paternal reports of victimization

Maternal parenting data

Paternal parenting data

Bullying involvement data

Dating violence data

Pro-violence attitude data

Details of the measures and observations are presented in table 1 (see attached).

Date proposal received: 
Wednesday, 28 November, 2007
Date proposal approved: 
Wednesday, 28 November, 2007
Keywords: 
Depression, Mental Health
Primary keyword: 

B589 - The predictive validity of infant temperament on childhood mental health problems - 27/11/2007

B number: 
B589
Principal applicant name: 
Dr Kapil Sayal (University of Nottingham, UK)
Co-applicants: 
Dr Paul Ramchandani (Imperial College London, UK)
Title of project: 
The predictive validity of infant temperament on childhood mental health problems
Proposal summary: 

Research Questions

1) Do temperamental characteristics up to the age of 3 years predict later mental health problems?

2) Which temperamental traits best predict psychiatric disorder at the age of 7 years?

3) Can temperamental characteristics in infancy (age 6 months) predict later psychiatric disorder?

Background

In recent years, there has been increasing interest in the early identification of and the development of interventions for infant mental health problems. It is unclear as to which children grow out of these difficulties and which might benefit from further monitoring and assessment by child health and educational professionals. In particular, we wish to investigate whether parent-identified temperamental traits up to the age of 3 years predict an independent diagnosis of psychiatric disorder at age 7 that also takes information from teachers into account?

Key Measures

Predictor: Temperament measures - the Carey scales at 6 and 24 months & EAS scale at 38 months

Outcomes: Child mental health - externalising and internalising problems as measured by the SDQ at later time points, parent and teacher DAWBAs, & Mood & Feelings Questionnaires.

Confounder variables: The analyses will control for key confounding factors including child gender and maternal mental health.

Analytical Approach: Following initial bivariate analyses, multivariable logistic regression analyses will assess the effect of temperament measures at each time point on the presence of any psychiatric disorder at age 7. Maternal EPDS will be included at each time point to cover rater factors. As sample attrition may be related to both the exposure and outcome, response status at follow-up will be related to baseline variables.

Concept Specific measure Person Source Time point(s)

Temperament Carey & EAS scale Mother Questionnaire Birth to 3 years

Mental Health SDQ Mother Questionnaire 47 months to 13 years

Mental Health SDQ Teacher Questionnaire 93-108 months

Mental Health DAWBA Mother &Teacher Questionnaire 7 years to 13 years

Mental Health MFQ Mother Questionnaire 9 years to 13 years

Maternal EPDS Mother Questionnaire Birth to 5 years Depression

Date proposal received: 
Tuesday, 27 November, 2007
Date proposal approved: 
Tuesday, 27 November, 2007
Keywords: 
ADHD, Behavioural Problems
Primary keyword: 

B587 - Development of depression and smoking in adolescents - 27/11/2007

B number: 
B587
Principal applicant name: 
Dr Carol Joinson (University of Bristol, UK)
Co-applicants: 
Prof Marcus Munafo (University of Bristol, UK), Prof Ricardo Araya (University of Bristol, UK), Dr Jon Heron (University of Bristol, UK)
Title of project: 
Development of depression and smoking in adolescents
Proposal summary: 

Applications are invited from suitably qualified psychology graduates to join a team investigating the development of depressive symptoms. The PhD will be undertaken in the Department of Community Based Medicine and will focus on examining the nature of the relationship between depressive symptoms and smoking.

Previous studies have found evidence for an association between depression and smoking in adolescence, but the nature and direction of the relationship is unclear. Some studies have found evidence that depressive symptoms precede the onset of smoking; others have found that smoking precedes depression, and some studies report a bi-directional relationship. The PhD student will have the opportunity to develop skills in statistical modelling of longitudinal data to model the developmental heterogeneity of depression and smoking from late childhood into adolescence and examine potential covariates including gender, behaviour and conduct problems, social adversities, stressful life events, and parent-child relationships.

The project will take advantage of the unique and extensive longitudinal data collected by ALSPAC, an ongoing longitudinal population-based study investigating a wide range of environmental and other influences on the health and development of children. Detailed information on the ALSPAC study is available on the web site: http://www.alspac.bris.ac.uk.

Data required:

Depression- Mood and feelings questionnaire (child and parent report) from 9-15 years.

Smoking- (child and parent report) from 8-15 years.

(we are aware that data from the 15/16 year questionnaire/clinic is not yet available)

Other possible data requirements: Behaviour and emotional problems- DAWBA, SDQ, antisocial behaviour questionnaire.

Social adversities and stressful life events.

Questions on parent-child relationships.

Date proposal received: 
Tuesday, 27 November, 2007
Date proposal approved: 
Tuesday, 27 November, 2007
Keywords: 
ADHD, Behavioural Problems
Primary keyword: 

B586 - Role of rs17822931 in traits dependent on earwax colostrum or body odour and phenome scan - 22/11/2007

B number: 
B586
Principal applicant name: 
Prof Ian Day (Univeristy of Bristol, UK)
Co-applicants: 
Prof Jean Golding (University of Bristol, UK), Prof George Davey Smith (University of Bristol, UK), Dr Tom Gaunt (University of Bristol, UK), Dr Susan Ring (University of Bristol, UK)
Title of project: 
Role of rs17822931 in traits dependent on earwax, colostrum or body odour; and phenome scan
Proposal summary: 

No outline received

Date proposal received: 
Thursday, 22 November, 2007
Date proposal approved: 
Thursday, 22 November, 2007
Keywords: 
Genetics
Primary keyword: 

B585 - Victimisation in childhood and borderline personality disorder in a non-clinical population of 11 year olds results from the ALSPAC birth cohort - 20/11/2007

B number: 
B585
Principal applicant name: 
Prof Dieter Wolke (University of Warwick, UK)
Co-applicants: 
Andrea Schreier (University of Warwick, UK)
Title of project: 
Victimisation in childhood and borderline personality disorder in a non-clinical population of 11 year olds: results from the ALSPAC birth cohort
Proposal summary: 

The aim of the present study is to examine various victimization experiences (domestic, physical harshness) and peer victimization, and their association with BPD in a longitudinal study of a young general population sample with detailed assessment of traumatic events as well as BPD. The specific questions to be answered are: (1) What is the association between peer victimisation versus other traumatic victimisation in childhood and BPD at the of 11? (2) Is there a dose-response relationship between the number of victimisation events and the risk for BPD (3) Are the observed associations independent or mediated by other psychopathology?

Date proposal received: 
Tuesday, 20 November, 2007
Date proposal approved: 
Tuesday, 20 November, 2007
Keywords: 
ADHD, Behavioural Problems
Primary keyword: 

B466 - EMMETT VIP - 14/11/2007

B number: 
B466
Principal applicant name: 
Dr Pauline Emmett (University of Bristol, UK)
Co-applicants: 
(University of Bristol, UK)
Title of project: 
EMMETT VIP
Proposal summary: 

No outline received

Date proposal received: 
Wednesday, 14 November, 2007
Date proposal approved: 
Wednesday, 14 November, 2007
Keywords: 
Primary keyword: 

B465 - Mattocks VIP - 14/11/2007

B number: 
B465
Principal applicant name: 
Mr Calum Mattocks (University of Bristol, UK)
Co-applicants: 
Title of project: 
Mattocks VIP
Proposal summary: 

No outline received

Date proposal received: 
Wednesday, 14 November, 2007
Date proposal approved: 
Wednesday, 14 November, 2007
Keywords: 
Primary keyword: 

B610 - Investigating the role of a novel fasting glucose varient in fetal growth - 13/11/2007

B number: 
B610
Principal applicant name: 
Prof Mark McCarthy (University of Oxford, UK)
Co-applicants: 
Prof Tim Frayling (Peninsula College of Medicine, University of Plymouth, UK), Prof Andrew Hattersley (Peninsula College of Medicine, University of Plymouth, UK), Nick Timpson (University of Bristol, UK), Dr Rachel Freathy (University of Exeter & Plymouth, UK), Prof George Davey Smith (University of Bristol, UK), Dr Ele Zeggini (University of Oxford, UK), Dr Michael N Weedon (Not used 0, Not used 0), Dr Cecilia Lindgren (University of Oxford, UK)
Title of project: 
Investigating the role of a novel fasting glucose varient in fetal growth
Proposal summary: 
Date proposal received: 
Tuesday, 13 November, 2007
Date proposal approved: 
Tuesday, 13 November, 2007
Keywords: 
Genetics
Primary keyword: 

B582 - Breastfeeding and Childrens outcomes - 13/11/2007

B number: 
B582
Principal applicant name: 
Dr Maria Iacovou (Essex University,Colchester, UK)
Co-applicants: 
Dr Brigitta Rabe (Essex University,Colchester, UK), Dr Emila del Bono (Essex University,Colchester, UK), Dr Chiara Pronzato (Essex University,Colchester, UK), Dr Almudena Sevilla Sanz (Essex University,Colchester, UK)
Title of project: 
Breastfeeding and Children's outcomes
Proposal summary: 

We are applying to use ALSPAC data as part of a large project for which we will be requesting funding from the ESRC. This project will not focus solely on ALSPAC data, but will also use data from the Millennium Cohort Study (MCS) which has already been made available to us, and the Infant Feeding Survey (IFS). We envisage our project as comprising four sub-projects. Not all of these will make use of ALSPAC data; however. In the proposal below, we include a brief outline of those parts of the project which involve other data sets, as this provides useful context for the investigations which do use ALSPAC.

There is already an extensive literature on the effects of breastfeeding on a number of outcomes: allergy and asthma; developmental delay in children; childhood blood pressure, and many others. There is also a recognition that standard multivariate analytical techniques may overestimate the positive effects of breastfeeding, due to a mother's propensity to breastfeed being correlated with unobservable (or simply unobserved) factors which are themselves associated with favourable child's outcomes. This problem of endogeneity is likely to lead to the effects of breastfeeding being overestimated. This project aims to carry out a causal analysis of the effects of breastfeeding: that is, an analysis which, as far as possible, overcomes the effects of endogeneity.

The ideal data with which to undertake such a causal analysis of the effects of breastfeeding would arise from a large-scale randomised experiment on infant feeding. However, the ethical considerations involved make such an experiment almost inconceivable. In order to study this issue, therefore, researchers must exploit variation in infant feeding patterns arising from other factors. Here, we propose to use two distinct analytical techniques to examine the extent to which estimates of the effects of breastfeeding are biased if one does not account for the endogeneity of the decision to breastfeed; and to attempt to uncover the causal effect of breastfeeding. We propose four inter-related projects, the first two of which examine children's cognitive outcomes, the third of which examines mothers' mental health, and the last of which examines parents' time off work looking after sick children.

1. The effect of breastfeeding on children's cognitive skills, using an Instrumental Variables approach

This project will identify the causal effect of breastfeeding on children's cognitive development, using an instrumental variables approach. The project will use data from the MCS, and will employ as instrument an exogenous variation in breastfeeding rates determined by whether or not the hospital at which a mother gave birth subscribed to the Unicef Baby Friendly Initiative (BFI). Several studies show that breastfeeding rates (initiation and/or duration) are higher in Baby Friendly hospitals. The IV method relies on the assumption that BFI status is exogeous. We believe this is a reasonable assumption: although mothers in the UK are free to choose the hospital at which they want to give birth, in most cases they are restricted in this choice by travel distance.

2. The effect of breastfeeding on children's cognitive skills, using a Propensity Score Matching approach

This project will also examine the relationship between breastfeeding and children's cognitive skills - but it will use a different data set (ALSPAC) and a different analytical technique (Propensity Score Matching, or PSM). This technique is described by Dehejia and Wahba (2002) and others, and has been used extensively in economics to assess causal effects. Using this technique, the analyst generates two samples of individuals who have and who have not undergone a "treatment" (here, breastfeeding), matched on a wide range of characteristics, as well as by their estimated propensity to breastfeed. The difference in outcomes between the two matched groups provides an estimate of the causal effect of breastfeeding. ALSPAC lends itself well to PSM, containing a wealth of data on parents' attitudes to breastfeeding, their prior intentions to breastfeed, and events during and after birth which may affect whether children are eventually breastfed.

The outcome variables on which we propose to focus are as follows:

* Key Stage 1 SATs results (we would like to use KS2 SATs results as well, but understand these are not yet available

* Results of school entrance assessments from the SATs files

* Teacher assessments: the child's ability group (Year 6); the Year 4 maths test; and teacher ratings of children's ability in Year 3.

* Parents' assessments of their children's development - particularly their assessments of vocabulary and other language-related skills - from the parent-completed questionnaires at 15, 24 and 38 months.

3. Breastfeeding and mothers' mental health: A PSM approach

This section would use data from both ALSPAC and the MCS to examine the relationship between breastfeeding and mothers' mental health. Kendall-Tackett (2007) presents evidence that breastfeeding protects against post-natal depression via two mechanisms: reducing stress, and reducing inflammation. We propose to build on this by investigating the relationship between breastfeeding and maternal wellbeing, using the analytical techniques described above to control for the possible endogeneity of the decision to breastfeed, and to identify the causal relationships involved.

In ALSPAC, the outcome variables of interest would be:

* Crown-Crisp Experiential Scores from birth until 33 months, and subscales where available

* Edinburgh Post-Natal Depression Scores from birth until 33 months

* Other indicators of wellbeing and relationship to child (for example, J151, mum has felt unattached to study child, in the mother's questionnaire at 47 months).

4. Breastfeeding and mothers' work: a cost-benefit analysis

There is a considerable body of research looking at the return to work as a determinant of breastfeeding behaviour. Here, we propose to look at the relationship between breastfeeding and mothers' paid work, by allowing for causal effects in both directions. A mother's decision to breastfeed might influence the time at which she chooses to return to work, but recent research has shown that the length of the period of maternity leave may in turn affect decisions about initiation and duration of breastfeeding.

In addition, we propose to examine the effect of breastfeeding on the number of days parents take off work to look after sick children. Existing research shows that breastfed babies are at lower risk of a number of childhood illnesses; we propose to examine whether this translates to the parents of breastfed children taking less time off work to look after sick children. This is not an easy question to address, since data on this aspect are not available in all waves of ALSPAC. However, by combining data on hospital admissions, the number of illnesses (including ear infections and attacks of gastro-enteritis), and the amount of time parents have taken off work to look after children with ear and other general health problems (asked at 33 and 47 months), we may begin to make some informed assumptions about whether breastfeeding has economic benefits by reducing working parents' absenteeism rates and therefore is beneficial for employers as well as mothers and children.

Date proposal received: 
Tuesday, 13 November, 2007
Date proposal approved: 
Tuesday, 13 November, 2007
Keywords: 
Diet, Eating disorders
Primary keyword: 

B581 - Phenotypic effects from birth to adolescence of puttative causal genetic variants - 13/11/2007

B number: 
B581
Principal applicant name: 
Prof George Davey Smith (University of Bristol, UK)
Co-applicants: 
Prof Laurie Beilin (Not used 0, Not used 0), Prof Ian Day (University of Bristol, UK), Dr Dave Evans (University of Bristol, UK), Dr Tom Gaunt (University of Bristol, UK), Dr Beate Glaser (University of Bristol, UK), Pedro Hallal (Not used 0, Not used 0), Prof Bernado Lessa Horta (Not used 0, Not used 0), Prof Debbie A Lawlor (University of Bristol, UK), Prof Lyle Palmer (Not used 0, Not used 0), Prof Craig Pennell (Not used 0, Not used 0), Dr Susan Ring (University of Bristol, UK), Dr Nic Timpson (University of Bristol, UK), Prof Cesa Victora (Not used 0, Not used 0)
Title of project: 
Phenotypic effects from birth to adolescence of puttative causal genetic variants
Proposal summary: 

No outline received

Date proposal received: 
Tuesday, 13 November, 2007
Date proposal approved: 
Tuesday, 13 November, 2007
Keywords: 
Genetics
Primary keyword: 

B583 - Replication attempt of a signal observed in a genome-wide association study for childhood obesity - 09/11/2007

B number: 
B583
Principal applicant name: 
Struan F A Grant (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
Replication attempt of a signal observed in a genome-wide association study for childhood obesity
Proposal summary: 

No outline received

Date proposal received: 
Friday, 9 November, 2007
Date proposal approved: 
Friday, 9 November, 2007
Keywords: 
Genetics
Primary keyword: 

B579 - Interaction of FLG and SPINK5 polymorphisms in exczema in children - 09/11/2007

B number: 
B579
Principal applicant name: 
Prof John Henderson (University of Bristol, UK)
Co-applicants: 
Dr Alan Irvine (Not used 0, Not used 0), Dr Kate Northstone (University of Bristol, UK), Prof George Davey Smith (University of Bristol, UK), Prof W H Irwin McLean (University of Dundee, UK)
Title of project: 
Interaction of FLG and SPINK5 polymorphisms in exczema in children
Proposal summary: 

Filaggrin is a barrier protein in the skin. Two common variants of the filaggrin gene were reported by Palmer et al (Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature Genetics 2006 Apr;38(4):441-6) to be strongly associated with eczema & these findings have been replicated by others, including us. SPINK5 (serine protease inhibitor Kazal-Type5) gene was discovered in association with Netherton Syndrome, a rare disorder that is ubiquitously associated with severe allergy.

Our collaborators have examined the associations of mutations in SPINK5 and FLG with eczema in a German population. The expected strong association between FLG and eczema was found. There appeared to be no strong evidence of a gene-only association of three mutations of SPINK5 and eczema in this cohort but there was evidence of a possible interaction between SPINK5 and FLG in association with eczema (see Appendix). We now wish to extend these observations by applying the same analyses to the data we have collected as part of our ongoing collaboration on FLG and allergis diseases.

The data are already available in a suitable form for analysis (Kate Northstone). THis proposal is to export these data (questionnaire and clinical assessments of eczema from birth to 13 years) to Dr Irvine & Mclean's German colaborators to carry out identical analytical methods to the attached. This will be more effieicient than analysing the data in-house. THe collaborators are willing to sign a confidentialiuty agreement and they will have access to a limited dataset (only that which is requred for this project under usual ALSPAC rules).

The genotyping costs of this project (FLG & SPINK5) have already been borne by the applicants. There are no additional resoucre issues for this project, which is part of an ongoing programme of analyses in collaboration with ALSPAC core personnel (JH, GDS, KN).

Date proposal received: 
Friday, 9 November, 2007
Date proposal approved: 
Friday, 9 November, 2007
Keywords: 
Allergies, Respiratory, Atopy
Primary keyword: 

B578 - The role of genotype and maternal smoking during pregnancy on offspring smoking initiation - 09/11/2007

B number: 
B578
Principal applicant name: 
Prof Marcus Munafo (University of Bristol, UK)
Co-applicants: 
Prof Ian Day (University of Bristol, UK)
Title of project: 
The role of genotype and maternal smoking during pregnancy on offspring smoking initiation
Proposal summary: 

We will seek to definitively clarify the relationship between maternal cigarette smoking during pregnancy and subsequent offspring smoking behaviour, and specifically identify any critical risk periods during pregnancy when nicotine exposure is associated with increased risk of offspring smoking.

We will use biochemical validation of smoking and both maternal and offspring genotype to accurately characterise foetal nicotine exposure and validate offspring smoking status, and to determine whether the association of nicotine exposure with subsequent smoking behaviour is explained by, or moderated by transmitted genotype.

We will assess offspring's response to first cigarette to investigate whether any association between foetal nicotine exposure and subsequent smoking behaviour is mediated by sensitivity to nicotine.

Specific research questions:

1. Is there an association between foetal nicotine exposure and subsequent offspring smoking behaviour, in particular initiation?

2. Is variation in nAChR and CYP2A6 genotype associated with subsequent offspring smoking behaviour?

3. Is any observed association between foetal nicotine exposure and offspring smoking explained by transmission of nAChR and CYP2A6 genotypes?

