Trial Outcomes & Findings for Maternal Metabolic and Molecular Changes Induced by Preconception Weight Loss and Their Effects on Birth Outcomes (NCT NCT03244722)

Last Updated: 2026-09-04

Results Overview

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).

Recruitment status

COMPLETED

Study phase

Target enrollment

147 participants

Primary outcome timeframe

Baseline to conception (up to 68 weeks post enrollment)

Results posted on

2026-09-04

Participant Flow

Participant milestones

Participant milestones
Measure	Obese - Very Low Energy Diet (VLED) Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	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 Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN Healthy weight women followed in parallel. No dietary intervention prior to conceiving.
Overall Study STARTED	49	45	53
Overall Study COMPLETED	22	27	35
Overall Study NOT COMPLETED	27	18	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Obese - Very Low Energy Diet (VLED) Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	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 Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN Healthy weight women followed in parallel. No dietary intervention prior to conceiving.
Overall Study Did not become pregnant within 12 month window	13	6	10
Overall Study Withdrawal by Subject	7	3	2
Overall Study Lost to Follow-up	3	4	2
Overall Study Removed from study by NIH, due to inadequate time for post-conception follow-up before study end	4	5	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Obese - Very Low Energy Diet (VLED) n=22 Participants Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	Obese - Standard of Care (SOC) n=27 Participants Participants will receive the standard of care for obese dietary education and advice to incorporate a low-calorie food based diet Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN n=35 Participants Healthy weight women followed in parallel. No dietary intervention prior to conceiving.	Total n=84 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=23 Participants	0 Participants n=23 Participants	34 Participants n=22 Participants	37 Participants n=21 Participants
Age, Continuous	31.8 years STANDARD_DEVIATION 4.1 • n=23 Participants	32.1 years STANDARD_DEVIATION 3.4 • n=23 Participants	31.0 years STANDARD_DEVIATION 4.0 • n=22 Participants	31.6 years STANDARD_DEVIATION 3.8 • n=21 Participants
Sex: Female, Male Female	22 Participants n=23 Participants	27 Participants n=23 Participants	35 Participants n=22 Participants	84 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=23 Participants	0 Participants n=23 Participants	0 Participants n=22 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=23 Participants	27 Participants n=23 Participants	1 Participants n=22 Participants	47 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=23 Participants	0 Participants n=23 Participants	0 Participants n=22 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized White	19 Participants n=23 Participants	21 Participants n=23 Participants	30 Participants n=22 Participants	70 Participants n=21 Participants
Race/Ethnicity, Customized Black	1 Participants n=23 Participants	3 Participants n=23 Participants	1 Participants n=22 Participants	5 Participants n=21 Participants
Race/Ethnicity, Customized Other	2 Participants n=23 Participants	3 Participants n=23 Participants	4 Participants n=22 Participants	9 Participants n=21 Participants
Region of Enrollment United States	22 Participants n=23 Participants	27 Participants n=23 Participants	35 Participants n=22 Participants	84 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to conception (up to 68 weeks post enrollment)

Outcome measures

Outcome measures
Measure	Obese - Very Low Energy Diet (VLED) n=22 Participants Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	Obese - Standard of Care (SOC) n=27 Participants Participants will receive the standard of care for obese dietary education and advice to incorporate a low-calorie food based diet Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN n=35 Participants Healthy weight women followed in parallel. No dietary intervention prior to conceiving.
Preconception Weight Loss BMI at conception	31.0 kg/m2 Standard Deviation 3.6	35.0 kg/m2 Standard Deviation 4.5	23.1 kg/m2 Standard Deviation 1.9
Preconception Weight Loss Baseline (preconception) BMI	35.0 kg/m2 Standard Deviation 2.9	35.9 kg/m2 Standard Deviation 4.3	23.2 kg/m2 Standard Deviation 1.8

PRIMARY outcome

Timeframe: Throughout pregnancy (up to 108 weeks post enrollment)

