Effects of a prenatal anxiety randomized controlled trial intervention on infant development in Pakistan.

OBJECTIVES: Given that infant development is influenced by caregiver mental health, we tested whether an intervention to reduce antenatal anxiety could affect infant development. A secondary aim was to test depressive symptoms, maternal responsiveness, and maternal infant bonding as mediators of this relationship. METHODS: Between 2020 and 2022, pregnant women participated in a randomized controlled trial of the Happy Mother-Healthy Baby (HMHB) program based on cognitive behavioral therapy. We collected data on child development from 202 intervention and 198 control participants in a public hospital in Pakistan. Child development was measured using the Ages and Stages Questionnaires-Version 3 at six weeks postpartum. Using intent-to-treat analyses, we examined whether the intervention was associated with performance on the five ASQ-3 domains. Causal mediation analysis was used to assess depressive symptoms, bonding, and maternal-infant responsiveness as mediators. RESULTS: Socio-demographic characteristics were evenly distributed between study arms. Intervention arm infants showed a 2.1-point increase (95% CI: 0.12, 4.17) in communication scores compared to controls. Though not achieving statistical significance, intervention infants also showed a 2.0-point increase (95% CI:-0.06, 4.09) in gross motor development performance. Bonding, depression, and responsiveness were mediators between the intervention and infant communication (Bindirect=1.94 (95%CI: 0.86, 3.25) depression; Bindirect=0.57 (95% CI: 0.09, 1.16) bonding; Bindirect=0.53 (95% CI: 0.01, 1.21) responsiveness; and Bindirect=1.94 (95%CI: 0.86, 3.25). Bonding, responsiveness, and depression mediated 25%, 23%, and 87% of the total association, respectively. CONCLUSIONS: HMHB positively affected infant communication at six-week follow-up. Larger studies with longer follow-up are needed to confirm and extend these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT03880032; https://clinicaltrials.gov/ct2/show/NCT03880032.

Impact of an intervention for perinatal anxiety on breastfeeding: findings from the Happy Mother-Healthy Baby randomized controlled trial in Pakistan.

BACKGROUND: The study examined the effects of Happy Mother-Healthy Baby (HMHB), a cognitive-behavioural therapy (CBT) intervention on breastfeeding outcomes for Pakistani women with prenatal anxiety. METHODS: Breastfeeding practices were evaluated in a randomized controlled trial between 2019 and 2022 in a public hospital in Pakistan. The intervention group was randomized to receive six HMHB sessions targeted towards prenatal anxiety (with breastfeeding discussed in the final session), while both groups also received enhanced usual care. Breastfeeding was defined in four categories: early breastfeeding, exclusive early breastfeeding, recent breastfeeding, and exclusive recent breastfeeding. Early breastfeeding referred to the first 24 h after birth and recent breastfeeding referred to the last 24 h before an assessment at six-weeks postpartum. Potential confounders included were mother's age, baseline depression and anxiety levels, stress, social support, if the first pregnancy (or not) and history of stillbirth or miscarriage as well as child's gestational age, gender. Both intent-to-treat and per-protocol analyses were examined. Stratified analyses were also used to compare intervention efficacy for those with mild vs severe anxiety. RESULTS: Out of the 1307 eligible women invited to participate, 107 declined to participate and 480 were lost to follow-up, resulting in 720 women who completed the postpartum assessment. Both intervention and control arms were similar on demographic characteristics (e.g. sex, age, income, family structure). In the primary intent-to-treat analysis, there was a marginal impact of the intervention on early breastfeeding (OR 1.38, 95% CI: 0.99-1.92; 75.4% (N = 273) vs. 69.0% (N = 247)) and a non-significant association with other breastfeeding outcomes (OR1.42, 95% CI: 0.89-2.27; (47) 12.9% vs. (34) 9.5%, exclusive early breastfeeding; OR 1.48, 95% CI: 0.94-2.35; 90% (N = 327) vs. 86% (N = 309), recent breastfeeding; OR1.01, 95% CI: 0.76-1.35; 49% (N = 178) vs 49% (N = 175) exclusive recent breastfeeding). Among those who completed the intervention's six core sessions, the intervention increased the odds of early breastfeeding (OR1.69, 95% CI:1.12-2.54; 79% (N = 154) vs. 69% (N = 247)) and recent breastfeeding (OR 2.05, 95% CI:1.10-3.81; 93% (N = 181) vs. 86% (N = 309)). For women with mild anxiety at enrolment, the intervention increased the odds of recent breastfeeding (OR 2.41, 95% CI:1.17-5.00; 92% (N = 137) vs. 83% (N = 123). CONCLUSIONS: The study highlights the potential of CBT-based interventions like HMHB to enhance breastfeeding among women with mild perinatal anxiety, contingent upon full participation in the intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT03880032.