4. Does variation in nAChR and CYP2A6 genotype moderate the association of foetal nicotine exposure and offspring smoking behaviour?

5. Is any association betwee foetal nicotine exposure and/or genotype and subsequent offspring smoking behaviour mediated by subjective response to first cigarette?

Existing Data:

Maternal self-reported smoking status (pregnancy-15 years)

Paternal self-reported smoking status (pregnancy-15 years)

Offspring self-reported smoking status (11-15 years)

Offspring self-report subjective experience of first cigarette (15 years)

Maternal DNA

Offspring DNA

New Data:

Maternal self-reported smoking status (17 years)

Paternal self-reported smoking status (17 years)

Offspring self-reported smoking status (17 years)

Maternal urinary cotinine assay (pregnancy)

Offspring urinary cotinine assay (11-17 years)

Date proposal received: 
Friday, 9 November, 2007
Date proposal approved: 
Friday, 9 November, 2007
Keywords: 
Alcohol, Drugs, Genetics, Smoking
Primary keyword: 

B584 - Investigating the role of a novel fasting glucose varient in fetal growth - 06/11/2007

B number: 
B584
Principal applicant name: 
Prof Tim Frayling (Peninsula College of Medicine, University of Plymouth, UK)
Co-applicants: 
Title of project: 
Investigating the role of a novel fasting glucose varient in fetal growth
Proposal summary: 

No outline received

Date proposal received: 
Tuesday, 6 November, 2007
Date proposal approved: 
Tuesday, 6 November, 2007
Keywords: 
Genetics
Primary keyword: 

B580 - Tonsillectomy for recurrent paediatric tonsillitis - does it work The ALSPAC experience - 06/11/2007

B number: 
B580
Principal applicant name: 
(Not used -1, Not used -1)
Co-applicants: 
Prof Mark Griffiths (Not used 0, Not used 0)
Title of project: 
Tonsillectomy for recurrent paediatric tonsillitis - does it work? The ALSPAC experience
Proposal summary: 

Background:

Debate continues as to the benefit of tonsillectomy. A recent Cochrane review found that there were insufficient trials to fully evaluate the effectiveness of tonsillectomy (1). However, the author of the only studies included in this review stand by their conclusion that tonsillectomy was efficacious in reducing sore throat episodes (1). Furthermore, recent comment from a leading ENT academic asks the pertinent question of the whether the perceived supremacy of this type of review for answering questions related to the use of surgical interventions is justified (2).

Primary question:

Is there a manifest, bias balanced benefit from tonsillectomy versus non-operative management for children with recurrent tonsillitis?

Rationale for using ALSPAC data:

Although there are many studies into the benefit of tonsillectomy, we believe that the ALSPAC database will contain information to add significantly to this debate. Last year there were nearly 30,000 tonsillectomies carried out across England in the 0-14 age group (3). Assuming the national average rate of tonsillectomy applies to the ALSPAC population we expect around 300 tonsillectomies to have been performed on this cohort of children. This study size is comparable with other studies (1).

The incidence of self-reported sore throat is included in the questionnaires, this is the primary outcome that has been previously used to assess benefit of the intervention. However, other outcome measures such as SAT scores and school attendance may be used to demonstrate an association with tonsillectomy. Also, confounders such as socio-economic and smoking status may be examined to balance any potential bias.

Plan of action:

1. We intend to review the ALSPAC database to ascertain the incidence of the exposure variable (tonsillectomy) and the outcome measure (primary being reported sore throat episodes, secondary measures being school attendance/performance).

2. Assess likely bias from confounders between groups.

3. Extract data.

4. Statistical analysis (3. and 4. to be supported by the ALSPAC statistics team, funded by the applicants).

5. Presented locally, regionally and nationally.

6. Publish in the ENT-UK journal (Clinical Otolaryngology).

Date proposal received: 
Tuesday, 6 November, 2007
Date proposal approved: 
Tuesday, 6 November, 2007
Keywords: 
Hearing
Primary keyword: 

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