(No outline received).

Aims and Objectives

To determine if children of mothers with eating disorders have different patterns of: physical development, eating habits and levels of physical activity in childhood, compared to children born to women with other psychiatric disorders and control women, using a large longitudinal prospective design (ALSPAC).

Background

Lifestyle choices such as diet and exercise begin to develop at a very early age in life. Parental influences are an important factor in childhood dietary patterns, physical activity, weight and growth [1, 2]. This is a challenge for mothers suffering with eating disorders, who are often unable to appropriately judge and manage their own dietary and exercise needs, therefore leaving their children at risk of developing similar eating pathology.

Diet and Growth

Research suggests that there is a link between early childhood feeding problems and the presence of a maternal eating disorder [3-7]. Infant under nutrition [8] and growth retardation has also been reported in the offspring of women with anorexia nervosa [9]. Furthermore, the rates of conflict at meal times [10, 11] and over concern for their child's weight or shape [5, 12] have found to be higher in mothers with eating disorders.

ALSPAC Studies

A recent study of the ALSPAC data found that infants of women with anorexia nervosa had a heightened risk for feeding difficulties up to six months of age, compared with healthy controls and women with other psychiatric problems [13]. On the other hand, women suffering from bulimia were shown to be associated with accelerated growth rates and being overweight at nine months [13].

Results from studies of obesity within the ALSPAC cohort suggest that there are key factors associated with a risk of childhood obesity, including: parental obesity and early activity patterns [14]. Furthermore, delayed introduction of certain foods has been associated with increased feeding problems[15]. Additionally, ALSPAC results indicate that maternal characteristics such as social, demographic and lifestyle factor have a strong influence on the early eating patterns of their children [16]. Specifically, Ong et al [17] described a marked and prolonged effect of maternal smoking, parity and breast vs. bottle feeding on childhood growth rates.

Physical Activity

Excessive exercise is common in women suffering with eating disorders, however there are very few studies in this area, or indeed the impact that high rates of physical activity in mothers may have on their children. In one of the few studies, Davis (2005) [18] found that parental levels of physical activity were related to their daughters activity levels. In addition, hyperactivity is common in women suffering with anorexia and has been observed in varying rates across studies, ranging from 31-81% of AN cases [19, 20].

Recent evidence, from both animal and human studies [19], suggests that hyperactivity may be a trait in women suffering with eating disorders, which may therefore be linked to increased activity levels in their offspring. This has never been research within an eating disorder population. Furthermore, excessive exercising may be an early warning sign for the development of an eating disorder in children, and as such is an important area of research for early detection and prevention of eating disorders.

Hypothesis under investigation:

1) Children born to mothers with anorexia nervosa will eat less and be leaner in childhood compared to children born to control mothers.

2) Children of mothers with bulimia nervosa will be heavier than average in childhood, they will have a tendency to eat more and to eat "snacky"-type foods in childhood.

3) Children of mothers with anorexia will have higher levels of physical activity than healthy controls, and children of women with other psychiatric problems and women with bulimia.

Methodology

Design: A longitudinal prospective study with contrast groups

Participants: This study is based on data collected from the Avon Longitudinal Study of Parents and Children (ALSPAC) 21. ALSPAC is a longitudinal birth cohort study, which enrolled all pregnant women living with-in Avon, England, who were due to deliver their baby between the 1st April 1991 and 31st December 1992. It is estimated that approximately 85-90% of those eligible for inclusion chose to take part and the sample has been shown to be representative of the UK population. The core ALSPAC sample consists of 14,541 pregnancies, 69 of which had unknown birth outcomes. Data was obtained on the remaining 14,272 via postal questionnaires.

For the purpose of this study women will be excluded if they did not respond to the 12 week questionnaire (2,019) or if they had multiple births (208). The remaining 12,254 women are included in the analysis. Of this sample, 171 (1.4%) responded that they had anorexia, 199 (1.6%) reported having bulimia, 82 (0.7%) reported having had anorexia and bulimia and 1,166 (9.5%) reported having had another psychiatric problem. The remaining 10,636 (86.8%) reported no history or current psychiatric problem.

Outcomes: At 12 weeks gestation participants were asked if they had any recent or past psychiatric disorder including depression, schizophrenia, anorexia nervosa and bulimia nervosa. Eating disorder behaviours and attitudes pre and during pregnancy were collected by self report. Socio-demographic data, including smoking, age, occupation, marital status was also obtained via self report. At 18 weeks gestation women were asked if their pregnancy was intentional and if so how long they had been trying to conceive as well as their reactions to pregnancy.

Children have been followed up yearly and data are available on their physical development (body composition), activity levels, and diet up to the age of 11 years.

Data Analysis: The hypotheses will be tested using linear and logistic regression analyses in which maternal eating disorders are used to predict outcomes in childhood. All of the central analyses will include covariates. Data available at several time-points will be initially analysed cross-sectionally; longitudinal and growth modelling will be used as a subsequent step. With the available sample sizes, small to moderate group differences in continuous outcomes can be detected with a power of 90% at the 5% test level. Group differences in proportions amounting to odd ratios above 6 could also be detected with a 90% chance. Data will be analysed taking into account missing data.

REFERENCES

1. Klesges RC, Coates TJ, Brown G, Sturgeon-Tillisch J, Moldenhauer-Klesges LM, Holzer B, et al. Parental influences on children's eating behavior and relative weight. Journal of Applied Behavior Analysis 1983;16(4):371-8.

2. Lopez-Dicastillo O, Grande G, Callery P. Parents' contrasting views on diet versus activity of children: Implications for health promotion and obesity prevention. Patient Education and Counseling 2009.

3. Steiner H, Smith C, Rosenkranz RT, Litt I. The early care and feeding of anorexics. Child Psychiatry and Human Development 1991;21(3):163-7.

4. Agras S, Hammer L, McNicholas F. A prospective study of the influence of eating-disordered mothers on their children. International Journal of Eating Disorders 1999;25(3):253-62.

5. Stein A, Fairburn CG. Children of mothers with bulimia nervosa. British Medical Journal 1989;299(6702):777-8.

6. Stein A, Woolley H, Murray L, Cooper P, Cooper S, Noble F, et al. Influence of psychiatric disorder on the controlling behaviour of mothers with 1-year-old infants. A study of women with maternal eating disorder, postnatal depression and a healthy comparison group. British Journal of Psychiatry 2001;179:157-62.

7. Jacobi C, Agras WS, Hammer L. Predicting children's reported eating disturbances at 8 years of age. Journal of the American Academy of Child and Adolescent Psychiatry 2001;40(3):364-72.

8. Russell GF, Treasure J, Eisler I. Mothers with anorexia nervosa who underfeed their children: their recognition and management. Psychological Medicine 1998;28(1):93-108.

9. van Wezel-Meijler G, Wit JM. The offspring of mothers with anorexia nervosa: a high-risk group for undernutrition and stunting? European Journal of Pediatrics 1989;149(2):130-5.

10. Stein A, Woolley H, Cooper SD, Fairburn CG. An observational study of mothers with eating disorders and their infants. Journal of Child Psychology and Psychiatry and Allied Disciplines 1994;35(4):733-48.

11. Stein A, Woolley H, McPherson K. Conflict between mothers with eating disorders and their infants during mealtimes. British Journal of Psychiatry 1999;175:455-61.

12. Fahy T, Treasure J. Children of mothers with bulimia nervosa. BMJ 1989;299(6706):1031.

13. Micali N, Simonoff E, Treasure J. Infant feeding and weight in the first year of life in babies of women with eating disorders. Journal of Pediatrics 2009;154(1):55-60 e1.

14. Reilly JJ, Armstrong J, Dorosty AR, Emmett PM, Ness A, Rogers I, et al. Early life risk factors for obesity in childhood: cohort study. BMJ 2005;330(7504):1357.

15. Coulthard H, Harris G, Emmett P. Delayed introduction of lumpy foods to children during the complementary feeding period affects child's food acceptance and feeding at 7 years of age. Maternal and Child Nutrition 2009;5(1):75-85.

16. North Stone K, Fleming P, Golding J. Socio-demographic associations with digit and pacifier sucking at 15 months of age and possible associations with infant infection. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. Early Human Development 2000;60(2):137-48.

17. Ong KK, Elmlinger M, Jones R, Emmett P, Holly J, Ranke MB, et al. Growth hormone binding protein levels in children are associated with birth weight, postnatal weight gain, and insulin secretion. Metabolism: Clinical and Experimental 2007;56(10):1412-7.

18. Davis C, Blackmore E, Katzman DK, Fox J. Female adolescents with anorexia nervosa and their parents: a case-control study of exercise attitudes and behaviours.Psychological Medicine 2005;35(3):377-86.

19. Hebebrand J, Exner C, Hebebrand K, Holtkamp C, Casper RC, Remschmidt H, et al.Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia. Physiology and Behavior 2003;79(1):25-37.

20. Hillebrand JJ, Kas MJ, van Elburg AA, Hoek HW, Adan RA. Leptin's effect on hyperactivity: potential downstream effector mechanisms. Physiology and Behavior 2008;94(5):689-95.

21. Golding J, Pembrey M, Jones R. ALSPAC--the Avon Longitudinal Study of Parents and Children. I. Study methodology. Paediatric and Perinatal Epidemiology 2001;15(1):74-87.

This is a gene-environment and gene-gene interaction study in a longitudinal child cohort to investigate the role in childhood behavioural problems of abundant functional polymorphisms that have previously been linked to aggression and ADHD.

(No outline received).

(No outline received).

(No outline received).

The broad aim of this project is to study the determinants of fracture risk in children using the ALSPAC cohort. ALSPAC is a large and unique dataset that recruited all pregnant women resident in Avon between April 1991 and December 1992. This has resulted in 14,000 children of whom 10,000 are under active follow-up. ALSPAC has comprehensive information from early pregnancy to now. From the time of the child's birth, many different aspects have been measured and collected on an annual basis. At aged 9, all children are undergoing a dual energy X-ray absorptiometry (DXA) to assess their bone mass.

This project has 4 specific aims: (1) to examine the association between bone mass measured at 9 years of age and fracture risk over the the following 2 years; (2) to examine the association between potential risk factors that are thought to affect fractures independently of bone mass (e.g. participation in sporting activities); (3) to examine the association between early life factors that are thought to effect bone accretion and subsequent peak bone mass, and lifetime fracture risk at aged 11 years (e.g. breastfeeding); and (4) to examine the association between possible endocrine determinants of early life growth (such as cord blood leptin) and lifetime fracture risk at aged 11.

(No outline received).

The specific aims of this study are twofold: 1) to define and concurrently describe sub-groups of ADHD according to DSM-IV criteria based on parent and teacher report measures at 8 years of age. 2) to identify the factors from pregnancy through infancy, preschool and early school years that predict ADHD and test whether these are similar or different for three subtypes of ADHD and for boths sexes.

The proposed study will thus identify the affected children and provide an empirically tested model of the relevant environmental factors that increase the risk for or protect against ADHD. This information, highly relevant for developing effective preventative models. will furthermore provide the basis for future groundbreaking research at the molecular level, testing for gene-environment interactions (to be applied for separately). This will be possible due to recent developments in pinpointing promising candidate genes (Zametkin et al., 2001) and the fact that ALSPAC has DNA on 10,000 of the children and most of their mothers. Samples of paternal DNA are planned for the future.