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.

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. 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. 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). 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.

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