Obesity; Familial, Pregnancy Related
Conditions
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.
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.
Interventions
DIETARY_SUPPLEMENTVery-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
OTHERStandard 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
Sponsors
University of Michigan
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Preconception Weight Loss | Baseline to conception (up to 68 weeks post enrollment) | 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). |
| Maternal Diagnosis | Throughout pregnancy (up to 108 weeks post enrollment) | Gestational diabetes or hypertensive disorders in pregnancy |
| Offspring Body Fat Mass | Delivery (up to 108 weeks post enrollment) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fetal Growth Will be Assessed by Ultrasound | 2nd trimester (up to 90 weeks post enrollment) and 3rd trimester (up to 102 weeks post enrollment) of pregnancy | Abdominal circumference (cm) will be assessed through ultrasound to determine fetal growth. |
| Ponderal Index | Delivery (up to 108 weeks post enrollment) up to 12 month post delivery follow-up (up to 160 weeks post enrollment) | 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). |
| Mode of Delivery | Delivery (up to 108 weeks post enrollment) | Categorical as caesarean or vaginal delivery |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAmy Rothberg, MD
University of Michigan
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 31.6 years STANDARD_DEVIATION 3.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Black | 3 Participants |
| Race/Ethnicity, Customized Other | 9 Participants |
| Race/Ethnicity, Customized White | 70 Participants |
| Region of Enrollment United States | 27 Participants |
| Sex: Female, Male Female | 84 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 45 | 0 / 53 |
| other Total, other adverse events | 10 / 49 | 29 / 45 | 31 / 53 |
| serious Total, serious adverse events | 2 / 49 | 0 / 45 | 1 / 53 |
Outcome results
None listed