The immune phenotype of perinatal anxiety in an anxiety-focused behavioral intervention program in Pakistan.

BACKGROUND: Dysregulation of the immune system has been associated with psychiatric disorders and pregnancy-related complications, such as perinatal depression. However, the immune characteristics specific to perinatal anxiety remain poorly understood. In this study, our goal was to examine specific immune characteristics related to prenatal anxiety within the context of a randomized controlled trial designed to alleviate anxiety symptoms-the Happy Mother - Healthy Baby (HMHB) study in Rawalpindi, Pakistan. MATERIALS AND METHODS: Pregnant women (n = 117) were followed prospectively in the 1st, 2nd, and 3rd trimesters (T1, T2, T3) and at 6 weeks postpartum (PP6). Each visit included a blood draw and anxiety evaluation (as measured by the anxiety subscale of the Hospital Anxiety and Depression Scale - HADS -using a cutoff ≥ 8). We enrolled both healthy controls and participants with anxiety alone; those with concurrent depression were excluded. RESULTS: K-means cluster analysis revealed three anxiety clusters: Non-Anxiety, High and Consistent Anxiety, and Decreasing Anxiety. Principal components analysis revealed two distinct clusters of cytokine and chemokine activity. Women within the High and Consistent Anxiety group had significantly elevated chemokine activity across pregnancy (in trimester 1 (ß = 0.364, SE = 0.178, t = 2.040, p = 0.043), in trimester 2 (ß = 0.332, SE = 0.164, t = 2.020, p = 0.045), and trimester 3 (ß = 0.370, SE = 0.179, t = 2.070, p = 0.040) compared to Non-Anxiety group. Elevated chemokine activity was associated with low birthweight (LBW) and small for gestational age (SGA). CONCLUSION: Our findings reveal a unique pattern of immune dysregulation in pregnant women with anxiety in a Pakistani population and offer preliminary evidence that immune dysregulation associated with antenatal anxiety may be associated with birth outcomes. The dysregulation in this population is distinct from that in our other studies, indicating that population-level factors other than anxiety may play a substantial role in the differences found. (Clinicaltrials.gov # NCT04566861).

Social Support and Spousal Relationship Quality Improves Responsiveness among Anxious Mothers.

Maternal responsiveness, a mother's ability to consistently identify infant cues and then act on them, is critical for healthy child development. A woman's social support and spousal relationship may affect responsiveness to an infant, especially among mothers with anxiety. We assessed how social support and spousal relationship quality is associated with responsiveness among anxious mothers, and if postpartum depression (PPD) moderated these associations. Cross-sectional data were collected from 2019 to 2022 in a public hospital in Pakistan from 701 women at six-weeks postpartum. Eligible women had at least mild anxiety in early- to mid- pregnancy. Linear regression analyses assessed if spousal relationship quality and social support from family and friends were associated with maternal responsiveness, measured using the Maternal Infant Responsiveness Instrument. Interaction terms were used to examine if PPD moderated these associations. Spousal relationship quality (B = 2.49, 95% CI: 1.48, 3.50) and social support (B = 1.07, 95% CI: 0.31, 1.83) were positively related to maternal responsiveness to the infant. Emotional support from a spouse was positively associated with responsiveness (B = 1.08, 95% CI: 0.12, 2.03 depressed; B = 2.96, 95% CI: 1.34, 4.58 non-depressed), and conflict with the spouse was negatively associated with responsiveness (B=-1.02, 95% CI: -1.94, -0.09 depressed; B=-2.87, 95% CI: -4.36, -1.37 non-depressed). However, social support was related to responsiveness only in non-depressed women (B = 2.61, 95% CI: 1.14, 4.07). While spousal relationships and social support enhance maternal responsiveness, for depressed women, spousal relationships were particularly critical. In considering maternal-infant interventions to improve child development outcomes, our study indicates the importance of supportive relationships that foster effective responsiveness.

Delivering the Thinking Healthy Programme as a universal group intervention integrated into routine antenatal care: a randomized-controlled pilot study.

BACKGROUND: Women with perinatal depression and their children are at increased risk of poor health outcomes. There is a need to implement non-stigmatizing interventions into existing health systems which reduce psychosocial distress during pregnancy and prevent perinatal depression. We adapted the WHO-endorsed Thinking Healthy Programme (THP) to be delivered universally to all women attending routine online pregnancy schools in Istanbul, Turkey. This study aimed to evaluate the feasibility and acceptability of this intervention. METHODS: This mixed-methods study incorporated a two-arm pilot randomized controlled trial and qualitative evaluation of the feasibility and acceptability of the adapted THP - Brief Group version (THP-BGV) to a range of stakeholders. We recruited pregnant women at 12-30 weeks' gestation through pregnancy schools within the University Hospital's catchment area. Women in the intervention arm received five online sessions of the THP-BGV delivered by antenatal nurses. The intervention employed principles of cognitive behaviour therapy to provide psychoeducation, behaviour activation, problem-solving strategies and group support to participants. In the control arm, women received usual care consisting of routine online educational pregnancy classes aided by the antenatal nurses. The women were assessed for depressive symptoms with the Edinburgh Postnatal Depression Scale at baseline and 4-6 weeks post-intervention and also evaluated for anxiety, perceived social support, partner relationship, level of disability and sleep quality. In-depth interviews were conducted with women and other key stakeholders. RESULTS: Of the 99 consecutive women referred to the pregnancy schools, 91 (91.9%) were eligible and 88 (88.8%) consented to participate in the study and were randomized. Eighty-two (83%) completed the final assessments. Our main findings were that this preventive group intervention was feasible to be integrated into routine antenatal educational classes and it was valued by the women and delivery-agents. While the study was not powered to detect differences between intervention and control conditions, we found small trends towards reduction in anxiety and depressive symptoms favoring the intervention arm. No serious adverse events were reported. CONCLUSIONS: Given the paucity of preventive interventions for perinatal depression in low and middle-income countries, a fully powered definitive randomized controlled trial of this feasible and acceptable intervention should be conducted. TRIAL REGISTRATION: The study was registered at Clinical Trails.gov ( NCT04819711 ) (Registration Date: 29/03/2021).

Adaptation and integration of the thinking healthy programme into pregnancy schools in Istanbul, Turkey.

BACKGROUND: Perinatal mental health is a major public health concern. In Turkey, public hospitals operate pregnancy schools which provides an opportunity to integrate an evidence-based Thinking Healthy Programme (THP) for perinatal depression. The aim of this study is to adapt the THP for universal use in the group setting and to understand its acceptability and feasibility for integration into the existing antenatal care programme for both face-to-face and online delivery. METHODS: Following an expert-led adaptation process using the Bernal Framework, field testing was conducted on a group of women and facilitators followed by in-depth interviews (n:8) and group discussions (n = 13). Data were analysed using Thematic Framework Analysis. RESULTS: Minor but significant adaptations were made to the individually delivered THP for use in the universal group pregnancy schools. Initial findings indicate that the THP-group version was acceptable to its target population and could be integrated into the antenatal care plan for delivery during face-to-face and online group classes. CONCLUSION: THP is transferable to the Turkish cultural and healthcare context. The THP-group version has the potential to add value to Turkey's existing perinatal healthcare programme.

Perceived Social Support and Women's Empowerment and Their Associations with Pregnancy Experiences in Anxious Women: A Study from Urban Pakistan.

OBJECTIVES: Psychological distress in pregnancy is associated with adverse postnatal outcomes. We aimed to identify how social support and women's empowerment are associated with pregnancy-specific daily experiences among women suffering antenatal anxiety in Pakistan. METHODS: Data were collected as part of a randomized controlled trial of a psychosocial intervention for antenatal anxiety in a tertiary hospital in Pakistan. We included 594 women in early pregnancy (≤ 22 weeks) who endorsed mild to severe anxiety symptoms. Generalized linear regression models were used to analyze the associations of perceived social support and women's empowerment in relation to pregnancy-specific daily hassles and uplifts using a culturally adapted and psychometrically validated version of the Pregnancy Experience Scale-Brief. RESULTS: High social support was positively associated with frequency and intensity of positive pregnancy-specific experiences (B = 0.39, 95% CI 0.23-0.54 uplifts frequency; and B = 0.17, 95% CI 0.12-0.22 uplifts intensity), and was inversely associated with frequency of negative pregnancy-specific experiences (B = - 0.44, 95% CI - 0.66, - 0.22). Women's household empowerment was associated with greater uplifts frequency and intensity (B = 0.55, 95% CI 0.20-0.90 frequency; and B = 0.28, 95% CI 0.17-0.40 intensity). High social support and household empowerment were inversely related to PES hassle-to-uplift ratio scores. CONCLUSIONS FOR PRACTICE: Greater social support and household empowerment were associated with positive pregnancy-specific experiences in the context of antenatal anxiety in Pakistan.

