Predictive BioMArkers of AlTERed NeurologicAL Trajectories Consequent to PrenataL InflammatorY Insults

NCT06852703 | Recruiting

• 1 other identifier: ID 18657
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Inflammation during pregnancy represents an important risk factor for the development of neuropsychiatric disorders in the offspring. Despite clear epidemiological data supporting this association, translational studies aimed at identifying early predictive biomarkers and possible interventional strategies for this pathological condition are still missing. The MATERNALLY proposal aims to assess in a large patient cohort a novel multiparametric approach for the identification of predictive postnatal behavioral and circulating biomarkers. In parallel, a controlled mouse model for maternal immune activation will be exploited to understand the basic molecular mechanism that links inflammation with aberrant neural circuit formation and to unveil possible therapeutic targets. The integration of the two approaches will allow identifying early predictive biomarkers and proof of principle interventional strategies for this condition of high practical relevance to the neonatologist community

Conditions

Biomarkers; Neurodevelopmental Disorders; Inflammation, Brain

Outcome Measures

Primary Outcomes (7)

• Biomarkers analysis on blood samples collected from healthy and infected mothers

  Assesment of the immune profile in both cohorts recruited. In particular, we will measure the circulating levels of IL-6, CRP, PCT, TSH and Vitamine D at 20 and 30 weeks gestation to obtain a longitudinal immune profile across gestation. The analysis will be carried out using ELISA kit in the serum collected from both cohorts.

  32 month

• Sonographic examination at fetal level

  Brain ultra-sound study involves axial, coronal and sagittal planes to obtain qualitative anatomic parameters related to Head shape, Integrity of falx cerebri,, Cavum septum pellucidum, Thalami, Insulae lobes, Cerebral hemispheres, Third and fourth ventricles, Parieto-occipital fissure

  Once during the second and the third trimester of pregnancy

• Sonographic examination at fetal level

  Brain ultra-sound study involves axial, coronal and sagittal planes to obtain quantitative anatomic parameters related to (in mm) Head circumference and biparietal diameter (axial plan), Antero-posterior diameter of corpus callosum (sagittal plan), Cerebellum (axial plan), Cerebellar vermis, cranio-caudal diameter (sagittal plan), Lateral ventricles, latero-lateral diameter (axial plan), Cisterna magna, antero-posterior diameter (axial plan)

  Once during the second and the third trimester of pregnancy

• Sonographic examination at fetal level

  Brain ultra-sound study involves axial, coronal and sagittal planes to obtain quantitative anatomic parameters (in angle) related to Sylvian fissure (coronal plan)

  Once during the second and the third trimester of pregnancy

• Sonographic examination at fetal level

  Quantitative and qualitative evaluation of fetal movements including, Flexion and extension of fetal of arms or legs, Sucking movements, Swallowing movements, Situation changes (longitudinal or trasversal) or presentation changes (cephalic, breech), Breathing movements

  Once during the second and the third trimester of pregnancy

• Newborns: assessment of spontaneous movements

  Assessment of spontaneous movements based on Prechtl method of general movements assessment. From longitudinal videorecordings performed by the parents in a structured home setting, we will assess the GM optimality score. The scale between 0 and 38 points from 0-9 weeks post-term; and 5-28 points from 10-20 weeks post-term. A lower score means poorer predicted motor outcome

  3 times between birth and 20 weeks post-term

• Infant behavioral and motor assessment

  Infant behavioral and motor assessment according to Alberta Infant Motor Scale. The scale is between 0 and 58 points. A lower score on the Alberta Infant Motor Scale (AIMS) indicates delayed or less advanced motor development

  12 months infant age

Secondary Outcomes (4)

• Newborns: Magnetic resonance imaging (MRI)

  Once between birth and 8 weeks infant age

• Newborns: Magnetic resonance imaging (MRI)

  Once between birth and 8 weeks infant age

• Newborns: Magnetic resonance imaging (MRI)

  Once between birth and 8 weeks infant age

• Newborns: Magnetic resonance imaging (MRI)

  Once between birth and 8 weeks infant age

Study Arms (2)

Control

healthy mothers

diseased

Infected mothers

Other: Infection during pregnancy

Interventions

Infection during pregnancy OTHER

any bacterial or viral infection acquired during pregnancy

diseased

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Not applied

You may qualify if:

• Age between 18 and 40 years. BMI between 18 kg/m2 and 25 kg/m2. Negative remote medical history for chronic conditions (rheumatological, immunological, endocrinological).
• Negative obstetric history for significant pathologies (pre-eclampsia, gestational diabetes, preterm birth).
• Reassuring combined test

You may not qualify if:

• Pre-gestational diabetes
• Multiple pregnancy
• Threatened preterm labor and/or premature rupture of membranes
• Pre-eclampsia
• Intrauterine growth restriction (IUGR)
• Fetal macrosomia (biometrics \>90th percentile)
• Chromosomal syndromes, genetic conditions, or multiple fetal malformations or major fetal malformations
• Withdrawal of informed consent
• Smoking patients are not excluded from the study, nor are patients who develop gestational diabetes during pregnancy.

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead
• IRCCS Fondazione Stella Maris: collaborator
• Azienda Ospedaliero, Universitaria Pisana: collaborator

Study Sites (1)

AOUP

Pisa, PI, 56126, Italy

RECRUITING

MeSH Terms

Conditions

Neurodevelopmental Disorders; Encephalitis

Condition Hierarchy (Ancestors)

Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Central Study Contacts

Antonella Pisano, Dr.

CONTACT

+39 02 82244501; contratti.ricerca@humanitas.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2024
• First Posted: February 28, 2025
• Study Start: September 1, 2021
• Primary Completion: April 30, 2024
• Study Completion: August 31, 2025
• Last Updated: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)