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

Not Applicable

Completed

Conditions: Anxiety

Interventions: Behavioral: Cognitive Behavioral Therapy (CBT) for anxiety during pregnancy

Registration Number: NCT04566861

Lead Sponsor: Johns Hopkins Bloomberg School of Public Health

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 117

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 anemia
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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anxious pregnant women - intervention group	Cognitive Behavioral Therapy (CBT) for anxiety during pregnancy	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)

Primary Outcome Measures

Name	Time	Method
Peripheral Markers of Inflammation	trimester 1, trimester 2, trimester 3, 6 weeks postpartum	Differences in levels of peripheral inflammatory markers and change in these markers across time (trimester 1 (T1), trimester 2 (T2), trimester 3 (T3) and postpartum (PP)) between anxious and healthy women, and between intervention and control women. Markers include IFNgamma, IL6, IL8, IL10, IL12p70, TNFalpha, IL17A, TARC, MIP1alpha, MCP4, Eotaxin
Allopregnanolone Levels and Anxiety Symptoms Across the Peripartum	trimester 2, trimester 3, 6 weeks postpartum	Measure differences in level of allopregnanolone (mean) at each time point and across time (trimester 1 (T1), trimester 2 (T2), trimester 3 (T3) and postpartum (PP)) between anxious women and healthy women, and between intervention and control. The results are measured by log-transformed values of the concentration of each cytokine in the plasma, in ng/mL (nanogram per milliliter).
Allopregnanolone Levels Predicting Postpartum Depression	Trimester 2	Differences in allopregnanolone levels at the second trimester between women who do and do not go on to develop postpartum depression (PPD). The results are measured by log-transformed values of the concentration of allopregnanolone in the plasma, in ng/ml (nanogram per milliliter. Women who have Allopregnanolone (ALLO) levels and developed PPD are analyzed.
Allopregnanolone (ALLO) and Immune Function	trimester 2, trimester 3, 6 weeks postpartum	Measure the relationship between ALLO levels and levels of peripheral inflammatory markers across time (trimester 2 (T2), trimester 3 (T3) and 6 weeks postpartum (W6))

Secondary Outcome Measures

Name	Time	Method
Birth Outcomes	at birth	Differences in birth outcomes (preterm birth, small 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.
Infant Neuro-development Using Ages & Stages Questionnaire, Third Edition (ASQ-3)	6 weeks postpartum	Measure infant neuro-development using Ages \& Stages Questionnaire to measure differences in infant neurodevelopment (communication, gross motor, fine motor, personal-social and problem solving) using a standardized questionnaire between those high in inflammatory markers vs. those low, and also between anxious and healthy women communication cut-off score 22.77 gross motor cut-off score 41.84 fine motor cut-off score 30.16 personal-social cut-off score 24.62 problem solving cut-off score 33.71 Number of participants with impaired neuron-developmental infants (below cut-off scores) are reported below