Technology-assisted peer therapy: a new way of delivering evidence-based psychological interventions.

In low-income settings, ninety percent of individuals with clinical depression have no access to evidence-based psychological interventions. Reasons include lack of funds for specialist services, scarcity of trained mental health professionals, and the stigma attached to mental illness. In recent years there have been many studies demonstrating effective delivery of psychological interventions through a variety of non-specialists. While these interventions are cost-effective and less stigmatising, efforts to scale-up are hampered by issues of quality-control, and what has been described by implementation scientists as 'voltage-drop' and 'programme-drift.' Using principles of Human Centred Design in a rural setting in Pakistan, we worked with potential users to co-design a Tablet or Smartphone-based App that can assist a lay-person deliver the Thinking Healthy Programme, a World Health Organization-endorsed evidence-based intervention for perinatal depression. The active ingredients of this cognitive-therapy based intervention are delivered by a virtual 'avatar' therapist incorporated into the App which is operated by a 'peer' (a woman from the neighbourhood with no prior experience of healthcare delivery). Using automated cues from the App, the peer reinforces key therapeutic messages, helps with problem-solving and provides the non-specific but essential therapeutic elements of empathy and support. The peer and App therefore act as co-therapists in delivery of the intervention. The peer can deliver the intervention with good fidelity after brief automated in-built training. This approach has the potential to be applied to other areas of mental health and help bridge the treatment gap, especially in resource-poor settings. This paper describes the process of co-development with end-users and key features of the App.

Improving access to psychosocial interventions for perinatal depression in low- and middle-income countries: lessons from the field.

Over 90% women with perinatal depression in low and middle-income countries do not receive treatment. Scale-up of evidence-based psychosocial interventions is a key challenge. We developed the Thinking Healthy Programme (THP), a psychosocial intervention that can be delivered by non-specialist providers such as community health workers in primary and secondary care settings. Our research showed that three out of 4 women with perinatal depression who received the programme recovered, and there were beneficial effects on infant outcomes. In over a decade since the original research, policy and practice uptake of the programme globally has been promising. We describe factors contributing to this: the programme is relatively inexpensive and culturally transferable; the intervention can be integrated with existing maternal and child health programmes; the programme is amenable to 'task-sharing' via peers, nurses, community health-workers and other frontline workers; cascaded models of training and supervision, and the use of technology for training and delivery provide exciting future avenues for scaled-up implementation. These innovations are relevant to the neglected field of public mental health, especially in the post COVID19 era when rates of anxiety and depression are likely to rise globally.

Mother-to-mother therapy in India and Pakistan: adaptation and feasibility evaluation of the peer-delivered Thinking Healthy Programme.

BACKGROUND: Perinatal depression is highly prevalent in South Asia. Although effective and culturally feasible interventions exist, a key bottleneck for scaled-up delivery is lack of trained human resource. The aim of this study was to adapt an evidence-based intervention so that local women from the community (peers) could be trained to deliver it, and to test the adapted intervention for feasibility in India and Pakistan. METHODS: The study was conducted in Rawalpindi, Pakistan and Goa, India. To inform the adaptation process, qualitative data was collected through 7 focus groups (four in Pakistan and three in India) and 61 in-depth interviews (India only). Following adaptation, the intervention was delivered to depressed mothers (20 in Pakistan and 24 in India) for six months through 8 peers in Pakistan and nine in India. Post intervention data was collected from depressed mothers and peers through 41 in-depth interviews (29 in Pakistan and 12 in India) and eight focus groups (one in Pakistan and seven in India). Data was analysed using Framework Analysis approach. RESULTS: Most mothers perceived the intervention to be acceptable, useful, and viewed the peers as effective delivery-agents. The simple format using vignettes, pictures and everyday terms to describe distress made the intervention easy to understand and deliver. The peers were able to use techniques for behavioural activation with relative ease. Both the mothers and peers found that shared life-experiences and personal characteristics greatly facilitated the intervention-delivery. A minority of mothers had concerns about confidentiality and stigma related to their condition, and some peers felt the role was emotionally challenging. CONCLUSIONS: The study demonstrates the feasibility of using peers to provide interventions for perinatal depression in two South Asian settings. Peers can be a potential resource to deliver evidence-based psychosocial interventions. TRIAL REGISTRATION: Pakistan Trial: ClinicalTrials.gov Identifier: NCT02111915 (9 April 2014), India Trial: ClinicalTrials.gov Identifier: NCT02104232 (1 April 2014).

Group psychological intervention for postnatal depression: a nested qualitative study with British South Asian women.

BACKGROUND: Postnatal depression affects 10-15 % of all mothers in Western societies and remains a major public health concern for women from diverse cultures. British Pakistani and Indian women have a higher prevalence of depression in comparison to their white counterparts. Research has shown that culturally adapted interventions using Cognitive Behavioural Therapy (CBT) may be acceptable and may help to address the needs of this population. The aim of this study was to assess the acceptability and overall experience of the Positive Health Programme by British South Asian mothers. METHODS: This was a nested qualitative study, part of an exploratory randomized controlled trial (RCT) conducted to test the feasibility and acceptability of a culturally-adapted intervention (Positive Health Programme or PHP) for postnatal depression in British South Asian women. In-depth interviews (N = 17) were conducted to determine the views of the participants on the feasibility and acceptability of the intervention. RESULTS: The participants found the intervention acceptable and experienced an overall positive change in their attitudes, behaviour, and increased self-confidence. CONCLUSIONS: The findings suggest that the culturally adapted Positive Health Programme is acceptable to British South Asian women. These results support that culturally sensitive interventions may lead to better health outcomes and overall satisfaction. TRIAL REGISTRATION: Protocol registered on Clinicaltrials.gov NCT01838889.

Effectiveness of peer-delivered interventions for severe mental illness and depression on clinical and psychosocial outcomes: a systematic review and meta-analysis.

PURPOSE: To evaluate the effectiveness of peer-delivered interventions in improving clinical and psychosocial outcomes among individuals with severe mental illness (SMI) or depression. METHODS: Systematic review and meta-analysis of randomised controlled trials comparing a peer-delivered intervention to treatment as usual or treatment delivered by a health professional. Random effect meta-analyses were performed separately for SMI and depression interventions. RESULTS: Fourteen studies (10 SMI studies, 4 depression studies), all from high-income countries, met the inclusion criteria. For SMI, evidence from three high-quality superiority trials showed small positive effects favouring peer-delivered interventions for quality of life (SMD 0.24, 95 % CI 0.08-0.40, p = 0.003, I (2) = 0 %, n = 639) and hope (SMD 0.24, 95 % CI 0.02-0.46, p = 0.03, I (2) = 65 %, n = 967). Results of two SMI equivalence trials indicated that peers may be equivalent to health professionals in improving clinical symptoms (SMD -0.14, 95 % CI -0.57 to 0.29, p = 0.51, I (2) = 0 %, n = 84) and quality of life (SMD -0.11, 95 % CI -0.42 to 0.20, p = 0.56, I (2) = 0 %, n = 164). No effect of peer-delivered interventions for depression was observed on any outcome. CONCLUSIONS: The limited evidence base suggests that peers may have a small additional impact on patient's outcomes, in comparison to standard psychiatric care in high-income settings. Future research should explore the use and applicability of peer-delivered interventions in resource poor settings where standard care is likely to be of lower quality and coverage. The positive findings of equivalence trials demand further research in this area to consolidate the relative value of peer-delivered vs. professional-delivered interventions.

Results of a cognitive behavior therapy-based intervention for antenatal anxiety on birth outcomes in Pakistan: a randomized control trial.

Antenatal anxiety is among the risk factors for adverse birth outcomes, which are common in Pakistan. Between 2019 and 2022, we conducted a randomized controlled trial to evaluate the effects of the Happy Mother-Healthy Baby program, designed to reduce anxiety during pregnancy through use of Cognitive Behavior Therapy, on birth outcomes with 796 women in Rwalpindi, Pakistan. We performed intent-to-treat analysis and per protocol analyses. Intention-to-treat analyses showed no difference in the odds of low birthweight (LBW) (Adj. OR = 0.82, 95% CI 0.55-1.28 p = 0.37), preterm birth (PTB) (Adj. OR = 1.20 95% CI 0.83-1.71, p = 0.33) or small-for-gestational age (SGA) birth, (Adj. OR = 0.76, 95% CI 0.56-1.09, p = 0.16). Among completers who received ≥ 5 intervention sessions, the odds of LBW and SGA were 39% and 32% lower (Adj. OR = 0.61, 95% CI 0.43-0.87, p < 0.01; Adj. OR = 0.68, 95% CI 0.53-0.89, p < 0.01). The significant LBW and SGA results among the intervention completers suggest that the program may be effective when a sufficient dose is received. However, confirmation of these findings is needed due to the fact that randomization is not maintained in completer analyses.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT03880032, 19/03/2019.

