An interventional study of Multidomain Neuropsychological and Reading-Free Screening Tool (RSFT) Assessment Battery - Grade 2 and MRI - Grade 2 in Preterm Birth and Developmental Dyslexia, sponsored by Università Vita-Salute San Raffaele. Enrolling by invitation at 1 site in Italy. Open to participants aged 6 Years to 9 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-07-18.
Sponsored by Università Vita-Salute San Raffaele · Not applicable, Interventional, and Screening
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.
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.
2,550 studies on the registry are indexed under Premature Birth; 500 are open to participants now.
This study's planned enrollment of 45 is below the median of 84 across 1,666 interventional studies indexed under Premature Birth.
Browse Premature Birth studies →Università Vita-Salute San Raffaele is the lead sponsor of 85 studies on the registry; 33 are open to participants now.
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For Preterm-Born (PTB) Children:
For At-Term-Born (ATB) Children:
Exclusion Criteria:
For Preterm-Born (PTB) Children:
For At-Term-Born (ATB) Children:
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Contraindication
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Preterm-born children group
Behavioral: Multidomain Neuropsychological and Reading-Free Screening Tool (RSFT) Assessment Battery - Grade 2 · Diagnostic Test: MRI - Grade 2 · Behavioral: Multidomain Neuropsychological and Reading-Free Screening Tool (RSFT) Assessment Battery - Grade 3
At-term-born children group
Behavioral: Multidomain Neuropsychological and Reading-Free Screening Tool (RSFT) Assessment Battery - Grade 2 · Diagnostic Test: MRI - Grade 2 · Behavioral: Multidomain Neuropsychological and Reading-Free Screening Tool (RSFT) Assessment Battery - Grade 3
* Behavioral testing: standardized neuropsychological battery (language, reading, attention, memory, intelligence) * RFST: Reading-Free Screening Tool assessing pre-reading cognitive markers
■ Diagnostic Imaging: structural and resting-state functional MRI (T1-weighted and rs-fMRI)
* Behavioral testing: standardized neuropsychological battery (language, reading, attention, memory, intelligence) * RFST: Reading-Free Screening Tool assessing pre-reading cognitive markers
Change in RFST Auditory Modality Composite Score From Grade 2 to Grade 3 in Preterm Children
Composite score summarizing auditory-based sensorimotor, timing, discrimination, and inhibitory control abilities measured via the ReadFree Screening Tool (RFST) auditory modality tasks. Includes: * Auditory Reaction Time (median RTs of 8 trials) * Tapping and Entrainment to Metronome (tapping onset) * Free Tapping (motor rhythm without auditory cue) * Tone Discrimination (smallest perceptible pitch interval) * Cocktail Party Task (d-prime, target detection in multitalker noise) * Auditory Go/No-Go (d-prime, inhibition) * Auditory Anticipatory Timing (tapping onset accuracy) Each task is z-scored and aggregated into a single composite. Higher scores indicate better auditory sensorimotor and temporal processing.
Time frame: From Grade 2 baseline to Grade 3 follow-up assessment (approx. 8-10 months)
Change in RFST Visual Modality Composite Score From Grade 2 to Grade 3 in Preterm Children
Composite score summarizing visual-based sensorimotor, discrimination, and inhibitory control abilities from the RFST visual modality tasks. Includes: * Visual Reaction Time (median RTs of 8 trials) * Tapping and Entrainment to Visual Cue (tapping onset) * Free Tapping (motor rhythm without visual cue) * Grey-Scale Discrimination (smallest perceptible luminance interval) * Visual Go/No-Go (d-prime, visual inhibition) * Visual Anticipatory Timing (accuracy of tapping onset) * RAN-Shapes (number of shapes named in 30s) Each score is converted to z-units and averaged to yield a composite metric. Higher scores indicate better visual-motor and perceptual timing performance.
Time frame: From Grade 2 baseline to Grade 3 follow-up assessment (approx. 8-10 months)
Grade 2 Composite Language Score in Preterm Children
A standardized composite language score derived from z-transformed or scalar scores of the following assessments: * Phoneme Deletion * BVL Auditory Discrimination (HIT-False Alarm Index, range: -100% to +100%) * NEPSY-II Subtests: L1, L3, L4, L5. The composite reflects mean z-scores (normalized against internal sample distribution) across all measures. Higher scores indicate better language functioning.
Time frame: Grade 2 baseline assessment
Grade 2 Composite Attention Score in Preterm Children
A composite attention score computed from standardized or scalar scores across the following assessments: * Colored Raven Matrices (Percentiles by age: 3rd-95th) * NEPSY-II Subtests: * A1 Visual Search * A2 Figural Fluency * A3 Auditory Attention * A4 Inhibition (Time; Accuracy) * A6 Categorization Each test is converted to a z-score and averaged for a domain-wide summary score. Higher scores indicate better attention performance.
Time frame: Grade 2 baseline assessment
Grade 2 Composite Reading Score in Preterm Children
Composite score combining metrics from multiple timed and accuracy-based reading assessments: * Lapel Reading Song (Words per minute: 21-157; Errors: 0-10) * PIN Reading (Words and Pseudo-words): * Reading Time * Syllables/sec * Number of Errors Each metric is z-normalized and averaged per task, then aggregated for a domain-level composite. Higher composite scores indicate better learning performance.
Time frame: Grade 2 baseline assessment
Grade 2 Resting-State fMRI Network Segregation Score in Preterm Children
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
Grade 2 Resting-State fMRI Network Integration Score in Preterm Children
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 2 baseline MRI session
Language Score at Grade 3 in Preterm Children
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
Composite Attention Score at Grade 3 in Preterm Children
This outcome reflects attentional functioning based on multiple neuropsychological measures, aggregated as a domain-level composite. Tests include: * Mea Figural Fluency (percentiles) * Mea Cancellation (Sheets 5 \& 10) (percentiles) * Mea PASOT (percentiles) * Mea Categorization (percentiles) * Colored Raven Matrices (age-based percentiles) * BVN Forward and Backward Span (z-scores or percentiles by age) * Prose Memory (number of correctly recalled morphological units; max 34) * VAUMELF - Repetition of Non-Words (correctness score, range: 0-40) Each test score is standardized (z-transformed or percentile-normalized as appropriate) and averaged into a single composite score representing domain-level attentional performance. Higher composite values indicate better attention function.
Time frame: Grade 3 follow-up assessment (8-10 months post-baseline)
Composite Reading Score at Grade 3 in Preterm Children
This outcome reflects reading and learning-related cognitive performance based on the following assessments: * MT3 Clinics Song Reading (Syllables/sec; number of errors; percentiles from 5th-90th) * DDE-2 Reading Words (z-score of speed and accuracy) * DDE-2 Reading Non-Words (z-scores of speed and accuracy) * BVSCO-3 Sentence Dictation (total errors; percentiles from 5th-95th) * AC-MT Judgment of Magnitude (number of correct responses; 5th-90th percentiles) * BDE-2 Triplets (total correct responses; clinical bands and percentile ranks) 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 3 follow-up assessment
Grade 2 Global Efficiency Score from Resting-State Functional Connectivity in Preterm Children
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.
Time frame: Grade 2 baseline assessment
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