Happy Mother-Healthy Baby: An Anxiety-focused Early Prenatal Intervention (HMHB)

• ClinicalTrials.gov Identifier: NCT03880032
• Recruitment Status: Completed
• First Posted: March 19, 2019
• Results First Posted: February 15, 2024
• Last Update Posted: February 15, 2024
• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborator: Human Development Research Foundation, Pakistan
• Information provided by (Responsible Party): Johns Hopkins Bloomberg School of Public Health

Study Description

Brief Summary:

In the proposed study the investigators will develop an early prenatal preventive intervention targeting anxiety and conduct a randomized controlled trial in Pakistan to test its efficacy in reducing generalized anxiety disorder and major depression in mothers in late pregnancy and the postnatal period. Investigators will evaluate the impact of the intervention on fetal and infant growth restriction as well as examine how the impact of the intervention is mediated (to elucidate mechanisms) and/or modified (to help optimize future adaptations of the program) by various social factors. A cost-effectiveness evaluation will shed light on the costs and benefits of intervention components in relation to outcomes, enabling policy-makers and public health planners to scale up this intervention according to resource budgeting requirements.

Condition or disease	Intervention/treatment	Phase
Postpartum Depression; Small for Gestational Age at Delivery; Preterm Birth; Anxiety; Birth Weight	Behavioral: Cognitive Behavioral Therapy Intervention for Anxiety	Not Applicable

Detailed Description:

Common mental disorders (CMDs) such as anxiety and depression occur frequently in pregnancy and the postnatal period in lower- and middle income countries (LMICs). Prenatal anxiety, both subthreshold and clinical, adversely affects maternal wellbeing and outcomes among offspring, and is a major predictor of subsequent depression. Preventive approaches have enormous potential to reduce the negative effects of postnatal mental disorders in mothers and improve child outcomes. The study team proposes to create a scalable and sustainable early prevention intervention focusing on anxiety symptoms in pregnant women, to be delivered by non-specialist providers (Aim 1). The investigators will evaluate this preventive intervention through a trial by randomizing 1200 pregnant women from a public hospital in Islamabad Pakistan to either our Cognitive Behavioral Therapy-based (CBT-based) early-in-pregnancy program or to usual care. The investigators will study the effects of the intervention on 1) CMDs in the 3rd trimester of pregnancy and at 6 weeks postpartum (Aim 2) and on 2) fetal and newborn small-for-gestational age (SGA) outcomes (Aim 3). The investigators will also examine if interpersonal violence, perceived stress and social support mediate and/or modify the intervention effects on CMDs and perinatal outcomes (Aim 4). Finally, the investigators will conduct a cost-effectiveness evaluation, comparing costs and healthcare utilization for women in the prenatal intervention and enhanced usual care groups (Aim 5). Focusing on anxiety reduction is a major innovation; anxiety has not been addressed within prenatal intervention packages in LMICs, despite its association with increased postpartum depression and suboptimal fetal and infant outcomes. Pakistan has high prevalence of both women with prenatal anxiety (35% to 49%) and SGA newborns (~47%), providing an ideal research opportunity. The CBT-based approach, appropriate given its indication for anxiety and depression, is grounded in preliminary work in this population, where the investigators have previously successfully reduced postpartum depression. Intervening early in pregnancy is a further innovation that is critical for building the evidence base for preventative approaches to reduce maternal CMDs and related perinatal outcomes. The proposed mediation and effect modification analyses will improve understanding of mechanism(s) of action and help identify subpopulations for programmatic targeting. The use of non-specialized providers and integration within the primary care environment will guide scale up, while incorporating a cost-effectiveness analysis will aid policy-makers in resource allocation decisions. This study will inform the integration of preventive strategies that target anxiety with existing approaches for treatment of perinatal depression to further the evidence-base for transdiagnostic mental health initiatives globally, and will inform policies to support lifelong maternal mental health and resilience across generations

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Women with at least mild anxiety but not depression will be enrolled simultaneously into an intervention or an enhanced usual care group during pregnancy. Women in the intervention group will receive individual-based cognitive behavioral therapy. Women in the control group with receive enhanced usual care.
• Masking: Double (Investigator, Outcomes Assessor)
• Masking Description: To maintain masking during the trial, intervention and assessment teams will not have any interaction during the trial, as they will be placed at separate locations within the Obstetrics Department of Holy Family Hospital (HFH). Furthermore, participants will be instructed not to disclose which type of treatment they are receiving to the assessment team. Fidelity of masking will be measured by having assessors guess the trial arm of each participant at the end of follow-up assessment. We hypothesize that assessors will only be able to correctly guess the condition of participants at a chance rate of nearly 50% at follow-up assessments, indicating that masking is maintained.
• Primary Purpose: Prevention
• Official Title: Happy Mother-Healthy Baby: An Anxiety-focused Early Prenatal Intervention for the Prevention of Common Mental Disorders in Pakistan
• Actual Study Start Date: April 16, 2019
• Actual Primary Completion Date: October 7, 2022
• Actual Study Completion Date: October 7, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cognitive Behavioral Therapy Intervention for Anxiety; Pregnant women experiencing anxiety randomized to the Happy Mother Healthy Baby (HMHB) intervention receive a CBT-based psychosocial intervention (with six core and up to six booster sessions). HMHB is a facility-based intervention delivered by non-specialist providers. It is aimed to raise psychosocial awareness and facilitate positive change inter personal wellbeing, social support, and bonding with their baby during pregnancy. It addresses with relapse prevention, planning for the baby's arrival, and in management of emotional challenges in the early postnatal period. Family member/s will be invited to attend 3 core sessions.	Behavioral: Cognitive Behavioral Therapy Intervention for Anxiety; Happy Mother Healthy Baby (HMHB) is a CBT-based psychosocial intervention for expectant women experiencing anxiety during their pregnancy. Strategies such as empathetic listening, thought challenging, behavior activation, problem management, take-home exercises, and family involvement are employed by HMHB.
No Intervention: Enhanced Usual Care; Women randomized to the control group will receive enhanced usual care (EUC). The World Health Organization (WHO) recommends 8 antenatal visits for a positive pregnancy experience, the number of visits our EUC control group participants will receive (depending on their gestational week). Usual care will also be enhanced by hospital staff receiving additional training in mental health treatment and counseling. 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 intervention group).

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Combined Common Mental Disorders (CMDs, i.e. Anxiety and Depression). [ Time Frame: 6 weeks postpartum ]
   Data reported is the number of participants with Common Mental Disorders (CMDs), which is defined as a woman having either high anxiety or clinical depression at the time of follow-up. Both CMDs, anxiety was indicated by moderate to severe symptoms on the anxiety portion of the Hospital and Anxiety Scale (HADS). A cutoff of >10 was used as the threshold for moderate to severe levels of anxiety. A Major Depressive Episode (MDE) was measured with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID), which is a semi-structured interview used to make major Axis I Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses. Its scoring will be based on case or non-case basis.

Secondary Outcome Measures :

1. Number of Preterm Births [ Time Frame: at birth ]
   Number of infants born with <37 weeks' gestation
2. Small-for-gestational Age Birth [ Time Frame: at birth ]
   <10th% for gestational age at birth compared to the reference population
3. Low Birthweight [ Time Frame: at birth ]
   weight of ≤2500 grams

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. ability to understand spoken Urdu
2. pregnant, ≤22 weeks' gestation
3. age ≥18 years
4. residence ≤20 km of Holy Family Hospital
5. intent to reside in the study areas until the completion of the study
6. score ≥8 for anxiety on the Hospital Anxiety and Depression Scale (HADS)

Exclusion Criteria:

1. Current major a depressive episode (MDE on SCID) or life-threatening health conditions including e.g. active severe depression or suicidal ideation
2. Self-report of past or current significant learning disability
3. 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)
4. medical disorders or severe maternal morbidity that require inpatient management that would preclude participation (101)
5. ICU admission indicated by diagnosis (not only for assessment)

Contacts and Locations

Locations

Pakistan

Holy Family Hospital

Rawalpindi, Pakistan

Sponsors and Collaborators

Johns Hopkins Bloomberg School of Public Health

Human Development Research Foundation, Pakistan

Investigators

• Principal Investigator: Pamela J. Surkan, PhD; Johns Hopkins Bloomberg School of Public Health

  Study Documents (Full-Text)

Documents provided by Johns Hopkins Bloomberg School of Public Health:

Study Protocol and Statistical Analysis Plan  [PDF] April 1, 2022

Informed Consent Form  [PDF] July 25, 2019

More Information

Publications of Results:

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.

