B355 - Second Methods Grant Role of placental size and shape in predicting childhood growth - 09/05/2006

B number: 
B355
Principal applicant name: 
Dr Dawn Misra (Wayne State University, USA)
Co-applicants: 
Prof George Davey Smith (University of Bristol, UK), Dr Carolyn Salafia (North Carolina State University, USA), Prof David Barker (University of Southampton, UK), Prof Debbie A Lawlor (University of Bristol, UK)
Title of project: 
Second 'Methods' Grant (Role of placental size and shape in predicting childhood growth).
Proposal summary: 

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.

Date proposal received: 
Tuesday, 9 May, 2006
Date proposal approved: 
Tuesday, 9 May, 2006
Keywords: 
Growth, Placenta
Primary keyword: