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

Peer victimization in childhood and internalizing problems in adolescence : a prospective longitudinal study

Traumatic childhood experiences have been found to predict later internalizing problems. This prospective longitudinal study investigated whether repeated and intentional harm doing by peers (peer victimization) in childhood predicts internalizing symptoms in early adolescence. 3,692 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), as well as their mothers and teachers, reported on bullying in childhood (7–10 years) and internalizing problems in early adolescence (11–14 years). Controlling for prior psychopathology, family adversity, gender and IQ, being a victim of bullying was associated with higher overall scores, as well as increased odds of scoring in the severe range (>90th percentile) for emotional and depression symptoms. Victims were also more likely to show persistent depression symptoms over a 2-year period. These associations were found independent of whether mothers, teachers or the children reported on bullying. It is concluded that peer victimization in childhood is a precursor of both short-lived and persistent internalizing symptoms, underlining the importance of environmental factors such as peer relationships in the etiology of internalizing problems

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

Maternal thyroid function and child educational attainment: prospective cohort study

Objective: To determine if first trimester maternal thyroid dysfunction is a critical determinant of child scholastic performance and overall educational attainment. Design: Prospective cohort study. Setting: Avon Longitudinal Study of Parents and Children cohort in the UK. Participants: 4615 mother-child pairs with an available first trimester sample (median 10 weeks gestation, interquartile range 8-12). Exposures: Free thyroxine, thyroid stimulating hormone, and thyroid peroxidase antibodies assessed as continuous measures and the seven clinical categories of maternal thyroid function. Main outcome measures: Five age-specific national curriculum assessments in 3580 children at entry stage assessment at 54 months, increasing up to 4461 children at their final school assessment at age 15. Results: No strong evidence of clinically meaningful associations of first trimester free thyroxine and thyroid stimulating hormone levels with entry stage assessment score or Standard Assessment Test scores at any of the key stages was found. Associations of maternal free thyroxine or thyroid stimulating hormone with the total number of General Certificates of Secondary Education (GCSEs) passed (range 0-16) were all close to the null: free thyroxine, rate ratio per pmol/L 1.00 (95% confidence interval 1.00 to 1.01); and thyroid stimulating hormone, rate ratio 0.98 (0.94 to 1.02). No important relationship was observed when more detailed capped scores of GCSEs allowing for both the number and grade of pass or when language, mathematics, and science performance were examined individually or when all educational assessments undertaken by an individual from school entry to leaving were considered. 200 (4.3%) mothers were newly identified as having hypothyroidism or subclinical hypothyroidism and 97 (2.1%) subclinical hyperthyroidism or hyperthyroidism. Children of mothers with thyroid dysfunction attained an equivalent number of GCSEs and equivalent grades as children of mothers with euthyroidism. Conclusions: Maternal thyroid dysfunction in early pregnancy does not have a clinically important association with impaired child performance at school or educational achievement

The impact of pupil behaviour and wellbeing on educational outcomes

A review of previous literature suggests that wellbeing and learning are associated with one another; however, there is less information on how multiple dimensions of wellbeing together predict later changes in educational outcomes for children and teenagers. The simultaneous examination of different dimensions of wellbeing across primary and secondary school will help clarify their relative importance during the key stages of schooling. This project examines how various dimensions of children’s wellbeing are associated with their educational outcomes, including a review of relevant literature and an analysis using data from the Avon Longitudinal Study of Parents and Children (ALSPAC)

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

Childhood IQ and risk of bipolar disorder in adulthood: prospective birth cohort study

Background: Intellectual ability may be an endophenotypic marker for bipolar disorder. Aims: Within a large birth cohort, we aimed to assess whether childhood IQ (including both verbal IQ (VIQ) and performance IQ (PIQ) subscales) was predictive of lifetime features of bipolar disorder assessed in young adulthood. Method: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a large UK birth cohort, to test for an association between measures of childhood IQ at age 8 years and lifetime manic features assessed at age 22–23 years using the Hypomania Checklist-32 (HCL-32; n=1881 individuals). An ordinary least squares linear regression model was used, with normal childhood IQ (range 90–109) as the referent group. We adjusted analyses for confounding factors, including gender, ethnicity, handedness, maternal social class at recruitment, maternal age, maternal history of depression and maternal education. Results: There was a positive association between IQ at age 8 years and lifetime manic features at age 22–23 years (Pearson's correlation coefficient 0.159 (95% CI 0.120–0.198), P>0.001). Individuals in the lowest decile of manic features had a mean full-scale IQ (FSIQ) which was almost 10 points lower than those in the highest decile of manic features: mean FSIQ 100.71 (95% CI 98.74–102.6) v. 110.14 (95% CI 107.79–112.50), P>0.001. The association between IQ and manic features was present for FSIQ, VIQ and for PIQ but was strongest for VIQ. Conclusions: A higher childhood IQ score, and high VIQ in particular, may represent a marker of risk for the later development of bipolar disorder. This finding has implications for understanding of how liability to bipolar disorder may have been selected through generations. It will also inform future genetic studies at the interface of intelligence, creativity and bipolar disorder and is relevant to the developmental trajectory of bipolar disorder. It may also improve approaches to earlier detection and treatment of bipolar disorder in adolescents and young adults

Cannabis use and hypomania in young people: a prospective analysis

Background: Cannabis use in young people is common and associated with psychiatric disorders. However, the prospective link between cannabis use and bipolar disorder symptoms has rarely been investigated. The study hypothesis was that adolescent cannabis use is associated with hypomania in early adulthood via several potential etiological pathways. Methods: Data were used from the Avon Longitudinal Study of Parents and Children, a UK birth cohort study. The prospective link between cannabis use at age 17 and hypomania at age 22–23 years was tested using regression analysis, adjusted for gender, early environmental risk factors, alcohol and drug use, and depression and psychotic symptoms at age 18 years. Path analysis examined direct and indirect effects of the link and whether gender, childhood family adversity, or childhood abuse are associated with hypomania via an increased risk of cannabis use. Results: Data were available on 3370 participants. Cannabis use at least 2–3 times weekly was associated with later hypomania (OR = 2.21, 95% CI = 1.49–3.28) after adjustment. There was a dose–response relationship (any use vs weekly). Cannabis use mediated the association of both childhood sexual abuse and hypomania, and male gender and hypomania. The cannabis use-hypomania link was not mediated by depression or psychotic symptoms. Conclusions: Adolescent cannabis use may be an independent risk factor for future hypomania, and the nature of the association suggests a potential causal link. Cannabis use mediates the link between childhood abuse and future hypomania. As such it might be a useful target for indicated prevention of hypomania

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

Child undernutrition in affluent societies: what are we talking about?

In this paper we set out to explore the prevalence of child undernutrition found in community studies in affluent societies, but a preliminary literature review revealed that, in the absence of a gold standard method of diagnosis, the prevalence largely depends on the measure, threshold and the growth reference used, as well as age. We thus go on to explore describe the common clinical ‘syndromes’ of child undernutrition: wasting, stunting and failure to thrive (weight faltering) and how we have used data from two population-based cohort studies, this paper to explore how much these different ‘syndromes’ overlap and the extent to which they reflect true undernutrition. This analysis revealed that when more than one definition is applied to the same children, a majority are below the lower threshold for only one measure. However, those with both weight faltering and low BMI in infancy, go on in later childhood to show growth and body composition patterns suggestive of previous undernutrition. In older children there is even less overlap and most children with either wasting or low fat seem to be simply growing at one extreme of the normal range. We conclude that in affluent societies the diagnosis of undernutrition is only robust when it relies on a combination of both, that is decline in weight or BMI centile and wasting