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
Active Comparator: Obese - Standard of care (SOC); Participants will receive the standard of care for obese dietary education and advice to incorporate a low-calorie food based diet	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
No Intervention: LEAN; Healthy weight women followed in parallel. No dietary intervention prior to conceiving.

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 conception (up to 68 weeks post enrollment)
Maternal Diagnosis	Gestational diabetes or hypertensive disorders in pregnancy	Throughout pregnancy (up to 108 weeks post enrollment)
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 (up to 108 weeks post enrollment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal Growth Will be Assessed by Ultrasound	Abdominal circumference (cm) will be assessed through ultrasound to determine fetal growth.	2nd trimester (up to 90 weeks post enrollment) and 3rd trimester (up to 102 weeks post enrollment) of pregnancy
Ponderal Index	Trained staff will measure infant length and weight to the nearest .1cm and .1kg using an infant length board and digital infant scale. Ponderal index will be calculated and used to assess growth from baseline to 12 months post birth. Ponderal index is weight/length (grams/cubic centimeters).	Delivery (up to 108 weeks post enrollment) up to 12 month post delivery follow-up (up to 160 weeks post enrollment)
Mode of Delivery	Categorical as caesarean or vaginal delivery	Delivery (up to 108 weeks post enrollment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrauterine Abnormalities	Categorical as miscarriage, intrauterine growth restriction (IUGR), fetal demise, fetal anomalies	Throughout pregnancy
Metabolome	Multivariate computational models will assess the association of maternal and neonate metabolite to fetal growth and newborn weight (g) and adiposity (g).	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.	Delivery
Epigenetic Marks	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
Health-related Quality-of-life and Other Behavioral Assessments	Health-related quality-of-life and other behavioral assessments based on validated survey instruments	Baseline, 12 month follow-up

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Amy Rothberg, MD, 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 (Actual): September 4, 2026
• Last Update Submitted That Met QC Criteria: September 2, 2026
• Last Verified: July 1, 2026

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