Exploring preference for delivery methods for a psychosocial intervention for prenatal anxiety: A qualitative study from a tertiary care hospital in Pakistan.

Objective: This qualitative study explores therapists' and participants' preferences for delivery methods (face-to-face and phone sessions) of a cognitive behavioral therapy-based psychosocial intervention for prenatal anxiety delivered in a tertiary care hospital. Setting: The research was conducted in a randomized controlled trial in Pakistan, where a shift from face-to-face to phone-based therapy occurred during the coronavirus disease-2019 (COVID-19) pandemic. Participants: Twenty in-depth interviews and a focus group discussion were conducted with participants and therapists, respectively. Transcripts were analyzed using thematic analysis. Results: Participants generally preferred face-to-face sessions for rapport building, communication, and comprehension. However, barriers like venue accessibility, childcare, and lack of family support hindered engagement. Telephone sessions were favored for easy scheduling and the comfort of receiving the session at home, but there were challenges associated with phone use, distractions at home, and family members' limited mental health awareness. A mix of face-to-face and telephone sessions was preferred, with rapport from in-person sessions carrying over to telephone interactions. Conclusion: This study underscores the need for adaptable intervention delivery strategies that consider cultural norms, logistical challenges, and individual family dynamics. By combining the benefits of both delivery methods, mental health interventions can be optimized to effectively address prenatal anxiety and promote well-being in resource-constrained settings like Pakistan.

Anxiety-focused cognitive behavioral therapy delivered by non-specialists to prevent postnatal depression: a randomized, phase 3 trial.

Anxiety experienced by women during pregnancy is highly prevalent, especially in resource-poor settings and strongly predicts postnatal common mental disorders (CMDs), anxiety and depression. We evaluated the effectiveness of an anxiety-focused early prenatal intervention on preventing postnatal CMDs. This study was a phase 3, two-arm, single-blind, randomized controlled trial conducted in Pakistan with women who were ≤22 weeks pregnant and had at least mild anxiety without clinical depression. Participants were randomized to the Happy Mother-Healthy Baby program, based on cognitive behavioral therapy, consisting of six one-on-one intervention sessions in pregnancy delivered by non-specialist providers, or to enhanced care alone. The primary outcome was major depression, generalized anxiety disorder or both at 6 weeks after delivery. Overall, 755 women completed postnatal assessments (380 (50.3%), intervention arm; 375 (49.7%) enhanced-care arm). The primary outcomes were met. Examined jointly, we found 81% reduced odds of having either a major depressive episode (MDE) or moderate-to-severe anxiety for women randomized to the intervention (adjusted odds ratio (aOR) = 0.19, 95% CI 0.14-0.28). Overall, 12% of women in the intervention group developed MDE at 6 weeks postpartum, versus 41% in the control group. We found reductions of 81% and 74% in the odds of postnatal MDE (aOR = 0.19, 95% CI 0.13-0.28) and of moderate-to-severe anxiety (aOR = 0.26, 95% CI 0.17-0.40), respectively. The Happy Mother-Healthy Baby program early prenatal intervention focusing on anxiety symptoms reduced postpartum CMDs. ClinicalTrials.gov identifier NCT03880032 .

Piloting a psychosocial intervention for perinatal depression, the Thinking Healthy Programme-Peer delivered (THPP), in a primary care setting in Lilongwe District, Malawi.

Despite the evidence for the effectiveness of psychosocial interventions for perinatal depression, their uptake is low in Low- and Middle-Income Countries. Reasons for this include the lack of contextually adapted interventions and mental health specialists to deliver them. This study aimed to test the acceptability and feasibility of a psychosocial intervention for perinatal depression, the Thinking Healthy Programme-Peer Delivered, adapted for use in rural Malawi. A multi-method evaluation of feasibility and acceptability of the intervention was conducted using a one-group pretest-posttest quasi-experimental design and an exploratory qualitative study. Pre-post intervention change in depression scores (paired t-test) and recruitment, retention and session adherence rates were calculated. Qualitative data were collected through 29 in-depth interviews (22 mothers and 7 peer volunteers) and 1 Focus Group Discussion (18 mothers). Thematic analysis approach was used to analyse qualitative data. Seven (7) out of 8 peer volunteers were successfully trained to deliver the intervention. A total of 31 pregnant women with Edinburgh Postnatal Depression Scale (EPDS) score ≥12 were offered intervention, of whom 24 were enrolled (recruitment rate 77.4%). Out of these 24 women, 22 completed the intervention (retention rate 91.6%). Mean difference between pre- and post-test EPDS scores one week after 8th session was 7.59 (95% CI 4.98 to 10.19), p<0.001. Qualitative evaluation showed that the intervention was acceptable despite some challenges including stigma and issues around incentivization of peer volunteers. The Thinking Healthy Programme-Peer Delivered, adapted for use in Malawi, was feasible to deliver and acceptable to its target population. The intervention may be useful in management of perinatal depression in primary care settings in Malawi. However, definitive trials are needed to evaluate its effectiveness.

Pregnancy stressors and postpartum symptoms of depression and anxiety: the moderating role of a cognitive-behavioural therapy (CBT) intervention.

Background: Little is known about the association between stressors (especially positive stressors) during pregnancy and postpartum depression and anxiety. Aims: We investigated the association between positive and negative stress events during different stages of pregnancy and postpartum mental health outcomes among low-income pregnant women with symptoms of anxiety in Pakistan and evaluated whether an intervention based on cognitive-behavioural therapy (CBT) had a regulatory effect. Methods: Participants were 621 pregnant Pakistani women with mild anxiety. Using the Pregnancy Experience Scale-Brief Version, six scores were created to assess positive and negative stressors. We performed a multivariate linear regression to examine whether these six scores, measured both at baseline and in the third trimester, were associated with postpartum anxiety and depressive symptoms. The effect of the intervention on this relationship was examined by adding an interaction term to the regression model. Results: Hassles frequency measured in the third trimester was positively associated with depression (B=0.22, 95% confidence interval (CI): 0.09 to 0.36) and anxiety (B=0.19, 95% CI: 0.08to 0.30). At the same timepoint, uplifts intensity was negatively associated with symptoms of depression (B=-0.82, 95% CI: -1.46 to -0.18) and anxiety (B=-0.70, 95% CI: -1.25 to -0.15), whereas hassles intensity was positively related to symptoms of depression (B=1.02, 95% CI: 0.36 to 1.67) and anxiety (B=0.90, 95% CI: 0.34 to 1.47). The intensity ratio of hassles to uplifts reported in the third trimester was positively related to both depression (B=1.40, 95% CI: 0.59 to 2.20) and anxiety (B=1.26, 95% CI: 0.57 to 1.96). The intervention strengthened the overall positive effects of uplifts and the negative effects of hassles. Pregnancy experiences at baseline during early pregnancy to mid-pregnancy were not associated with mental health outcomes. Conclusions: Stressors in the third trimester but not earlier in pregnancy were associated with postpartum symptoms of anxiety and depression. The CBT intervention modified the association between pregnancy stressors and postpartum mental health outcomes. Programmes that promote positive experiences and reduce negative experiences, especially in late pregnancy, may mitigate postpartum mental health consequences. Trial registration number: NCT03880032.

Self-reported problems and functional difficulties in anxious pregnant women in Pakistan: The use of a patient-generated mental health outcome measure.

Anxiety during pregnancy affects women worldwide and is highly prevalent in Pakistan. The Psychological Outcome Profiles (PSYCHLOPS) questionnaire is an instrument used in therapy to assess patient-generated problems and the consequent functional difficulties. Using the PSYCHLOPS, we aimed to describe the type of problems and the consequent functional difficulties faced by anxious pregnant women in Pakistan. Secondarily, we sought to explore if a cognitive behavioral therapy (CBT)-based intervention brought about changes in the severity score for certain problems or functional difficulties. Anxious pregnant women were recruited from the Obstetrics/Gynecology Department of a tertiary hospital in Rawalpindi, Pakistan. Of 600 pregnant women randomized to receive a psychosocial intervention for prenatal anxiety delivered by non-specialist providers, 450 received ≥1 intervention session and were administered the PSYCHLOPS. Eight types of problems were identified; worries about the unborn baby's health and development (23%), concerns about family members (13%), and financial constraints (12%) were the most frequently reported primary problems. Severity scores between baseline and the last available therapy session indicated the largest decrease for relationship problems (mean = 2.4) and for concerns about family members (mean = 2.2). For functional difficulties, 45% of the participants reported difficulties in performing household chores, but the intervention showed the greatest decrease in severity scores for mental or emotional functional difficulties. Focus on certain types of patient-generated problems, e.g., relationship problems, could anchor therapy delivery in order to have the greatest impact. Tailored CBT-based intervention sessions have the potential to address important but neglected problems and functional difficulties in anxious pregnant women.