Other Publications:

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.

Rowther AA, Kazi AK, Nazir H, Atiq M, Atif N, Rauf N, Malik A, Surkan PJ. "A Woman Is a Puppet." Women's Disempowerment and Prenatal Anxiety in Pakistan: A Qualitative Study of Sources, Mitigators, and Coping Strategies for Anxiety in Pregnancy. Int J Environ Res Public Health. 2020 Jul 8;17(14):4926. doi: 10.3390/ijerph17144926.

Rauf N, Zulfiqar S, Mumtaz S, Maryam H, Shoukat R, Malik A, Rowther AA, Rahman A, Surkan PJ, Atif N. The Impact of the COVID-19 Pandemic on Pregnant Women with Perinatal Anxiety Symptoms in Pakistan: A Qualitative Study. Int J Environ Res Public Health. 2021 Aug 4;18(16):8237. doi: 10.3390/ijerph18168237.

Kazi AK, Rowther AA, Atif N, Nazir H, Atiq M, Zulfiqar S, Malik A, Surkan PJ. Intersections between patient-provider communication and antenatal anxiety in a public healthcare setting in Pakistan. PLoS One. 2021 Feb 5;16(2):e0244671. doi: 10.1371/journal.pone.0244671. eCollection 2021.

Nazir H, Rowther AA, Rauf N, Atiq M, Kazi AK, Malik A, Atif N, Surkan PJ. 'Those whom I have to talk to, I can't talk to': Perceived social isolation in the context of anxiety symptoms among pregnant women in Pakistan. Health Soc Care Community. 2022 Nov;30(6):e5885-e5896. doi: 10.1111/hsc.14019. Epub 2022 Sep 19.

Zaidi A, Khan A, Rowther A, Nazir H, Perin J, Rauf N, Mumtaz S, Naseem H, Atif N, Rahman A, Surkan PJ, Malik A. Cultural adaptation and psychometric validation of the Pregnancy Experience Scale-Brief version (PES-Brief) in Pakistani women with antenatal anxiety symptoms. SSM Ment Health. 2022 Dec;2:100055. doi: 10.1016/j.ssmmh.2021.100055. Epub 2021 Dec 24.

Atif N, Rauf N, Nazir H, Maryam H, Mumtaz S, Zulfiqar S, Shouket R, Rowther AA, Malik A, Rahman A, Surkan PJ. Non-specialist-delivered psychosocial intervention for prenatal anxiety in a tertiary care setting in Pakistan: a qualitative process evaluation. BMJ Open. 2023 Feb 23;13(2):e069988. doi: 10.1136/bmjopen-2022-069988.

Malik A, Park S, Mumtaz S, Rowther A, Zulfiqar S, Perin J, Zaidi A, Atif N, Rahman A, Surkan PJ. Perceived Social Support and Women's Empowerment and Their Associations with Pregnancy Experiences in Anxious Women: A Study from Urban Pakistan. Matern Child Health J. 2023 May;27(5):916-925. doi: 10.1007/s10995-023-03588-6. Epub 2023 Feb 6.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yonemoto N, Nagai S, Mori R. Schedules for home visits in the early postpartum period. Cochrane Database Syst Rev. 2021 Jul 21;7(7):CD009326. doi: 10.1002/14651858.CD009326.pub4.

• Responsible Party: Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT03880032
• Other Study ID Numbers: R01MH111859-01 ( U.S. NIH Grant/Contract )
• First Posted: March 19, 2019
• Results First Posted: February 15, 2024
• Last Update Posted: February 15, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: The study protocol and statistical analysis plan (SAP) have been shared in the study protocol paper published in BMJ Open (PMID: 32300002; PMCID: PMC7200036). The Informed Consent Forms (ICF) have been published accessed and as the Supplementary Material associated with that article.
• Access Criteria: There is a link to the Informed Consent Forms (ICF) on the open access website for our protocol paper. Please see: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200036/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Johns Hopkins Bloomberg School of Public Health:

anxiety; depression; birth outcomes

Additional relevant MeSH terms:

Premature Birth; Depression, Postpartum; Birth Weight; Depression; Anxiety Disorders; Behavioral Symptoms; Depressive Disorder; Mood Disorders; Mental Disorders; Body Weight; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders