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

Pregnancy Related Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03244722
• Other study ID #: HUM00124673
• Secondary ID: 1R01DK124862
• Status: Recruiting
• Phase: N/A
• Start date: April 10, 2018
• Est. completion date: August 31, 2025

Study information

• Verified date: September 2023
• Source: University of Michigan
• Contact: Shannon Considine, MPH, MSW
• Phone: 734-232-6483
• Email: sconsidi[@]umich.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 352
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity; Familial
• Pregnancy Related
• Weight Loss

Intervention

Dietary Supplement:
• Very-low energy Diet (VLED)
Structured, intensive dietary intervention using liquid meal replacements aimed at providing 800 kcal/day with a weight loss goal of 15% from baseline

Other:
• Standard of care (SOC)
Standard consultation with registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss in obese women. Standard of care for normal weight women

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mode of delivery	Categorical as caesarean or vaginal delivery	Delivery
Other	Fetal growth abnormalities	Categorical as miscarriage, intrauterine growth restriction (IUGR), fetal demise, fetal anomalies	Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)
Other	Maternal diagnosis	Categorical as maternal cardiac dysfunction, maternal proteinuria, maternal sleep apnea, fatty liver disease, gestational diabetes, preeclampsia, indicated preterm birth date, failed trial of labor, endometritis, venous thrombosis, COVD-19, surgical wound complications, postpartum anemia, postpartum depression, early termination of breastfeeding.	Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery
Primary	Preconception weight loss	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).	Baseline to post dietary intervention (16 weeks)
Primary	Metabolome and inflammatory markers	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).	Delivery
Primary	Offspring body fat mass	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).	Delivery
Primary	Cord blood related to neonate outcomes	The maternal metabolome (~metabolites) will be related to neonate adiposity, gestational weight gain, pregnancy complications, and intrauterine fetal growth rate.	Before and after dietary intervention (16 weeks), delivery
Primary	DNA methylation	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.	Delivery
Secondary	Participant waist circumference in centimeters	The change in waist circumference (cm) will be assessed using a retractable, soft nylon measuring tape.	Baseline and post dietary intervention (16 weeks), each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)
Secondary	Fetal growth will be assessed by ultrasound	Gestational sac dimensions (mm), fundal height (mm), biparietal diameter (mm), head circumference (mm), and waist circumference (mm) will be assessed through ultrasound to determine fetal growth.	Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)
Secondary	Infant length and weight	Trained staff will measure infant length and weight to the nearest .1cm and .1kg using an infant length board and digital infant scale at delivery, 2-, 4-, 6-, 9-, and 12-months. Ponderal index will be calculated and used to assess change in growth.	Delivery to 12 month follow-up
Secondary	Metabolite levels	Relationships between metabolite levels (~2000 metabolites) in maternal blood at each trimester and cord blood mononuclear cell DNA methylation will be compared	Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery