Unveiling Maternal-fetal BRAin-body Interactions in Pregnant WOmen Affected by Depression (BRAWO)

November 6, 2026 updated by: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

The goal of this study is to learn how depression during pregnancy is linked to changes in the brain and body of the mother and to the development of the baby, in pregnant women with major depressive disorder (MDD) and pregnant women without depression.

The main questions it aims to answer are:

  • How common is major depressive disorder during pregnancy in a European multi-site cohort?
  • Do pregnant women with MDD show differences in hippocampal volume compared with pregnant women without depression?
  • Do maternal blood, placenta, cord blood, brain imaging and heart activity measures, and the brain and development of the babies, differ between the two groups?

Pregnant women will be screened within the 20th week of pregnancy and assigned to the MDD group or to the control group based on a structured clinical interview. They will not receive any study drug: women with depression will receive the usual care recommended by clinical guidelines.

Participants will:

  • Have clinical, psychiatric and psychological assessments (interviews and questionnaires) at screening, at 22, 26 and 32 weeks of pregnancy, at birth, and at 1 and 6 months after birth
  • Have a brain MRI with simultaneous EEG-ECG or photoplethysmography (PPG) at about 22 weeks of pregnancy
  • Have a fetal MRI by 22 weeks and fetal ultrasound scans at 22, 26 and 32 weeks
  • Give blood samples at 22, 26 and 32 weeks of pregnancy, and a cord blood sample at birth (placenta samples in a subgroup at the Milan center only)

Their newborns will have a neurological and visual examination, a brain MRI and an EEG-ECG or PPG recording after birth, and a developmental assessment (Bayley Scales) at 6 months.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

BRAWO is a non-pharmacological, international, multicenter, non-profit study conducted in Italy (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, coordinating center), Spain (Institute of Biomedicine of Seville, IBiS) and Germany (Philipps University Marburg). It implements Work Package 3 of the BRAWO research project, funded under the ERA-NET NEURON Joint Transnational Call 2024 "Bidirectional brain-body interactions".

The study is classified as interventional because it includes procedures that are not part of standard clinical care (maternal, fetal and neonatal MRI, EEG-ECG/PPG recordings, biological sampling). These procedures are non-invasive or minimally invasive. No investigational medicinal product is tested; women with MDD receive standard care, which may include SSRI antidepressants.

Groups:

  • Group 1: pregnant women with MDD diagnosed with the SCID-5-CV at screening
  • Group 2: pregnant women without current or past psychiatric disorders
  • Newborns of enrolled women, enrolled at birth after consent from both parents

Visits: V0 screening (within 20 gestational weeks, GW), V1 (by 22 GW), V2 (26 GW), V3 (32 GW), V4 (birth), V5 (1 month postpartum), V6 (6 months postpartum).

Maternal clinical assessments include clinician-rated scales (Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Global Assessment of Functioning) and self-rated questionnaires (EPDS, STAI Y1-2, SCL-90-R, CES-D); bonding, couple and family scales (MPAS, PBQ, ECR-R, RQI, DAS, FES, PSI-SF) are administered at 1 and 6 months postpartum.

Biological samples: maternal plasma at V1, V2 and V3, umbilical venous cord blood at birth, and placental tissue (elective cesarean deliveries, about 10 participants per group, Milan only). Proteomic analyses (LC-MS/MS) are centralized in Milan; placental samples also undergo RNA sequencing and histological analyses. With specific consent, residual samples are stored in the Policlinico biobank.

Neuroimaging and electrophysiology: maternal multimodal MRI (structural, diffusion, task and resting-state functional MRI) with simultaneous EEG-ECG (Milan) or ECG/PPG (Seville, Marburg); fetal MRI; neonatal MRI and EEG-ECG/PPG at 40+0 to 43+6 weeks of gestational age. Data are harmonized across sites (e.g., ComBat).

Sample size: a screening target of 600 pregnant women was calculated to estimate MDD prevalence (expected 15%, precision ±3.42%, 95% confidence level, 30% dropout). At least 60 women per group completing follow-up to 6 months postpartum provide >90% power to detect hippocampal volume differences (two-sample t-test, alpha 0.05). In total, 600 pregnant women and 120 newborns are expected to be enrolled. An interim analysis of dropout rate and data quality is planned at about half of enrollment.

Pre-collected data from a previous study at the coordinating center (MINI protocol) and publicly available data from the developing Human Connectome Project (dHCP) will be used to train multivariate, machine learning and dynamical systems models, which will be tested on BRAWO data to predict maternal and infant outcomes at 6 months.

Data are collected in REDCap and imaging data in XNAT.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
720

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Germany
    • Hesse
      • Marburg, Hesse, Germany, 35039
        • Not yet recruiting
        • Department of Psychiatry and Psychotherapy, Philipps University Marburg
  • Italy
    • Lombardy
      • Milan, Lombardy, Italy, 20122
        • Recruiting
        • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Spain
      • Seville, Spain, 41013
        • Not yet recruiting
        • Instituto de Biomedicina de Sevilla (IBiS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 45 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Pregnant women with major depressive disorder (Group 1):

  • Signed informed consent and ability to understand and provide it
  • Age between 18 and 45 years
  • IQ > 70 (4 subtests of WAIS-IV: Vocabulary, Similarities, Block Design, Matrix Reasoning)
  • Diagnosis of major depressive disorder according to the SCID-5-CV at screening (within 20 gestational weeks)

Pregnant women without depression (Group 2):

  • Signed informed consent and ability to understand and provide it
  • Age between 18 and 45 years
  • IQ > 70 (4 subtests of WAIS-IV: Vocabulary, Similarities, Block Design, Matrix Reasoning)
  • No current or past psychiatric disorders (SCID-5-CV)
  • No family history of psychiatric disorders (SCID-5-CV and FIGS)

Placental tissue sampling (Milan only, Groups 1 and 2):

  • Elective cesarean delivery
  • Absence of labor

Newborns:

  • Informed consent signed by both parents
  • Full-term birth (gestational age at birth of 37 weeks or more)

Exclusion Criteria:

Pregnant women (Groups 1 and 2):

  • History of head trauma with loss of consciousness
  • Neurological or degenerative disorders
  • Comorbid psychiatric disorders
  • Twin pregnancy
  • Pregnancy resulting from assisted reproductive technology with egg donation
  • History of perinatal alcohol or drug abuse
  • Infectious or autoimmune diseases
  • Use of systemic corticosteroids
  • Congenital, genetic or neurological disorders affecting the mother or the fetus
  • Body mass index (BMI) > 30
  • Severe prior obstetric conditions
  • Absolute or relative contraindications to MRI

Newborns:

  • Congenital, genetic or neurological disorder of the newborn

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Pregnant Women With Major Depressive Disorder (Group 1)

Pregnant women aged 18-45 years diagnosed with major depressive disorder (SCID-5-CV) at screening (within 20 gestational weeks), followed until 6 months postpartum, and their newborns. Participants receive standard clinical care for depression, which may include SSRI antidepressants; no study drug is administered.
Diagnostic test: Multimodal MRI and EEG-ECG/PPG recordings

Study-specific, non-invasive acquisitions: maternal brain MRI (structural, diffusion, task and resting-state fMRI) with simultaneous EEG-ECG (Milan) or ECG/PPG (Seville, Marburg) by 22 gestational weeks; fetal MRI by 22 gestational weeks; fetal ultrasound at 22, 26 and 32 gestational weeks; neonatal brain MRI and polygraphic EEG-ECG (Milan, Marburg) or MRI with PPG (Seville, Marburg) at 40+0 to 43+6 weeks of gestational age, during spontaneous sleep without sedation.

Procedure: Biological sampling

Maternal peripheral blood sampling at 22, 26 and 32 gestational weeks (plasma aliquots stored at -80 °C); umbilical venous cord blood sampling at birth; placental tissue sampling in a subgroup of about 10 participants per group with elective cesarean delivery (Milan only). Proteomic analysis by LC-MS/MS; placental RNA sequencing and histology. Residual samples stored in the Policlinico biobank with specific consent.

Other: Clinical and neurodevelopmental assessments

Maternal clinician-rated scales (HDRS, HARS, GAF) and self-rated questionnaires (EPDS, STAI Y1-2, SCL-90-R, CES-D) from screening to 6 months postpartum; bonding, couple and family scales (MPAS, PBQ, ECR-R, RQI, DAS, FES, PSI-SF) at 1 and 6 months postpartum; neonatal Hammersmith Neonatal Neurological Examination and visual function assessment after birth; Bayley Scales of Infant and Toddler Development, Third Edition at 6 months.
Other: Pregnant Women Without Depression (Group 2)

Pregnant women aged 18-45 years without current or past psychiatric disorders and without family history of psychiatric disorders (SCID-5-CV and FIGS), followed until 6 months postpartum, and their newborns.
Diagnostic test: Multimodal MRI and EEG-ECG/PPG recordings

Study-specific, non-invasive acquisitions: maternal brain MRI (structural, diffusion, task and resting-state fMRI) with simultaneous EEG-ECG (Milan) or ECG/PPG (Seville, Marburg) by 22 gestational weeks; fetal MRI by 22 gestational weeks; fetal ultrasound at 22, 26 and 32 gestational weeks; neonatal brain MRI and polygraphic EEG-ECG (Milan, Marburg) or MRI with PPG (Seville, Marburg) at 40+0 to 43+6 weeks of gestational age, during spontaneous sleep without sedation.

Procedure: Biological sampling

Maternal peripheral blood sampling at 22, 26 and 32 gestational weeks (plasma aliquots stored at -80 °C); umbilical venous cord blood sampling at birth; placental tissue sampling in a subgroup of about 10 participants per group with elective cesarean delivery (Milan only). Proteomic analysis by LC-MS/MS; placental RNA sequencing and histology. Residual samples stored in the Policlinico biobank with specific consent.

Other: Clinical and neurodevelopmental assessments

Maternal clinician-rated scales (HDRS, HARS, GAF) and self-rated questionnaires (EPDS, STAI Y1-2, SCL-90-R, CES-D) from screening to 6 months postpartum; bonding, couple and family scales (MPAS, PBQ, ECR-R, RQI, DAS, FES, PSI-SF) at 1 and 6 months postpartum; neonatal Hammersmith Neonatal Neurological Examination and visual function assessment after birth; Bayley Scales of Infant and Toddler Development, Third Edition at 6 months.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Prevalence of Major Depressive Disorder Among Screened Pregnant Women
Time Frame: At screening (within 20 gestational weeks)

Percentage of pregnant women screened within 20 gestational weeks who meet DSM-5 criteria for major depressive disorder according to the Structured Clinical Interview for DSM-5, Clinical Version (SCID-5-CV). The prevalence will be reported with its 95% confidence interval.
At screening (within 20 gestational weeks)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Left Hippocampal Volume
Time Frame: At Visit 1 (by 22 gestational weeks)

Left hippocampal volume, expressed in milliliters (mL), estimated from 3D T1-weighted brain MRI processed with CAT12, compared between pregnant women with major depressive disorder and pregnant women without depression.
At Visit 1 (by 22 gestational weeks)
Right Hippocampal Volume
Time Frame: At Visit 1 (by 22 gestational weeks)

Right hippocampal volume, expressed in milliliters (mL), estimated from 3D T1-weighted brain MRI processed with CAT12, compared between pregnant women with major depressive disorder and pregnant women without depression.
At Visit 1 (by 22 gestational weeks)
Hamilton Depression Rating Scale (HDRS) Total Score at 6 Months Postpartum
Time Frame: 6 months postpartum

Maternal depressive symptom severity assessed with the clinician-administered Hamilton Depression Rating Scale (HDRS). Higher scores indicate more severe depression.
6 months postpartum
Number of Depressive Relapses After Birth
Time Frame: From birth to 6 months postpartum

Number of depressive relapses per participant in the 6 months after birth, confirmed with the SCID-5-CV by a psychiatrist or psychologist.
From birth to 6 months postpartum
Bayley-III Cognitive Composite Score
Time Frame: 6 months of age

Infant cognitive development assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), cognitive scale. Composite scores have a mean of 100 and a standard deviation of 15; higher scores indicate better development.
6 months of age
Bayley-III Language Composite Score
Time Frame: 6 months of age

Infant language development (receptive and expressive) assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), language scale. Composite scores have a mean of 100 and a standard deviation of 15; higher scores indicate better development.
6 months of age
Bayley-III Motor Composite Score
Time Frame: 6 months of age

Infant motor development (fine and gross) assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), motor scale. Composite scores have a mean of 100 and a standard deviation of 15; higher scores indicate better development.
6 months of age

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Preterm Birth
Time Frame: At birth

Number of participants delivering at 28 weeks or more but before 37 completed weeks of gestation.
At birth
Number of Newborns With Low Birth Weight
Time Frame: At birth

Number of newborns with birth weight below 2500 grams.
At birth
Number of Newborns Small for Gestational Age
Time Frame: At birth

Number of newborns classified as small for gestational age (SGA) based on birth weight for gestational age.
At birth
Number of Newborns With Apgar Score Below 7
Time Frame: 1 and 5 minutes after birth

Number of newborns with an Apgar score below 7 at 1 and at 5 minutes after delivery. The Apgar score ranges from 0 to 10, with lower scores indicating poorer condition at birth.
1 and 5 minutes after birth
Hammersmith Neonatal Neurological Examination (HNNE) Total Score
Time Frame: Within the first days after birth

Neonatal neurological maturity assessed with the Hammersmith Neonatal Neurological Examination (posture, tone, reflexes, movements, abnormal signs and behavior). Higher scores indicate more optimal neurological status.
Within the first days after birth
Edinburgh Postnatal Depression Scale (EPDS) Total Score
Time Frame: 1 month and 6 months postpartum

Maternal self-reported depressive symptoms assessed with the 10-item Edinburgh Postnatal Depression Scale. Total score ranges from 0 to 30; higher scores indicate more severe symptoms.
1 month and 6 months postpartum

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Milan
Instituto de Biomedicina de Sevilla
Philipps University Marburg

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Paolo Brambilla, MD, PhD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 29, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 6, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 12, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BRAWO
  • JTC2024 - Brain-Body_BRAWO_1 (Other Grant/Funding Number: ERA-NET NEURON (Italian Ministry of Health))
  • 6730 (Other Identifier: Comitato Etico Territoriale Lombardia 3)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Individual participant data sharing will be decided by the BRAWO consortium according to the Consortium Agreement and applicable data protection regulations (GDPR).

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings