- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03522597
Metabolism, Breastmilk, and Microbiome
Maternal Metabolism, Breast Milk Composition, and Infant Outcomes: The 4M Project
Study Overview
Status
Conditions
Detailed Description
The incidence of both obesity and diabetes are on a staggering rise. Many studies suggest that by 2030, 40-50% of the population will be obese. The prevalence of gestational diabetes (GDM) is also increasing, and was recently reported to be 9%. GDM increases risk of obesity and impaired glucose tolerance in their children, but the mechanisms by which this occurs are not well defined.
The benefits of breastfeeding are numerous, including protection from sudden infant death and infection, positive cognitive outcomes, reduced prematurity complications, and decreased risk of cancer, as well as some evidence of protection against child obesity. One area that has yet to be thoroughly explored is whether there are differences in breast milk composition in women with diabetes as compared to non-diabetic women after adjusting for obesity and other diabetes co-morbidities, and how these differences could affect infant metabolic health and body composition. Experimental studies argue strongly for a causal relationship of the gut microbiome to the risk of obesity and diabetes. Breast milk strongly shapes the gut microbiome, as it contains unique oligosaccharides as well as hormones and immunologic factors that cultivate the growth of specific microbiota in the infant gut. Indeed over 90% of early infant fecal bacteria are Bifidobacteria, where in most formula-fed infants Bifidobacteria are non-detectable, which has been linked to the rapid growth and greater adiposity in formula-fed versus breastmilk-fed infants. Given that most pregnant women in the United States are now either overweight, obese, or diabetic, our study has high public health significance in that it seeks to understand how maternal metabolic factors such as these hinder the development of a healthy gut microbiome during the critical period of infancy.
In this study, the following study questions will be examined:1) does maternal metabolic state relate to the milk microbiome (bacterial and fungal diversity and abundance relationships, and microbiome function) and how they are transmitted to the infant gut? 2) does maternal metabolic state relate to the concentration of appetite and growth-regulating hormones and cytokines present in breast milk?; 3) are maternal serum concentrations of hormones and milk microbiomes associated with each other?; and 4) are milk hormones and/or milk microbiomes related to infant growth and body composition in the first 6 months of life?
Amplicon-based and deep (shotgun) metagenomic sequencing will be utilized to characterize species and strain level characteristics of maternal milk and infant fecal microbiomes. ELISA assays will be used to quantify adipose-tissue derived hormones (leptin, adiponectin) and immune factors (CRP, IL-6, TNF-α) as well as insulin/growth axis hormones (insulin, IGF-1, IGFBP-3) in breast milk. Infant body composition will be assessed using air displacement plethysmography and dual energy x-ray absorptiometry.
The above work will involve new recruitment enrollment, and pregnancy data collection from 50 diabetic mothers recruited through the Maternal Fetal Medicine and Women's Health Specialists at M Health. The pregnant non-diabetic (normal weight and obese) woman cohorts (and their infants and samples) for this study already exist as part of Clinical Trial NCT03301753 (Maternal Obesity, Breast Milk Composition, and Infant Growth (MILK) study), which is currently in the sample collection phase. The current study will form the first comprehensive comparison of multiple aspects of breastmilk composition in women with pregnancy diabetes as compared to non-diabetic women.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Locations
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Minnesota
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Minneapolis, Minnesota, United States, 55454
- University of Minnesota
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
(For new enrollment of 50 pregnant women with gestational diabetes and their infants. Enrollment of normal weight and obese cohort comparators already accomplished under ClinicalTrial NCT03301753):
- Pregnant women
- age 21-45 at time of delivery
- report during enrollment procedures that they have social support for and intention to exclusively breastfeed for at least 3 months (breastfeeding intentions are known to be correlated with actual behavior), and if parity >1, that they successfully breastfed after a previous pregnancy for at least 3 months
- singleton pregnancy
- known gestational diabetes Definition of Gestational Diabetes: 1) an elevated glucose challenge test >200 mg/dL or 2) two abnormal values on the glucose tolerance test according to Carpenter-Coustan criteria.
Exclusion Criteria:
- alcohol consumption >1 drink per week during pregnancy/lactation
- tobacco consumption during pregnancy/lactation,
- inability to speak/understand English
- known congenital metabolic, endocrine disease, or congenital illness affecting infant feeding
- planned delivery at a site other than the University of Minnesota Medical Center- West Bank campus.
- preexisting diabetes
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Normal weight
Normal weight (BMI) women and their infants
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Obese
Obese (BMI) women and their infants
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Diabetic
Women with gestational diabetes and their infants
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Breastmilk and infant microbiomes
Time Frame: 1, 3, and 6 months postpartum
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Change in the diversity and abundance of breast milk and infant gut bacterial and fungal species and strains, and functional microbiome profiles
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1, 3, and 6 months postpartum
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hormones in breastmilk
Time Frame: 1 and 3 months postpartum
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Change in breastmilk concentrations of appetite and growth regulating hormones (leptin, insulin, adiponectin) and proteins (IGF-1, IGFBP3, CRP, IL-6) from milk.
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1 and 3 months postpartum
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Hormones and cytokines in maternal serum
Time Frame: At time of delivery (time 0)
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Maternal serum concentrations of appetite and growth regulating hormones (leptin, insulin, adiponectin) and proteins (IGF-1, IGFBP3, CRP, IL-6), and cytokines.
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At time of delivery (time 0)
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Hormones and cytokines in infant serum
Time Frame: At time of delivery (time 0) and 6 months postpartum
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Change in the concentrations of appetite and growth regulating hormones (leptin, insulin, adiponectin) and proteins (IGF-1, IGFBP3, CRP, IL-6), and cytokines from birth to age 6 months.
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At time of delivery (time 0) and 6 months postpartum
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Cheryl A Gale, M.D., University of Minnesota
- Principal Investigator: Ellen W Demerath, Ph.D., University of Minnesota
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- OBGYN-2018-26409
- R01HD080444 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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