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

Published online by Cambridge University Press:  15 March 2023

Ahmed Waqas*
Affiliation:
Department of Primary Care & Mental Health, Institute of Population Health, University of Liverpool, Liverpool, UK
Syeda Wajeeha Zafar
Affiliation:
Global Institute of Human Development, Shifa Tameer-e-Millat University, Islamabad, Pakistan
Parveen Akhtar
Affiliation:
Department of Psychology, Capital University of Science and Technology, Islamabad, Pakistan
Sadiq Naveed
Affiliation:
Department of Psychiatry, Eastern Connecticut Health Network, Manchester, CT, USA
Atif Rahman
Affiliation:
Department of Primary Care & Mental Health, Institute of Population Health, University of Liverpool, Liverpool, UK
*
Author for correspondence: Ahmed Waqas, Email: ahmed.waqas@liverpool.ac.uk
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Abstract

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.

Type
Overview Review
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2023. Published by Cambridge University Press

Impact statement

Perinatal depression is very prevalent worldwide. It is associated with poor maternal and infant health outcomes and thus, a significant public health concern. Cognitive behavioral (CB) therapy is an evidence-based and one of the most effective treatments for perinatal depression. This systematic review and meta-analysis provide an overview of interventional research testing different CB approaches for perinatal depression. It synthesizes findings about the development of CB-based approaches delivered either individually, in groups or electronically. Thereafter, using established frameworks, this review also dissects the interventions into their components. Quantitative evidence is provided regarding the factors which could improve or worsen the efficacy of these interventions. These include but are not limited to the characteristics of women undergoing CB treatment, the format of delivery, and approaches utilized in these intervention programs. It is hoped that this synthesis of literature would guide researchers, clinicians, and implementors in better delivery of CB approaches for perinatal depression in different settings.

Background

Perinatal depression (PND) is a public health priority due to its high prevalence and ill effects on child health (Husain et al., Reference Husain, Bevc, Husain, Chaudhry, Atif and Rahman2006; Gelaye et al., Reference Gelaye, Rondon, Araya and Williams2016; Anderson et al., Reference Anderson, Hatch, Comacchio and Howard2017; Bowers et al., Reference Bowers, Ding, Yolton, Ji, Nidey, Meyer, Ammerman, Van Ginkel and Folger2021). It is one of the most common mental disorders among perinatal women and is studied widely in low- and middle-income countries (LMICs) (Gelaye et al., Reference Gelaye, Rondon, Araya and Williams2016). In LMICs, approximately 25.3% of antenatal women and 19% of postpartum women report depressive symptoms (Gelaye et al., Reference Gelaye, Rondon, Araya and Williams2016). Women with PND are at a higher risk of developing perinatal complications, including intrauterine growth retardation, preterm deliveries, low birth weight, and infectious illnesses among their infants (Gelaye et al., Reference Gelaye, Rondon, Araya and Williams2016). In addition, untreated PND affects child health postnatally, leading to poorer growth, neurodevelopmental, socioemotional, and academic outcomes (Dubowitz et al., Reference Dubowitz, Papas, Black and Starr2002; Ashman et al., Reference Ashman, Dawson and Panagiotides2008; Betts et al., Reference Betts, Williams, Najman and Alati2015; Bao et al., Reference Bao, Jing, Jin, Hu, Liu and Hu2016; Fanti and Kimonis, Reference Fanti and Kimonis2017; Netsi et al., Reference Netsi, Pearson, Murray, Cooper, Craske and Stein2018; Chae et al., Reference Chae, East, Delva, Lozoff and Gahagan2020; Bowers et al., Reference Bowers, Ding, Yolton, Ji, Nidey, Meyer, Ammerman, Van Ginkel and Folger2021). Therefore, strategies to address maternal mental health are increasingly becoming the focus of maternal and child public health initiatives, especially in LMICs (Rahman et al., Reference Rahman, Malik, Sikander, Roberts and Creed2008; Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018; Sikander et al., Reference Sikander, Ahmad, Atif, Zaidi, Vanobberghen, Weiss, Nisar, Tabana, Ul Ain, Bibi, Bilal, Bibi, Sharif, Zulifiqar, Fuhr, Price, Patel and Rahman2019a; Sikander et al., Reference Sikander, Ahmad, Bates, Gallis, Hagaman, O’Donnell, Turner, Zaidi, Rahman and Maselko2019b).

Fortunately, efficacious preventive and treatment interventions exist for PND in the form of psychological and psychosocial therapies (Sockol, Reference Sockol2015; Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018; Li et al., Reference Li, Laplante, Paquin, Lafortune, Elgbeili and King2022; Waqas et al., Reference Waqas, Zafar, Meraj, Tariq, Naveed, Fatima, Chowdhary, Dua and Rahman2022b). Experimental evidence, however, is still lacking for pharmacotherapies for PND (Howard and Khalifeh, Reference Howard and Khalifeh2020; Brown et al., Reference Brown, Wilson, Ayre, Robertson, South, Molyneaux, Trevillion, Howard and Khalifeh2021). Several meta-analyses of randomized controlled trials (RCTs) have repeatedly shown that cognitive-behavioral therapies (CBTs) are among the most efficacious treatments for PND (Sockol, Reference Sockol2015; Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018; Li et al., Reference Li, Laplante, Paquin, Lafortune, Elgbeili and King2022; Waqas et al., Reference Waqas, Zafar, Meraj, Tariq, Naveed, Fatima, Chowdhary, Dua and Rahman2022b). For instance, strong effect sizes were reported for CBT-based treatment interventions for PND Standardized Mean Difference (SMD = 0.65, 95% confidence interval [CI]: 0.54–0.76) (Sockol, Reference Sockol2015). However, CBT interventions have yielded weak-to-moderate strength effect sizes in the prevention of PND (SMD = 0.39, 95%CI: 0.17–0.60) (Sockol, Reference Sockol2015). These therapies are also acceptable among the stakeholders and end-consumers in LMIC and, thus, suitable for large-scale implementation (Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018).

Research evidence demonstrates CBT interventions’ adequate effectiveness, utility, and implementation (Sockol, Reference Sockol2015; Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018; Li et al., Reference Li, Laplante, Paquin, Lafortune, Elgbeili and King2022; Waqas et al., Reference Waqas, Zafar, Meraj, Tariq, Naveed, Fatima, Chowdhary, Dua and Rahman2022b). However, there is a paucity of evidence delineating what works and for whom. Answering these questions is important to optimize psychotherapies for different populations, for example, by choosing the right treatments for the right candidates (Delgadillo et al., Reference Delgadillo, Ali, Fleck, Agnew, Southgate, Parkhouse, Cohen, DeRubeis and Barkham2022). An increasing body of research has shown that these treatments work in different settings (Sockol, Reference Sockol2015). However, there is little research evidence on how and for whom these interventions work (Cuijpers et al., Reference Cuijpers, Reijnders and Huibers2019; Furukawa et al., Reference Furukawa, Suganuma, Ostinelli, Andersson, Beevers, Shumake, Berger, Boele, Buntrock, Carlbring, Choi, Christensen, Mackinnon, Dahne, Huibers, Ebert, Farrer, Forand, Strunk, Ezawa, Forsell, Kaldo, Geraedts, Gilbody, Littlewood, Brabyn, Hadjistavropoulos, Schneider, Johansson, Kenter, Kivi, Björkelund, Kleiboer, Riper, Klein, Schröder, Meyer, Moritz, Bücker, Lintvedt, Johansson, Lundgren, Milgrom, Gemmill, Mohr, Montero-Marin, Garcia-Campayo, Nobis, Zarski, O’Moore, Williams, Newby, Perini, Phillips, Schneider, Pots, Pugh, Richards, Rosso, Rauch, Sheeber, Smith, Spek, Pop, Ünlü, van Bastelaar, van Luenen, Garnefski, Kraaij, Vernmark, Warmerdam, van Straten, Zagorscak, Knaevelsrud, Heinrich, Miguel, Cipriani, Efthimiou, Karyotaki and Cuijpers2021). Thus, delineating the mechanistic pathways of different psychotherapeutic treatments has gained priority in the research agenda for depression (Huibers et al., Reference Huibers, Lorenzo-Luaces, Cuijpers and Kazantzis2020). Mediation research is an important tool to understand how psychotherapies work, while prediction and moderation research help identify for whom these interventions work (Huibers et al., Reference Huibers, Lorenzo-Luaces, Cuijpers and Kazantzis2020). Using these tools, we can attempt to unpack the black box of psychological therapies, a challenge for the field identified as early as 1967 by Paul (Reference Paul1967) and Huibers et al. (Reference Huibers, Lorenzo-Luaces, Cuijpers and Kazantzis2020).

