Happy Mother - Healthy Baby: Supplement Study on Biological Processes Underlying Anxiety During Pregnancy

Study Overview
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Brief Summary
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As a supplement to the ongoing randomized evaluation of the Cognitive Behavioral Therapy (CBT) anxiety prevention intervention in Pakistan (R01-MH111859), the investigators propose to explore potential biological mechanisms (related to inflammation and endocrine functioning) of antenatal anxiety through additional data collection with 300 pregnant women.

Detailed Description
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This study will leverage the ongoing randomized evaluation of the CBT anxiety prevention intervention in Pakistan (R01-MH111859) to explore potential biological mechanisms. This CBT intervention targets both sub-threshold anxiety symptoms and generalized anxiety disorder (GAD) in early- to mid- pregnancy, aiming to both prevent and treat Common Mental Disorders (CMDs) (GAD and major depressive episodes (MDE)) as well as improve birth outcomes. The study team proposes to additionally study biological correlates of antenatal anxiety (i.e., immune and endocrine functioning) in 300 women: in addition to 200 drawn from our randomized trial (100 intervention, 100 usual care), the study will also include 100 healthy women without anxiety or depression. The aims are to 1) characterize the immune phenotype of anxious women across the peripartum, specifically by measuring the relation among anxiety symptoms and peripheral markers of inflammation within and across women (both anxious and healthy) and between those receiving the intervention and control; 2) determine the relation between levels of allopregnanolone (ALLO) in pregnancy and concurrent anxiety symptoms and future symptoms of postpartum depression (PPD), 3) examine the relation between changes in immune functioning and ALLO levels in anxious pregnancy across time, 4) examine whether immune function and/or ALLO are mediators or moderators of the association between antenatal anxiety and preterm birth and/or small-for-gestational age, and 5) examine the effects of both anxiety and the intervention (including biomarkers) on infant development at six weeks postpartum.

Official Title
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Biological Processes Underlying Anxiety During Pregnancy: A Substudy of an Anxiety-focused Early Prenatal Intervention for the Prevention of Common Mental Disorders in Pakistan

Conditions
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Anxiety

Intervention / Treatment
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* Behavioral: Cognitive Behavioral Therapy (CBT) for anxiety during pregnancy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ability to understand spoken Urdu pregnant, ≤22 weeks' gestation age ≥18 years residence ≤20 km of Holy Family Hospital intent to reside in the study areas until the completion of the study Exclusion Criteria: Current major depressive episode (MDE on SCID) or life-threatening health conditions including e.g. active severe depression or suicidal ideation Self-report of past or current significant learning disability Self-report of past or current psychiatric disorder (e.g. bipolar disorder or schizophrenia) or psychiatric care (e.g. current use of anxiolytic drug and/or other psychotropic drug) medical disorders or severe maternal morbidity that require inpatient management that would preclude participation (101) ICU admission indicated by diagnosis (not only for assessment)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Within women in a larger randomized trial (randomized to the intervention or enhanced care group), we propose to study biological correlates of antenatal anxiety (i.e., immune and endocrine functioning) in 300 women: in addition to 200 drawn from our randomized trial (100 intervention, 100 usual care), we will also include 100 healthy women without anxiety or depression. These enrollment goals were modified after interruptions by the Covid-19 pandemic.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anxious pregnant women - intervention group<br>100 pregnant women who have at least mild anxiety will be randomized to the intervention group where they will receive six one-on-one core sessions of Cognitive Behavioral Therapy during pregnancy (plus possible booster sessions) | Behavioral: Cognitive Behavioral Therapy (CBT) for anxiety during pregnancy<br>* Women who are randomized to the intervention group will receive six core Cognitive Behavioral Therapy (CBT) sessions for anxiety during pregnancy (and possible booster sessions) to treat symptoms of anxiety.<br>|
| No Intervention: Anxious pregnant women - enhanced usual care group<br>100 pregnant women who have at least mild anxiety will be randomized to the enhanced usual care group. They will not receive intervention sessions but will receive transportation vouchers to come to the hospital and facilitation by study staff to attend to their regular antenatal care visits. | |
| No Intervention: Non-anxious pregnant women - healthy control<br>100 pregnant women who do not have symptoms of anxiety or depression be followed in the healthy control group. They will not receive intervention sessions but will receive transportation vouchers to come to the hospital and facilitation by study staff to attend to their regular antenatal care visits. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral markers of inflammation | We will measure differences in levels of peripheral inflammatory markers and change in these markers across time between anxious and healthy women, and between intervention and control women. Markers include IL-6, CCL3, CXCL8, Eotaxin, VEGF, and GM-CSF | during pregnancy until six weeks postpartum | 
| Allopregnanolone levels and anxiety symptoms across the peripartum | We will measure differences in level of allopregnanolone at each time point and across time between anxious women and healthy women, and between intervention and control | during pregnancy until six weeks postpartum | 
| Allopregnanolone levels predicting postpartum depression | We will measure differences in allopregnanolone levels at the second trimester between women who do and do not go on to develop postpartum depression. | during pregnancy until birth | 
| Allopregnanolone and immune function | We will measure the relationship between ALLO levels and levels of peripheral inflammatory markers across time, both concurrent and predictive | through pregnancy until six weeks postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Birth outcomes | We will measure differences in birth outcomes (preterm birth, small or large for gestational age, low birth weight) between women with high inflammatory markers vs. those low in inflammatory markers, and also between anxious and healthy women. | through pregnancy and at birth | 
| Infant neurodevelopment | We will measure differences in infant neurodevelopment using a standardized questionnaire between those high in inflammatory markers vs. those low, and also between anxious and healthy women | through pregnancy up to and including 6 weeks postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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randomized controlled trial, inflammation, hormones