Maternal Metabolic and Molecular Changes Induced by Preconception Weight Loss and Their Effects on Birth Outcomes
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Obesity; Familial
- Sponsor
- University of Michigan
- Enrollment
- 147
- Locations
- 1
- Primary Endpoint
- Preconception weight loss
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
Our hypothesis is that aggressive preconception weight loss in obese women will improve the metabolic health of the mother and the intrauterine environment. An optimized developmental environment will normalize fetal growth and improve clinical fetal and infant outcomes, and theoretically reduce future susceptibility to obesity and cardiometabolic disease.
Detailed Description
Further, our hypothesis is that the metabolic profiles in the mother and infant cord blood and epigenetic profiles in cord blood leukocytes will be improved in the very-low energy diet (VLED) group compared to standard practice nutrition counseling and support (SOC) group and approach the profiles found in normal weight (LEAN) individuals. We will relate these changes to the changes in the offspring clinical profiles. With these data in hand, we will develop a model to understand the potential molecular markers associated with offspring size and adiposity at birth, risk factors for later onset non-communicable diseases. We will use these insights to define, adopt and implement future interventions that mitigate the downstream risk of adiposity and cardiometabolic diseases.
Investigators
Amy E Rothberg
Project Investigator
University of Michigan
Eligibility Criteria
Inclusion Criteria
- •BMI \> 30 ≤ 45 for obese participants OR
- •BMI ≤ 25 for healthy body weight participants
- •No known infertility
- •No known risk factors for tubal disease
Exclusion Criteria
- •Significant medical co-morbidities (e.g. heart, kidney, liver, autoimmune disease)
- •Significant anemia
- •Cancer other than minor skin cancers
- •Conditions that would complicate pregnancy
- •Recent use of anti-obesity drugs or appetite suppressants
- •Previous bariatric surgery
- •Endometriosis AFS (American Fertility Society classification class III or IV)
- •Progesterone \> 10 IU/ml
- •Current pregnancy
- •Use of sperm donor
Outcomes
Primary Outcomes
Preconception weight loss
Time Frame: Baseline to post dietary intervention (16 weeks)
Primary pre-specified outcome is BMI change (kg/m2) after dietary intervention. Trained staff will measure height and weight to the nearest .1cm and .1kg using a wall-mounted, precision stadiometer and calibrated digital scale. BMI will be calculated (kg/m2).
Metabolome and inflammatory markers
Time Frame: Delivery
Multivariate computational models will assess the association of maternal and neonate metabolite and inflammatory markers to fetal growth and newborn weight (g) and adiposity (g).
Offspring body fat mass
Time Frame: Delivery
Percentage body fat (adiposity) in the offspring of women randomized to Very Low Energy Diet (VLED) compared to those randomized to Standard of Care (SOC). Body composition will be assessed by PeaPod (fat mass in grams).
Cord blood related to neonate outcomes
Time Frame: Before and after dietary intervention (16 weeks), delivery
The maternal metabolome (\~metabolites) will be related to neonate adiposity, gestational weight gain, pregnancy complications, and intrauterine fetal growth rate.
DNA methylation
Time Frame: Delivery
Differences in site-specific DNA methylation (\~450,000 sites) in offspring cord blood mononuclear cells between the Standard of Care (SOC), Very Low Energy Diet (VLED) and lean groups will be assessed.
Secondary Outcomes
- Fetal growth will be assessed by ultrasound(Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks))
- Infant length and weight(Delivery to 12 month follow-up)
- Metabolite levels(Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery)
- Participant waist circumference in centimeters(Baseline and post dietary intervention (16 weeks), each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks))