Mother-baby bedsharing is associated with an increased risk of unexpected infant death, particularly for mothers who smoke or drink alcohol, but little is known of the potential beneficial effects of bedsharing (e.g. establishment or maintenance of breastfeeding), and recent US data has confirmed the beneficial effects of breastfeeding in reducing infant mortality. The Avon Longitudinal Study of Parents And Children (ALSPAC) has collected information on health, growth, development, medical, environmental and social factors from pregnancy to the present, in a cohort of 14,000 children born in 1991-2 and their families. Detailed information has been collected on sleep patterns, duration and place for the infants and their parents. Preliminary analysis of the data on sleep in infancy and childhood has shown that in the first 6 months 33-70% infants share a bedroom with their mother, and routine mother-baby bedsharing for night time sleep is common throughout infancy and early childhood, varying between 9% and 18%. Many factors (e.g. birthweight, breastfeeding), are associated with sleep patterns and duration, and, whilst short sleep duration in early infancy is associated with obesity in later childhood, breastfeeding (which is associated with bedsharing) may reduce the risk of obesity.

We will use complex statistical modelling techniques to analyse the data from ALSPAC children and families, to identify factors contributing to parents choices about bedsharing in infancy, together with any immediate or long term adverse consequences or benefits of bedsharing, room sharing or separate sleeping, for both children and mothers. The large size and completeness of the data from the ALSPAC cohort will allow us to take account of multiple psychological, medical, social and environmental factors that may have influenced decisions about infant care practices, and may themselves have been associated with potential benefits or adverse consequences (e.g. breastfeeding, maternal smoking, socio-economic deprivation, pacifier use).

Aims

• To use SNPs in linkage disequilibrium with IL-1RN*2 to genotype the 'Children in Focus' (CIF) cohort of the ALSPAC study.
• To test for association of the inferred IL-1RN*2 genotype with birth weight.

(No outline received).

Aim :To test for associations between habitual physical activity and executive function at age 11- the ALSPAC cohort provides a unique opportunity to test this hypothesis due to its combination of large sample size, good measures of habitual physical activity (accelerometry) and executive function, and key confounders.

Denervation of pelvic organs taking place at vaginal delivery results in subsequent reinnervation and wide-ranging gynaecological symptoms e.g. vulvodynia, dyspareunia, chronic pelvic pain, irritative bladder symptoms, rectal hypersensitivity, menorrhagia and dysmenorrhoea (1-12). All benign myometrial pathology e.g. endometriosis, adenomyosis, leiomyomata, etc. has specific neural abnormalities in the spectrum of denervation-reinnervation (4-7). Reinnervation, in several different patterns, has been described in every female pelvic organ often in association with a prior history of difficult vaginal delivery including premature, or prolonged, maternal voluntary efforts (8-12).

In nulliparous women, straining to achieve defaecation has been demonstrated to cause specific neurological lesions in different pelvic viscera (8, 9, 12), and this mechanism, operating at the endometrial-myometrial nerve plexus , has been proposed as a source of impaired placentation in nulliparous pre-eclampsia. intrauterine growth retardation, abruption, placenta accrete/percreta (13, 14).

The question arises: "Do nulliparous women with severe obstetric problems e.g. early-onset preeclampsia. IUGR, preterm delivery, abruption, etc. suffer subsequent gynaecological symptoms e.g. menorrhagia, dysmenorrhoea, chronic pelvic pain, that require specific medical and surgical interventions e.g. hysteroscopy, laparoscopy, hysterectomy, etc. within the subsequent 10 years".

Applications are invited from suitably qualified psychology graduates to join a team investigating the development of depressive symptoms. The PhD will be undertaken in the Department of Community Based Medicine and will focus on examining the nature of the relationship between depressive symptoms and smoking.

Previous studies have found evidence for an association between depression and smoking in adolescence, but the nature and direction of the relationship is unclear. Some studies have found evidence that depressive symptoms precede the onset of smoking; others have found that smoking precedes depression, and some studies report a bi-directional relationship. The PhD student will have the opportunity to develop skills in statistical modelling of longitudinal data to model the developmental heterogeneity of depression and smoking from late childhood into adolescence and examine potential covariates including gender, behaviour and conduct problems, social adversities, stressful life events, and parent-child relationships.

The project will take advantage of the unique and extensive longitudinal data collected by ALSPAC, an ongoing longitudinal population-based study investigating a wide range of environmental and other influences on the health and development of children. Detailed information on the ALSPAC study is available on the web site: http://www.alspac.bris.ac.uk.

Data required:

Depression- Mood and feelings questionnaire (child and parent report) from 9-15 years.

Smoking- (child and parent report) from 8-15 years.

(we are aware that data from the 15/16 year questionnaire/clinic is not yet available)

Other possible data requirements: Behaviour and emotional problems- DAWBA, SDQ, antisocial behaviour questionnaire.

Social adversities and stressful life events.

Questions on parent-child relationships.

(No outline received).

We propose a pilot analysis using the placental data already collected from the Chidlren in Focus subset (CIF, N=1050), and BMI, waist & fat & lean mass (DXA) at age 9. These pilot analyses will provide strong support for our (generally well received) October submission, and we are optimistic about receiving funding based on our July resubmission. Jon Heron and Jeremy Miles will work together on data analysis, which will be incorporated into the July grant that will include Dr Lawlor, Dr Davey-Smoth and potentially Dr David Barker in the research team.

Previously submitted and approved protocol (our ref B355)

We propose to develop an R01 application utilizing placental data to be submitted as a supplement to the NIH funded R01 "Maternal overnutrition and offspring fat mass, metabolic and vascular function" (Principal Investigator: Dr. Debbie Lawlor, University of Bristol). We outline below the specific aims for such a supplement and provide a model illustrating the integration of these aims with the aims of the currently funded study. While Dr. Lawlor's grant aims refer to "offspring" generally, we have explicitly separated out the neonatal (birth outcomes) within our aims given the focus on the placenta.

SPECIFIC AIMS

Specific Aim 1: To investigate the influence of maternal BMI, weight gain, and diet during pregnancy on placental anthropometric measures. Specifically, we will assess and study the following placental parameters: placental weight, thickness, diameters; umbilical cord length; shape; symmetry measures; chorionic vascular branching pattern). The following null hypotheses will be tested:

1A. Maternal BMI does not explain variation in placental size and shape.

1B. Maternal weight gain does not explain variation in placental size and shape.

1C. Maternal diet does not explain variation in placental size and shape.

Specific Aim 2: To determine whether and how placental size and shape influences birth size. The following null hypotheses will be tested:

2A. Placental size and shape are not associated with birth size (e.g. weight, birth weight ratio, length, ponderal index).

2B. Associations between maternal factors and birth size are mediated by variation in placental size and shape.

Specific Aim 3: To determine whether and how placental size and shape influence offspring growth. Offspring growth was measured at multiple time points beginning at age 1 year up to 15 years of age and includes measures of adiposity (DXA assessed fat mass and fat distribution), vascular function (blood pressure, pulse pressure and endothelial function), and metabolic function (fasting glucose, insulin and lipids). The following null hypotheses will be tested:

3A. Placental size and shape are not associated with offspring childhood adiposity.

3B. Placental size and shape are not associated with offspring childhood vascular function.

3C. Placental size and shape are not associated with offspring childhood metabolic function.

3D. Associations between placental size and shape with offspring outcomes are mediated by effects of the placenta on birth size.

Specific Aim 4: To investigate the role of genetic variation on placental size and shape. DNA was extracted from mothers and offspring in the parent study. The following null hypotheses will be tested:

4A. Genetic variation does not explain variation in placental size and shape.

4B. Interactions between genes and the selected maternal factors (BMI, weight gain, diet) do not explain additional variations in placental size or shape.

Specific Aim 5: To develop and validate a placental index to identify offspring at risk for adverse outcomes with regard to adiposity, vascular function, and metabolic function.

(No outline received).