Effectiveness of a group psychological intervention to reduce psychosocial distress in adolescents in Pakistan: a single-blind, cluster randomised controlled trial.

BACKGROUND: Emotional problems in adolescents living in low-income and middle-income countries (LMICs) remain largely unaddressed; key reasons include a scarcity of trained mental health professionals and unavailability of evidence-based, scalable psychological interventions. We aimed to evaluate the effectiveness of a non-specialist-delivered, group psychological intervention to reduce psychosocial distress in school-going adolescents in Pakistan. METHODS: In a two-arm, single-blind, cluster randomised controlled trial, eligible public school clusters from a rural subdistrict of Gujar Khan, Rawalpindi, Pakistan, were randomised (1:1, stratified by sex) using permuted block randomisation into intervention (n=20) and wait-list control (n=20) groups. Adolescents aged 13-15 years who provided informed assent and caregivers' consent were screened for psychosocial distress using the youth-reported Pediatric Symptoms Checklist (PSC; total psychosocial distress scores from 0 to 70), and those scoring 28 or more and their caregivers were enrolled into the trial. Adolescents in the intervention group received seven weekly group sessions and their caregivers received three biweekly group sessions in school settings from trained non-specialists. The primary outcome was change from baseline in the total PSC scores at 3 months post-intervention. The trial was registered prospectively with the International Standard Randomised Controlled Trial Number registry, ISRCTN17755448. FINDINGS: From the 40 school clusters that were included, 282 adolescents in the intervention group and 284 adolescents in the wait-list control group were enrolled between Nov 2 and Nov 30, 2021. At 3 months, adolescents in the intervention group had significantly lower mean total score on the PSC compared with adolescents in the control group (mean difference in change from baseline 3·48 [95% CI 1·66-5·29], p=0·0002, effect size 0·38 [95% CI 0·18-0·57]; adjusted mean difference 3·26 (95% CI 1·46-5·06], p=0·0004, effect size 0·35 (0·16-0·55). No adverse events were reported in either group. INTERPRETATION: The group psychological intervention most likely represents a feasible and effective option for adolescents with psychosocial distress in school settings. FUNDING: UK Medical Research Council, Foreign Commonwealth and Development Office, Department of Health and Social Care. TRANSLATION: For the Urdu translation of the abstract see Supplementary Materials section.

"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.

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.

An alignment-free method for detection of missing regions for phylogenetic analysis.

Phylogenetic tree estimation using conventional approaches usually requires pairwise or multiple sequence alignment. However, sequence alignment has difficulties related to scalability and accuracy in case of long sequences such as whole genomes, low sequence identity, and in presence of genomic rearrangements. To address these issues, alignment-free approaches have been proposed. While these methods have demonstrated promising results, many of these lead to errors when regions are missing from the sequences of one or more species that are trivially detected in alignment-based methods. Here, we present an alignment-free method for detecting missing regions in sequences of species for which phylogeny is to be estimated. It is based on counts of k-mers and can be used to filter out k-mers belonging to regions in one species that are missing in one or more of the other species. We perform experiments with real and simulated datasets containing missing regions and find that it can successfully detect a large fraction of such k-mers and can lead to improvements in the estimated phylogenies. Our method can be used in k-mer based alignment-free phylogeny estimation methods to filter out k-mers corresponding to missing regions.

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.

Genome wide association studies on seven yield-related traits of 183 rice varieties in Bangladesh.

Rice genetic diversity is regulated by multiple genes and is largely dependent on various environmental factors. Uncovering the genetic variations associated with the diversity in rice populations is the key to breed stable and high yielding rice varieties. We performed genome wide association studies (GWASs) on seven rice yielding traits (grain length, grain width, grain weight, panicle length, leaf length, leaf width, and leaf angle) based on a population of 183 rice landraces of Bangladesh. Our GWASs reveal various chromosomal regions and candidate genes that are associated with different traits in Bangladeshi rice varieties. Noteworthy was the recurrent implication of chromosome 10 in all three grain-shape-related traits (grain length, grain width, and grain weight), indicating its pivotal role in shaping rice grain morphology. Our study also underscores the involvement of transposon gene families across these three traits. For leaf related traits, chromosome 10 was found to harbor regions that are significantly associated with leaf length and leaf width. The results of these association studies support previous findings as well as provide additional insights into the genetic diversity of rice. This is the first known GWAS study on various yield-related traits in the varieties of Oryza sativa available in Bangladesh-the fourth largest rice-producing country. We believe this study will accelerate rice genetics research and breeding stable high-yielding rice in Bangladesh.

Born in Bradford's Age of Wonder cohort: protocol for adolescent data collection.

Background: Adolescence and transition into adulthood are periods shaping life-long mental health, cardiometabolic risk, and inequalities. However, they are poorly studied and understood. By extending and expanding the Born in Bradford (BiB) cohort study through this period using innovative, co-produced approaches to collect and analyse data, we aim to understand better the interplay of factors that influence health and wellbeing, and inform/evaluate interventions to improve them and reduce inequalities. Protocol: BiB Age of Wonder (AoW) is a large, whole city cohort that will capture the contemporary lived experience amongst multi-ethnic adolescents progressing into young adulthood. We will collect repeated data from existing BiB participants and their peers (N~30,000 adolescents). The protocol for the first phase of the quantitative methods, involving survey measurements and health assessments in mainstream secondary schools is described here. We describe the co-production behind these methods, and lessons learned from the first year of data collection.

Born in Bradford have been following the health and wellbeing of over 13,000 Bradford children since they were born. This group of children are now in their teenage years ­ a time that is crucial for their future mental and physical health. Age of Wonder aims to capture this journey through adolescence and early adulthood with up to 30,000 young people in Bradford over 7 years. In the first phase of this project, data collection is taking part in secondary schools in Bradford. This protocol describes how this data collection is currently being carried out in the schools. Young people aged 12-15 are being asked to complete questionnaires, covering topics such as mental and physical health. These topics have been designed with groups of young people, schools and other partners, to make sure we are capturing data on the things most important to young people. Those in Year 9 (13-14 years old), are also asked to take part in physical health measurements such as height, weight, blood pressure and a blood sample, as well as computer-based assessments of cognition (memory), movement and language. There have been a number of lessons learned from the first full year of data collection, such as how to make the research as easy as possible for schools to take part in when they have so many competing demands on their time.

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).

Editorial: Equity/inequality, diversity and inclusion in child and adolescent mental health - a perspective from the South Asian region.

Over 1.8 billion people, about a quarter of the world's population live in the seven countries of South Asia: Afghanistan, Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka. The population is characterized by a significant demographic youth bulge, with over 40% under the age of 18. This young population poses challenges related to ensuring their well-being and development. Issues such as poverty, undernutrition, lack of early stimulation, limited access to quality education and health care, and gender disparities persist in large parts of South Asia, affecting the lives of many children and adolescents. The promotion of child and adolescent mental health remains a challenge. Accumulating evidence suggests that early interventions can provide long-term health and socioeconomic benefits by prevention of the onset of mental health problems and their development into chronic disorders. This needs to be coupled with specialist services that can cater to the needs of children with greater needs, and support the community and schools-based non-specialist led services. Addressing child and adolescent mental health in South Asia presents a window of opportunity, because this regional youth bulge can contribute significantly to the global economy of the future.

Multicomponent Behavioural Intervention during Pregnancy to Reduce Home Exposure to Second-Hand Smoke: A Pilot Randomised Controlled Trial in Bangladesh and India.

BACKGROUND: Pregnant women exposed to second-hand smoke (SHS) are at increased risk of poor birth outcomes. We piloted multicomponent behavioural intervention and trial methods in Bangalore, India, and Comilla, Bangladesh. METHODS: A pilot individual randomised controlled trial with economic and process evaluation components was conducted. Non-tobacco-using pregnant women exposed to SHS were recruited from clinics and randomly allocated to intervention or control (educational leaflet) arms. The process evaluation captured feedback on the trial methods and intervention components. The economic component piloted a service use questionnaire. The primary outcome was saliva cotinine 3 months post-intervention. RESULTS: Most pregnant women and many husbands engaged with the intervention and rated the components highly, although the cotinine report elicited some anxiety. Forty-eight (Comilla) and fifty-four (Bangalore) women were recruited. The retention at 3 months was 100% (Comilla) and 78% (Bangalore). Primary outcome data were available for 98% (Comilla) and 77% (Bangalore). CONCLUSIONS: The multicomponent behavioural intervention was feasible to deliver and was acceptable to the interventionists, pregnant women, and husbands. With the intervention, it was possible to recruit, randomise, and retain pregnant women in Bangladesh and India. The cotinine data will inform sample size calculations for a future definitive trial.

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.

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.

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 .

scGIST: gene panel design for spatial transcriptomics with prioritized gene sets.

A critical challenge of single-cell spatial transcriptomics (sc-ST) technologies is their panel size. Being based on fluorescence in situ hybridization, they are typically limited to panels of about a thousand genes. This constrains researchers to build panels from only the marker genes of different cell types and forgo other genes of interest, e.g., genes encoding ligand-receptor complexes or those in specific pathways. We propose scGIST, a constrained feature selection tool that designs sc-ST panels prioritizing user-specified genes without compromising cell type detection accuracy. We demonstrate scGIST's efficacy in diverse use cases, highlighting it as a valuable addition to sc-ST's algorithmic toolbox.

Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan.

Background: Mothers with perinatal depression can show different symptom trajectories and may spontaneously remit from depression, however, the latter is poorly understood. This is the first study which sought to investigate predictors of spontaneous remission and longer-term recovery among untreated women with perinatal depression. Methods: We analysed data from two randomised controlled trials in women with perinatal depression in India and Pakistan. Analyses were restricted to women in the control groups who did not receive active treatment. Generalised estimating equations and logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for within-person correlation. Results: In multivariable analyses, remission was associated with a husband who is not working (adjusted OR, aOR = 2.04, 95% CI 1.02-4.11), lower Patient Health Questionnaire-9 score at baseline (aOR = 0.43, 95% CI 0.20-0.90 for score of ≥20 vs. 10-14) and better social support at baseline (aOR = 2.37, 95% CI 1.32-4.27 for high vs. low social support). Conclusions: Women with low baseline severity may remit from perinatal depression with adequate social support from family and friends. These factors are important contributors to the management of perinatal depression and the prevention of clinical worsening, and should be considered when designing low-threshold psychological interventions.

Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis.

Cognitive behavioral therapies (CBT) have been demonstrated efficacious in treating perinatal depression (PND). This has been demonstrated in several meta-analyses of randomized controlled trials and quasi-experimental studies. However, there is a need for up-to-date meta-analytical evidence providing reliable estimates for CBT's effectiveness in treating and preventing PND. Furthermore, with the world moving toward precision medicine, approaches require a critical synthesis of psychotherapies, especially to unpack their mechanisms of action and to understand what approaches work best for whom. Therefore, the present systematic review and meta-regression analyses aim to answer these research questions. We searched six academic databases through February 2022 and identified 56 studies for an in-depth review. Using pretested data extraction sheets, we extracted patient-level and intervention-level characteristics and effect size data from each study. Random-effects meta-analyses and mixed-effect subgroup analyses were run to delineate the effectiveness and moderators of CBT interventions for PND, respectively. CBT-based interventions yielded a strong effect size (SMD = -0.74, 95% confidence interval [CI]: -0.91 to -0.56, n = 9,722) in alleviating depressive symptoms. These interventions were effective across different delivery formats (individual, group, and electronic) and could be delivered effectively by specialists and nonspecialists. Longer duration CBT interventions may not necessarily be more effective than shorter ones. Moreover, CBT-based interventions should consider including various behavioral ingredients to maximize intervention benefits.

Research Review: Psychological and psychosocial interventions for children and adolescents with depression, anxiety, and post-traumatic stress disorder in low- and middle-income countries - a systematic review and meta-analysis.

BACKGROUND: The incidence of depression, anxiety, and post-traumatic stress disorder (PTSD) among children and adolescents residing in low- and middle-income countries (LMICs) poses a significant public health concern. However, there is variation in the evidence of effective psychological interventions. This meta-analysis aims to provide a complete overview of the current body of evidence in this rapidly evolving field. METHODS: We conducted searches on PubMed, Embase.com, and EBSCO/APA PsycInfo databases up to June 23, 2022, identify randomized controlled trials (RCTs) investigating the effectiveness of psychological interventions in LMICs that targeted children and adolescents with elevated symptoms above a cut-off score for depression, anxiety, and PTSD, comparing a psychological or psychosocial intervention with other control conditions. We conducted random effects meta-analyses for depression, anxiety, and PTSD symptoms. Sensitivity analysis for outliers and high-risk studies, and analyses for the publication bias were carried out. Subgroup analyses investigated how the intervention type, intervention format, the facilitator, study design, and age group of the participant predicted effect sizes. RESULTS: Thirty-one RCTs (6,123 participants) were included. We found a moderate effect of interventions on depression outcomes compared to the control conditions (g = 0.53; 95% CI: 0.06-0.99; NNT = 6.09) with a broad prediction interval (PI) (-1.8 to 2.86). We found a moderate to large effect for interventions on anxiety outcomes (g = 0.88; 95% CI: -0.03 to 1.79; NNT = 3.32) with a broad PI (-3.14 to 4.9). Additionally, a moderate effect was observed on PTSD outcomes (g = 0.54; 95% CI: 0.19-0.9; NNT = 5.86) with a broad PI (-0.64 to 1.72). CONCLUSIONS: Psychological and psychosocial interventions aimed at addressing depression, anxiety, and PTSD among children and adolescents in LMICs have demonstrated promising results. However, future studies should consider the variation in evidence and incorporate long-term outcomes to better understand the effectiveness of these interventions.