Childhood Outcomes of Preterm Brain Abnormalities

April 9, 2024 updated by: Natasha Lepore, Children's Hospital Los Angeles

Predicting the Early Childhood Outcomes of Preterm Brain Shape Abnormalities

Prematurely born children are at higher risk of cognitive impairments and behavioral disorders than full-term children. There is growing evidence of significant volumetric and shape abnormalities in subcortical structures of premature neonates, which may be associated to negative long-term neurodevelopmental outcomes. The general objective is to look directly at the long-term neurodevelopmental implications of these neonatal subcortical structures abnormalities. Investigators propose to develop biomarkers of prematurity by comparing the morphological and diffusion properties of subcortical structures between preterm, with and without associated brain injuries, and full-term neonates using brain MRI. By combining subcortical morphological and diffusion properties, investigators hypothesize to be able to: (1) delineate specific correlative relationships between structures regionally and differentially affected by normal maturation and different patterns of white matter injury, and (2) improve the specificity of neuroimaging to predict neurodevelopmental outcomes earlier. The specific aims and general methodology are: 1) Build a new toolbox for neonatal subcortical structures analyses that combine a group lasso-based analysis of significant regions of shape changes, a structural correlation network analysis, a neonatal tractography, and tensor-based analysis on tracts; 2) Ascertain biomarkers of prematurity in neonates with different patterns of abnormalities using correlational and connectivity analysis within and between structures features; 3) Assess the predictive potential of subcortical imaging on neurodevelopmental outcomes by correlating neonatal imaging results with long-term neurodevelopmental scores at 9 and 18 months, and 6-8 years, follow-up. In each of these aims, investigators will use advanced neuroimaging analysis developed by their group and collaborator, including multivariate tensor-based morphometry and multivariate tract-based analysis. This application will provide the first complete subcortical network analysis in both term and preterm neonates. In the first study of its kind for prematurity, investigators will use sparse and multi-task learning to determine which of the biomarkers of prematurity at birth are the best predictors of long-term outcome. Once implemented, these methods will be available to compare subcortical structures for other pathologies in newborns and children.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Detailed Description

The last months of pregnancy are particularly important for the development of the child's brain, and the consequences of premature birth on its development can be substantial. Prematurely born children are at higher risk of various cognitive impairments and exhibits more behavioral disorders than full-term born children. Thus early detection and management of at risk children are essential. There is growing evidence of significant volumetric abnormalities in subcortical structures of premature neonates, which may be associated to negative long-term neurodevelopmental outcomes. Understanding these abnormalities could help elucidate the underlying pathophysiology and enable early determination of at-risk patients, both of which would inform the design of novel treatment strategies. However, to date there is still a lack of sensitive, reliable, and accessible algorithms capable of characterizing the influence of prematurity on the anatomy of neonatal brain subcortical structures. In addition, few studies have looked directly at the long-term neurodevelopmental implications of these neonatal subcortical structures abnormalities. Predicting long-term neurodevelopmental outcomes early on - and preferably at neonatal ages - is likely to have a transformative effect on their outcome. Our preliminary data indicate significant morphological differences in the putamen, ventricles, corpus callosum, and thalamus between preterm and term neonates. Investigators propose to develop biomarkers of prematurity by statistically comparing the morphological and diffusion properties of subcortical structures between preterm and term neonates using brain MRI. These results will further be used in a sparse learning framework to predict long-term neurodevelopmental outcomes of prematurity. Hypotheses: By combining subcortical morphological and diffusion properties, we will be able to: (1) delineate specific correlative relationships between structures regionally and differentially affected by normal maturation and different patterns of white matter injury, and (2) improve the specificity of neuroimaging to predict neurodevelopmental outcomes earlier. Aim 1: Build a new toolbox for neonatal subcortical structures analyses that combine 1) a group lasso-based analysis of significant regions of shape changes, 2) a structural correlation network analysis, 3) a neonatal tractography, and 4) tensor-based analysis on tracts. Aim 2: Ascertain biomarkers of prematurity in neonates with different patterns of abnormalities. Aim 3: Assess the predictive potential of imaging and clinical features on neurodevelopmental outcomes among premature children at 9 and 18 months and 6-8 years of age. Impact: This application will provide the first complete subcortical network analysis in both term and preterm neonates. In the first study of its kind for prematurity, investigators will use sparse and multi-task learning to determine which of the biomarkers of prematurity at birth are the best predictors of long-term outcome. The expected findings could improve the ability to predict these outcomes and enable the design of early treatments - before years of pathological brain development and symptoms occur.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Contacts and Locations

