Unveiling Maternal-fetal BRAin-body Interactions in Pregnant WOmen Affected by Depression (BRAWO)
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.
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Paolo Brambilla, MD, PhD
- 電話番号：+39 02 5503 6313
- メール：psichiatria@policlinico.mi.it
研究場所
-
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Lombardy
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Milan、Lombardy、イタリア、20122
- 募集
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
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-
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Seville、スペイン、41013
- まだ募集していません
- Instituto de Biomedicina de Sevilla (IBiS)
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-
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Hesse
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Marburg、Hesse、ドイツ、35039
- まだ募集していません
- Department of Psychiatry and Psychotherapy, Philipps University Marburg
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
他の：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. |
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. 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. 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. |
|
他の：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. |
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. 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. 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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Prevalence of Major Depressive Disorder Among Screened Pregnant Women
時間枠：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)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Left Hippocampal Volume
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of Participants With Preterm Birth
時間枠：At birth
|
Number of participants delivering at 28 weeks or more but before 37 completed weeks of gestation. |
At birth
|
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Number of Newborns With Low Birth Weight
時間枠：At birth
|
Number of newborns with birth weight below 2500 grams. |
At birth
|
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Number of Newborns Small for Gestational Age
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
捜査官
- 主任研究者：Paolo Brambilla, MD, PhD、Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- BRAWO
- JTC2024 - Brain-Body_BRAWO_1 (その他の助成金/資金番号：ERA-NET NEURON (Italian Ministry of Health))
- 6730 (その他の識別子：Comitato Etico Territoriale Lombardia 3)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
Individual participant data sharing will be decided by the BRAWO consortium according to the Consortium Agreement and applicable data protection regulations (GDPR).
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米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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