An Examination of Infants' Microbiome, Nutrition, and Development Study.

Study Overview
=================
Brief Summary
-----------------
This study is examining the relationship between infant nutrition, gut health, and development. The fecal microbiota changes and develops, in large part due to the food that infants eat. These changes are important for many aspects of development. This study is designed to examine how the fecal microbiota changes when exclusively breastfed infants are first introduced to solid food, and how changes of the fecal microbiota are related to other aspects of development.

Detailed Description
-----------------
The purpose of this study is to determine: 1) how the gut bacteria of exclusively breastfed infants changes in response to ingesting solid foods; 2) how infant cognition develops in response to ingesting solid foods; and 3) the relationship between infant gut bacteria and infant cognition during the first year of life. This study is designed to determine how specific complex carbohydrates in commonly used first foods encourage the growth of different bacteria in the infant gut. The two foods used in this study are commercially-available sweet potato (Plum Organics) and pear (Earth's Best). These two foods have been chosen because they differ substantially from each other in their carbohydrate composition. For example, sweet potato is mostly made up of starch which is digestible and pear is made up of other types of sugars found in fruits and vegetables that are not digestible and may have prebiotic effects (food for good bacteria in the gut). Thus, the use of these two foods could provide a good contrast for comparing how gut bacteria respond to different carbohydrate compositions during complementary feeding.

Official Title
-----------------
The Infant MiND Study: An Examination of Infants' Microbiome, Nutrition, and Development Study.

Conditions
-----------------
Microbial Colonization, Infant Development

Intervention / Treatment
-----------------
* Other: Sweet Potatos
* Other: Pears


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women, age 21 to 45 years who have delivered a healthy single infant by vaginal delivery and their infants, age 4 to 7.5 months; Infants who are developmentally ready for solids; Generally healthy women and infants; Mothers who plan to exclusively (without solids or infant formula) breastfeed (at the breast or feed breast milk by bottle) their infants for at least 5 months of age and plan to continue to breastfeed with solids and/or infant formula until 12 months of age; Mothers who are willing to either use their own breast pump, or hand-express, or use a manual pump provided by the study to collect milk samples; Mothers who are willing to refrain from feeding their infants infant formula, non-study solid foods; probiotic or iron supplements (confounding variables of the intestinal microbiome) before the end of the feeding intervention period; Term infants born >37 weeks gestation; Mother-infant pairs who live within a 20-mile radius from University of California, Davis campus in Davis, California (includes Woodland, Vacaville, Dixon and surrounding areas) or within a 20-mile radius of the University of California, Davis Medical Center (UCDMC) (2221 Stockton Blvd, Sacramento, CA 95817). Exclusion Criteria: Infants with any GI tract abnormalities; Infants born by cesarean section; Family history of immunodeficiency syndrome(s); Multiple infants born to one mother at the same time (no twins, triplets, etc.); Infants born with medical complications such as: respiratory distress syndrome, birth defects, and infection; Mothers diagnosed with any metabolic or endocrine, liver, kidney disease, any autoimmune disease, cirrhosis, hepatitis C, HIV, AIDS, cancer, obesity (pre-pregnancy BMI >34.9), polycystic ovary syndrome (PCOS), celiac disease, Crohn's disease, heart disease, hyper- or hypothyroidism, hyper- or hypotension (including pre-eclampsia), type 1 or type 2 diabetes. Mothers who smoked cigarettes less than one month before becoming pregnant, during pregnancy, and currently or mothers who plan to initiate smoking during the study duration; Infants who have taken antibiotics within the past 4 weeks; Infants who have taken iron supplements within the past 4 weeks; Infants who have consumed infant formula in the past 4 weeks; Infants who have consumed infant formula more than 10 days between birth and 4 weeks prior to screening; Infants who have consumed any solids; Mothers who plan to feed infants solids before 5 months of age; Mothers who plan to administer any probiotics to infants throughout the feeding intervention period (first 18 days of the study); Infants who have consumed probiotics containing Bifidobacterium within the past 4 weeks or other probiotics within the past 7 days; Mothers who live in more than one location (should only live in one house to ensure samples are correctly collected and stored); Infants who have hypotonia, Infants who have been diagnosed with any medical or nutritional condition that would require iron supplementation. Infants who on average pass less than one stool per week.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study is designed as a combined randomized, crossover interventional and observational trial. At the start of the study, infants will enter a 7-day lead-in period to establish gut microbiome and GI tolerability baselines. After the 7-day lead-in period, infants will be randomized into one of two feeding arms comprised of two commercially available baby foods: sweet potato (SP) (Plum Organics, Just Sweet Potato) and pears (P) (Earth's Best, First Pears). The first food, either sweet potato or pears, will be consumed for 7 days followed by a 4-day washout period of exclusive breast milk before initiating the alternate 7-day feeding arm of pears or sweet potato, respectively. The second feeding arm will be followed by an additional 4-day washout period of exclusive breast milk before the introduction of any other solid foods. Once the first month of the study is complete, infants will enter an observational phase for the remainder of the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sweet Potatos<br>Infants will consume commercially available baby food sweet potato (SP) (Plum Organics, Just Sweet Potato) for 7 days followed by a 4 day washout period of exclusive breast milk. Participants will be instructed to offer 1-2 tablespoons of sweet potato to their infant at least three times per day for seven days in a row. | Other: Sweet Potatos<br>* Plum Organics, Just Sweet Potato<br>|
| Experimental: Pears<br>Infants will consume commercially available baby food pear (P) (Earth's Best, First Pears) for 7 days followed by a 4 day washout period of exclusive breast milk. Participants will be instructed to offer 1-2 tablespoons of pears to their infant at least three times per day for seven days in a row. | Other: Pears<br>* Earth's Best, First Pears<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infant fecal microbiota composition | The difference in the relative abundance of the infant fecal microbiome at the order level (top 22 taxonomic orders with abundance expressed as both on log10 scale and a percent of total bacteria) between baseline and post-complementary food intake for each intervention arm (sweet potato vs. pear). | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Infant fecal microbial diversity | The difference in the infant fecal microbial diversity and microbial function between baseline and post-complementary food intake for each arm (sweet potato vs. pear) | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Incidence of Adverse Events and Treatments | Incidence of gastrointestinal symptoms (discomfort passing bowel movements, vomiting, constipation, colic or irritability), illnesses, health care visits for sickness, high fevers, antibiotic and medication use. | Baseline-days 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dietary composition | The relationship between the relative abundance of the infant fecal microbiome and function, and food glycan composition. | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Infant cognition | The relationship between the relative abundance of the infant fecal microbiome, microbial diversity and function, and infant cognition measured at 6, 8 and 12 months of age | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Infant sleep | The relationship between the relative abundance of the infant fecal microbiome, microbial diversity and function, and infant sleep, activity and vocalizations measured throughout the study period. | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Maternal secretor status and infant fecal microbiota | The relationship between maternal secretor status (via measurement of human milk oligosaccharides in breast milk) and the relative abundance of the infant fecal microbiome, microbial diversity and function before, during and after introduction of complementary foods. | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Infant secretor status and fecal microbiota | The relationship between infant secretor status (via measurement of oligosaccharides in saliva) the relative abundance of the infant fecal microbiome, microbial diversity and function before, during and after introduction of complementary foods. | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Maternal and infant fecal microbiota | The relationship between maternal and infant fecal microbiome. | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Infant fecal human milk oligosaccharide concentrations | The change in infant fecal human milk oligosaccharide concentrations before, during and after introduction of complementary foods. | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Infant weight | Determine the relationship between infant weight and the relative abundance of the infant fecal microbiome, microbial diversity and function before, during and after introduction of complementary foods | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Human milk metabolomics | Determine the relationship between human milk metabolomics (metabolites, fatty acids, proteins) and the infant fecal microbiome. | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Fecal metabolomics | Determine the relationship between fecal metabolites (metabolites, fatty acids, proteins) and fecal microbiome. | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Infant gastrointestinal function | Change in GI function as a means to monitor tolerability before, during and after introduction of complementary foods (through the measurement of fecal inflammatory mediators, GI barrier function markers and fecal LPS). | Change from baseline, days 14, 19, 25, 29, 60, 90, 120, 150, 180 | 
| Glycosidic linkages | Evaluate the glycosidic linkages in interventional foods and the infant fecal microbiome. | Change from baseline to day 29 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breastfeeding, First foods