Background

There is some evidence to suggest that adverse perinatal maternal life events are related to an increased risk of psychosis in offspring. There is, however, limited evidence linking maternal perinatal depression with future risk of psychosis in offspring. The only three studies identified investigate the same birth cohort and yield unclear results (Maki, Riekki et al., Jones et al., Maki et al.). In addition, maternal depression was not assessed using any standardised measure.

Maternal perinatal depression may influence the risk of psychosis in offspring via an effect on foetal development in utero as well as by exerting an environmental influence during infancy. Schizophrenia is considered to be a neurodevelopmental disorder and if there were an association between maternal perinatal depression and schizophrenia it would support a neurodevelopmental perspective.

Investigation of this possible association is important due to the relatively frequent occurrence of perinatal depression and the potential for intervention. Adolescents who report psychotic experiences may be at increased risk of developing a psychotic disorder therefore study of this group may yield important information regarding early life risk factors for psychotic disorders.

Maternal cognitive style is thought to be associated with depression in adolescent offspring. Such cogntive styles may also be related to offspring psychotic experiences and would again offer a potential target for intervention in those at hgh risk of psychotic disorder.

Objective

The primary objective of this study is to establish whether there is an association between maternal perinatal depression and the development of psychotic experience in their offspring during late adolescence.

Hypothesis

Our hypothesis is that maternal perinatal depression is associated with an increased of psychotic experiences in offspring in late adolescence.

Maternal perinatal depression may influence risk of psychosis in offspring through a number of interlinked mechanisms acting both during the intra-uterine period and during early childhood. In order to explore the mechanisms the association between paternal perinatal depression and adolescent psychotic experience will also be explored.

Aims

To examine gender differences in carer reported child health from ages 5 to 16 (age range varies depending on item).

Aim:

The Aid SAM project will examine associations between specific antibiotic treatments given to mothers during pregnancy (and lactation) and overweight/obesity in childhood as well as specific antibiotics given to children during early infancy (0-6 months) and overweight/obesity in childhood and later life. The three main cohorts we will use to investigate this is the Danish National Birth Cohort (DNBC), the Nothern Finland Birth Cohort (NFBC) and the Alspac cohort. Furthermore, an adult Danish population will be used to identify possible associations between antibiotics and CVD in adults through a data-driven approach. This approach may further help to identify the most interesting subtypes and combinations of antibiotics. The plan is to start of with analyses in the DNBC and then replicate analyses/interesting findings in the NFBC and ALSPAC. This approach gives more power to findings, which otherwise could be surpressed by/if multiple testing correction are applied. Findings will be dissiminated either in one or several publications, with possibility of back to back publication. The main applicant will perform analyses, but possible data-driven analyses will be performed by AB Jensen, bio-informatitician from Soren Brunaks Group. In addition other collaborators from Bristol in addition to George D Smith could come into play

Aim:

1) identify novel parent of origin variants in relation to DNA methylation in ALSPAC;

2) investigate the effects of known/established parent of origin variants (related to common disease) in relation to DNA methylation in ALSPAC;

3) Investigate the relationship between genotype, methylation and phenotype to better understand parent-of-origin effects on phenotype.

I am currently writing a book chapter and paper about different causal methods and using breast feeding with different outcomes as an illustrative example (largely using published work, including some publications that have used ALSPAC data). I would like to include as an e.g. a negative outcome control study i.e. a study in which I would look at the association of breast feeding with an outcome that biologically it would not be expected to affect (but might be associated with via confounding).

ALSPAC has questions on whether the family home had ever been invaded by rats, dogs, cats, mice, cockroaches, pigeons, woodlice etc. (see picture attached with this email) which would be ideal as negative controls.

In both the book chapter and paper these analyses would be a small part of the whole document

I would look at the simple association of breast feeding with one or more of the 'animal/insect home invasion' responses - depending on how common they are in the cohort.

Aim: To assess bone mineral density (BMD) and bone mineral content (BMC) of offspring born from a preeclamptic pregnancy.

Hypothesis: We hypothesise, based on the limited available evidence on this topic, that offspring who were 'exposed' to preeclampsia will have a higher bone mineral density than those who were not exposed.

Exposure variables: Preeclampsia and gestational hypertension

Outcome variables: Bone mineral density and content (as measured by DXA and pQCT)

Confounding/mediator variables: SES, maternal smoking, maternal BMI, maternal ethnicity, maternal age, maternal alcohol consumption, maternal physical activity, maternal vitamin D & Calcium intake, offspring weight/height, offspring total body fat mass/lean mass, CTX, Insulin, parity, birthweight, gestational age.

Summary:

Preeclampsia is the leading cause of perinatal and maternal mortality and morbiditiy and effects around 3% of all pregnancies worldwide. The only current cure is the delivery of the placenta and thus often results in an iatrogenic preterm delivery. The fetus has the greatest demand for calcium during the third trimester, so consequently a preterm delivery can result in insufficient bone mineralization (Weiler et al. 2002). A recent study has suggested that in pregnancies compliated by preeclampsia additional mechanisms may exist which result in protective effects on long term bone health in the offspring, both in preterm and term births (Miettola et al. 2013). However, this study was limited by a small sample size and no maternal lifestyle information. This study warrants replicating with larger numbers and more comprehensive confounder adjustment.

We hope to use the ALSPAC data to explore the association between preeclampsia (and gestational hypertension) in term and preterm births with bone parameters from recently collected DXA and pQCT scan data.

References

Miettola S, Hovi P, Andersson S et al. Maternal preeclampsia and bone mineral density of the adult offspring. Obstetrics. Am J Obstet Gynecol 2013;20:443.e1-10

Weiler HA, Yuen CK, Seshia MM. Growth and bone mineralization of young adults weighing less than 1500g at birth. Early Hum Dev. 2001; 67: 101-12

Aims:

1) To identify differentially methylated regions (DMRs) that are associated with age at menarche. This will be tested in both ALSPAC mothers using recalled age at menarche, and in young participants using DNA methylation measured at 15-17 years and age at menarche reported at the 21/22 year visit.

2) To explore whether identified DMRs are already apparent at birth, or if they are established over the course of childhood and adolescence.

3) To understand how common genetic variation underlies differences in methylation relating to menarche timing.

Aims

This project aims to generate valuable information to prioritize obesity targets and will include:

a)Replication of genetic association with obesity related traits

b)Analysis of associations with lifestyle/biomarker/diet to generate mechanistic hypotheses.

AIMS AND OBJECTIVES

The overall aims of the study are: (1) to identify the predictors of Pb, Cd and Hg levels in pregnancy with a view to providing advice and interventions that will minimise exposure at this vulnerable time; (2) to identify the predictive value of maternal levels in a variety of childhood outcomes up to the age of age 18 years. This will include a study of the effects of maternal genetics and epigenetics in modifying these relationships. All analyses will involves initial work in identifying and taking into account relevant confounders to determine the features of the mothers' backgrounds that are related to exposure to Pb, Cd or Hg exposure (e.g. age, educational levels, occupational exposure, smoking history, exposure to passive smoking, dietary components, etc.). Results will be presented as odds ratios or effect sizes with confidence intervals, and in unadjusted and adjusted models if appropriate. The complex causal analyses will be undertaken in consultation with Professor George Davey Smith (Professor of Clinical Epidemiology, University of Bristol).