Proposal summaries
B507 - IS JOINT HYPERMOBILITY A RISK FACTOR FOR THE DEVELOPMENT OF CHRONIC MUSCULOSKELETAL PAIN IN ADOLESCENCE - 18/05/2007
Aims
We wish to investigate the relationship between JH and chronic musculoskeletal pain and other aspects of musculoskeletal health in ALSPAC as follows:-
1. Relationship between JH and chronic musculoskeletal pain in adolescence.
* Prospective analyses will investigate whether JH, as defined by Beighton score greater than 6 at age 13, is associated with an increased risk of chronic musculoskeletal pain at age 17, as assessed by questionnaire.
* Factors which influence any association between JH and chronic musculoskeletal pain will be explored, such as lower socio-economic status and clumsiness. We would also look at parental JH and chronic pain patterns.
2. Health and social impacts of JH.
* Prospective studies will investigate whether JH at age 13 is associated with adverse health impacts associated with chronic musculoskeletal pain at age 17, as assessed by questionnaire.
* Cross sectional and prospective studies will examine associations between JH at age 13, and physical activity as assessed by accelerometry at age 13 and 15.
3. Relationship between JH and other aspects of musculoskeletal health.
Cross sectional and prospective analyses will determine whether JH at age 13 is related to bone mass as measured by DXA (age 13 and 15) and pQCT (age 15), or to scoliosis (ages 13 and 15).
B494 - A longitudinal study of emotional symptoms based on the SDQ - 14/05/2007
We are currently in the process of applying to the ESRC for a grant to fit longitudinal models to the repeated MFQ depression measures administered to both the mother (in child-based questionnaires) and to the child (in the clinic).
We feel that whether or not this grant is successful (we expect to hear by the autumn) it will be useful to have carried out some preliminary work using SDQ measures (47mn, 81mn, 9/11/13 years). These measures will avoid many of the methodogical problems expected when using the MFQ, and we anticipate the fifth of these measures to become available within the next few months.
Consequently we are proposing to fit a series of Longituginal Latent Class Analysis (LLCA) and Latent Class Growth Analysis (LCGA) models to these repeat measures, much in the same way as the recent asthma and bedwetting models and that this would stand up as a paper in it's own right.
B491 - The association of physical activity during pregnancy with reduced risk of preeclampsia - 04/05/2007
No outline received
B493 - Objective quantitative stratification of cannabis exposure in ALSPAC using hair-based biomarkers pilot study - 01/05/2007
This pilot study will compare hair-based toxicological assessment of cannabis exposure with self-reported use of cannabis over the same historical period amongst a purposive sample of 100 people selected to represent a range of cannabis exposure levels. Self-reported use will be assessed through completion of the assessment schedule currently incorporated in the 15+ ALSPAC Focus clinic (where hair samples are being collected and stored). For convenience, cannabis negative controls (10) will be sought amongst volunteers from the Department of Social Medicine. A further 90 individuals with a range of cannabis use levels from low (monthly or less) to high (daily) will be recruited through advertisements amongst students and users of community drugs projects with whom we have contacts. These sources have been successfully used in the past to recruit to focus groups; participants will be offered a £20 inconvenience fee and will be given assurances of complete confidentiality. Following completion of the questionnaire, an investigator will check participant responses. Participants will then provide a hair sample for toxicology. Assessments of use in the past 3 months provided by toxicology will be compared to those from self-report. Hair samples will be collected via the standard procedures used in ALSPAC.Colour of hair and use of any cosmetic treatments (e.g. perming or bleaching) will be recorded as these can influence toxicology results (though seldom to the point of producing false negatives).
Toxicological assessment will be undertaken at the TrichoTech laboratories in Cardiff. Quantitative assessment of cannabis content of the samples will be undertaken using gas chromatography/mass spectrometry. Cannabis dose exposure as inferred by the amounts and frequencies reported by questionnaire in the same participants will also be calculated and ranked. The two assessments will be compared using weighted Kappa scores to compare categorical assessments of dose/ consumption. Intraclass correlations also will be used to assess association between continuous measures of consumption. Based on a sample size of 100 and consideringthe percentage agreement for a binary outcome, for example "heavy" consumption defined as the top quintile of each distribution, we will be able to detect agreement between the two methods of 60% or more based on the width of the one-sided 95% confidence interval.[i]
High Kappa or correlation scores will be taken as evidence of low levels of reporting bias in the self-reported cannabis measures. Conversely, low agreement between self-report and toxicological assessment will be taken to suggest that the former may have been influenced by social desirability bias.
