Maternal Metabolic and Molecular Changes Induced by Preconception Weight Loss and Their Effects on Birth Outcomes

Maternal Metabolic and Molecular Changes Induced by Preconception Weight Loss and Their Effects on Birth Outcomes

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.

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.

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