Maternal Risk, Fetal-Neonatal Brain Connectivity, and Early Neurodevelopment: A Longitudinal Observational Study

Enrolling by invitationOBSERVATIONAL
Enrollment

160

Participants

Timeline

Start Date

July 31, 2025

Primary Completion Date

November 30, 2031

Study Completion Date

January 31, 2033

Conditions
PregnancyNeurodevelopmentBrain ConnectivityNeurodevelopment Outcome
Interventions
BEHAVIORAL

Maternal Frailty Inventory (MaFra) Questionnaire

A validated psychometric inventory designed to assess maternal clinical, psychological, and lifestyle risk factors during pregnancy. The composite risk score is used to stratify participants into low- or medium/high-risk categories. Administered during pregnancy, the inventory informs classification and predictive modeling of fetal and child neurodevelopmental outcomes.

DIAGNOSTIC_TEST

Fetal Resting-State Functional MRI

Non-invasive resting-state functional MRI scans performed during gestation (fetal) life to assess functional connectivity across sensorimotor, auditory, visual, language, and attention networks. Imaging data are analyzed to derive local and global connectivity measures and indices of segregation and integration among functional brain systems. Structural MRI is used to confirm normal brain morphology.

BEHAVIORAL

Maternal Emotional Reactivity

During fetal rs-fMRI acquisition, mothers listen to emotionally evocative musical excerpts while rating their emotional responses. These self-reported ratings (valence and arousal) are later correlated with fetal brain connectivity responses.

DIAGNOSTIC_TEST

Neonatal Resting-State Functional MRI

Non-invasive MRI scanning protocol conducted during the neonatal period to acquire resting-state functional MRI (rs-fMRI) data. The scan is performed while the newborn is in a natural sleep state, using motion-optimized sequences to assess functional connectivity between brain regions. The focus is on sensorimotor, auditory, visual, language, and attention networks. Structural MRI is also acquired to verify normative brain morphology. Imaging outcomes are used in longitudinal analyses to link early brain connectivity with cognitive and behavioral development.

BEHAVIORAL

Longitudinal Neurodevelopmental Testing Battery

Standardized neuropsychological and behavioral assessments are administered at multiple timepoints between birth and 72 months of age. Domains evaluated include sensorimotor skills, cognitive abilities, language development, executive function, social-emotional regulation, and adaptive behaviors. Data are used to compute specific and composite scores that reflect neurocognitive and behavioral profiles. These are later integrated with prenatal and neonatal brain imaging and maternal risk data to model individual neurodevelopmental trajectories.

Trial Locations (1)

20132

Neuroradiology Unit and CERMAC, IRCCS Ospedale San Raffaele, Milan

All Listed Sponsors
lead

IRCCS San Raffaele

OTHER