"If it has happened once, it can happen again". The impact of previous pregnancy loss on anxious women's ongoing pregnancies: A qualitative study from Pakistan.

BACKGROUND: Pregnancy loss that includes both miscarriage and stillbirth cause significant psychological distress for women including anxiety, depression, and grief that persist long after physical recovery. This study focuses on the experiences of women in Pakistan, where pregnancy loss rates are high. OBJECTIVE: To explore how pregnant women with anxiety symptoms and a history of pregnancy loss perceive their past experiences with the loss and how it affects overall well-being in their current pregnancy. DESIGN: Qualitative methods were used to explore the impact of previous pregnancy loss on the well-being of pregnant women. SETTING: This qualitative research was embedded within a randomized control trial conducted in a tertiary care facility in Rawalpindi, Pakistan. PARTICIPANTS: Data were collected through in-depth interviews with 18 pregnant women who had experienced pregnancy loss. Data was analyzed using Framework Analysis. FINDINGS: The findings revealed several factors influencing participants' well-being during pregnancies that resulted in a loss, such as unsupportive and abusive environments, unintended pregnancies, certain superstitious beliefs, poor health, and lack of access to quality healthcare. The study also highlighted the adverse impact of previous pregnancy loss on the ongoing pregnancy, including deterioration of physical and mental health and aversion of healthcare services. However, some participants reported positive changes in medical and self-care practices and an enhanced faith and reliance on destiny in their subsequent pregnancies. CONCLUSION: Our study highlights the lasting impact of past pregnancy loss on subsequent pregnancies, affecting overall wellbeing and leading to healthcare avoidance. We identified persistent anxiety along with positive outcomes like enhanced medical practices and strengthened faith. Results suggest the need for culturally responsive interventions to support the overall well-being of anxious pregnant women with a history of pregnancy loss in resource-constrained settings.

Non-specialist-delivered psychosocial intervention for prenatal anxiety in a tertiary care setting in Pakistan: a qualitative process evaluation.

OBJECTIVES: A manualised cognitive-behavioural therapy-based psychosocial intervention for prenatal anxiety called Happy Mother Healthy Baby is being tested for its effectiveness through a randomised control trial in Pakistan. The aim of this study was to evaluate the intervention delivery process and the research process. DESIGN: Qualitative methods were used to explore in depth the intervention delivery and research process. SETTING: This process evaluation was embedded within a randomised control trial conducted in a tertiary care facility in Rawalpindi, Pakistan. PARTICIPANTS: Data were collected through in-depth interviews (n=35) with the trial participants and focus group discussions (n=3) with the research staff. Transcripts were analysed using a Framework Analysis. RESULTS: The evaluation of the intervention delivery process indicated that it can be effectively delivered by non-specialist providers trained and supervised by a specialist. The intervention was perceived to be culturally acceptable and appropriately addressing problems related to prenatal anxiety. Lack of awareness of 'talking' therapies and poor family support were potential barriers to participant engagement. The evaluation of the research process highlighted that culturally appropriate consent procedures facilitated recruitment of participants, while incentivisation and family involvement facilitated sustained engagement and retention. Lack of women's empowerment and mental health stigma were potential barriers to implementation of the programme. CONCLUSION: We conclude that non-specialists can feasibly deliver an evidence-based intervention integrated into routine antenatal care in a tertiary hospital. Non-specialist providers are likely to be more cost effective and less stigmatising. Inclusion of family is key for participant recruitment, retention and engagement with the intervention. TRIAL REGISTRATION NUMBER: NCT03880032.

Technology-assisted cognitive-behavior therapy delivered by peers versus standard cognitive behavior therapy delivered by community health workers for perinatal depression: study protocol of a cluster randomized controlled non-inferiority trial.

BACKGROUND: The lack of trained mental health professionals is a key barrier to scale-up of evidence-based psychological interventions in low and middle-income countries. We have developed an app that allows a peer with no prior experience of health-care delivery to deliver the cognitive therapy-based intervention for perinatal depression, the Thinking Healthy Programme (THP). This trial aims to assess the effectiveness and cost-effectiveness of this Technology-assisted peer-delivered THP versus standard face-to-face Thinking Healthy Programme delivered by trained health workers. METHODS: We will employ a non-inferiority stratified cluster randomized controlled trial design comparing the two formats of intervention delivery. A total of 980 women in the second or third trimester of pregnancy with a diagnosis of Major Depressive Episode, evaluated with the Structured Clinical Interview for DSM-V Disorders (SCID), will be recruited into the trial. The unit of randomization will be 70 village clusters randomly allocated in a 1:1 ratio to the intervention and control arms. The primary outcome is defined as remission from major depressive episode at 3 months postnatal measured with the SCID. Data will also be collected on symptoms of anxiety, disability, quality of life, service use and costs, and infant-related outcomes such as exclusive breastfeeding and immunization rates. Data will be collected on the primary outcome and selected secondary outcomes (depression and anxiety scores, exclusive breastfeeding) at 6 months postnatal to evaluate if the improvements are sustained in the longer-term. We are especially interested in sustained improvement (recovery) from major depressive episode. DISCUSSION: This trial will evaluate the effectiveness and cost-effectiveness of a technology-assisted peer-delivered cognitive behavioral therapy-based intervention in rural Pakistan. If shown to be effective, the novel delivery format could play a role in reducing the treatment gap for perinatal depression and other common mental disorders in LMIC. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov (NCT05353491) on 29 April 2022.

Biological Mechanisms in Pregnant Women With Anxiety (Happy Mother-Healthy Baby Supplement Study): Protocol for a Longitudinal Mixed Methods Observational Study.

BACKGROUND: Anxiety and depression are common in the perinatal period and negatively affect the health of the mother and baby. Our group has developed "Happy Mother-Healthy Baby" (HMHB), a cognitive behavioral therapy-based psychosocial intervention to address risk factors specific to anxiety during pregnancy in low- and middle-income countries (LMICs). OBJECTIVE: The purpose of this study is to examine biological mechanisms that may be linked to perinatal anxiety in conjunction with a randomized controlled trial of HMHB in Pakistan. METHODS: We are recruiting 120 pregnant women from the Holy Family Hospital, a public facility in Rawalpindi, Pakistan. Participants are assessed for at least mild anxiety symptoms using the Hospital Anxiety and Depression Scale (ie, a score ≥8 on the anxiety scale is necessary for inclusion in the anxiety groups and <8 for inclusion in the healthy control group). Women who meet the criteria for an anxiety group are randomized into either the HMHB intervention group or an enhanced usual care (EUC) control group. Participants receive HMHB or EUC throughout pregnancy and undergo blood draws at 4 time points (baseline, second trimester, third trimester, and 6 weeks post partum). We will assess peripheral cytokine concentrations using a multiplex assay and hormone concentrations using gas chromatography and mass spectrometry. The statistical analysis will use generalized linear models and mixed effects models to assess the relationships across time among anxiety, immune dysregulation, and hormone levels, and to assess whether these biological factors mediate the relationship between anxiety and birth and child development outcomes. RESULTS: Recruitment started on October 20, 2020, and data collection was completed on August 31, 2022. The start date for recruitment for this biological supplement study was delayed by approximately half a year due to the COVID-19 pandemic. The trial was registered at ClinicalTrials.gov (NCT03880032) on September 22, 2020. The last blood samples were shipped to the United States on September 24, 2022, where they will be processed for analysis. CONCLUSIONS: This study is an important addition to the HMHB randomized controlled trial of an intervention for antenatal anxiety. The intervention itself makes use of nonspecialist providers and, if effective, will represent an important new tool for the treatment of antenatal anxiety in LMICs. Our biological substudy is one of the first attempts to link biological mechanisms to antenatal anxiety in an LMIC in the context of a psychosocial intervention, and our findings have the potential to significantly advance our knowledge of the biological pathways of perinatal mental illness and treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03880032; https://clinicaltrials.gov/ct2/show/NCT03880032. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43193.