More recently, two complementary research streams in psychotherapy have emerged: one that focuses on harmonizing terminology across different schools of psychotherapies (Chorpita et al., Reference Chorpita, Daleiden and Weisz2005; Chowdhary et al., Reference Chowdhary, Sikander, Atif, Singh, Ahmad, Fuhr, Rahman and Patel2014; Singla et al., Reference Singla, Kohrt, Murray, Anand, Chorpita and Patel2017), and the other focuses on empirical causal processes of change brought about by psychological interventions (Singla et al., Reference Singla, MacKinnon, Fuhr, Sikander, Rahman and Patel2021). Important research in the former domain includes the works of Chorpita et al. (Reference Chorpita, Daleiden and Weisz2005) and Abraham and Michie (Reference Abraham and Michie2008), who sought to harmonize the taxonomy of treatment strategies utilized across different psychotherapies. Based on this work, researchers have posited that there are commonalities between different forms of psychotherapies. While having different theoretical underpinnings, these psychotherapies may work through similar mechanisms.

Two classes of therapeutic ingredients of psychotherapies have been posited: specific and nonspecific or common ingredients (Singla et al., Reference Singla, Kohrt, Murray, Anand, Chorpita and Patel2017). Specific active ingredients emerge from the theoretical models of different psychotherapies. For instance, cognitive behavior therapy is based on cognitive theory and is hypothesized to work through challenging and changing maladaptive thought patterns or cognitive schemas, while behavioral therapies work by correcting maladaptive behaviors. Similarly, interpersonal psychotherapy is hypothesized to act through interpersonal change mechanisms (Chorpita et al., Reference Chorpita, Daleiden and Weisz2005; Kahl et al., Reference Kahl, Winter and Schweiger2012; Cuijpers et al., Reference Cuijpers, Reijnders and Huibers2019; Huibers et al., Reference Huibers, Lorenzo-Luaces, Cuijpers and Kazantzis2020). However, common ingredients or elements include techniques used by therapists during the delivery of therapy sessions, e.g., building rapport and empathy or helping the client to identify sources of social support. These common active ingredients are shared across all forms of psychotherapy. Rosenzweigh cites these common ingredients as the primary reason for comparable effect sizes across different psychotherapies (Rosenzweigh, Reference Rosenzweigh1936; Eyesenck, Reference Eyesenck1955).

Even after decades of research, none of the theories has yielded conclusive empirical evidence, and the black box of psychotherapies remains unpacked. Moreover, there is also a paucity of evidence on optimizing and personalizing treatment with psychotherapies. Therefore, the present systematic review and meta-regression analysis aims to:

  1. i. Assess the effectiveness of CBT-based interventions for the prevention and treatment of PND.

  2. ii. Explore the settings in which these interventions work the best.

  3. iii. Explore the individual level and intervention level factors driving PND’s prognosis among women undergoing CBT.

  4. iv. Explore the active ingredients of CBT interventions for PND.

Methods

Search strategy

This systematic review and meta-analysis have been conducted per the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines (Page et al., Reference Page, Moher, Bossuyt, Boutron, Hoffmann, Mulrow, Shamseer, Tetzlaff, Akl, Brennan, Chou, Glanville, Grimshaw, Hrobjartsson, Lalu, Li, Loder, Mayo-Wilson, McDonald, McGuinness, Stewart, Thomas, Tricco, Welch, Whiting and McKenzie2021). Before the conduct of this review, its protocol was registered on the PROSPERO database (Waqas and Rahman, Reference Waqas and Rahman2022). The current systematic review does not report findings concerning secondary outcomes mentioned in the PROSPERO protocol. Using a pretested search strategy (Supplementary Table 1), we searched six academic databases, including PubMed, Medline, Web of Science, PsycInfo, Cochrane central registry of trials, and CINAHL, through February 2022.

Inclusion & exclusion criteria

We included all randomized and cluster RCTs that reported the effectiveness of cognitive, behavioral, and third-wave psychotherapeutic interventions as standalone or as part of complex multicomponent interventions (Supplementary Table 2). We included CBT-based interventions for PND, delivered during the antenatal period and up to 1-year postnatal. Those trials were considered that reported either the rate of PND or symptom severity of perinatal depressive symptoms as a primary outcome. Preventive interventions were considered for both indicated (populations with prodromal symptoms) and targeted (at-risk) populations. However for treatment interventions, we included those which recruited perinatal women who were either screened positive for PND using psychometric scales or diagnosed clinically using International Statistical Classification of Diseases and Related Health Problems (ICD) or The Diagnostic and Statistical Manual of Mental Disorders (DSM) clinical diagnostic criteria. Interventions conducted among peripartum women with medical comorbidities were also considered. When available, we also reviewed intervention manuals and secondary publications associated with the eligible RCTs. This was done to aid in synthesizing evidence on the active ingredients of CBT interventions.

We excluded studies that did not report PND (rates of diagnoses or severity of symptoms) as an outcome. We also excluded studies not available in the English language and short formats of publications such as brief reports, letters to editors, conference papers, and abstracts.

Outcomes

As primary outcomes, we considered on either rate of PND assessed using clinical criteria of diagnoses or scores on valid and reliable psychometric scales; assessed post-intervention. This review does not report findings pertaining to secondary outcomes outlined in the PROSPERO protocol.

Study selection procedures and data extraction

Teams comprising two independent reviewers screened database records against inclusion and exclusion criteria using a two-phased approach (titles and abstracts followed by full texts). After the identification of studies fulfilling the eligibility criteria, data on characteristics of intervention and study samples were extracted. Study-level characteristics included the year of publication, study design, type of control group, and inclusion and exclusion criteria. However, patient-level characteristics included mean age, the proportion of participants belonging to minority ethnic groups and lower income class, parity, family structure, and intervention timing (antenatal or gestational age if available, or postpartum period). We also cataloged intervention-level characteristics such as the scope of the intervention (targeted prevention, indicated prevention, and treatment), the theoretical underpinning of interventions, the format of delivery (individual, group, electronic), setting of intervention, delivery agent (specialist and nonspecialist), and the number of sessions of intervention. These variables were selected a priori as described in the systematic review protocol (Waqas and Rahman, Reference Waqas and Rahman2022).

Taxonomy of interventions: Distillation & matching framework

This exercise was done to delineate different elements and active ingredients of cognitive behavioral interventions included in this review. It is based on the premise that interventions to improve mental health are varied and may comprise: (i) a combination of specific or nonspecific active ingredients underpinned by a single theory-based approach, often called a therapy (e.g., CBT) or (ii) a combination of elements drawn from different theories, forming a multicomponent intervention or eclectic therapy. An additional complication is that multicomponent interventions usually comprise ingredients that may be derived from another discipline, e.g., CBT may be delivered in tandem exercise or yoga. All this creates a problem for the field as it is important for policymakers to know which interventions provide the best evidence for effectiveness and feasibility (Chorpita et al., Reference Chorpita, Daleiden and Weisz2005; Abraham and Michie, Reference Abraham and Michie2008; Michie et al., Reference Michie, Richardson, Johnston, Abraham, Francis, Hardeman, Eccles, Cane and Wood2013; Cuijpers et al., Reference Cuijpers, Reijnders and Huibers2019; Huibers et al., Reference Huibers, Lorenzo-Luaces, Cuijpers and Kazantzis2020; Furukawa et al., Reference Furukawa, Suganuma, Ostinelli, Andersson, Beevers, Shumake, Berger, Boele, Buntrock, Carlbring, Choi, Christensen, Mackinnon, Dahne, Huibers, Ebert, Farrer, Forand, Strunk, Ezawa, Forsell, Kaldo, Geraedts, Gilbody, Littlewood, Brabyn, Hadjistavropoulos, Schneider, Johansson, Kenter, Kivi, Björkelund, Kleiboer, Riper, Klein, Schröder, Meyer, Moritz, Bücker, Lintvedt, Johansson, Lundgren, Milgrom, Gemmill, Mohr, Montero-Marin, Garcia-Campayo, Nobis, Zarski, O’Moore, Williams, Newby, Perini, Phillips, Schneider, Pots, Pugh, Richards, Rosso, Rauch, Sheeber, Smith, Spek, Pop, Ünlü, van Bastelaar, van Luenen, Garnefski, Kraaij, Vernmark, Warmerdam, van Straten, Zagorscak, Knaevelsrud, Heinrich, Miguel, Cipriani, Efthimiou, Karyotaki and Cuijpers2021). Furthermore, it also complicates the understanding of mediational or causal mechanisms that drive an intervention’s efficacy.

To decompose the CBT-based interventions into their components or active ingredients, we utilized the distillation and matching framework for psychotherapies devised by Chorpita et al. (Reference Chorpita, Daleiden and Weisz2005). This approach was further informed by Michie and colleagues’ hierarchically clustered taxonomy of behavior change techniques (Abraham and Michie, Reference Abraham and Michie2008; Michie et al., Reference Michie, Richardson, Johnston, Abraham, Francis, Hardeman, Eccles, Cane and Wood2013). These frameworks were used to harmonize the definitions of active ingredients across the studies included in this review. To devise a hierarchal taxonomy suitable for this review, we used the definitions proposed by the Institute of Medicine’s framework for psychotherapies (England et al., Reference England, Butler and Gonzalez2015). The hierarchy comprised three levels: elements, strategies, and active ingredients. We defined the elements as either specific or nonspecific. Nonspecific elements are fundamental engagement strategies (e.g., showing empathy) and are essential for building an effective client-therapist alliance. Specific elements are unique to a particular theoretical orientation underpinned by behavioral, cognitive, interpersonal, and emotional domains. This categorization is recommended by Singla et al. and widely adopted by the stakeholders (Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018; Waqas et al., Reference Waqas, Zafar, Meraj, Tariq, Naveed, Fatima, Chowdhary, Dua and Rahman2022b). All these elements and active ingredients have been defined in the World Health Organization’s guidelines for preventing and treating PND and anxiety (Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018) and presented here for review. The finalized hierarchy of active ingredients comprised 58 most utilized behavior change techniques and treatment elements (Supplementary Tables 3 and 4). Using the above frameworks, we could also harmonize and standardize strategies utilized across different disciplines and theories. For example, “thought records” in CBT were considered similar to “mood ratings” in interpersonal psychotherapy (England et al., Reference England, Butler and Gonzalez2015).

This phase was conducted by three experts trained in clinical psychology and psychiatry at postgraduate levels. The reviewers evaluated the content of the interventions as detailed in the trial papers and associated manuals (if available) to identify commonly utilized approaches.

Risk of bias

The risk of bias among RCTs was assessed using the Cochrane tool for risk of bias assessments (Higgins et al., Reference Higgins, Thomas, Chandler, Cumpston, Li, Page and Welch2019). It was assessed across five domains, including the method for random sequence generation, allocation concealment, blinding of outcome assessment, attrition bias, and selective reporting. We did not rate risk across blinding of participants and personnel domain as it is challenging to maintain during trials of psychotherapies.

Data analysis

We conducted a meta-analysis for depressive symptoms according to psychometric scales and the rate of perinatal depressive disorders (ICD/DSM criteria) assessed after the intervention. Findings on secondary outcomes were only synthesized narratively. For continuous outcomes about depressive symptoms severity on psychometric scales, we extracted the mean (standard deviation [SD]) and sample size of intervention and control groups. For binary outcomes, we extracted both groups’ number of events and sample sizes. In case scores on psychometric scales were presented as binary outcomes in studies, we converted them to standardized mean differences using the following formula: SMD = √3/ π ln OR (Higgins et al., Reference Higgins, Thomas, Chandler, Cumpston, Li, Page and Welch2019).

We expected a high clinical heterogeneity in the eligible studies due to varied approaches for the assessment of clinical outcomes, theoretical underpinnings of included therapies, and population studies. Therefore, we utilized random effects (Der Simonian & Laird method) to pool data across the studies. Study-level and pooled effect sizes were visualized as a forest plot. Sensitivity analyses were conducted to adjust meta-analytical estimates for outliers. Publication bias in the study was assessed statistically using Egger’s regression and visualized as Begg’s funnel plot (Thornton and Lee, Reference Thornton and Lee2000). To identify moderators of effect sizes, we conducted subgroup analyses for study, intervention, and patient-level variables if reported in more than four studies (Borenstein et al., Reference Borenstein, Hedges, Higgins and Rothstein2021). Meta-regression was done to assess the association of quantitative variables with effect size. To ensure optimum power, meta-regression was only performed when continuous variables were reported in at least 10 studies. (Borenstein et al., Reference Borenstein, Hedges, Higgins and Rothstein2021).

Results

Screening process

The electronic database searches yielded 515 titles and abstracts, out of which 116 duplicate records were removed using Endnote. Out of 399 titles and abstracts, 323 records were excluded after assessing their titles and abstracts against the eligibility criteria for this review. Finally, full texts of 76 studies were appraised, out of which 34 were excluded. A total of 42 studies were eligible to be included in the review. The main reasons for exclusion were non-RCT/cRCT study design (n = 30), intervention not for PND (n = 2), and short forms of publication (n = 2). Fourteen studies were included after the manual screening of bibliographies of included studies and consultations with experts (Figure 1).

Figure 1. PRISMA flowchart showing the process of inclusion of studies.

Among these 56 studies, there were 59 interventions. Among the included studies, a high proportion of the interventions were delivered individually (n = 24), followed by group (n = 25) and electronic (n = 10) delivery format. These interventions were tested among participants with a mean age of 28.48 years (2.99), married (x̄ = 66.8%, SD = 31.95), and (x̄ = 48.26%, SD = 18.03). Among the participants in included studies, approximately 41% reported low-income levels (SD = 22.32) and poor education (x̄ = 35.25, SD = 23.69).

Quality of trials

These interventions were tested in generally high-quality trials, where the random sequence generated was rated at low risk of bias among 41 studies, allocation concealment (n = 29), blinding of outcomes assessment (n = 26), attrition bias (n = 35), and selective reporting (n = 56). The risk of bias was unclear for allocation concealment in 27 studies, blinding of outcome assessment (n = 27), attrition bias (n = 13), and random sequence generation (n = 10) (Figure 2).

Figure 2. Risk of bias in included studies.

Interventions delivered to individuals

Among these interventions (Supplementary Table 5), nine were delivered during the antenatal period (Cho et al., Reference Cho, Kwon and Lee2008; Silverstein et al., Reference Silverstein, Feinberg, Cabral, Sauder, Egbert, Schainker, Kamholz, Hegel and Beardslee2011; Hayden et al., Reference Hayden, Perantie, Nix, Barnes, Mostello, Holcomb, Svrakic, Scherrer, Lustman and Hershey2012; Ammerman et al., Reference Ammerman, Putnam, Altaye, Stevens, Teeters and Van Ginkel2013; Burns et al., Reference Burns, O’Mahen, Baxter, Bennert, Wiles, Ramchandani, Turner, Sharp, Thorn, Noble and Evans2013; Dimidjian et al., Reference Dimidjian, Goodman, Felder, Gallop, Brown and Beck2014, Reference Dimidjian, Goodman, Felder, Gallop, Brown and Beck2016; Yazdanimehr et al., Reference Yazdanimehr, Omidi, Sadat and Akbari2016; Nejad et al., Reference Nejad, Shahraki, Nejad, Moghaddam, Jahani and Divsalar2021), followed by postnatal (n = 8) (Chabrol et al., Reference Chabrol, Teissedre, Saint-Jean, Teisseyre, RogÉ and Mullet2002; Cooper et al., Reference Cooper, Murray, Wilson and Romaniuk2003; Morrell et al., Reference Morrell, Warner, Slade, Dixon, Walters, Paley and Brugha2009; Hou et al., Reference Hou, Hu, Zhang, Lu, Wang, Yin, Chen and Zou2014; Ngai et al., Reference Ngai, Wong, Leung, Chau and Chung2015; Kordi et al., Reference Kordi, Nasiri, Gharavi and Lotfabadi2018; Van Horne et al., Reference Van Horne, Nong, Cain, Sampson, Greeley and Puryear2021) and both periods (n = 7) (Prendergast and Austin, Reference Prendergast and Austin2001; McKee et al., Reference McKee, Zayas, Fletcher, Boyd and Nam2006; Rahman et al., Reference Rahman, Malik, Sikander, Roberts and Creed2008; O’Mahen et al., Reference O’Mahen, Himle, Fedock, Henshaw and Flynn2013a; Trevillion, Reference Trevillion2014; Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018; Tandon et al., Reference Tandon, Ward, Hamil, Jimenez and Carter2018; Sikander et al., Reference Sikander, Ahmad, Bates, Gallis, Hagaman, O’Donnell, Turner, Zaidi, Rahman and Maselko2019b). Eleven interventions were delivered in communities, especially through home visits (Prendergast and Austin, Reference Prendergast and Austin2001; Chabrol et al., Reference Chabrol, Teissedre, Saint-Jean, Teisseyre, RogÉ and Mullet2002; Cooper et al., Reference Cooper, Murray, Wilson and Romaniuk2003; Rahman et al., Reference Rahman, Malik, Sikander, Roberts and Creed2008; Morrell et al., Reference Morrell, Warner, Slade, Dixon, Walters, Paley and Brugha2009; Ammerman et al., Reference Ammerman, Putnam, Altaye, Stevens, Teeters and Van Ginkel2013; Burns et al., Reference Burns, O’Mahen, Baxter, Bennert, Wiles, Ramchandani, Turner, Sharp, Thorn, Noble and Evans2013; Tandon et al., Reference Tandon, Ward, Hamil, Jimenez and Carter2018; Sikander et al., Reference Sikander, Ahmad, Atif, Zaidi, Vanobberghen, Weiss, Nisar, Tabana, Ul Ain, Bibi, Bilal, Bibi, Sharif, Zulifiqar, Fuhr, Price, Patel and Rahman2019a; Van Horne et al., Reference Van Horne, Nong, Cain, Sampson, Greeley and Puryear2021), three in multiple settings (McKee et al., Reference McKee, Zayas, Fletcher, Boyd and Nam2006; Silverstein et al., Reference Silverstein, Feinberg, Cabral, Sauder, Egbert, Schainker, Kamholz, Hegel and Beardslee2011; Dimidjian et al., Reference Dimidjian, Goodman, Sherwood, Simon, Ludman, Gallop, Welch, Boggs, Metcalf, Hubley, Powers and Beck2017), while the rest were delivered in healthcare settings (clinic or hospital) (Cho et al., Reference Cho, Kwon and Lee2008; Hayden et al., Reference Hayden, Perantie, Nix, Barnes, Mostello, Holcomb, Svrakic, Scherrer, Lustman and Hershey2012; O’Mahen et al., Reference O’Mahen, Himle, Fedock, Henshaw and Flynn2013a; Hou et al., Reference Hou, Hu, Zhang, Lu, Wang, Yin, Chen and Zou2014; Trevillion, Reference Trevillion2014; Ngai et al., Reference Ngai, Wong, Leung, Chau and Chung2015; Dimidjian et al., Reference Dimidjian, Goodman, Felder, Gallop, Brown and Beck2016; Yazdanimehr et al., Reference Yazdanimehr, Omidi, Sadat and Akbari2016; Kordi et al., Reference Kordi, Nasiri, Gharavi and Lotfabadi2018; Nejad et al., Reference Nejad, Shahraki, Nejad, Moghaddam, Jahani and Divsalar2021). A higher proportion of studies utilized The Edinburgh Postnatal Depression Scale (EPDS) for outcome assessment (n = 12), followed by The Beck Depression Inventory (BDI) (n = 6), The Hamilton Rating Scale for Depression (HDRS) (n = 2), The Patient Health Questionn aire (PHQ-9) (n = 2), The Quick Inventory of Depressive Symptomatology (QIDS), and The Depression Anxiety Stress Scales (DASS-21) (n = 2).

