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 at 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).

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.

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.

Family concerns and relationship problems in anxious pregnant women and their associations with postnatal functional disability in Pakistan.

OBJECTIVE: Expanding on existing research suggesting that strategies to reduce prenatal anxiety can decrease functional disability (e.g., difficulties in performing everyday activities and social participation), we examined if this effect varied by type of anxiety-producing problem (i.e., having family concerns and relationship problems versus other problems) reported during pregnancy. Further, we explored if perceived social support mediated this relationship. METHODS: We used longitudinal data on 310 anxious Pakistani women who received any psychosocial intervention sessions as part of a program that was based on Cognitive Behavioral Therapy. The Psychological Outcome Profiles (PSYCHLOPS) was used to assess whether women had 'family concerns and relationship problems' or 'other problems.' The WHO Disability Assessment Schedule 2.0 assessed functional disability at six-weeks after delivery. Lack of support was measured using a 12-item Multi-dimensional Scale of Perceived Social Support. We employed linear regression to examine associations between types of problems reported during pregnancy and postnatal functional disability. Causal mediation analysis was used to assess whether postnatal social support mediated this relationship. RESULTS: Of anxious pregnant women, 34% reported family concerns or relationship problems as primary problems in pregnancy. They were more likely to report higher functional disability at six-weeks after delivery than women who reported other problems (adjusted B = 2.40, 95% CI: 0.83-3.97). Lack of overall social support (Estimateindirect = 0.69, 95% CI: 0.04-1.38) and lack of support from friends (Estimateindirect = 0.62, 95% CI: 0.01-1.29) significantly mediated the relationship. CONCLUSIONS: Findings suggest that complementing pre- and post-natal care with support programs and services that address family concerns and relationship problems, as well as enhancing social support is important to functional disability.

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.

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 .

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.

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.

Cultural adaptation and psychometric validation of the Pregnancy Experience Scale-Brief version (PES-Brief) in Pakistani women with antenatal anxiety symptoms.

Background: Pregnancy experiences influence fetal and birth outcomes. There is scarcity of locally validated tools to assess pregnancy experiences. We aimed to validate the Pregnancy Experience Scale-Brief (PES-Brief) in pregnant Pakistani women with anxiety symptoms. Methods: A two-step process was used including 1) adaptation via translation/back-translation followed by cognitive interviewing with 10 participants and 2) factor analysis and validation with 605 women in Rawalpindi Pakistan who had mild-moderate symptoms of anxiety, attended the antenatal clinic, and were ≤22 weeks of gestation and ≥18 years old. We calculated internal consistency and reliability and conducted exploratory and confirmatory factor analyses. Results: Cultural adaptation led to inclusion of one item of the hassles subscale and exclusion of one item in the uplifts subscale, resulting in 9 uplifts and 11 hassles. Exploratory factor analysis supported a two-factor structure, with the adapted items exhibiting loading values of ≥0.24 for their respective factors. Internal consistency was demonstrated for uplifts (Cronbach's alpha = 0.89) and hassles (Cronbach's alpha = 0.85) subscales. Uplift intensity was moderately correlated with the Hospital Anxiety and Depression Scale anxiety subscale (r = 0.54, 95% CI:0.30-0.77). Conclusion: The Urdu PES-Brief is a reliable and valid tool for use in Pakistani pregnant women with antenatal anxiety. Future studies on its validity are needed on women without symptoms anxiety.

Psychometric Validation of the Multidimensional Scale of Perceived Social Support During Pregnancy in Rural Pakistan.

Background: The Multidimensional Scale of Perceived Social Support (MSPSS) is a short and reliable instrument that assesses perceived social support from the social network of an individual. A previous study in Pakistan among postpartum women has demonstrated a unidimensional factor structure in contrast to the original three-factor structure. The emergence of a one-factor structure for postpartum women in Pakistan may be due to traditional postpartum practices unique to the women of the subcontinent. Building upon the previous evidence, this study aims to explore the psychometric properties of MSPSS among pregnant women in their third trimester in rural Pakistan. Methods: A cross-sectional survey was conducted from October 2014 to February 2016, in rural Pakistan. A sample of 1,154 pregnant women (aged ≥ 18 years) in their third trimester who were registered with the local Lady Health Worker Program and were living in the north of the Punjab Province was included in this study. They were assessed using Urdu translated scales of Patient Health Questionnaire, MSPSS, Maternal Social Support Index, and Perceived Stress Scale. Principal Axis Factoring was used to assess the construct validity of the MSPSS. Results: The MSPSS scale showed an excellent internal consistency, yielding a Cronbach's α-value of 0.933. The MSPSS scale exhibited an excellent construct validity, and confirmatory factor analysis retained three factors (family, friends, and significant others) for both the depressed and non-depressed samples. Internal reliability and construct validity were also established. Conclusion: The psychometric findings suggest that the tridimensional structure of MSPSS is a valid and reliable measure of perceived social support among the Pakistani population with and without perinatal depression. The perceived social support is an important predictor of maternal mental well-being and psychopathologies, and the MSPSS can serve as a useful tool in mental health research in Pakistan.

Longitudinal effects of perinatal social support on maternal depression: a marginal structural modelling approach.

BACKGROUND: Depression in the perinatal period, during pregnancy or within 1 year of childbirth, imposes a high burden on women with rippling effects through her and her child's life course. Social support may be an important protective factor, but the complex bidirectional relationship with depression, alongside a paucity of longitudinal explorations, leaves much unknown about critical windows of social support exposure across the perinatal period and causal impacts on future depressive episodes. METHODS: This study leverages marginal structural models to evaluate associations between longitudinal patterns of perinatal social support and subsequent maternal depression at 6 and 12 months postpartum. In a cohort of women in rural Pakistan (n=780), recruited in the third trimester of pregnancy and followed up at 3, 6 and 12 months postpartum, we assessed social support using two well-validated measures: the Multidimensional Scale of Perceived Social Support (MSPSS) and the Maternal Social Support Index (MSSI). Major depressive disorder was assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM IV). RESULTS: High and sustained scores on the MSPSS through the perinatal period were associated with a decreased risk of depression at 12 months postpartum (0.35, 95% CI: 0.19 to 0.63). Evidence suggests the recency of support also matters, but estimates are imprecise. We did not find evidence of a protective effect for support based on the MSSI. CONCLUSIONS: This study highlights the protective effect of sustained social support, particularly emotional support, on perinatal depression. Interventions targeting, leveraging and maintaining this type of support may be particularly important for reducing postpartum depression.

Effectiveness of a peer-delivered, psychosocial intervention on maternal depression and child development at 3 years postnatal: a cluster randomised trial in Pakistan.

BACKGROUND: Maternal depression has a recurring course that can influence offspring outcomes. Evidence on how to treat maternal depression to improve longer-term maternal outcomes and reduce intergenerational transmission of psychopathology is scarce, particularly for task-shifted, low-intensity, and scalable psychosocial interventions. We evaluated the effects of a peer-delivered, psychosocial intervention on maternal depression and child development at 3 years postnatal. METHODS: 40 village clusters in Pakistan were randomly allocated using a computerised randomisation sequence to receive a group-based, psychosocial intervention and enhanced usual care for 36 months, or enhanced usual care alone. Pregnant women (≥18 years) were screened for moderate or severe symptoms of depression (patient health questionnaire-9 [PHQ-9] score ≥10) and were recruited into the trial (570 participants), and a cohort without depression (PHQ-9 score <10) was also enrolled (584 participants). Including the non-depressed dyads enabled us to determine how much of the excess risk due to maternal depression exposure the intervention could mitigate. Research teams responsible for identifying, obtaining consent, and recruiting trial participants were blind to the allocation status throughout the duration of the study, and principal investigators, site coordinators, statisticians, and members of the trial steering committee were also blinded to the allocation status until the analysis of 6-month data for the intervention. Primary outcomes were maternal depression symptoms and remission (PHQ-9 score <10) and child socioemotional skills (strengths and difficulties questionnaire [SDQ-TD]) at 36-months postnatal. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02658994. FINDINGS: From Oct 15, 2014 to Feb 25, 2016 46 village clusters were assessed for eligibility, of which 40 (including 1910 mothers were enrolled. After exclusions, 288 women were randomly assigned to the enhanced usual care group and 284 to the intervention group, and 1159 women were included in a group without prenatal depression. At 36-months postnatal, complete data were available from 889 mother-child dyads: 206 (72·5%) in the intervention group, 216 (75·3%) in the enhanced usual care group, and 467 (80·0%) women who did not have prenatal-depression. We did not observe significant outcome differences between the intervention group and the enhanced usual care group for the primary outcomes. The standardised mean difference of PHQ-9 total score was -0·13 (95% CI -0·33 to 0·07), relative risk of patient health questionnaire-9 remission was 1·00 (95% CI 0·88 to 1·14), and the SDQ-TD treatment estimate was -0·10 (95% CI -1·39 to 1·19). INTERPRETATION: Reduced symptom severity and high remission rates were seen across both the intervention and enhanced usual care groups, possibly masking any effects of the intervention. A multi-year, psychosocial intervention can be task-shifted via peers but might be susceptible to reductions in fidelity and dosage over time (which were not among the outcomes of this trial). Early intervention efforts might need to rely on multiple models (eg, collaborative care), be of greater intensity, and potentially targeted at mothers who are at high risk for depression to reduce the intergenerational transmission of psychopathology from mothers to children. FUNDING: National Institutes of Health.