Results of this pilot study will be used to support funding applications (for example to the NIH and the MRC) for toxicological assessment of the full ALSPAC cohort based on samples collected at the 15+ Focus clinic and subsequently.
[i] Machin D, Campbell M, Fayers P, Pinol A. Sample size tables for clinical studies 2nd Ed. Blackwell, Oxford 1997.
B482 - Impact of mild traumatic brain injury on cognition emotional/behaviorial functioning and Health Related Quality of Life HRQL in childhood and adolescents a population based study - 20/04/2007
This study uses a contemporary population- based longitudinal study (ALSPAC) to
investigate the outcome of mild traumatic brain injury (TBI) in children, in terms of
executive function, emotional/behavioural status and Health Related Quality of Life.
Outcomes of mild TBI will be assessed at 12 and at 16-17 years and compared with:
(i)age-matched participants who sustained severe or moderate TBI in childhood;
(ii) age-matched participants who sustained an orthopaedic injury in childhood but not a TBI; iii) age-matched participants who did not sustain TBI or orthopaedic injury in childhood.
Cognitive, psychological and behavioural measures collected pre and post injury will be
compared, and the influence of familial and environmental factors on outcome will be
assessed. The results will answer the question whether mild head injury has long term
impacts, and inform rehabilitation approaches.
B489 - Effects of prenatal alcohol consumption and alcohol metabolising genes on child growth and neurodevelopment - 19/04/2007
(a) Aims of the project
To determine whether there is a causal association between:
- low-to-moderate prenatal alcohol exposure
- binge drinking during pregnancy
- polymorphisms of the main alcohol metabolizing genes in mother and child
and birth weight, length at birth, head circumference at 8 months; growth at 7/8 years; and neurodevelopmental outcome through to age 11?
B483 - CONTAMED Contaminant mixtures and human reproductive health - novel strategies for human health impact and risk assessment of endocrine disrupters - 16/04/2007
CONTAMED has the following main objectives:
* To prepare the ground for epidemiological studies able to capture cumulative EDC exposure by developing and evaluating biomarkers for total effective internal EDC load. This will rely on in vitro bioassays representative of various EDC actions ("mode-of-action screens") and will utilize tissue specimens from three existing European mother-child cohorts.
* To substantiate observations from human studies in extended developmental toxicity rat studies by investigating the possible role of mixtures of estrogens, anti-androgens and other classes of EDC in producing long-lasting delayed adverse reproductive effects at environmentally relevant levels.
* To bring together human epidemiology and predictive toxicological risk assessment by comparing internal EDC exposures in humans with those resulting from controlled exposures producing clear effects in laboratory animal experiments. This will enhance the usefulness of animal data in making extrapolations to the human.
* To search for previously unrecognised EDCs in human tissues by combining analytical chemistry with in vitro EDC mode-of-action screens in
3
CONTAMED - Contaminant mixtures and human reproductive health
bioassay-directed fractionations ("toxicity identification and evaluation", TIE) and by using metabolomic profiling to identify xenobiotic as well as endogenous biomarker metabolites.
* To strengthen the European Environment and Health Action Plan and the Endocrine Disrupter Strategy by reflecting on the implications of project results for practical policy measures and human b
B488 - A genome-wide study of copy number variation gene expression and quantitative traits in the ALSPAC population cohort - 12/04/2007
No outline received
B478 - Somatic and cognitive/neurodevelopmental trajectory in childhood See B355 - 22/03/2007
No outline received
B477 - Stability of overweight and progression to obesity in the ALSPAC cohort - 21/03/2007
Assessments of the stability of overweight and obesity require longitudinal data on changes in BMI over time. Published assessments to date have been severely limited by three factors: small sample size; older samples (stability lower in older cohorts living in less obesogenic environments); generalisability to the UK unclear. All three weaknesses would be addressed in an analysis of data already collected in ALSPAC and available to us as part of an existing BHF funded project.
B476 - ADAM 33 polymorphisms asthma lung function and bronchial responsiveness in children - 20/03/2007
This project builds on the work of our group on the genetic aetiology of asthma in children and utilises previously collected data on objective outcome measures. There remains uncertainty about therole of ADAM33 in the context of asthma risk and this study gives the opportuntity to investigate several different (but related) respiratory oucomes in a population-based sample.