A total of 18 interventions were tested for PND treatment and underpinned by CBT (n = 16). Three trials tested Problem solving therapy (PST) (Silverstein et al., Reference Silverstein, Feinberg, Cabral, Sauder, Egbert, Schainker, Kamholz, Hegel and Beardslee2011; Kordi et al., Reference Kordi, Nasiri, Gharavi and Lotfabadi2018; Van Horne et al., Reference Van Horne, Nong, Cain, Sampson, Greeley and Puryear2021), mindfulness-based stress reduction or cognitive therapy (n = 3; Dimidjian et al., Reference Dimidjian, Goodman, Felder, Gallop, Brown and Beck2016; Yazdanimehr et al., Reference Yazdanimehr, Omidi, Sadat and Akbari2016; Nejad et al., Reference Nejad, Shahraki, Nejad, Moghaddam, Jahani and Divsalar2021), and Behavioral activation (BA) therapy (n = 1) (Dimidjian et al., Reference Dimidjian, Goodman, Sherwood, Simon, Ludman, Gallop, Welch, Boggs, Metcalf, Hubley, Powers and Beck2017). These interventions were delivered by either specialists (n = 14), nonspecialists (n = 8), or multidisciplinary teams (n = 2). Delivery agents reported diverse disciplinary backgrounds and experience in the delivery of care. Nonspecialists ranged from peers (Sikander et al., Reference Sikander, Ahmad, Atif, Zaidi, Vanobberghen, Weiss, Nisar, Tabana, Ul Ain, Bibi, Bilal, Bibi, Sharif, Zulifiqar, Fuhr, Price, Patel and Rahman2019a), health visitors (Morrell et al., Reference Morrell, Warner, Slade, Dixon, Walters, Paley and Brugha2009; Tandon et al., Reference Tandon, Ward, Hamil, Jimenez and Carter2018), and allied health professionals such as lady health workers (Rahman et al., Reference Rahman, Malik, Sikander, Roberts and Creed2008), midwives (Ngai et al., Reference Ngai, Wong, Leung, Chau and Chung2015), early childhood nurses (Prendergast and Austin, Reference Prendergast and Austin2001), and social workers (McKee et al., Reference McKee, Zayas, Fletcher, Boyd and Nam2006; Hayden et al., Reference Hayden, Perantie, Nix, Barnes, Mostello, Holcomb, Svrakic, Scherrer, Lustman and Hershey2012; Ammerman et al., Reference Ammerman, Putnam, Altaye, Stevens, Teeters and Van Ginkel2013; Van Horne et al., Reference Van Horne, Nong, Cain, Sampson, Greeley and Puryear2021) and graduate students in social work, public health, and medical sciences (Silverstein et al., Reference Silverstein, Feinberg, Cabral, Sauder, Egbert, Schainker, Kamholz, Hegel and Beardslee2011). While delivery agents specializing in mental health included practising clinical psychologists, graduate students, recent graduates (Chabrol et al., Reference Chabrol, Teissedre, Saint-Jean, Teisseyre, RogÉ and Mullet2002; Cho et al., Reference Cho, Kwon and Lee2008; Burns et al., Reference Burns, O’Mahen, Baxter, Bennert, Wiles, Ramchandani, Turner, Sharp, Thorn, Noble and Evans2013), counselors, and well-being practitioners (Hou et al., Reference Hou, Hu, Zhang, Lu, Wang, Yin, Chen and Zou2014; Trevillion, Reference Trevillion2014). Half of these interventions (n = 12) were integrated into healthcare settings (Ammerman et al., Reference Ammerman, Putnam, Altaye, Stevens, Teeters and Van Ginkel2013; Dimidjian et al., Reference Dimidjian, Goodman, Felder, Gallop, Brown and Beck2016; Dimidjian et al., Reference Dimidjian, Goodman, Sherwood, Simon, Ludman, Gallop, Welch, Boggs, Metcalf, Hubley, Powers and Beck2017; Hou et al., Reference Hou, Hu, Zhang, Lu, Wang, Yin, Chen and Zou2014; Morrell et al., Reference Morrell, Warner, Slade, Dixon, Walters, Paley and Brugha2009; Ngai et al., Reference Ngai, Wong, Leung, Chau and Chung2015; Prendergast J, 2001; Rahman et al., Reference Rahman, Malik, Sikander, Roberts and Creed2008; Sikander et al., Reference Sikander, Ahmad, Atif, Zaidi, Vanobberghen, Weiss, Nisar, Tabana, Ul Ain, Bibi, Bilal, Bibi, Sharif, Zulifiqar, Fuhr, Price, Patel and Rahman2019a; Tandon et al., Reference Tandon, Ward, Hamil, Jimenez and Carter2018; Trevillion, Reference Trevillion2014; Van Horne et al., Reference Van Horne, Nong, Cain, Sampson, Greeley and Puryear2021).

The number of sessions ranged from one for prevention intervention by Chabrol et al., (Reference Chabrol, Teissedre, Saint-Jean, Teisseyre, RogÉ and Mullet2002) to 16 for treatment (Thinking Healthy Programme) of PND (Rahman et al., Reference Rahman, Malik, Sikander, Roberts and Creed2008). Among nonspecific interventions, the most frequently utilized nonspecific active ingredients were active listening (n = 10), empathy (n = 9), collaboration (n = 9), and inciting social support (n = 9) and normalization (n = 7). Assigning homework (n = 8) and goal setting (n = 8) were the most frequently utilized in-session techniques.

Among specific ingredients, interpersonal strategies were frequently utilized, including identifying and eliciting social support (n = 14), communication skills (n = 11), and identifying affect (n = 10). Among behavioral strategies, problem-solving (n = 16), relaxation (n = 7), emotional regulation and stress management, and decision-making (n = 5 each) were frequently utilized. Essential cognitive strategies were identifying thoughts and behaviors and their links (n = 19), cognitive restructuring (n = 16), self-awareness (n = 8), and mood monitoring (n = 7). Caregiver coping (n = 8), parent–child interaction (n = 6), and psychoeducation regarding birth procedures or specific health areas of children (n = 6) were also important (Supplementary Figures 1 to 3).

Intervention delivered in groups

Among these 25 interventions (Supplementary Table 6), 14 were delivered antenatally (Brugha et al., Reference Brugha, Wheatley, Taub, Culverwell, Friedman, Kirwan, Jones and Shapiro2000; Austin et al., Reference Austin, Frilingos, Lumley, Hadzi-Pavlovic, Roncolato, Acland, Saint, Segal and Parker2008; Futterman et al., Reference Futterman, Shea, Besser, Stafford, Desmond, Comulada and Greco2010; Lara et al., Reference Lara, Navarro and Navarrete2010; Le et al., Reference Le, Perry and Stuart2011; Kozinszky et al., Reference Kozinszky, Dudas, Devosa, Csatordai, Toth, Szabo, Sikovanyecz, Barabas and Pal2012; Kaaya et al., Reference Kaaya, Blander, Antelman, Cyprian, Emmons, Matsumoto, Chopyak, Levine and Fawzi2013; Leung et al., Reference Leung, Lee, Chiang, Lam, Kuen and Wong2013; Bittner et al., Reference Bittner, Peukert, Zimmermann, Junge-Hoffmeister, Parker, Stöbel-Richter and Weidner2014; Jesse et al., Reference Jesse, Gaynes, Feldhousen, Newton, Bunch and Hollon2015; Van Ravesteyn et al., Reference Van Ravesteyn, Kamperman, Schneider, Raats, Steegers, Tiemeier, Hoogendijk and Lambregtse-van den Berg2018; Khamseh et al., Reference Khamseh, Parandeh, Hajiamini, Tadrissi and Najjar2019; Zemestani and Fazeli Nikoo, Reference Zemestani and Fazeli Nikoo2019), postnatally (n = 7; Hagan et al., Reference Hagan, Evans and Pope2004; Milgrom et al., Reference Milgrom, Negri, Gemmill, McNeil and Martin2005; Graciela Rojas et al., Reference Graciela Rojas, Solis, Jadresic, Castillo, González, Guajardo, Lewis, Peters and Araya2007; Christine Puckering et al., Reference Christine Puckering, Hickey and Longford2010; Mao et al., Reference Mao, Li, Chiu, Chan and Chen2012; Leung et al., Reference Leung, Lee, Wong, Wong, Leung, Chiang, Yung, Chan and Chung2016; Van Lieshout et al., Reference Van Lieshout, Layton, Savoy, Haber, Feller, Biscaro, Bieling and Ferro2022), and four during both periods (Muñoz et al., Reference Muñoz, Le, Ippen, Diaz, Urizar, Soto, Mendelson, Delucchi and Lieberman2007; Tandon et al., Reference Tandon, Leis, Mendelson, Perry and Kemp2014; Ngai et al., Reference Ngai, Wong, Chung, Chau and Hui2019). Only three of these interventions were conducted in communities (Muñoz et al., Reference Muñoz, Le, Ippen, Diaz, Urizar, Soto, Mendelson, Delucchi and Lieberman2007; Tandon et al., Reference Tandon, Leis, Mendelson, Perry and Kemp2014; Van Lieshout et al., Reference Van Lieshout, Layton, Savoy, Haber, Feller, Biscaro, Bieling and Ferro2022), while the rest were conducted in healthcare settings. EPDS was the most frequently utilized scale for outcome assessment, followed by BDI I/II (n = 5). Seven interventions were delivered by specialists, 14 by nonspecialists, and four by multidisciplinary teams. Delivery agents were heterogeneous in terms of disciplines and experience and included counseling or clinical psychologists, academics and doctoral students in psychology, nurses, midwives, doctors, obstetricians, social workers, occupational therapists, art therapists, infant mental health specialists, and peers. Thirteen of these interventions were integrated into healthcare systems, while the rest were delivered as standalone.

A total of 13 interventions were tested for treatment and 12 for prevention of PND. Twenty trials tested classical CBT interventions, PST (n = 2), psychoeducation (n = 2), and Mindfulness-based cognitive therapy (MCBT) (n = 1). The sessions ranged from 1 (Ngai et al., Reference Ngai, Wong, Chung, Chau and Hui2019) to 14 (Christine Puckering et al., Reference Christine Puckering, Hickey and Longford2010). Among group therapies, the most frequently utilized nonspecific ingredients were inciting social support (n = 12), normalization (n = 9), and involvement of significant other (n = 6). Most frequently employed in-session techniques were assigning homework (n = 11), goal setting (n = 13), and interpersonal focus (n = 9). Among interpersonal strategies, the most frequently utilized ingredients were identifying affect (n = 15), identifying and eliciting social support (n = 13), and communication skills (n = 11). Problem-solving (n = 18), relaxation (n = 16), and stress management (n = 13) were most frequently utilized behavioral ingredients. Identifying thoughts, behaviors, and their links (n = 18), cognitive restructuring (n = 13), and mood monitoring (n = 6) were important cognitive ingredients. Caregiver coping skills (n = 8) and parent–child interaction coaching (n = 6) were imparted in a small proportion of trials (Supplementary Figures 4 to 6).

Interventions delivered online

Seven of these interventions (Supplementary Table 7) were tested during postpartum (O’Mahen et al., Reference O’Mahen, Woodford, McGinley, Warren, Richards, Lynch and Taylor2013b; Milgrom et al., Reference Milgrom, Danaher, Gemmill, Holt, Holt, Seeley, Tyler, Ross and Ericksen2016; Wozney et al., Reference Wozney, Olthuis, Lingley-Pottie, McGrath, Chaplin, Elgar, Cheney, Huguet, Turner and Kennedy2017; Loughnan et al., Reference Loughnan, Butler, Sie, Grierson, Chen, Hobbs, Joubert, Haskelberg, Mahoney, Holt, Gemmill, Milgrom, Austin, Andrews and Newby2019a; Fonseca et al., Reference Fonseca, Alves, Monteiro, Gorayeb and Canavarro2020; Jannati et al., Reference Jannati, Mazhari, Ahmadian and Mirzaee2020; Van Lieshout et al., Reference Van Lieshout, Layton, Savoy, Brown, Ferro, Streiner, Bieling, Feller and Hanna2021) and three during the antenatal period (Forsell et al., Reference Forsell, Bendix, Holländare, Szymanska von Schultz, Nasiell, Blomdahl-Wetterholm, Eriksson, Kvarned, Lindau van der Linden, Söderberg, Jokinen, Wide and Kaldo2017; Duffecy et al., Reference Duffecy, Grekin, Hinkel, Gallivan, Nelson and O’Hara2019; Loughnan et al., Reference Loughnan, Sie, Hobbs, Joubert, Smith, Haskelberg, Mahoney, Kladnitski, Holt, Milgrom, Austin, Andrews and Newby2019b). Two of these interventions were for the prevention of PND (Duffecy et al., Reference Duffecy, Grekin, Hinkel, Gallivan, Nelson and O’Hara2019; Fonseca et al., Reference Fonseca, Alves, Monteiro, Gorayeb and Canavarro2020), while the rest were treatment interventions. All interventions were designed to be used by individuals, except Duffecy et al. and Van Lieshout et al. who delivered to groups of participants (Duffecy et al., Reference Duffecy, Grekin, Hinkel, Gallivan, Nelson and O’Hara2019; Van Lieshout et al., Reference Van Lieshout, Layton, Savoy, Brown, Ferro, Streiner, Bieling, Feller and Hanna2021). Only two of these interventions were guided either by specialist mental health professionals (Van Lieshout et al., Reference Van Lieshout, Layton, Savoy, Brown, Ferro, Streiner, Bieling, Feller and Hanna2021) or nonspecialists (Wozney et al., Reference Wozney, Olthuis, Lingley-Pottie, McGrath, Chaplin, Elgar, Cheney, Huguet, Turner and Kennedy2017). The number of sessions of interventions ranged from 1 (Van Lieshout et al., Reference Van Lieshout, Layton, Savoy, Brown, Ferro, Streiner, Bieling, Feller and Hanna2021) to 16 (Duffecy et al., Reference Duffecy, Grekin, Hinkel, Gallivan, Nelson and O’Hara2019). Only one intervention was integrated into healthcare settings (Forsell et al., Reference Forsell, Bendix, Holländare, Szymanska von Schultz, Nasiell, Blomdahl-Wetterholm, Eriksson, Kvarned, Lindau van der Linden, Söderberg, Jokinen, Wide and Kaldo2017).

All interventions were based on CBT except Fonseca et al. and O’Mahen et al., who tested Acceptance and Commitment Therapy (CBT-ACT) and BA-based interventions (O’Mahen et al., Reference O’Mahen, Woodford, McGinley, Warren, Richards, Lynch and Taylor2013b; Fonseca et al., Reference Fonseca, Alves, Monteiro, Gorayeb and Canavarro2020). Among these interventions, inciting social support (n = 6) was the most frequently utilized nonspecific ingredient. Identifying affect (n = 9), identifying and eliciting social support (n = 8), and communication skills training (n = 7) were important interpersonal strategies. Problem-solving (n = 7), relaxation (n = 7), and self-monitoring were important behavioral approaches. Among cognitive approaches, identifying thoughts (n = 10), cognitive restructuring (n = 8), and mood monitoring (n = 7) were important elements. Assigning homework (n = 6) was frequently employed in-session technique. Caregiver coping and parent–child interaction coaching were utilized in four interventions.