Measuring the implementation strength of a perinatal mental health intervention delivered by peer volunteers in rural Pakistan.

The South Asian region, including Pakistan, reports one of the highest rates of perinatal depression. Effective task-shifting perinatal mental health interventions exist and are gaining attention of policy makers, as a potential solution to bridge the existing treatment gap. However, no specific indicators are available to gauge the level of implementation for such interventions in the South Asian region. The Thinking Healthy Programme Peer-delivered (THPP) is a perinatal mental health intervention delivered, at scale, by peer volunteers (PVs). An effectiveness trial for THPP based on 570 depressed pregnant women was conducted in rural Rawalpindi, Pakistan. In addition, we also examined the implementation processes of THPP in order to develop an index to gauge implementation strength of this intervention. The key components of this index are based on four important intervention processes related to service provision which include; i) the competence of PVs, ii) supervisions attended by PVs and iii) number and iv) duration of THPP sessions. We attempt to inform an implementation strength index which best correlates with reduced perinatal depression and disability at 6 months post childbirth. Knowledge of such an implementation strength index for a task-shifted perinatal depression intervention carries implications for scale up strategies.

Effectiveness of the Thinking Healthy Programme for perinatal depression delivered through peers: Pooled analysis of two randomized controlled trials in India and Pakistan.

BACKGROUND: The Thinking Healthy Programme (THP) is recommended to treat perinatal depression in resource-limited settings, but scale-up is hampered by a paucity of community health workers. THP was adapted for peer-delivery (THPP) and evaluated in two randomized controlled trials in India and Pakistan. Our aim was to estimate the effectiveness of THPP on maternal outcomes across these two settings, and evaluate effect-modification by country and other pre-defined covariates. METHODS: Participants were pregnant women aged≥18 years with depression (Patient Health Questionnaire (PHQ-9) score≥10), randomized to THPP plus enhanced usual care (EUC) or EUC-only. Primary outcomes were symptom severity and remission (PHQ-9 score<5) 6 months post-childbirth. Secondary outcomes included further measures of depression, disability and social support at 3 and 6 months post-childbirth. RESULTS: Among 850 women (280 India; 570 Pakistan), 704 (83%) attended 6-month follow-up. Participants in the intervention arm had lower symptom severity (PHQ-9 score adjusted mean difference -0.78 (95% confidence interval -1.47,-0.09)) and higher odds of remission (adjusted odds ratio 1.35 (1.02,1.78)) versus EUC-only. There was a greater intervention effect on remission among women with short chronicity of depression, and those primiparous. There were beneficial intervention effects across multiple secondary outcomes. LIMITATIONS: The trials were not powered to assess effect-modifications. 10-20% of participants were missing outcome data. CONCLUSIONS: This pooled analysis demonstrates the effectiveness, acceptability and feasibility of THPP, which can be scaled-up within a stepped-care approach by engaging with the existing health care systems and the communities to address the treatment gap for perinatal depression in resource-limited settings.

Cohort Profile: Perinatal depression and child socioemotional development ; the Bachpan cohort study from rural Pakistan.

PURPOSE: This is a prospective pregnancy-birth cohort designed to investigate the effects of depression on socioemotional development of children. Perinatal depression is a risk factor for poor child development and for many it has a recurring chronic course. Thus, the exposure to depression can continue through the early years of the child with detrimental developmental outcomes. PARTICIPANTS: Between October 2014 and February 2016, we recruited 1154 pregnant women from a rural subdistrict of Pakistan. Data include longitudinal and repeated measures of maternal psychosocial measures and child growth, cognitive and socioemotional measures. Follow-up include mother-child dyad assessments at 3rd, 6th, 12th, 24th and 36th months of child age. All these follow-ups are community based at the household level. We have competed baseline assessment. FINDINGS TO DATE: Of the eligible dyads, we followed 885 (76.6%), 929 (91%) and 940 (93.3%) at 3, 6 and 12 months post-childbirth. We include a subsample mother-child dyad DNA and inflammatory biomarkers, 73 and 104, respectively. FUTURE PLANS: While we continue to do 24-month and 36-month follow-up assessments, we plan to follow these mother-child dyads up to the age of 7-8 years with some children being exposed to at least 1 year of school environment. Investigators interested in learning more about the study can contact (jmaselko@unc.edu) and (siham.sikander@hdrfoundation.org).

Delivering the Thinking Healthy Programme for perinatal depression through volunteer peers: a cluster randomised controlled trial in Pakistan.

BACKGROUND: The Thinking Healthy Programme (THP), which is endorsed by WHO, is an evidence-based intervention for perinatal depression. We adapted THP for delivery by volunteer peers (laywomen from the community) to address the human resource needs in bridging the treatment gap, and we aimed to assess its effectiveness and cost-effectiveness in Rawalpindi, Pakistan. METHODS: In this cluster randomised controlled trial, we randomly assigned 40 village clusters (1:1) to provide either THP peer-delivered (THPP) and enhanced usual care (EUC; intervention group) or EUC only (control group) to the participants within clusters. These villages were randomly selected from eligible villages by an independent researcher. The participants were pregnant women aged 18 years or older who had scored at least 10 on the Patient Health Questionnaire-9 (PHQ-9), who we recruited from households within communities in Rawalpindi, Pakistan. The research teams who were responsible for recruiting trial participants were masked to treatment allocations. Participants attended follow-up visits at 3 and 6 months after childbirth. The primary outcomes were the severity of depressive symptoms (assessed by PHQ-9 score) and the prevalence of remission (defined as a PHQ-9 score of less than 5) in participants with available data 6 months after childbirth, which was assessed by researchers who were masked to treatment allocations. We analysed outcomes by intention to treat, adjusting for covariates that were defined a priori or that showed imbalance at baseline. The trial was registered with ClinicalTrials.gov, number NCT02111915. FINDINGS: Between April 15 and July 30, 2014, we randomly selected 40 of 46 eligible village clusters for assessment, as per sample size calculations. Between Oct 15, 2014, and Feb 25, 2016, we identified and screened 971 women from 20 village clusters that had been randomly assigned to the THPP and EUC group and 939 women from 20 village clusters that had been randomly assigned to the EUC only group. In the intervention group, 79 women were ineligible for inclusion, 11 women refused screening, 597 women screened negative on the PHQ-9, and one woman did not consent to participate. In the control group, 75 women were ineligible for inclusion, 14 women refused screening, 562 women screened negative on the PHQ-9, and one woman did not consent to participate. We enrolled 283 (29%) women in the intervention group and 287 (31%) women in the control group. At 6 months after childbirth, 227 (80%) women in the THPP and EUC group and 226 (79%) women in the EUC only group were assessed for the primary outcome. The severity of depression (assessed by PHQ-9 scores; standardised mean difference -0·13, 95% CI -0·31 to 0·06; p=0·07) and prevalence of remission (49% in the intervention group vs 45% in the control group; prevalence ratio 1·12, 95% CI 0·95 to 1·29; p=0·14) did not significantly differ between the groups 6 months after childbirth. There was no evidence of significant differences in serious adverse events between the groups. INTERPRETATION: THPP had no effect on symptom severity or remission from perinatal depression at 6 months after childbirth, but we found that it was beneficial on some other metrics of severity and disability and that it was cost-effective. THPP could be a step towards use of an unused human resource to address the treatment gap in perinatal depression. FUNDING: National Institute of Mental Health (USA).

The effectiveness of the peer delivered Thinking Healthy Plus (THPP+) Programme for maternal depression and child socio-emotional development in Pakistan: study protocol for a three-year cluster randomized controlled trial.

BACKGROUND: The negative effects of perinatal depression on the mother and child start early and persist throughout the lifecourse (Lancet 369(9556):145-57, 2007; Am J Psychiatry 159(1):43-7, 2002; Arch Dis Child 77(2):99-101, 1997; J Pak Med Assoc 60(4):329; J Psychosoma Res 49(3):207-16, 2000; Clin Child Fam Psychol Rev 14(1):1-27, 2011). Given that 10-35 % of children worldwide are exposed to perinatal depression in their first year of life (Int Rev Psychiatry 8(1):37-54, 1996), mitigating this intergenerational risk is a global public health priority (Perspect Public Health 129(5):221-7, 2009; Trop Med Int Health 13(4):579-83, 2008; Br Med Bull 101(1):57-79, 2012). However, it is not clear whether intervention with depressed women can have long-term benefits for the mother and/or her child. We describe a study of the effectiveness of a peer-delivered depression intervention delivered through 36 postnatal months, the Thinking Healthy Program Peer-delivered PLUS (THPP+) for women and their children in rural Pakistan. METHODS/DESIGN: The THPP+ study aims are: (1) to evaluate the effects of an extended 36-month perinatal depression intervention on maternal and index child outcomes using a cluster randomized controlled trial (c-RCT) and (2) to determine whether outcomes among index children of perinatally depressed women in the intervention arm converge with those of index children born to perinatally nondepressed women. The trial is designed to recruit 560 pregnant women who screened positive for perinatal depression (PHQ-9 score ≥10) from 40 village clusters, of which 20 receive the THPP+ intervention. An additional reference group consists of 560 perinatally nondepressed women from the same 40 clusters as the THPP+ trial. The women in the nondepressed group are not targeted to receive the THPP+ intervention; but, by recruiting pregnant women from both intervention and control clusters, we are able to evaluate any carryover effects of the THPP+ intervention on the women and their children. Perinatally depressed women in the THPP+ intervention arm receive bimonthly group-based sessions. Primary outcomes are 3-year maternal depression and 3-year child development indicators. Analyses are intention-to-treat and account for the clustered design. DISCUSSION: This trial, together with the reference group, has the potential to further our understanding of the early developmental lifecourse of children of both perinatally depressed and perinatally nondepressed women in rural Pakistan and to determine whether intervening with women's depression in the perinatal period can mitigate the negative effects of maternal depression on 36-month child development. TRIAL REGISTRATION: THPP-P ClinicalTrials.gov Identifier: NCT02111915 (registered on 9 April 2014). THPP+ ClinicalTrials.gov Identifier: NCT02658994 (registered on 21 January 2016). SPONSOR: Human Development Research Foundation (HDRF).

Xanthan production in a plunging jet reactor.

A plunging jet reactor (0.04-0.08 m(3)) was used for the production of the exopolysaccharide xanthan with Xanthomonas campestris. The microorganism was not affected by the pump shear force. Similar specific growth rates and xanthan space-time yields to those in other reactor types were achieved at much lower specific power input. The better oxygen sorption efficiency in the jet reactor overcompensated for the effect of poor mixing in the wall region at high xanthan concentrations.