The Combination of Maternal Risk Factors and Functional/Structural Connectivity in Fetuses and Neonates to Predict Neurodevelopment From Birth Through Early Childhood: A Single-Center Observational Cohort Study
Trial ID: NCT07059286
Status: ENROLLING_BY_INVITATION
Study type: OBSERVATIONAL
Start date: 2025-07
Completion date: 2033-01
Sponsor: IRCCS San Raffaele
Conditions: Pregnancy; Neurodevelopment; Brain Connectivity; Neurodevelopment Outcome
Interventions: Maternal Frailty Inventory (MaFra) Questionnaire; Fetal Resting-State Functional MRI; Maternal Emotional Reactivity; Neonatal Resting-State Functional MRI; Longitudinal Neurodevelopmental Testing Battery
Locations: Neuroradiology Unit and CERMAC, IRCCS Ospedale San Raffaele
Countries: Italy
Enrollment: 160
Age range: 18 Years - None
Sex: FEMALE

Summary:
This study aims to understand how a pregnant woman's health, lifestyle, and psychological state-especially when associated with known risk factors-might influence the developing brain of her baby, both before and after birth. Specifically, the research investigates whether differences in brain connectivity observed through fetal and neonatal magnetic resonance imaging (MRI) can predict how a child will develop cognitively, emotionally, and behaviorally from birth through early childhood.

This is a prospective, observational study that will follow 160 pregnant women and their children over time. Participants will be enrolled at the Gynecology and Obstetrics Unit of San Raffaele Hospital in Milan. Using advanced brain imaging techniques (resting-state functional MRI), the study will examine how key brain systems-such as those involved in movement, hearing, vision, language, and attention-are connected during fetal life and shortly after birth. The study also evaluates how these patterns of brain connectivity relate to later developmental outcomes, assessed through standard neuropsychological tests from birth up to 6 years of age.

One of the study's core hypotheses is that early patterns of brain connectivity-especially when combined with detailed profiles of maternal health and risk-can serve as early markers of a child's neurodevelopmental path. To explore this, the study uses an integrated approach that combines imaging data with clinical and psychological information from the mother (e.g., her stress levels, medical history, and lifestyle habits).

Participants are grouped based on the "Maternal Frailty Inventory," a tool that captures the cumulative risk profile of each mother. The sample will include mothers with both low and medium-high risk scores. This grouping allows researchers to investigate how varying degrees of maternal risk are reflected in the baby's early brain organization and how this, in turn, influences developmental milestones.

A secondary aim of the study is to investigate how emotional responses to music may affect fetal brain activity. During the fetal MRI, mothers will listen to selected musical pieces. Researchers will examine if the baby's brain is influenced by the mother's emotional state.

Ultimately, the study hopes to build predictive models-using artificial intelligence and advanced statistical techniques-that can estimate a child's developmental trajectory based on early brain imaging and maternal data. This could provide an important step toward early identification of children who might benefit from developmental support or intervention, even before symptoms appear.

Eligibility criteria:
Inclusion Criteria:

* Pregnant women (biologically female) receiving care at the Gynecology and Obstetrics Unit, San Raffaele Hospital, Milan.
* Age ≥ 18 years at time of enrollment.
* Singleton pregnancy.
* Gestational age within the range suitable for fetal MRI acquisition (typically 24-35 weeks gestation).
* Willing and able to provide written informed consent.
* Willing to undergo fetal and/or neonatal resting-state fMRI as part of the observational study protocol.
* Willing to complete maternal questionnaires assessing clinical, lifestyle, and emotional factors (e.g., MaFra Inventory, anxiety scales).
* Willing to participate in postnatal follow-up assessments of the child, including neurodevelopmental evaluations from birth to 72 months.
* Fetuses with normal brain morphology confirmed by structural MRI.
* Fetuses and neonates without signal alterations on structural MRI.

Exclusion Criteria:

* Twin or multiple gestation pregnancies.
* Fetal diagnosis of any major structural or genetic anomaly known to impact neurodevelopment.
* Evidence of fetal brain parenchymal signal alterations or neurodevelopmental abnormalities as assessed by structural MRI and confirmed by an experienced neuroradiologist.
* Maternal contraindications to undergoing MRI (e.g., presence of non-MRI-compatible implants or severe claustrophobia).

Outcomes:
Correlation Between Fetal and Neonatal Functional Connectivity Markers and Neurodevelopmental Scores; Accuracy of AI-Based Predictive Models for Estimating Neurodevelopmental Outcomes.