None of the interventions employed reinforcement-oriented active ingredients. Four interventions included information on caregiver coping skills (O’Mahen et al., Reference O’Mahen, Woodford, McGinley, Warren, Richards, Lynch and Taylor2013b; Milgrom et al., Reference Milgrom, Danaher, Gemmill, Holt, Holt, Seeley, Tyler, Ross and Ericksen2016; Duffecy et al., Reference Duffecy, Grekin, Hinkel, Gallivan, Nelson and O’Hara2019; Fonseca et al., Reference Fonseca, Alves, Monteiro, Gorayeb and Canavarro2020) and four included parent–child interaction coaching (O’Mahen et al., Reference O’Mahen, Woodford, McGinley, Warren, Richards, Lynch and Taylor2013b; Milgrom et al., Reference Milgrom, Danaher, Gemmill, Holt, Holt, Seeley, Tyler, Ross and Ericksen2016; Wozney et al., Reference Wozney, Olthuis, Lingley-Pottie, McGrath, Chaplin, Elgar, Cheney, Huguet, Turner and Kennedy2017; Duffecy et al., Reference Duffecy, Grekin, Hinkel, Gallivan, Nelson and O’Hara2019). Psychoeducation, either on birth procedures, nutrition, breastfeeding, or sexual behaviors was provided in only two interventions (Milgrom et al., Reference Milgrom, Danaher, Gemmill, Holt, Holt, Seeley, Tyler, Ross and Ericksen2016; Duffecy et al., Reference Duffecy, Grekin, Hinkel, Gallivan, Nelson and O’Hara2019). Nutrition and substance use-related counseling were each provided in one study (Wozney et al., Reference Wozney, Olthuis, Lingley-Pottie, McGrath, Chaplin, Elgar, Cheney, Huguet, Turner and Kennedy2017; Duffecy et al., Reference Duffecy, Grekin, Hinkel, Gallivan, Nelson and O’Hara2019). Supplementary Tables 46 present the characteristics of studies included in this section. Supplementary Figures 79 present active ingredients utilized in online interventions.

Meta-analysis: Effectiveness

CBT-based interventions yielded a strong effect size (SMD = −0.74, 95% CI: −0.91 to −0.56, n = 9,722) in alleviating depressive symptoms. There was evidence of substantial heterogeneity in effect sizes across studies (I 2 = 92.65%, p < 0.001, and Q = 775.03). Sensitivity analysis did not reveal any substantial changes in effect size after removing outliers. There was substantial publication bias, as evidenced by the funnel plot (Supplementary Figure 10) and Egger’s regression statistic (p = 0.009). Duval and Tweedie’s trim and fill method adjusted pooled effect size for publication bias. After trimming 13 studies to the left of the mean, the adjusted SMD was −0.95 (95% CI: −1.14 to −0.76).

Forest plots were developed separately according to the mode of delivery of interventions. Interventions delivered electronically (n = 9) yielded strong effect sizes (SMD = −1.12, 95% CI: −1.80 to −0.63, n = 1,218) (Figure 3). There was substantial evidence of heterogeneity across studies (I 2 = 93.99%, p < 0.001, and Q = 133.12). There was no evidence of publication bias (Egger’s regression p = 0.65). Intervention delivered to individuals (Figure 4) also yielded strong effect sizes in favor of the intervention group (SMD = −0.63, 95% CI: −0.81 to −0.44, n = 3,589). There was evidence of significant heterogeneity across the studies (I 2 = 80.99%, p < 0.001, and Q = 121.02). There was evidence for significant publication bias (Egger’s regression P = 0.06), which after adjustment led to a higher effect size (SMD = −0.75, 95% CI: −0.94 to −0.55). Interventions delivered among groups (Figure 5) also yielded strong effect sizes in favor of the intervention group (SMD = –0.67, 95% CI: −0.96 to −0.38, n = 4,915). Statistical heterogeneity was substantial (I 2 = 94.59%, p < 0.001, and Q = 443.90). There was some evidence of publication bias (Egger’s regression p = 0.10), with the trim and fill method yielding a higher adjusted effect size (SMD = −1.00, 95% CI: −1.33 to −0.67). Sensitivity analysis did not reveal any substantial changes in effect size after removing outliers in any of the above analyses.

Figure 3. Forest plot showing effect sizes for interventions delivered online (n = 9).

Figure 4. Forest plot showing effect sizes for interventions delivered to individuals (n = 24).

Figure 5. Forest plot showing effect sizes for interventions delivered to groups (n = 25).

Moderator analyses: Intervention level characteristics

Moderator analyses for intervention-level characteristics yielded several important insights (Supplementary Table 8). Interventions for treatment (SMD = −0.94, 95% CI: −1.15 to −0.73) of perinatal depressive symptoms yielded significantly higher effect sizes than preventive ones (SMD = .–0.36, 95% CI: −0.65 to −0.07). Interventions offered as tested as stand-alone programs (SMD = −1.01, 95% CI: −1.24 to −0.79) performed better than those integrated into healthcare settings (SMD = −0.38, 95% CI: −0.63 to −0.14).

Effect sizes did not differ according to the delivery format, where no differences were observed between interventions delivered either through electronic means, face-to-face in groups, or individually (Q = 4.76 and p = 0.09). Delivery agents with varying disciplinary backgrounds, multidisciplinary teams, nonspecialists, online interventions, and those delivered by specialists, were effective. Although interventions delivered electronically and through specialists had slightly higher effect sizes, this did not reach statistical significance (Q = 4.05 and p = 0.26).

Moderator analysis: Participant-level characteristics

Higher effect sizes were associated with interventions recruiting perinatal women with higher age (b = −0.07, SE = 0.01, and p = <0.001; Supplementary Table 9). While interventions with a higher proportion of perinatal women belonging to minorities, low-income levels, reporting poorer education, and recurrent episodes of depression yielded smaller effect sizes. The proportion of married or primiparous women in trials was not associated with effect sizes yielded by included interventions. Interventions delivered during postnatal had a higher effect size than those delivered during the antenatal period, or during both periods; however, this was statistically non-significant.

Moderator analysis: Active ingredients

When considering the theoretical underpinnings of included interventions, the dose of intervention was inversely associated with effect sizes (b = 0.016 and p < 0.01). Most of the trial evidence included in this review tested CBT interventions (n = 42), which yielded strong effect sizes (SMD = −0.70, 95% CI: −0.91 to −0.49). PST was tested in five trials and yielded comparable effect sizes (−0.71, 95% CI: −1.32 to −0.11). BA yielded moderate-strength effect sizes (SMD = −0.32, 95% CI: −1.05 to 0.42). However, evidence about these was inconclusive due to overlapping effect sizes, despite reaching statistical significance.

Among intervention ingredients, using more behavioral ingredients in CBT interventions yielded high effect sizes (b = −0.079 and p < 0.01). An inverse trend was noted for interventions including reinforcement-related ingredients (b = 0.2 and p < 0.01). Interventions including a higher number of cognitive and interpersonal ingredients, parenting skills, psychoeducation, exercise, in-session techniques, nutrition, and substance use-related counseling did not yield statistical significance (Supplementary Tables 49). When individual active ingredients were considered, the presence or absence of interpersonal, cognitive, and behavioral ingredients did not alter effect sizes. Interventions utilizing identifying affect and self-awareness strategies yielded larger effect sizes than their counterparts (Supplementary Tables 410).

Discussion

The present systematic review presents up-to-date evidence regarding the effectiveness of CBT for PND. It delineates several interesting insights for optimizing CBT-based interventions for PND. We found that CBT interventions, including third-wave cognitive therapies, are highly effective in preventing and treating PND. CBT can be delivered effectively to individuals and in groups or online web or app-based software. The delivery of CBT can also be tailored according to the resources available, for instance, by employing specialists or nonspecialists’ delivery agents. Interventions integrated into healthcare settings and utilizing the available infrastructure may be less effective than stand-alone programs. Perinatal women experiencing adverse events and health inequalities report smaller effect sizes when treated with CBT. The effectiveness of CBT also depends on several intervention-level characteristics.

CBT interventions yielded strong effect sizes for treatment and moderate strength effect sizes for preventing PND. These findings are corroborated by previous meta-analyses, which have yielded similar effect sizes for CBT interventions for PND (Rahman et al., Reference Rahman, Fisher, Bower, Luchters, Tran, Yasamy, Saxena and Waheed2013; Sockol, Reference Sockol2015; Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018; Waqas et al., Reference Waqas, Zafar, Meraj, Tariq, Naveed, Fatima, Chowdhary, Dua and Rahman2022b). CBT interventions are also recommended by the US Preventive Services Taskforce and the WHO (Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018; Curry et al., Reference Curry, Krist, Owens, Barry, Caughey, Davidson, Doubeni, Epling, Grossman, Kemper, Kubik, Landefeld, Mangione, Silverstein, Simon, Tseng and Wong2019). Previous evidence has shown that CBT-based interventions are effective for PND and generally acceptable to stakeholders, delivery agents, and end-consumers (Morrell et al., Reference Morrell, Warner, Slade, Dixon, Walters, Paley and Brugha2009; Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018). CBT interventions can be tailored to settings depending on the availability of resources. Both the National Institute for Health and Care Excellence (NICE) and the WHO recommend a stepped-care approach to treating PND (Rahman et al., Reference Rahman, Fisher, Waqas, Hamdani, Zafar, Suleman, Zill-e-Huma, Holton and Le2018; National Institute for Health and Care Excellence, 2020; Delgadillo et al., Reference Delgadillo, Ali, Fleck, Agnew, Southgate, Parkhouse, Cohen, DeRubeis and Barkham2022), ranging from self-help psychoeducational materials to low-intensity and high-intensity psychotherapies.

