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Completed

NCT Number: NCT03244722

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.

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Key information

Conditions

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

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

University of Michigan

Ann Arbor, Michigan, 48106, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

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

Primary outcomes

  1. Preconception weight loss

    Time frame: Baseline to post dietary intervention (16 weeks)

    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).

  2. Metabolome and inflammatory markers

    Time frame: Delivery

    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).

  3. Offspring body fat mass

    Time frame: Delivery

    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).

  4. Cord blood related to neonate outcomes

    Time frame: Before and after dietary intervention (16 weeks), delivery

    The maternal metabolome (~metabolites) will be related to neonate adiposity, gestational weight gain, pregnancy complications, and intrauterine fetal growth rate.

  5. DNA methylation

    Time frame: Delivery

    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.

Secondary outcomes

  1. Participant waist circumference in centimeters

    Time frame: Baseline and post dietary intervention (16 weeks), each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)

    The change in waist circumference (cm) will be assessed using a retractable, soft nylon measuring tape.

  2. Fetal growth will be assessed by ultrasound

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

    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.

  3. Infant length and weight

    Time frame: Delivery to 12 month follow-up

    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.

  4. Metabolite levels

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

    Relationships between metabolite levels (~2000 metabolites) in maternal blood at each trimester and cord blood mononuclear cell DNA methylation will be compared

Other outcomes

  1. Mode of delivery

    Time frame: Delivery

    Categorical as caesarean or vaginal delivery

  2. Fetal growth abnormalities

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

    Categorical as miscarriage, intrauterine growth restriction (IUGR), fetal demise, fetal anomalies

  3. Maternal diagnosis

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

    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.

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Important dates

Study start
2018
Primary completion
2025
Study completion
2025
First posted
Aug 9, 2017
Registry last updated
Sep 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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