Neuroradiology Unit and CERMAC, IRCCS Ospedale San Raffaele
Milan, MI, 20132, Italy
NCT Number: NCT07072104
This study aims to identify early signs of developmental dyslexia (DD) and other reading difficulties in children born preterm, using behavioral, cognitive, and brain imaging data collected before reading problems typically become noticeable. Children born very early often face greater risk for reading and learning challenges, but these difficulties are not always detected in time for early support. This research seeks to fill that gap. A group of 30 children born preterm will be followed over time, alongside a control group of 15 children born at term. All children will be assessed during the second and third years of primary school (around ages 6-9). In Grade 2, children will undergo (a) a specially designed digital screening tool for reading difficulties that does not require actual reading (called the RFST), (b) standard tests of reading, language, and attention, and (c) structural and functional brain scans using Magnetic Resonance Imaging (MRI). In Grade 3, the children will be reassessed using the RFST and the cognitive and language tests. The goal is to identify specific behavioral and brain-based markers-particularly patterns of brain connectivity-that are already present in Grade 2 and can predict which children will go on to show reading difficulties in Grade 3. By comparing data from preterm and term-born children, researchers aim to discover early warning signs that are specific to children born preterm. By detecting these risks early, before reading delays become severe, the study hopes to guide new tools for screening and early intervention, tailored specifically to the unique developmental paths of children born preterm. This could help prevent later academic struggles and promote better long-term outcomes.
Interested in participating?
Request Info6 year–9 year
All sexes
Interventional
Not applicable
Milan, MI, 20132, Italy
This longitudinal study, titled "Longitudinal assessment of multidomain reading-FREE neurocognitive markers for early detection of Developmental Dyslexia (FREE-DD)", investigates early neurocognitive predictors of developmental dyslexia (DD) and related reading disorders in children born preterm (PTB), as compared to children born at term (ATB). Children born preterm are at elevated risk for neurodevelopmental vulnerabilities, including difficulties with language, attention, and reading acquisition, yet early identification of these risks remains limited.
The main objective of the study is to identify early connectomic and neurocognitive markers-obtained during second grade-that can predict the development of reading difficulties in PTB children by third grade. Particular emphasis is placed on connectomic features derived from functional and structural brain imaging, as well as on a specially designed behavioral tool: the Reading-Free Screening Tool (RFST), which assesses reading-related cognitive abilities without requiring the child to read.
The study adopts a prospective, longitudinal, monocentric cohort design, with two assessment waves:
The study population includes 30 preterm-born (PTB) children and 15 term-born (ATB) children, all aged between 6 and 9 years, native Italian speakers, and right-handed. Children with structural brain lesions, congenital anomalies, or known neurological/psychiatric conditions will be excluded.
Primary Objective The primary goal is to determine whether functional brain network characteristics (measured via resting-state fMRI), along with morpho-structural, microstructural, and cognitive metrics collected at grade 2, can predict changes in RFST performance and reading skills between grade 2 and grade 3.
Secondary Objectives
Secondary aims include:
Exploratory Objectives The study also seeks to explore the role of combined behavioral and neuroimaging data in outlining early neurocognitive trajectories specific to prematurity, which may indicate susceptibility to developmental dyslexia and related disorders. These exploratory outcomes will help refine developmental models and screening strategies.
Methodology
Participants will complete:
Analysis will proceed in three main steps:
Timeline and Duration
The findings from this study aim to inform the development of screening tools and targeted early interventions for children born preterm, potentially reducing the long-term impact of developmental dyslexia and enhancing academic and cognitive outcomes.
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
For Preterm-Born (PTB) Children:
For At-Term-Born (ATB) Children:
Exclusion criteria
For Preterm-Born (PTB) Children:
For At-Term-Born (ATB) Children:
■ Diagnostic Imaging: structural and resting-state functional MRI (T1-weighted and rs-fMRI)
Time frame: From Grade 2 baseline to Grade 3 follow-up assessment (approx. 8-10 months)
Composite score summarizing auditory-based sensorimotor, timing, discrimination, and inhibitory control abilities measured via the ReadFree Screening Tool (RFST) auditory modality tasks. Includes:
Time frame: From Grade 2 baseline to Grade 3 follow-up assessment (approx. 8-10 months)
Composite score summarizing visual-based sensorimotor, discrimination, and inhibitory control abilities from the RFST visual modality tasks. Includes:
Time frame: Grade 2 baseline assessment
A standardized composite language score derived from z-transformed or scalar scores of the following assessments:
Time frame: Grade 2 baseline assessment
A composite attention score computed from standardized or scalar scores across the following assessments:
Time frame: Grade 2 baseline assessment
Composite score combining metrics from multiple timed and accuracy-based reading assessments:
Time frame: Grade 2 baseline MRI session
Resting-state functional connectivity-based modularity score, measuring the extent to which functional networks in the brain are subdivided into non-overlapping, highly interconnected communities. Higher modularity indicates greater network segregation.
Time frame: Grade 2 baseline MRI session
Participation coefficient derived from resting-state fMRI data, quantifying the extent to which brain nodes form diverse intermodular connections. Higher participation coefficient reflects greater network integration and communication between functional modules.
Time frame: Grade 3 follow-up assessment
The Peabody Picture Vocabulary Test (Italian version) is administered to assess receptive vocabulary. Raw scores are calculated by subtracting errors from the ceiling value. Age-standardized scores are derived from the raw score based on national norms. This outcome reflects language comprehension ability at Grade 3.
Time frame: Grade 3 follow-up assessment (8-10 months post-baseline)
This outcome reflects attentional functioning based on multiple neuropsychological measures, aggregated as a domain-level composite. Tests include:
Time frame: Grade 3 follow-up assessment
This outcome reflects reading and learning-related cognitive performance based on the following assessments:
Each raw test score is converted to a standardized value (z-score or percentile), and the resulting values are averaged to produce a single composite score. Higher scores indicate better learning and reading competence.
Time frame: Grade 2 baseline assessment
Global efficiency is computed as the average inverse shortest path length across the entire resting-state functional connectivity network. It reflects the brain's capacity for parallel information transfer across distributed regions. Higher scores indicate greater global integration and reduced communication cost across brain regions.
Università Vita-Salute San Raffaele
Other
Longitudinal Assessment of Multidomain Reading-FREE Neurocognitive Markers for Early Detection of Developmental Dyslexia (FREE-DD)
Acronym: FREE-DD
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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