Follow up of Long Term Neurodevelopmental Impact of the Type of Feeding During the First Year of Life at 10 Years Old

NCT ID: NCT06917625

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 5 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-03-11
• Study Completion Date: 2026-01-31

Brief Summary

The Chilean infant Nutrition Trial was a prospective, randomized, double-blind, controlled study conducted in Santiago, Chile, between 2016 and The study aimed to evaluate growth and body composition changes between birth and two years of age in a large sample of children who were randomized to receive either infant formula with or without added MFGM (milk fat globule membrane) through 12 months of age or received human milk as part of the reference group. In a subsample of 160 children, neurodevelopmental were assessed at 6 months and 24 months.

Detailed Description

To test our hypothesis, this study proposes to investigate our conceptual model's direct and indirect associations using a combination of low-field MRI, electrophysiology, and psychometric assessments of executive functioning and general cognitive development, expecting to re-enroll approx 100 participants. These children will undergo ERPs, low-field MRI and neurocognitive testing to evaluate brain structure, function, and cognitive development.

The Go/No-Go task assesses inhibitory control, one of the most important executive function. Its development has been studied electrophysiologically using event-related potentials (ERPs), in tasks that require active inhibition when there is a previously learned or prepotent response. The main relevant ERP components are the N2 and P300. The N2, an early negative deflection, has been interpreted to reflect attention, the P300, a later positive wave, is thought to reflect resource allocation. The P300 is typically greater in the inhibitory than in the prepotent response components of tasks such as the Go/No-Go task. Behavioral responses such as accuracy and reaction time have also been studied as measures of development (2). Using the collected data, inhibitory control, as one of the earliest executive functions to begin developing, will be studied.

The data acquired with the Low-field MRI quantify and compare brain structure and myelination patterns (derived from MRI) across the feeding groups in specific white matter pathways and brain regions involved in executive function (EF) and throughout the brain generally. MRI comparisons and comparisons will be complemented by comparisons of ERP measures collected during an inhibition task, which assesses functional development and processing speed.In addition to these group-wise comparisons,it will be explored the direct and indirect infant feeding -> brain structure and function -> executive function and cognitive performance associations using a series of ANCOVA and general linear modeling methods.

C. PRIMARY OBJECTIVE AND OUTCOME MEASUREMENTS:

The primary objective of this study is to determine whether additional intake of bMFGM during infancy (0-12 months of age) improves brain structure, function, and cognitive performance (specifically EF) at early school age (8-10 years of age).

The following measures will be collected, and EF domains assessed and comparisons made.

Brain Structure and Myelin Imaging. Low-Field MRI will be used to assess general brain growth and morphometry (total brain volume, whole-brain white and gray matter volume, and cortical and sub-cortical structure volumes) as well as myelination using myelin-sensitive MRI. Differences across all of these measures between the infant feeding groups (standard formula, added bMFGM, and breastfeeding reference) will be part of exploratory analysis. To examine specific hypothesized brain regions involved in EF, including prefrontal cortex, hippocampus, amygdala, thalamus, motor and somatosensory cortices, and auditory cortex will be studied. Connecting white matter regions, including corpus callosum, cingulum, superior longitudinal fasciculus, and anterior thalamic radiations will be compared as they are an indirect index of myelination grade.

Mean myelin measures will be calculated for each white matter pathway and compared across the three feeding groups using an ANCOVA and post hoc Tukey test to identify significant differences.

ERPs and Electrophysiology. ERPs will be recorded from 128 scalp sites using a recording system with a geodesic sensor net (Electric Geodesic, Inc., Eugene, Oregon). The vertex was used as the on-line reference electrode. The signal was sampled at 1000 Hz and bandpass filtered at 0.1 to 100 Hz. After recording, stimulus triggers were exported and analyzed using signal processing software (BESA Research 6.1 BESA® ,Germany). Signals were re-referenced off-line to an average (whole head) reference and bandpass filtered (0.1 to 10 Hz). The continuous EEG was segmented into epochs according to the three stimulus types: block 1 Go trials, block 2 Go trials, and block 2 No-Go trials with the segment length being the same as each onset-to-onset interval. Noisy segments of data with excessive electromyographic signal (EMG) were rejected by visual inspection, and noisy channels were identified and rejected using a 2.5% probability threshold and visual inspection. Each trial will last 1000ms and consist of 100ms of pre-stimulus presentation, 500ms of stimulus presentation, and 1000ms of stimulus recording. The intertrial interval was 500 to 700ms. For the ERP analysis, window time was selected to establish where to determine the components of interest, which were identified relative to the number of major positive and negative peaks following stimulus onset. All time window values were relative to stimulus onset, and the peak amplitudes were calculated relative to the baseline amplitude. Statistical analyses were conducted with SPSS software version 25.0.1 (SPSS Inc., Chicago, IL, USA). Behavioral measures were reaction time and accuracy. Electrophysiological measures were peak amplitude and latency for N2 and amplitude for P300. Covariates that indicated group differences were considered in subsequent analyses as potential confounders.

Age-appropriate EF Psychometric Assessments will be used to evaluate executive functions. The EFECO assessment that are the abbreviation Evaluation of executive function throughout conductual observation. The questionnaire will be filled by the adult in charge of the participant.

Conditions

Child Development

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

FM EM

During the first year of life the participants received

1. regular formula milk

2. enriched with Milk Fat Membrane Globule formula

Imaging

Intervention Type: DIAGNOSTIC_TEST

The participants will be assessed with a brain MRI and will performed a neurophysiological test to evaluate executive functions

Interventions

Imaging

The participants will be assessed with a brain MRI and will performed a neurophysiological test to evaluate executive functions

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Event related potential test

Eligibility Criteria

Exclusion Criteria

-

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Corporación de Apoyo de la Investigación Científica en Nutrición

OTHER

Sponsor Role: lead

Responsible Party

Cecilia Algarin

Adjunct Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patricio Peirano, MD

Role: STUDY_DIRECTOR

University of Chile

Locations

CINUT

Santiago, RM, Chile

Countries

Chile

Other Identifiers

MJCINUT8736

Identifier Type: -

Identifier Source: org_study_id