B475 - Prenatal exposure to alcohol and the development of conduct problems in childhood and adolescence - 15/03/2007
We would like to conduct a study into the longer-term behavioural outcomes of prenatal exposure to alcohol and the potential modifying influences of maternal and child metabolising genes. Although this is a topic of considerable public health importance, only a handful of studies, conducted in small convenience samples, have been conducted to date and many questions remain unanswered (please see scientific outline). ALSPAC is ultimately suited for such a study because it is large, population-based, a wealth of data already exists on pregnancy as well as offspring development throughout childhood and adolescence, while DNA has already been obtained as well.
B474 - Effect of diet on the mental performance of children Nutrimenthe - 09/03/2007
Aims
1. To re-analyze how the mother's diet during pregnancy and blood levels of DHA influence the WISC-III data from the ALSPAC study, considering the four indexes [verbal comprehension (VC), perceptual reasoning (PR), freedom from distractivility (FD) and processing speed (PS)]. The influence of FADS1, FADS2 and COMT polymorphisms as exposure variables, as well as other confounder factors will be also taken into consideration.
2. To study the potential long-lasting associations between mother's dietary intake of fish during pregnancy and the evolution of cognitive development. To achieve that, we will try to predict the cognitive score from 18 months to 8 years of age by comparing the scores from the Denver indexes with the WISC-III ones. After that, we will study the role of mother's blood DHA levels in the above hypotethized relationship.
Hypothesis
1. Maternal dietary intake of fish during pregnancy is correlated with the freedom from distractivility factor (FD) in WISC-III. FD is a factor which includes the subtests relating to working memory. In fact, FD is called working memory (WM) in the WISC-IV.
2. Children who show a high score in the Denver Scales at 18 months have also a high score in the WISC-III at 8 years old.
3. These relationships will be modulated by the influence of FADS1, FADS2 and COMT polymorphisms.
Statistical Procedure
1. To conduct an exploratory factorial analysis with the WISC-III subtests to obtain the factors/ indexes. Previous factor structure of the WISC-III was obtained in 2,200 children within a wide range of age from 6 to 16 years old (Weschler, 2003). However, it will be interesting to obtain a factorial structure for 8-9 year olds from ALSPAC, because some neuropsychological domains such us Working Memory have a critical period between 7 and 9 years of age.
2. For the second objective, regression analysis will be conducted using the WISC-III factors/indexes as dependent variables and the Denver indexes as predictors.
3. Once the factors are obtained, each factor will be related to the nutritional and genetic information.
Exposure variables
Mother's and children dietary intakes of fish
Mother's and child's blood levels of LC-PUFA (DHA & AA)
Genetic polymorphisms: FADS1, FADS2, FADS3, COMT
Outcome variables
WISC-III scores
Denver Developmental Screening Test
Confunder variables (all confounders considered in the ALSPAC Lancet paper in 2007).
Maternal age, mother's education, mother's BMI, smoking, breast-feeding, cultural level, Apgar score,..
This work would be a reanalysis of the data already used by Colin Steer for the Nutrimenthe work but looking at the neuropschological variables in more depth - the data can be compiled by Colin Steer so minimal support would be required from ALSPAC.
B470 - Diagnostic accuracy of waist circumference vs BMI percentile for high fat mass in children - 09/03/2007
The paediatric obesity epidemic has led to renewed interest in the development and validation of relatively simple methods for defining or diagnosing obesity which are suitable for clinical and epidemiological purposes (Reilly Int J Obes 2006;30: 595-597). Systematic reviews-which reviewed data up to the end of 2001(e.g. SIGN 69, www.sign.ac.uk)-concluded that the evidence base from diagnostic studies (including a previous collaboration between the applicant and ALSPAC, Reilly et al Int J Obes 2000; 24: 1623-1627) supports the use of a high BMI percentile or SD score as a means of diagnosing or defining obesity in children and adolescents. Defining obesity as a high BMI for age has high specificity and moderate sensitivity when a high fat mass is used as the reference definition of obesity. In addition, children with high fat mass are at significantly increased risk of a number of morbid conditions, so the definition is not just arbitrary but has biological/clinical meaning.
More recently, there has been increasing evidence that a high waist circumference for age may be a promising alternative definition of obesity for paediatric use (Reilly Int J Obes 2006; 30: 595-597) . At present however the diagnostic accuracy of a high waist circumference in children and adolescents is unclear- the optimal cut-off point in the waist circumference distribution is unknown , ie the cut-off which best defines children with high fat mass and those children at greatest risk of co-morbid conditions. We also lack evidence from paediatric studies which have made direct comparisons of the diagnostic accuracy of the BMI and waist circumference as all studies published to date have reported on one or the other index but not both in the same sample.
The aims of the present study are therefore to
a. Estimate the diagnostic accuracy (e.g. sensitivity, specificity, predictive values) of a high waist circumference for a high fat mass index (fat mass measured by DEXA adjusted for height; Wells & Cole 2002 Int J Obes 26: 947-952).
b. Use ROC analysis to identify the optimum cut-off point in the waist circumference SD distribution which best identifies children with high fat mass index.
c Make a direct comparison between the diagnostic accuracy of BMI and waist by estimating sensitivity, specificity and predictive values for the currently recommended definitions based on BMI (such as BMI above the 91st and 95th percentiles) and the optimum definition derived from the present study, aim b above.
Methods
B471 - Balance problems and dizziness in childhood - 08/03/2007
Aims of the project
The broad aim of this study is to look the prevalence and predictors of balance problems and dizziness in children at age 7 and age 10.
The specific aims are:
- To determine the prevalence of poor balance function and dizziness in 10 year old children
- To examine any associations between balance function at age 7 and balance function and dizziness at age 10.
- To describe the nature of symptoms of dizziness and imbalance, determining diagnoses where possible
- To explore some of the early predictors of poor balance function and dizziness in 10 year old children, specifically:
- To examine the associations with maternal factors
Factors such as smoking, drinking alcohol, illness and taking medication during pregnancy will be examined
- To examine the association between childhood anxiety and balance dysfunction
Anxiety disordered children have been shown to have excessive sensitivity to balance-challenging situations and it has been suggested that there may be a sub-clinical balance disorder in childhood anxiety (Erez et al, 2004)
- To examine the association between weight gain during childhood and balance
Balance in adulthood has been found to be associated with weight during childhood (Kuh et al, 2006).
- To examine the association with educational difficulties
Dyslexia, Attention Deficit Disorder and learning disabilities have been linked to cerebellar-vestibular dysfunction (Levinson, 1990); anti-motion sickness medications (Levinson, 1991) and vestibular exercises (Reynolds et al, 2003) have even been suggested as possible treatments.
A systematic review of evidence around these research questions will be incorporated.
B473 - Investigating the role of SNPs associated with stature in type 2 diabetes patients and controls in the ALSPAC study - 06/03/2007
We wish to use the ALSPAC study to investigate the effects of type 2 diabetes susceptibility variants at the KCNQ1 locus on fetal growth, growth in childhood and intermediate traits related to type 2 diabetes.
Recently, two genome-wide association (GWA) studies of East Asian subjects simultaneously reported a strong association between variants in the KCNQ1 gene and the odds of type 2 diabetes [1, 2]. The effect size estimates were large (OR 1.3-1.4) and the associations were robust, exceeding stringent criteria for statistical significance appropriate to GWA studies (Pless than 5x10-8).
This association had not been identified previously in European GWA studies due to the lower allele frequency (5% vs 40%) and consequently reduced power [3]. However associations were observed in European samples following the East Asian GWA studies, and the effect size estimates were consistent [1-3]. The index SNP, rs2237895, has also shown detectable effects on beta cell function in Europeans [4].
The associations with type 2 diabetes and beta cell function make the KCNQ1 locus an excellent candidate for influencing early growth. A variant that predisposes to reduced insulin secretion and diabetes in adulthood may also influence insulin secretion/action in utero, and thereby reduce birth weight [5]. Our preliminary data on the CDKAL1 and HHEX loci support this (PLoS Med, under review). Maternal diabetes genes may additionally influence birth weight through their effects on the intrauterine environment [6]. We have observed that the maternal risk alleles for fasting glucose and type 2 diabetes at GCK and TCF7L2, respectively, are associated with higher offspring birth weight [7, 8].
The KCNQ1 locus is of additional interest in relation to early growth because the locus is imprinted and may harbour elements that influence the imprinting of neighbouring genes [9, 10]. The region is implicated in Beckwith-Wiedemann syndrome and Silver-Russell syndrome, rare neonatal disorders of fetal overgrowth and growth restriction, respectively.
We therefore propose to analyse the polymorphisms in ALSPAC to test the following hypotheses:
1. Fetal genotype and maternal genotype are associated with fetal growth.
2. Fetal genotype and maternal genotype are associated with growth phenotypes (height, BMI, growth velocity) in childhood
3. Offspring genotype is associated with diabetes-related traits in childhood including fasting insulin, fasting glucose and insulin secretion (in the subset of offspring with OGTT data), triglycerides, HDL, LDL and total cholesterol, anthropometric measures including BMI, lean/fat body mass, WHR, waist circumference, skin folds where available.