There has been an increasing focus on preventing PND. Recently, based on evidence from high-income countries, The U.S. Preventive Services Task Force (USPSTF) has recommended the use of CBT and counseling interventions for PND (Curry et al., Reference Curry, Krist, Owens, Barry, Caughey, Davidson, Doubeni, Epling, Grossman, Kemper, Kubik, Landefeld, Mangione, Silverstein, Simon, Tseng and Wong2019). Although the WHO have recommended that all perinatal women should be offered psychosocial interventions to develop coping, stress management, and social skills (Guidelines Review Committee, 2022), women at high risk of developing PND should be offered psychological interventions such as CBT and interpersonal therapy. The provision of these interventions should be allowed as per the availability of resources and women’s preference. Our systematic review corroborates this evidence and presents CB-based approaches (both specialist and nonspecialist delivered) as effective in preventing depression during the perinatal period. We also found that CB-based approaches yield good effect sizes across all modes of delivery (electronic, individual, or group). This flexibility in delivery increases the utility of CB-based approaches in different settings.

While reviewing the intervention level characteristics, several valuable insights were revealed. First, these interventions work when delivered antenatally or postnatally, with little difference in effect sizes. This finding does not agree with our previous systematic review of preventive interventions where a higher effect size was demonstrated for interventions starting early during the antenatal period (Waqas et al., Reference Waqas, Zafar, Meraj, Tariq, Naveed, Fatima, Chowdhary, Dua and Rahman2022b). This finding also contradicts Sockol’s meta-analysis of 26 treatment interventions, where more considerable reductions were noted for interventions initiated during the postpartum period or across the perinatal period (Sockol, Reference Sockol2015). Second, CBT interventions delivered either to individuals or groups or online yield similar strength of effect sizes, also corroborated by previous systematic reviews (Sockol, Reference Sockol2015).

Interventions integrated into healthcare settings and utilizing the available infrastructure may be less effective than stand-alone programs. This interesting insight emphasizes the importance of effective implementation measures to ensure adequate implementation, supervision, and competency measures (Zafar et al., Reference Zafar, Sikander, Hamdani, Atif, Akhtar, Nazir, Maselko and Rahman2016; Ahmad et al., Reference Ahmad, Suleman, Waqas, Atif, Malik, Bibi, Zulfiqar, Nisar, Javed, Zaidi, Khan and Sikander2020). A critical case study in this context is that of the Thinking Healthy Programme developed by one of the co-authors (Rahman et al., Reference Rahman, Malik, Sikander, Roberts and Creed2008). It is a highly effective low-intensity CBT-based intervention that has been endorsed by the WHO for the treatment of PND (World Health Organization, 2015). Integrated into the primary healthcare system, it employed lady health workers as the delivery agents (Rahman et al., Reference Rahman, Malik, Sikander, Roberts and Creed2008). In the following years, a trial was run to test the effectiveness of Thinking Healthy Program (THP) delivered by peers with lived experience of PND (Sikander et al., Reference Sikander, Ahmad, Atif, Zaidi, Vanobberghen, Weiss, Nisar, Tabana, Ul Ain, Bibi, Bilal, Bibi, Sharif, Zulifiqar, Fuhr, Price, Patel and Rahman2019a). These innovations ensured that the THP remained cost-effective and acceptable to the stakeholders. In addition to innovations in delivery, newer approaches in enhanced supervision, competency assessments, and training at a large scale were also tested to ensure seamless implementation of the THP in communities (Zafar et al., Reference Zafar, Sikander, Hamdani, Atif, Akhtar, Nazir, Maselko and Rahman2016; Ahmad et al., Reference Ahmad, Suleman, Waqas, Atif, Malik, Bibi, Zulfiqar, Nisar, Javed, Zaidi, Khan and Sikander2020).

While reviewing the active ingredients of included interventions, several insights emerged. In comparison with the face-to-face delivered CBT programs, the ingredient of empathy was missing in electronically delivered interventions. However, this collection of interventions yielded pooled effect sizes comparable to the interventions delivered face to face. This is an important finding as empathy is the foundation for an effective therapeutic patient alliance (Morrell et al., Reference Morrell, Warner, Slade, Dixon, Walters, Paley and Brugha2009). Therefore, there is a need to open further the black box of the causal mechanisms at play that drive the effectiveness of electronic interventions without the opportunity to build an empathy-based therapeutic relationship. Another interesting finding was that longer interventions were associated with a decrease in effect size. This association may be driven by burnout among either the patient or therapist. We also investigated the dosage density of therapeutic strategies and their association with effect sizes. Only one significant association emerged, where an increase in behavioral ingredients in a therapeutic program led to an increase in effect size. This strengthens the previous notion that (Kahl et al., Reference Kahl, Winter and Schweiger2012) efficacy of the cognitive therapy depends critically on the behavioral activation component rather than its content-oriented cognitive approaches. However, this is inconclusive and warrants further investigation, especially for PND, due to the lack of RCTs, for instance, those comparing efficacy of BA with classical CBTs. This is indeed an important area for further research.

Lastly, we found that younger perinatal women reported poor education and belonging to lower economic, and minority ethnic classes reported a lower reduction in PND symptoms. This finding is significant and highlights the importance of contextual factors affecting community health and community-oriented policies and initiatives. Multidisciplinary approaches, such as mass education and poverty alleviation initiatives, are required to tackle this issue. In this regard, Banerjee and colleagues’ Nobel prize-winning multifaceted program rooted in developmental economics is a crucial case study (Banerjee et al., Reference Banerjee, Duflo, Goldberg, Karlan, Osei, Pariente, Shapiro, Thuysbaert and Udry2015). Such initiatives are necessary to curb the effects of societal adversities impeding the efficacy of psychological treatments. This has been shown in a huge body of literature demonstrating the complexity of PND among women facing adversities (Ashman et al., Reference Ashman, Dawson and Panagiotides2008; Bao et al., Reference Bao, Jing, Jin, Hu, Liu and Hu2016; Chae et al., Reference Chae, East, Delva, Lozoff and Gahagan2020).

Meta-regression analyses revealed a weakly inverse association between the proportion of women with a history of mental health problems and intervention effect size. There is unequivocal evidence that complex presentations of PND (increased severity, relapsing, and recurrent) are associated with poorer treatment response (Ahmed Waqas and Rahman, Reference Waqas, Nadeem and Rahman2023). A recent systematic review of observational studies demonstrates that perinatal women with complex and more severe forms of PND report more psychosocial adversities (Ahmed Waqas and Rahman, Reference Waqas, Nadeem and Rahman2022). Moreover, if left untreated, such PND symptoms contribute to intergenerational transfer of inequities; whereby children born to women with complex PND report poorer academic, mental, and physical health outcomes. Despite a plethora of observational research evidence, investigators have not yet focused on the development of bespoke interventions for either preventing relapse or treating recurrent episodes of perinatal depressive disorder. This is also true for pharmacological trials where little evidence is present for the prevention of relapse of depression during the perinatal period (Molyneaux et al., Reference Molyneaux, Telesia, Henshaw, Boath, Bradley and Howard2018). Evidence is emerging, however, where a recent two-arm, parallel-design RCT tested a parenting video-feedback therapy intervention added to CBT in the treatment of persistent postpartum depression (Stein et al., Reference Stein, Netsi, Lawrence, Granger, Kempton, Craske, Nickless, Mollison, Stewart, Rapa, West, Scerif, Cooper and Murray2018). The NICE recommends high-intensity psychotherapies or antidepressants for women at a high risk of relapse (National Institute for Health and Care Excellence, 2020).

Strengths and limitations

This systematic review has several strengths. First, this systematic review and meta-regression analysis provide a comprehensive and up-to-date estimate of the effectiveness of CBT. It provides reliable estimates of the effectiveness of CBT delivered by specialist and nonspecialist workforces. Furthermore, this review utilizes a large pool of RCTs. This allowed us to investigate the moderating effects of intervention and patient-level characteristics in detail. We also present novel findings on the active ingredients of CB-based approaches by leveraging the distillation and matching framework. Effects of dose density and active ingredients comprising CB interventions yielded valuable insights.

However, despite its strengths, this review has several limitations. First, conducting distillation and matching framework exercises to map active ingredients of therapies is complex. The accuracy of this endeavor depends on the information regarding the content of interventions provided in primary studies. Interventions such as the THP (developed by the co-author AR) (Rahman et al., Reference Rahman, Malik, Sikander, Roberts and Creed2008) provided details and content of the intervention in open-access manuals (World Health Organization, 2015). This approach is important and aids in future evidence synthesis studies and reproducibility and adaptability in different cultures. These analyses are also limited by the observational nature of meta-regression analyses used to study moderators of CB interventions. Therefore, this evidence should be interpreted with caution.