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Study Contact

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Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Children's Hospital Los Angeles
        • Contact:

Participation Criteria

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Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 8 years (Child)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Our MRI data will consist of two separate neonatal cohorts. Cohort 1 is an existing dataset of neonates scanned in Pittsburgh as part of a separate completed grant. This cohort was scanned at neonatal equivalent age and will be brought back for childhood neurodevelopmental outcomes at 6-8 years of age. Cohort 2 will be a new prospectively recruited cohort that will be scanned in Los Angeles as part of this proposal and will be brought back for infant neurodevelopmental outcome at 9 and 18 months.

Description

Inclusion Criteria:

  • Preterm birth (Gestational Age 21-36 weeks)
  • English or Spanish speaking families
  • PVL and Grade I and II IVH will be considered

Exclusion Criteria:

  • Shunt
  • Intubation, Cpap, Nasal Ventilation
  • Chromosomal/Genetic abnormalities
  • Mitochondrial/Metabolic Diseases
  • Treatment for extracorporeal membrane oxygenation (ECMO)
  • Grade III and IV IVH (optional)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Infant Control Group
The control arm (term born Infants) will receive an MRI at neonatal age and neurodevelopmental follow-up assessments, investigators will then compare significant morphological and diffusion properties within the brain to those of a Preterm brain.
Diagnostic test: MRI
MRI analysis
Diagnostic test: Neurodevelopmental/Neuropsychological Assessment
Standardized Cognitive and Developmental Tests
Infant Preterm Group
The experimental group will consist of preterm infants, who will receive an MRI at neonatal age and neurodevelopmental assessments. This groups scans will then be compared to those of the control arm. Significant biomarkers will then be identified.
Diagnostic test: MRI
MRI analysis
Diagnostic test: Neurodevelopmental/Neuropsychological Assessment
Standardized Cognitive and Developmental Tests
Childhood Control Group
The experimental group will consist of preterm born children aged 6-8 years, who received an MRI at neonatal age and will be called back for a neuropsychological assessment. This groups scans will then be compared to those of the children control arm. Significant biomarkers will then be identified.
Diagnostic test: Neurodevelopmental/Neuropsychological Assessment
Standardized Cognitive and Developmental Tests
Childhood Preterm Group
The experimental group will consist of term born children aged 6-8 years, who received an MRI at neonatal age and will be called back for a neuropsychological assessment. This groups scans will then be compared to those of the children preterm group. Significant biomarkers will then be identified.
Diagnostic test: Neurodevelopmental/Neuropsychological Assessment
Standardized Cognitive and Developmental Tests

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in Surface Area and Thickness of Subcortical Structures
Time Frame: 2018 - 2022
Measured in Voxel Size (mm)
2018 - 2022
Changes in Diffusion values of white matter Tracts
Time Frame: 2018 - 2022
Measured in mm squared per second
2018 - 2022
Differences in developmental Quotient / Neuropsychological scores
Time Frame: 2018 - 2022
Measured using standardized tests (Bayley-III and NIH toolbox)
2018 - 2022

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital Los Angeles

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Pittsburgh
Arizona State University

Publications and helpful links

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General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2018

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 19, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 24, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 25, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 10, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CHLA-17-00323

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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