Gestational diabetes or hypertensive disorders in pregnancy

Outcome measures

Outcome measures
Measure	Obese - Very Low Energy Diet (VLED) n=22 Participants Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	Obese - Standard of Care (SOC) n=27 Participants Participants will receive the standard of care for obese dietary education and advice to incorporate a low-calorie food based diet Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN n=35 Participants Healthy weight women followed in parallel. No dietary intervention prior to conceiving.
Maternal Diagnosis Hypertension	6 Participants	11 Participants	3 Participants
Maternal Diagnosis Gestational Diabetes	1 Participants	3 Participants	3 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Obese - Very Low Energy Diet (VLED) n=22 Participants Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	Obese - Standard of Care (SOC) n=27 Participants Participants will receive the standard of care for obese dietary education and advice to incorporate a low-calorie food based diet Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN n=35 Participants Healthy weight women followed in parallel. No dietary intervention prior to conceiving.
Offspring Body Fat Mass	15.7 percent body fat Standard Deviation 3.5	11.6 percent body fat Standard Deviation 4.0	13.2 percent body fat Standard Deviation 6.4

SECONDARY outcome

Timeframe: 2nd trimester (up to 90 weeks post enrollment) and 3rd trimester (up to 102 weeks post enrollment) of pregnancy

Population: These are the number of women who conceived spontaneously and had full term singleton pregnancy

Abdominal circumference (cm) will be assessed through ultrasound to determine fetal growth.

Outcome measures

Outcome measures
Measure	Obese - Very Low Energy Diet (VLED) n=22 Participants Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	Obese - Standard of Care (SOC) n=27 Participants Participants will receive the standard of care for obese dietary education and advice to incorporate a low-calorie food based diet Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN n=35 Participants Healthy weight women followed in parallel. No dietary intervention prior to conceiving.
Fetal Growth Will be Assessed by Ultrasound 2nd Trimester	12.9 cm Standard Deviation 2.8	13.2 cm Standard Deviation 2.5	13.0 cm Standard Deviation 2.2
Fetal Growth Will be Assessed by Ultrasound 3rd Trimester	30.89 cm Standard Deviation 2.62	30.83 cm Standard Deviation 2.57	30.07 cm Standard Deviation 2.27

SECONDARY outcome

Timeframe: Delivery (up to 108 weeks post enrollment) up to 12 month post delivery follow-up (up to 160 weeks post enrollment)

Population: All data collected is presented. Not all participants attended 12 month appointment at which time data is collected

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).

Outcome measures

Outcome measures
Measure	Obese - Very Low Energy Diet (VLED) n=22 Participants Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	Obese - Standard of Care (SOC) n=27 Participants Participants will receive the standard of care for obese dietary education and advice to incorporate a low-calorie food based diet Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN n=35 Participants Healthy weight women followed in parallel. No dietary intervention prior to conceiving.
Ponderal Index Delivery	2.8 g/cm3 Standard Deviation 0.3	2.8 g/cm3 Standard Deviation 0.9	2.5 g/cm3 Standard Deviation 0.3
Ponderal Index 12 months	2.20 g/cm3 Standard Deviation 0.18	2.31 g/cm3 Standard Deviation 0.24	2.17 g/cm3 Standard Deviation 0.19

SECONDARY outcome

Timeframe: Delivery (up to 108 weeks post enrollment)

Categorical as caesarean or vaginal delivery

Outcome measures

Outcome measures
Measure	Obese - Very Low Energy Diet (VLED) n=22 Participants Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	Obese - Standard of Care (SOC) n=27 Participants Participants will receive the standard of care for obese dietary education and advice to incorporate a low-calorie food based diet Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN n=35 Participants Healthy weight women followed in parallel. No dietary intervention prior to conceiving.
Mode of Delivery Caesarean delivery	10 Participants	9 Participants	8 Participants
Mode of Delivery Vaginal delivery	12 Participants	18 Participants	27 Participants

Adverse Events

Obese - Very Low Energy Diet (VLED)

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Obese - Standard of Care (SOC)

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

LEAN

Serious events: 1 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Obese - Very Low Energy Diet (VLED) n=49 participants at risk Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	Obese - Standard of Care (SOC) n=45 participants at risk Participants will receive the standard of care for obese dietary education and advice to incorporate a low-calorie food based diet Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN n=53 participants at risk Healthy weight women followed in parallel. No dietary intervention prior to conceiving.
Hepatobiliary disorders gallstones	4.1% 2/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years
Cardiac disorders supraventricular tachycardia	0.00% 0/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	1.9% 1/53 • Number of events 3 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions fetal hydrops	0.00% 0/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	1.9% 1/53 • Number of events 1 • up to 3.5 years

Other adverse events

Other adverse events
Measure	Obese - Very Low Energy Diet (VLED) n=49 participants at risk Participants will adopt a very-low energy diet 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 x 12 weeks with 4 week period of transition to low calorie food based diet prior to conceiving.	Obese - Standard of Care (SOC) n=45 participants at risk Participants will receive the standard of care for obese dietary education and advice to incorporate a low-calorie food based diet Standard of care (SOC): Standard consultation with a registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss of \~5% prior to conceiving.	LEAN n=53 participants at risk Healthy weight women followed in parallel. No dietary intervention prior to conceiving.
Pregnancy, puerperium and perinatal conditions Fall (during pregnancy)	0.00% 0/49 • up to 3.5 years	4.4% 2/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Vaginal bleeding (during pregnancy)	2.0% 1/49 • up to 3.5 years	4.4% 2/45 • up to 3.5 years	3.8% 2/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Pregnancy loss	0.00% 0/49 • up to 3.5 years	4.4% 2/45 • up to 3.5 years	3.8% 2/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions High blood pressure (gestational hypertension)	12.2% 6/49 • up to 3.5 years	24.4% 11/45 • up to 3.5 years	5.7% 3/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Concerns of high blood pressure with normal blood pressures in ED (during pregnancy)	4.1% 2/49 • up to 3.5 years	2.2% 1/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Superficial burn to arm (during pregnancy)	0.00% 0/49 • up to 3.5 years	2.2% 1/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Gestational Diabetes	2.0% 1/49 • up to 3.5 years	6.7% 3/45 • up to 3.5 years	5.7% 3/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Decreased fetal movement with reassuring nonstress test (during pregnancy)	2.0% 1/49 • up to 3.5 years	4.4% 2/45 • up to 3.5 years	13.2% 7/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Contractions without being in labor	0.00% 0/49 • up to 3.5 years	8.9% 4/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Heart palpitations or tachycardia (during pregnancy)	2.0% 1/49 • up to 3.5 years	2.2% 1/45 • up to 3.5 years	3.8% 2/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Chest pressure with normal investigation in ED	0.00% 0/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	1.9% 1/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Norovirus gastroenteritis (during pregnancy)	0.00% 0/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	1.9% 1/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Bat exposure (during pregnancy)	0.00% 0/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	1.9% 1/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Nausea and vomiting (during pregnancy)	0.00% 0/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	3.8% 2/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Headache (during pregnancy)	0.00% 0/49 • up to 3.5 years	6.7% 3/45 • up to 3.5 years	3.8% 2/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Syncope (during pregnancy)	0.00% 0/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	1.9% 1/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Mycotic vaginal infection (during pregnancy)	0.00% 0/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	1.9% 1/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Back pain (during pregnancy)	0.00% 0/49 • up to 3.5 years	4.4% 2/45 • up to 3.5 years	1.9% 1/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Kidney stone (renal calculus) (during pregnancy)	0.00% 0/49 • up to 3.5 years	2.2% 1/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Perirectal abscess (postpartum)	0.00% 0/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	1.9% 1/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Mastocystitis	0.00% 0/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	1.9% 1/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Postpartum vaginal bleeding	2.0% 1/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years
Pregnancy, puerperium and perinatal conditions Joint pain and swelling (postpartum)	0.00% 0/49 • up to 3.5 years	2.2% 1/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years
Skin and subcutaneous tissue disorders Rash	2.0% 1/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years
Musculoskeletal and connective tissue disorders Leg pain with normal investigation	2.0% 1/49 • up to 3.5 years	0.00% 0/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years
Eye disorders Visual disturbance	0.00% 0/49 • up to 3.5 years	2.2% 1/45 • up to 3.5 years	0.00% 0/53 • up to 3.5 years

Additional Information

Amy E Rothberg

University of Michigan

Phone: 7346475871

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place