Reading-FREE Markers for Early Detection of Developmental Dyslexia

NCT07072104 | Enrolling By Invitation DMC

• 2 other identifiers: CET 501-2024PRIN - Prot. 2022TA92HS
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Preterm Birth; Developmental Dyslexia

Keywords

Preterm birth; developmental dyslexia; reading-FREE; MRI; neurodevelopment

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  Grade 2 baseline MRI session

Secondary Outcomes (3)

• Language Score at Grade 3 in Preterm Children

  Grade 3 follow-up assessment

• Composite Attention Score at Grade 3 in Preterm Children

  Grade 3 follow-up assessment (8-10 months post-baseline)

• Composite Reading Score at Grade 3 in Preterm Children

  Grade 3 follow-up assessment

Other Outcomes (1)

• Grade 2 Global Efficiency Score from Resting-State Functional Connectivity in Preterm Children

  Grade 2 baseline assessment

Study Arms (2)

PTB

EXPERIMENTAL

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

ATB

EXPERIMENTAL

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

Interventions

Multidomain Neuropsychological and Reading-Free Screening Tool (RSFT) Assessment Battery - Grade 2 BEHAVIORAL

* Behavioral testing: standardized neuropsychological battery (language, reading, attention, memory, intelligence) * RFST: Reading-Free Screening Tool assessing pre-reading cognitive markers

ATB; PTB

MRI - Grade 2 DIAGNOSTIC_TEST

■ Diagnostic Imaging: structural and resting-state functional MRI (T1-weighted and rs-fMRI)

ATB; PTB

Multidomain Neuropsychological and Reading-Free Screening Tool (RSFT) Assessment Battery - Grade 3 BEHAVIORAL

* Behavioral testing: standardized neuropsychological battery (language, reading, attention, memory, intelligence) * RFST: Reading-Free Screening Tool assessing pre-reading cognitive markers

ATB; PTB

Eligibility Criteria

• Age: 6 Years - 9 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• For Preterm-Born (PTB) Children:
• Born preterm (i.e., gestational age \< 39 weeks)
• Aged between 6 and 9 years at enrollment
• Absence of structural brain lesions (as assessed by prior clinical imaging)
• Italian as the first language (L1)
• Right-hand dominant
• Male or female
• For At-Term-Born (ATB) Children:
• Born at term (i.e., gestational age between 39 and 42 weeks)
• Aged between 6 and 9 years at enrollment
• Absence of structural brain lesions (as assessed by prior clinical imaging)
• Italian as the first language (L1)
• Right-hand dominant
• Male or female

You may not qualify if:

• For Preterm-Born (PTB) Children:
• History of congenital infections
• Diagnosis of Multiple Congenital Anomalies Syndrome
• Presence of focal intracerebral parenchymal lesions
• Pathological findings on conventional MRI
• For At-Term-Born (ATB) Children:
• Presence of first-degree relatives diagnosed with developmental dyslexia (DD)
• Diagnosis of other learning or behavioral disorders
• Contraindications to MRI (e.g., metal implants, severe claustrophobia)

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead
• University of Urbino "Carlo Bo": collaborator
• University of Milano Bicocca: collaborator

Study Sites (1)

Neuroradiology Unit and CERMAC, IRCCS Ospedale San Raffaele

Milan, MI, 20132, Italy

Location

Related Publications (4)

• Canini, M., Cara, C., Oprandi, C., Katušić, A., Žunić Išasegi, I., Messina, A., Zambon, A. A., Pecco, N., Barni, S., Poloniato, A., Natali Sora, M. G., Falautano, M., Scifo, P., Barera, G., Tettamanti, M., Falini, A., Baldoli, C., & Della Rosa, P. A. (2025). Functional connectivity markers of prematurity at birth predict neurodevelopmental outcomes at 6, 12, 24, and 36 months. International Journal of Behavioral Development, 0(0). https://doi.org/10.1177/01650254241312136

  BACKGROUND

• Della Rosa PA, Canini M, Marchetta E, Cirillo S, Pontesilli S, Scotti R, Natali Sora MG, Poloniato A, Barera G, Falini A, Scifo P, Baldoli C. The effects of the functional interplay between the Default Mode and Executive Control Resting State Networks on cognitive outcome in preterm born infants at 6 months of age. Brain Cogn. 2021 Feb;147:105669. doi: 10.1016/j.bandc.2020.105669. Epub 2020 Dec 17.

  PMID: 33341657 BACKGROUND

• Baldoli C, Scola E, Della Rosa PA, Pontesilli S, Longaretti R, Poloniato A, Scotti R, Blasi V, Cirillo S, Iadanza A, Rovelli R, Barera G, Scifo P. Maturation of preterm newborn brains: a fMRI-DTI study of auditory processing of linguistic stimuli and white matter development. Brain Struct Funct. 2015 Nov;220(6):3733-51. doi: 10.1007/s00429-014-0887-5. Epub 2014 Sep 23.

  PMID: 25244942 BACKGROUND

• Carioti D, Stucchi NA, Toneatto C, Masia MF, Del Monte M, Stefanelli S, Travellini S, Marcelli A, Tettamanti M, Vernice M, Guasti MT, Berlingeri M. The ReadFree tool for the identification of poor readers: a validation study based on a machine learning approach in monolingual and minority-language children. Ann Dyslexia. 2023 Oct;73(3):356-392. doi: 10.1007/s11881-023-00287-3. Epub 2023 Aug 7.

  PMID: 37548832 BACKGROUND

MeSH Terms

Conditions

Premature Birth; Dyslexia

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Specific Learning Disorder; Learning Disabilities; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Andrea Falini, Doctor of Medicine

  1. Vita-Salute San Raffaele University, Milan, Italy 2. Neuroradiology Unit and CERMAC, IRCCS Ospedale San Raffaele, Milan, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor of Neuroradiology

Model Details: This study follows a parallel assignment interventional model, involving two distinct groups: preterm-born (PTB) and term-born (ATB) children. Although no therapeutic intervention is administered, both groups undergo the same structured assessments at two time points, including behavioral screening, neuropsychological testing, and neuroimaging in Grade 2 and neuropsychological testing in Grade 3. The parallel design enables between-group comparisons to identify early neurocognitive and connectomic markers associated with the development of reading skills in children born preterm. The model supports hypothesis-driven evaluation of group-specific developmental trajectories using standardized procedures across cohorts.

Study Record Dates

• First Submitted: June 25, 2025
• First Posted: July 18, 2025
• Study Start: July 1, 2025
• Primary Completion: January 1, 2026
• Study Completion: February 28, 2026
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)