4. Due to imprinting, association between the risk allele in the offspring and early growth is dependent upon the parent of origin (we will be able to assess this using informative mother-offspring pairs).
Whether the results are negative or positive they will help our understanding of how the KCNQ1 variants function and, if positive, provide important insights into growth and other diabetes-related phenotypes.
To do this we would like to genotype (at Kbiosciences) all ~20,000 ALSPAC samples. We will need the following phenotypes to test our hypotheses (a detailed list is in the next section):
1. Birth weight, length and head circumference
2. Growth measures in childhood (height, weight and BMI aged 7-11)
3. Covariates of birth weight to check if genotype is acting through them: gestational age, maternal age, maternal BMI, smoking , parity, twin status to exclude non-singletons, ethnicity as genotype frequency may alter with ethnic origin and confound analyses.
4. Type 2 diabetes-related intermediate traits including fasting insulin, fasting glucose and insulin secretion (in the subset of offspring with OGTT data), triglycerides, HDL, LDL and total cholesterol, anthropometric measures including BMI, lean/fat body mass, WHR, waist circumference, skin folds where available.
B496 - People of Britain transformations - 01/03/2007
No outline received
B492 - Pregnancy related weight gain and factors associated with the development of obesity after pregnancy - 01/03/2007
No outline received
B468 - The longitudinal course of depressive symptoms from late childhoood to early adolescence - 22/02/2007
Project outline: The longitudinal course of depressive symptoms from late childhood to early adolescence
The proposed 24-month project will investigate the developmental changes in depressive symptoms from late childhood (9 years) to adolescence (13 years) in the Avon Longitudinal Study of Parents and Children (ALSPAC). The research will exploit recent innovations in statistical modelling of longitudinal data that now make it possible to empirically test whether there are meaningful subgroups of individuals in the ALSPAC cohort that follow distinct developmental trajectories of depressive symptoms.
Using the statistical package Mplus (Muthen and Muthen 1998), the study will employ a range of approaches (both parametric, semi-parametric and non-parametric) to describe both the within-child and between child heterogeneity observed in a set of repeated measures of depressive symptoms. Techniques such as these will permit us to examine whether distinct developmental trajectories of depressive symptoms can be empirically identified in the ALSPAC cohort, and furthermore, allow us to test whether individuals cluster into distinct subgroups, each with a different trajectory profile of depressive symptoms. It is expected that there will be at least four distinct trajectory groupings relating to a) little or no depressive symptoms from childhood to adolescence (persistent low level); b) increasing levels of depressive symptoms from childhood into adolescence (increasing); c) onset of depressive symptoms in childhood with consistently high levels of depressed mood (chronic high); and d) moderate levels of depressed symptoms throughout the assessment period (moderate). Gender differences in the trajectory groupings will also be examined using two approaches: Firstly, by modelling the sample as a whole, it will be possible to examine the gender ratio observed within each trajectory group. Secondly, by fitting gender-specific models, we will be able to examine differences in trajectory shape. It is predicted that girls will show higher mean levels and sharper increases in depressive symptoms from childhood to adolescence than boys.
The second aim of the proposed study is to link distinctive trajectories with risk factors that might account for individual differences in the development of depressive symptoms.
By taking advantage of extensive longitudinal data from ALSPACon socio-demographic background, family adversity and parental psychopathology, the proposed study will compare the risk factors for depressive symptoms beginning in childhood (9-11 years) compared to adolescence (12-13 years). We will empirically test whether social disadvantage and family adversity are more strongly associated with childhood onset depressive symptoms (i.e. persistent depressive symptoms beginning in childhood) compared to those with depressive symptoms emerging in adolescence.
The study will use longitudinal data from the Mood and Feelings Questionnaire to measure depressive symptoms (MFQ, Angold et al. 1995; Sharp et al, 2006). The use of this instrument allows both a categorical view of likely depressive disorder, as well as a dimensional measure of total depressive symptoms with severity ranging from none to severe.
B469 - Childhood Cancer Research Group - 21/02/2007
Basically the study is a pilot to demonstrate that it is (or is not) possible to use neonatal Guthrie blood spots both for genotyping and separately immunological measures of infection contact. The ultimate aim is to study the relevance of (host resistance) genetic variation in the child (I know of the work on mannose binding lectin (MBL) in ALSPAC) but also immunological evidence in the child of specific infection contact during pregnancy (largely acquired by passive transfer of antibody from the mother, thoughherinfection contact may not have been during the pregnancy necessarily) for the occurrence of childhood tumours, particularly leukaemias.
