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.

Study Overview

• Status: Completed
• Conditions: Pregnancy Related; Obesity; Familial
• Intervention / Treatment: Dietary supplement: Very-low energy Diet (VLED); Other: Standard of care (SOC)

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.

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Obese - Very low energy diet (VLED); Participants will adopt a very-low energy diet	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: Obese - Standard of care (SOC); Participants will receive the standard of care for obese women looking to become pregnant.	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
Other: Lean - Standard of care (SOC); Participants will receive the standard of care for lean women looking to become pregnant.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mode of delivery	Categorical as caesarean or vaginal delivery	Delivery
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)
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

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Amy Rothberg, MD, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2018
• Primary Completion (Actual): June 14, 2025
• Study Completion (Actual): August 29, 2025

Study Registration Dates

• First Submitted: August 5, 2017
• First Submitted That Met QC Criteria: August 5, 2017
• First Posted (Actual): August 9, 2017

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: HUM00124673; 1R01DK124862 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No