History of the Avon Longitudinal Study of Parents and Children , c.1980-2000

Annotated and edited transcript of a Witness Seminar held on 24 May 2011. Introduction by Professor David Gordon, World Federation for Medical Education.Annotated and edited transcript of a Witness Seminar held on 24 May 2011. Introduction by Professor David Gordon, World Federation for Medical Education.Annotated and edited transcript of a Witness Seminar held on 24 May 2011. Introduction by Professor David Gordon, World Federation for Medical Education.Annotated and edited transcript of a Witness Seminar held on 24 May 2011. Introduction by Professor David Gordon, World Federation for Medical Education.The Avon Longitudinal Survey of Parents and Children (ALSPAC) arose from a proposal in the mid-1980s to design a cohort study in Europe which concentrated on the health of children. The UK-side of this was developed in the former county of Avon and the study has followed more than 14000 children, due between April 1991 and December 1992, from their mothers' pregnancies onwards. A vast amount of data has been collected on health, lifestyle, and environment as well as biological samples of urine, blood and DNA. This has been used to establish genetic and environmental determinants of development and health. With an introduction by Professor David Gordon, this volume addresses the origin and development of ALSPAC, the problems of funding such a major study, the variety of methodologies employed, and the ethical questions associated with the project. Contributors include several of the major scientists involved with ALSPAC including Professor Jean Golding, Scientific and Executive Director of the study until December 2005, as well as clinical scientists, epidemiologists, members of the ethics committee, field workers and study parents.https://qmro.qmul.ac.uk/xmlui/handle/123456789/272

Investigating the role of language in children's early educational outcomes

Most children develop speech and language skills effortlessly, but some are slow to develop these skills and then go on to struggle with literacy and academic skills throughout their schooling. It is the first few years of life that are critical to their subsequent performance.\ud This project looks at what we know about the early communication environment in a child’s first two years of life, and the role this plays in preparing children for school using data from a large longitudinal survey of young people (ALSPAC - the Avon Longitudinal Study of Parents and Children).\ud It examines the characteristics of the environment in which children learn to communicate (such as activities undertaken with children, the mother’s attitude towards her baby, and the wider support available to the family) and the extent to which this affects a child’s readiness for school entry (defined as their early language, reading, writing, and maths skills that they need in school).\ud \ud Key Findings:\ud •\ud There is a strong association between a child’s social background and their readiness for school as measured by their scores on school entry assessments covering language, reading, maths and writing.\ud •\ud Language development at the age of 2 years predicts children’s performance on entry to primary school. Children’s understanding and use of vocabulary and their use of two or three word sentences at 2 years is very strongly associated with their performance on entering primary school.\ud •\ud The children’s communication environment influences language development. The number of books available to the child, the frequency of visits to the library, parents teaching a range of activities, the number of toys available, and attendance at pre-school, are all important predictors of the child’s expressive vocabulary at 2 years. The amount of television on in the home is also a predictor; as this time increased, so the child’s score at school entry decreased.\ud •\ud The communication environment is a more dominant predictor of early language than social background. In the early stages of language development, it is the particular aspects of a child’s communication environment that are associated with language acquisition rather than the broader socio-economic context of the family.\ud •\ud The child’s language and their communication environment influence the child’s performance at school entry in addition to their social background. Children’s success at school is governed not only by their social background; the child’s communication environment\ud before their second birthday and their language at the age of two years also have a strong influence

Girl or boy? Prenatal lead, cadmium and mercury exposure and the secondary sex ratio in the ALSPAC study

AbstractThe aim of this study was to evaluate the effect of prenatal exposure to lead, cadmium and mercury levels on the secondary sex ratio. Whole blood samples were collected from pregnant women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) study at a median gestational age of 11 weeks and were analyzed for lead, cadmium and mercury. Regression analysis was used to identify associations between maternal lead, cadmium and mercury levels and the secondary sex ratio with adjustment for confounders. There was no evidence for associations between maternal lead, cadmium or mercury levels and the secondary sex ratio in this sample. It appears unlikely that alterations in the secondary sex ratio are influenced by exposure to heavy metals, but further work should be done in large cohorts in other countries to confirm these findings

A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure

The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 2D:4D, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 108) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 106). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 2D:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure

Cohort profile: the avon longitudinal study of parents and children: ALSPAC mothers cohort

The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19–22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17–18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on >10 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile

Testosterone Trajectories and Reference Ranges in a Large Longitudinal Sample of Male Adolescents

Pubertal dynamics plays an important role in physical and psychological development of children and adolescents. We aim to provide reference ranges of plasma testosterone in a large longitudinal sample. Furthermore, we describe a measure of testosterone trajectories during adolescence that can be used in future investigations of development.We carried out longitudinal measurements of plasma testosterone in 2,216 samples obtained from 513 males (9 to 17 years of age) from the Avon Longitudinal Study of Parents and Children. We used integration of a model fitted to each participant's testosterone trajectory to calculate a measure of average exposure to testosterone over adolescence. We pooled these data with corresponding values reported in the literature to provide a reference range of testosterone levels in males between the ages of 6 and 19 years.The average values of total testosterone in the ALSPAC sample range from 0.82 nmol/L (Standard Deviation [SD]: 0.09) at 9 years of age to 16.5 (SD: 2.65) nmol/L at 17 years of age; these values are congruent with other reports in the literature. The average exposure to testosterone is associated with different features of testosterone trajectories such as Peak Testosterone Change, Age at Peak Testosterone Change, and Testosterone at 17 years of age as well as the timing of the growth spurt during puberty.The average exposure to testosterone is a useful measure for future investigations using testosterone trajectories to examine pubertal dynamics

Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption we performed a population based genome-wide association study of ‘age at first tooth’ and ‘number of teeth’ using 5998 and 6609 individuals respectively from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2,446,724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of fifteen independent loci, with ten loci reaching genome-wide significance (p<5x10−8) for ‘age at first tooth’ and eleven loci for ‘number of teeth’. Together these associations explain 6.06% of the variation in ‘age of first tooth’ and 4.76% of the variation in ‘number of teeth’. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including a SNP in the protein-coding region of BMP4 (rs17563, P= 9.080x10−17). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development

Changes in marital quality over 6 years and its association with cardiovascular disease risk factors in men: findings from the ALSPAC prospective cohort study

Background: Marital relationship quality has been suggested to have independent effects on cardiovascular health outcomes. This study investigates the association between changes in marital relationship quality and cardiovascular disease (CVD) risk factors in men. Methods: We used data from The Avon Longitudinal Study of Parents and Children, a prospective birth cohort study (Bristol, UK). Our baseline sample was restricted to married study fathers with baseline relationship and covariate data (n=2496). We restricted final analysis (n=620) to those with complete outcome, exposure and covariate data, who were married and confirmed the study child’s father at 6.4 years and 18.8 years after baseline. Relationship quality was measured at baseline and 6.4 years and operationalised as consistently good, improving, deteriorating or consistently poor relationship. We measured CVD risk factors of blood pressure, resting heart rate, body mass index, lipid profile and fasting glucose at 18.8 years after baseline. Results: Improving relationships were associated with lower levels of low-density lipoprotein (−0.25 mmol/L, 95% CI −0.46 to −0.03) and relative reduction of body mass index (−1.07 kg/m2, 95% CI −1.73 to −0.42) compared with consistently good relationships, adjusting for confounders. Weaker associations were found between improving relationships and total cholesterol (−0.24 mmol/L, 95% CI −0.48 to 0.00) and diastolic blood pressure (−2.24 mm Hg, 95% CI −4.59 to +0.11). Deteriorating relationships were associated with worsening diastolic blood pressure (+2.74 mm Hg, 95% CI 0.50 to 4.98). Conclusions: Improvement and deterioration of longitudinal relationship quality appears associated with respectively positive and negative associations with a range of CVD risk factors

Is the growth of the child of a smoking mother influenced by the father's prenatal exposure to tobacco? A hypothesis generating longitudinal study

OBJECTIVES: Transgenerational effects of different environmental exposures are of major interest, with rodent experiments focusing on epigenetic mechanisms. Previously, we have shown that if the study mother is a non-smoker, there is increased mean birth weight, length and body mass index (BMI) in her sons if she herself had been exposed prenatally to her mother's smoking. The aim of this study was to determine whether the prenatal smoke exposure of either parent influenced the growth of the fetus of a smoking woman, and whether any effects were dependent on the fetal sex. DESIGN: Population-based prebirth cohort study. SETTING: Avon Longitudinal Study of Parents and Children. PARTICIPANTS: Participants were residents of a geographic area with expected date of delivery between April 1991 and December 1992. Among pregnancies of mothers who smoked during pregnancy, data were available concerning maternal and paternal prenatal exposures to their own mother smoking for 3502 and 2354, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: Birth weight, length, BMI and head circumference. RESULTS: After controlling for confounders, there were no associations with birth weight, length or BMI. There was a strong adjusted association of birth head circumference among boys whose fathers had been exposed prenatally (mean difference −0.35 cm; 95% CI −0.57 to −0.14; p=0.001). There was no such association with girls (interaction p=0.006). Similar associations were found when primiparae and multiparae were analysed separately. In order to determine whether this was reflected in child development, we examined the relationships with IQ; we found that the boys born to exposed fathers had lower IQ scores on average, and that this was particularly due to the verbal component (mean difference in verbal IQ −3.65 points; 95% CI −6.60 to −0.70). CONCLUSIONS: Head size differences concerning paternal fetal exposure to smoking were unexpected and, as such, should be regarded as hypothesis generating