Infant Nutrition and Brain Development

Study Overview
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Brief Summary
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Research study on the role of early life nutrition on brain and cognitive development during infancy and early childhood. Two blends of myelin-relevant nutrients at different levels were compared and a breastfed group was considered as epidemiological reference.

Detailed Description
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This nutritional intervention study involved assessments in both the mother and her infant. The mother was asked to complete self-report questionnaires and to undergo a brief cognitive assessment. If the mother was not breastfeeding, a study product was provided and was consumed by the infant daily up to 12 months of life. The study also involved magnetic resonance imaging (MRI) brain scans of the infant's brain while asleep as well as evaluation of cognitive outcomes, including general cognitive development, and social-emotional development. Once all trial subjects completed the 6-month timepoint (intervention part), an inferential statistical analysis of all data up to 6 months was performed. Product codes (blinding) were broken to compare groups and an appropriate operational framework was put in place to maintain the individual assignment unknown to the Sponsor and Sites until the end of the trial.

Official Title
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The Effect of Myelin-Relevant Nutrients in Infant Formula on Brain Myelination and Cognitive Development

Conditions
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Healthy, Infant Development

Intervention / Treatment
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* Other: Infant Formula: enriched level of myelin-relevant nutrients
* Other: Infant formula: standard level of myelin-relevant nutrients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Term infants (≥ 37 weeks) Neuro typical development No major risk factors for learning, neurologic, or psychiatric disorder Between 2 weeks and maximum 5 weeks of age. If mother is breastfeeding she can choose the infant begin the trial prior 2 weeks. Parents/legal guardians willing and able to complete the informed consent process Exclusion Criteria: Delayed birth (> 41 weeks gestation) Birth Weight < 2000 g or small for gestation age or large for gestational age Psychopharmacological treatment of mother using prohibited medications during pregnancy In utero exposure to alcohol abuse or illicit substances as per the American College of Obstetricians and Gynecologists Abnormalities on fetal ultrasound Complicated pregnancy Neonatal intensive care unit admission and/or emergency surgical delivery

Ages Eligible for Study
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Minimum Age: 2 Weeks
Maximum Age: 6 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, double blind, randomized, controlled, parallel group clinical trial, consisting of 2 arms randomized to receive either the investigational or the control product, and a nonrandomized, nonblinded arm of fully breastfed infants. 3 groups: enriched level of myelin-relevant nutrients in an Infant Formula, standard level of myelin-relevant nutrients in an Infant Formula, breastfed infants
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Reference Arm: Breastfed<br>Epidemiological reference group of breastfed infants. | |
| Experimental: Investigational<br>Infant Formula: enriched level of myelin-relevant nutrients | Other: Infant Formula: enriched level of myelin-relevant nutrients<br>* Feeding with the assigned infant formula begun as soon as the child was enrolled in the study (from 2 weeks up to 5 weeks of life) and lasted up to 12 months of age (+/- 2 weeks). The volume of feed required by the child per day depended upon age, weight, and appetite. The product was given daily ad libitum to the child from enrollment up to 12 months.<br>* Other names: Infant Formula;|
| Active Comparator: Control<br>Infant formula: standard level of myelin-relevant nutrients | Other: Infant formula: standard level of myelin-relevant nutrients<br>* Feeding with the assigned infant formula begun as soon as the child was enrolled in the study (from 2 weeks up to 5 weeks of life) and lasted up to 12 months of age (+/- 2 weeks). The volume of feed required by the child per day depended upon age, weight, and appetite. The product was given daily ad libitum to the child from enrollment up to 12 months.<br>* Other names: Infant Formula;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain structural connectivity | Longitudinal analysis de novo myelination and comparison between the 3 study arms De novo myelination being assessed by brain magnetic resonance imaging (MRI; multicomponent relaxometry). [Physiological marker, MRI]. | 3, 6, 12, 18, and 24 months of life | 
| Brain functional connectivity | Cross-sectional analysis de novo myelination and comparison between the 3 study arms De novo myelination being assessed by brain magnetic resonance imaging (MRI; multicomponent relaxometry). [Physiological marker, MRI]. | 3, 6, 12, 18, and 24 months of life | 
| Brain De novo myelination | Brain magnetic resonance imaging (MRI) derived measures (volumetric anatomical imaging) [Physiological marker, MRI]. | 3, 6, 12, 18, and 24 months of life | 
| Infant Cognitive Development | Standardized neurodevelopment test. | 6, 12, and 24 months of life | 
| Infant Early Learning Assessment | Computer-based cognitive tasks. | 18 and 24 months of life | 
| Infant Social Emotional Development | Parent report questionnaire. | 3, 6, 12, 18, and 24 months of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infant dietary assessment | Three days food records are planned at the specified time-frames. | 6, 9, 12, 18, and 24 months of life | 
| Breast milk nutrients profile | Nutrients (vitamins, minerals, and other nutrients) levels analyses in breast milk nutrients (subsample) [Physiological parameter]. | week 3, week 6, and 3 months of life | 
| Brain structure | MRI | 3, 6, 12, 18, and 24 months of life | 
| Blood nutrients profile (optional) | Nutrients (vitamins, minerals, and other nutrients) levels | 6, 12, and 24 months of life | 
| Sleep | Questionnaire | 3, 6, 12, 18, and 24 months of life | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nutrition, Brain Development, Cognition, Heathy Infants