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

NCT03244722 | Completed

• 2 other identifiers: HUM001246731R01DK124862
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity; Familial; Pregnancy Related

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (4)

• 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)

• 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

Other Outcomes (3)

• Mode of delivery

  Delivery

• Fetal growth abnormalities

  Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)

• Maternal diagnosis

  Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery

Study Arms (3)

Obese - Very low energy diet (VLED)

OTHER

Participants will adopt a very-low energy diet

Dietary Supplement: Very-low energy Diet (VLED)

Obese - Standard of care (SOC)

OTHER

Participants will receive the standard of care for obese women looking to become pregnant.

Other: Standard of care (SOC)

Lean - Standard of care (SOC)

OTHER

Participants will receive the standard of care for lean women looking to become pregnant.

Other: Standard of care (SOC)

Interventions

Very-low energy Diet (VLED) DIETARY_SUPPLEMENT

Structured, intensive dietary intervention using liquid meal replacements aimed at providing 800 kcal/day with a weight loss goal of 15% from baseline

Obese - Very low energy diet (VLED)

Standard of care (SOC) OTHER

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

Lean - Standard of care (SOC); Obese - Standard of care (SOC)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI \> 30 ≤ 45 for obese participants OR
• BMI ≤ 25 for healthy body weight participants
• No known infertility
• No known risk factors for tubal disease

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48106, United States

Location

MeSH Terms

Conditions

Obesity

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Amy Rothberg, MD, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Project Investigator

Study Record Dates

• First Submitted: August 5, 2017
• First Posted: August 9, 2017
• Study Start: April 10, 2018
• Primary Completion: June 14, 2025
• Study Completion: August 29, 2025
• Last Updated: September 10, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)