Happy Mother - Healthy Baby: Supplement Study on Biological Processes Underlying Anxiety During Pregnancy (HMHB-Bio)

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

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.

Study Overview

• Status: Completed
• Conditions: Anxiety
• Intervention / Treatment: Behavioral: Cognitive Behavioral Therapy (CBT) for anxiety during pregnancy

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.

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Rawalpindi, Pakistan
    • Holy Family Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anxious pregnant women - intervention group; 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; 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.
No Intervention: Anxious pregnant women - enhanced usual care group; 100 pregnant women who have at least mild anxiety will be randomized to the enhanced usual care group. Reminder calls were given, provider visits were facilitated (shorter wait times), and transportation to assist participants in attending appointments and medically indicated ultrasounds were paid for (as in the other group).
No Intervention: Non-anxious pregnant women - healthy control; 100 pregnant women who do not have symptoms of anxiety or depression be followed in the healthy control group. Reminder calls were given, provider visits were facilitated (shorter wait times), and transportation to assist participants in attending appointments and medically indicated ultrasounds were paid for (as in the other groups).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral Markers of Inflammation	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	trimester 1, trimester 2, trimester 3, 6 weeks postpartum
Allopregnanolone Levels and Anxiety Symptoms Across the Peripartum	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).	trimester 2, trimester 3, 6 weeks postpartum
Allopregnanolone Levels Predicting Postpartum Depression	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.	Trimester 2
Allopregnanolone (ALLO) and Immune Function	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))	trimester 2, trimester 3, 6 weeks postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth Outcomes	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.	at birth
Infant Neuro-development Using Ages & Stages Questionnaire, Third Edition (ASQ-3)	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	6 weeks postpartum

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: National Institute of Mental Health (NIMH); University of Liverpool; Human Development Research Foundation, Pakistan; Rawalpindi Medical College, Pakistan
• Investigators: Principal Investigator: Pamela J Surkan, ScD, Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

General Publications

• Atif N, Nazir H, Zafar S, Chaudhri R, Atiq M, Mullany LC, Rowther AA, Malik A, Surkan PJ, Rahman A. Development of a Psychological Intervention to Address Anxiety During Pregnancy in a Low-Income Country. Front Psychiatry. 2020 Jan 10;10:927. doi: 10.3389/fpsyt.2019.00927. eCollection 2019.
• Sherer ML, Malik A, Osborne LM, Rowther AA, Zaidi A, Atif N, Rahman A, Kahloon LE, Salman M, Yenokyan G, Surkan PJ. Biological Mechanisms in Pregnant Women With Anxiety (Happy Mother-Healthy Baby Supplement Study): Protocol for a Longitudinal Mixed Methods Observational Study. JMIR Res Protoc. 2023 Apr 11;12:e43193. doi: 10.2196/43193.
• Surkan PJ, Hamdani SU, Huma ZE, Nazir H, Atif N, Rowther AA, Chaudhri R, Zafar S, Mullany LC, Malik A, Rahman A. Cognitive-behavioral therapy-based intervention to treat symptoms of anxiety in pregnancy in a prenatal clinic using non-specialist providers in Pakistan: design of a randomised trial. BMJ Open. 2020 Apr 15;10(4):e037590. doi: 10.1136/bmjopen-2020-037590.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2020
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): August 31, 2022

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): November 20, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: randomized controlled trial; inflammation; hormones
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: 3R01MH111859-03S1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified project data from the study will be posted on ClinicalTrials.gov and the National Institute of Mental Health (NIMH) data archive.
• IPD Sharing Time Frame: The study protocol, statistical analysis plan and informed consent form are available upon request now.
• IPD Sharing Access Criteria: The can be access upon request from the study PI: psurkan@jhu.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No