In the absence of any really large centralised childhood biobanks in the UK of tissues other than neonatal blood spots (which exist in many discrete centres back to the 1980s) that could be used unambiguously to assess infection contact prior to childhood cancer diagnosis, it seems worthwhile to see whether it is technically feasible to make immunological measures in old blood spots.We know already that old blood spots (and other tissue samples) can be used reliably with amplification if necessary, to obtain DNA in sufficient quantities and quality for genotyping polymorphisms of interest (e.g. MBL, HLA).There are several reports also that it is possible to measure immunoglobulin evidence of specific infection contact, but we need to establish thoroughly whether we can do it reliably and in a multiplex way for several infections simultaneously given the everyday conditions of storage and availability of NHS blood spots.We will also need to
check those measures separately in maternal pregnancy sera, cord blood and perhaps childhood sera to demonstrate we can do it well, and the ALSPAC sample availability means this is possible.If we can demonstrate feasibility of such measurement, Scotland (which has stored centrally in one place blood spots for all children screened since 1968, and amongst whose childhood population we can identify about 3-4,000 cases of cancer) would be the place to carry out the definitive study, I think.
I have spoken to Dr Helena Kemp, Consultant Chemical Pathologist at North Bristol NHS Trust, and established that she holds easily retrievable blood spots for the Avon population born since about 1986, so the ALSPAC children should be included.With suitable permissions (I am not sure what ALSPAC families consented to) we could record-link ALSPAC to the NRCT here to define all childhood cancers in your cohort.I don't think this is intrinsically hugely interesting because there should only be about 30 cases, but power not withstanding, we should be able to use that event determination for other purposes also e.g. to study birthweight, growth and growth factors and risk, at least in a pilot sense.The meagre numbers also mean that it is unlikely anybody else will be particularly interested in childhood cancer in the ALSPAC cohort, so consumption of tissue for these kids and a small number of controls is unlikely to queer anybody else's future pitch.
We would like to use the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort in Bristol as the source material of choice in the pilot study. 14,541 pregnant women with a delivery date in 1991-92 were enrolled, and for many of those offspring in whom childhood leukaemia or other cancers were diagnosed, this will already be known to you, but we would propose to record link the cohort to the NRCT to determine fully the 30 or so malignancies (10 leukaemia, 20 other) the cohort of babies will have experienced by age 14. There is an abundance of other children to act as controls, and we propose concentrating on the 10 leukaemias, 20 other cases and 30 controls in this pilot study. For most women and children in the cohort there exists a maternal blood sample taken antenatally (gestation varies) and cord blood for the babies (and placenta/cord tissue sample). In addition though not directly relevant to us there is blood from each child who was followed at age 7 and blood on a 10% sample of the children for each of the first 5 years. The Guthrie blood spots for each child will have been obtained and stored separately by the Health Authority (Dr Kemp), rather than the ALSPAC team. Because the Guthrie spots might be a precious resource, undertaking the study in the ALSPAC cohort diminishes the force of the argument against consuming (part of) them in this way, because, unusually, similar tissue samples are known to exist for the same babies in the ALSPAC study if they were needed by others (and ALSPAC precious resources are unlikely to be wasted because few would want to focus particularly on the childhood cancer cases when the numbers in the cohort are so few, outside of a pilot study of the sort we propose). We would hope to obtain access in ALSPAC to the maternal antenatal blood, the baby's cord blood, and separately, (part of) the stored Guthrie samples. We would develop a method for immunological measurements in the blood spots (to be correlated with the maternal antenatal blood and foetal cord blood estimations) for one control infection (rubella) and one or two infections that might have occurred prenatally (or before the pregnancy) and be relevant to childhood leukaemia.
As prototype examples we would probably choose Influenza (many women will have been exposed in the 1989/90 epidemic, though 1991 and 1992 were relatively quiet flu years) and Epstein Barr virus, since significant frequency of recrudescence of this infection during pregnancy has now been linked twice to ALL risk and EBV is a plausible candidate infection for increasing risk.
The aim of the study is simply to demonstrate that for candidate infections of interest, markers of contact can be estimated in blood spots, which faithfully reflect other measures of contact by the mother before or during the pregnancy.If the ALSPAC team is happy to consider this request for a collaborative pilot study using your samples, I would be grateful if you could remind me of any costs that might need to be anticipated for use of data/samples on about one hundred children.