The present meta-analysis utilized subgroup analyses to compare the effectiveness of CB-based approaches utilizing specific active ingredients. These analyses can be improved by using meta-analytic structural equation modeling approaches (Harrer et al., Reference Harrer, Cuijpers, Furukawa and Ebert2021). The use of these complex methods can aid in our understanding of causal mediation mechanisms in psychotherapies.

Another key limitation inherent to using meta-regression analyses is the use of across-trial data and aggregated values for the participant and intervention-level characteristics for analyses. Such analyses are limited due to inherent aggregation bias and may not reflect actual treatment-covariate interactions (Kelley and Kelley, Reference Kelley and Kelley2012; Huh et al., Reference Huh, Mun, Walters, Zhou and Atkins2019). These limitations, in theory, can be offset by using two-stage Individual Participant Data Meta-analysis (IPDMA) approaches that use within-trial information to estimate treatment–covariation interactions (Kelley and Kelley, Reference Kelley and Kelley2012). IPDMAs involving a large pool of datasets are time and resource intensive; however, we encourage researchers to utilize these approaches in the future. A recent example of this approach is Furukawa and colleagues’ work (Furukawa et al., Reference Furukawa, Suganuma, Ostinelli, Andersson, Beevers, Shumake, Berger, Boele, Buntrock, Carlbring, Choi, Christensen, Mackinnon, Dahne, Huibers, Ebert, Farrer, Forand, Strunk, Ezawa, Forsell, Kaldo, Geraedts, Gilbody, Littlewood, Brabyn, Hadjistavropoulos, Schneider, Johansson, Kenter, Kivi, Björkelund, Kleiboer, Riper, Klein, Schröder, Meyer, Moritz, Bücker, Lintvedt, Johansson, Lundgren, Milgrom, Gemmill, Mohr, Montero-Marin, Garcia-Campayo, Nobis, Zarski, O’Moore, Williams, Newby, Perini, Phillips, Schneider, Pots, Pugh, Richards, Rosso, Rauch, Sheeber, Smith, Spek, Pop, Ünlü, van Bastelaar, van Luenen, Garnefski, Kraaij, Vernmark, Warmerdam, van Straten, Zagorscak, Knaevelsrud, Heinrich, Miguel, Cipriani, Efthimiou, Karyotaki and Cuijpers2021), which presents a web application to estimate relative efficacies, and additive and synergistic effects yielded through combinations of specific and nonspecific components in Internet-delivered CBT interventions in the context of patient-level variables. Future meta-investigations should also consider utilizing realist evaluation using both quantitative and qualitative approaches to distill important insights on CBT for PND.

Furthermore, the subgroup and meta-regression analyses in this systematic review were run for a limited number of participant-level and intervention-level factors. Many other factors such as experience of intimate partner violence (Keynejad et al., Reference Keynejad, Hanlon and Howard2020), family structure, social support networks, and chronicity of PND are important moderators and should be considered in future reviews (Waqas et al., Reference Waqas, Sikander, Malik, Atif, Karyotaki and Rahman2022a). Moreover, researchers should consider collecting detailed data on moderators of treatment for PND in their future trials. We focused on CB-based approaches to meta-analyze a homogeneous set of interventions in the present systematic review. Other psychotherapeutic modalities should be reviewed in future meta-analyses, keeping in mind the clinical and statistical heterogeneity often encountered in psychotherapy literature.

Conclusion

CBT are highly effective in reducing the severity of PND. Most of the trial evidence included in this review tested classical CBT approaches. And there is limited evidence for third-wave CBT for PND. CBT is effective when delivered across individual, group, and electronic platforms and thus can be tailored according to the financial and human resources available. Longer duration CBT interventions may not necessarily be more effective than shorter ones. Furthermore, CBT-based interventions should consider including various behavioral ingredients to maximize intervention benefits.

Open peer review

To view the open peer review materials for this article, please visit http://doi.org/10.1017/gmh.2023.8.

Supplementary materials

To view supplementary material for this article, please visit http://doi.org/10.1017/gmh.2023.8.

Data availability statement

All data associated with this manuscript are available as supplementary files.

Author contributions

This systematic review and meta-analysis was conceived by A.W. and A.R. A.W. and A.R. wrote the protocol and registered it in PROSPERO. A.W. & P.A. searched the databases and performed screening of titles and abstracts and full texts for eligibility. A.W. and S.N. extracted data on the characteristics of intervention and population. A.W., P.A., and S.W.Z. extracted data pertaining to components of interventions. A.W. and S.N. extracted quantitative data. A.W. conducted the meta-analysis. A.W. wrote the initial draft of the manuscript. All authors critically reviewed the manuscript and approved it for submission.

Financial support

This study has not received any funding.

Competing interest

The authors have no conflict of interest to report.

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Figure 0

Figure 1. PRISMA flowchart showing the process of inclusion of studies.

Figure 1

Figure 2. Risk of bias in included studies.

Figure 2

Figure 3. Forest plot showing effect sizes for interventions delivered online (n = 9).

Figure 3

Figure 4. Forest plot showing effect sizes for interventions delivered to individuals (n = 24).

Figure 4

Figure 5. Forest plot showing effect sizes for interventions delivered to groups (n = 25).

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Author comment: Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis — R0/PR1

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Review: Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis — R0/PR2

Conflict of interest statement

Reviewer declares none.

Comments

Comments to Author: Overall this is a very rigorous robust review which could be further strengthened with more articulations of the authors’ views on how to tailor CBT programmes for women who do not respond and other minor suggestions below.

The background is pertinent up-to-date and thoughtful. There are four aims of this review – three focused on effectiveness and active ingredients of CBT and the contexts for interventions – it would be helpful to clarify what was meant by contexts here in the background. The third aim was to explore factors driving prognosis and prescriptive factors among women undergoing CPD and, again, it would be helpful to clarify some of the terminology here in the background such as prescriptive factors.

The methods have many strengths including pre-registration of the protocol. This is a very extensive review as it includes both prevention and treatment of perinatal depression, though only the primary outcomes are reported here.

The results were written clearly and were well presented. I note that there were several important patient level characteristics included but some of the more sensitive variables such as intimate partner violence or childhood maltreatment were not and I would be surprised if none of the studies included such variables. I therefore wondered if it were possible to include more detail and include these and/or to mention this limitation in the discussion.

The Thinking Healthy Programme was often mentioned (not surprisingly in view of the impact it has had), with no explicit mention that this is the intervention developed and implemented by this review’s authors. My view is that it would be better to be very explicit therefore when mentioning the programme in both the results and discussion e.g. “their intervention” could be referred to as “our intervention” for transparency.

Some women e.g. those with a history of depression were found to be less likely to respond and it would be helpful if these authors, who are very experienced in delivering this intervention in low-income settings, could articulate their thought on how to help such women who continue to experience depressive symptoms. The discussion could also be strengthened by some thoughts on why this review’s findings differ from other systematic reviews.

Finally, in terms of what works best for whom, there are other methodological approaches which may be helpful in thinking about which individual woman would respond best to what treatment. For example, realist evaluations use both qualitative and quantitative methods and the authors could also discuss other methodological approaches.

Review: Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis — R0/PR3

Conflict of interest statement

Reviewer declares none.

Comments

Comments to Author: This is a thoughtful and thorough review of CBT-based psychotherapies for treatment and prevention of perinatal depression. The authors state that while there has been sufficient research to demonstrate the efficacy of CBT in treatment perinatal depression, there is a gap in summarizing the research on prevention of perinatal depression in particular and in ‘unpacking’ the ‘mechanisms of action to understand what approaches work best for whom.’

A few areas where the authors could provide additional clarification and information include:

- Clarifying why a specific focus on CBT-based interventions and what is lost by not including non-CBT-based psychotherapies and can this be mentioned in the limitations.

- It would be helpful in the results to more clearly specify and discussion intervention vs. prevention trials – particularly given the bigger gap in the prevention literature.

- The summary of the moderator results – which focus on meeting the goal of unpacking mechanisms to support what works best for whom - seem somewhat basic and could benefit from a deeper dive, particularly to support different programs using these results to inform their services. For example, providing more details about variation by who/how the interventions were delivered (there seems some variation despite all being effective) and whether other characteristics of the participant were explored in the studies (including history of trauma and violence, comorbid mental and behavioral health conditions).

Recommendation: Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis — R0/PR4

Comments

Comments to Author: The reviewers commend your systematic review but each have recommendations to strengthen the paper. Please address all the reviewers' comments.

Decision: Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis — R0/PR5

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Author comment: Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis — R1/PR7

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Recommendation: Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis — R1/PR8

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Decision: Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis — R1/PR10

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