Development of a Core Outcome Set (COS) for treatment of depression during or after pregnancy (antenatal and postpartum depression)

Reading time approx. 77 minutes Published: June 7, 2020 Publication type:

SBU Policy support

identifies and presents available scientific evidence to support policy and decision making, including the development of national guidelines, at other government agencies. In consultation with professional experts, SBU staff generates supporting documentation to address the various questions that have been posed.

Download summary

Contact SBU

Published: June 7, 2020 Report no: 314 Registration no: SBU 2019/290 ISBN: 978-91-88437-56-3 https://int.sbu.se/314e

Summary

Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU) has enabled relevant interested parties (particularly patients, researchers, and healthcare personnel), from Sweden and other countries, to agree on which outcomes should be included in a Core Outcome Set (COS) for future research studies in the treatment of antenatal and postpartum depression. In total, the COS included nine outcomes (Table 1).

Table 1. outcomes included in the core outcome set
* Outcomes which are included in the COS, based on the results of survey 2 the remaining outcomes were included after discussions during the consensus meeting.
Self-assessed symptoms of depression, assessed with a scale that captures differences in sleep*
Diagnosis of depression as assessed by a clinician should include a structured interview
Parent to infant bonding
Self-assessed symptoms of anxiety
Quality of life
Satisfaction with the study intervention
Suicidal thoughts, attempts or completed suicide*
Thoughts of harming the baby, including thoughts of extended suicide*
Adverse events including spontaneous or induced abortion, miscarriage, fetal death and neonatal death

Background

A core outcome set (COS) is an agreed standardised set of outcomes that should be assessed and reported, as a minimum, in all clinical trials in specific areas of health or health care. The outcomes that are to be included in different COS are selected by a consensus process, in which healthcare personnel, researchers, and patients should be included. By developing and implementing COS, the aim is to enable the results from various studies to be more readily comparable and synthesised, and that the basis for decisions, for patients and healthcare personnel, will therefore be strengthened (Figure 1).

Figure 1 A schematic picture of the intended use of Core Outcome Sets

Schematic illustration of 3 research studies that explores 6–8 outomes each, whereas 4 are mutual (Core Outcome Set)

Aim

Development of a COS for future research studies in the treatment of antenatal and postpartum depression.

The primary target groups for this report are researchers and research funders. The project has been commissioned by the Swedish government as part of its efforts for the promotion of women’s health. This is the first time SBU has facilitated the development of a COS.

The area of antenatal and postpartum depression was chosen based on the results from an overview of existing and ongoing COS within the field of maternal health [1].

Method

The project was registered in the COMET initiative registry [2] and is developed according to theCOS-STAD Recommendations [3]. The project followed an a priori established protocol (Appendix 1).

The study consisted of three parts: (1) a systematic overview of the outcomes reported in systematic reviews and randomised controlled trials (RCTs) published 2018-2019, as well as in ongoing RCT on the topic, (2) a two-round Delphi survey with relevant stakeholders to prioritise the outcomes used in the studies, and (3) a consensus meeting where the final COS is decided (Figure 2). The project does not address the questions of which method should be applied to assess the outcomes, or when the outcomes should be assessed.

Figure 2 Flow chart of the project.

Flow chart of the project: Suggestions from the project and working groups and Systematic overview of outcomes used in research to List of extracted outcomes to Delphi process by online survey x 2 To top ranked outcomes from survey = Core outcome set to Consensus meeting

Identifying outcomes in research

In order to identify outcomes used in current research, a literature search for relevant randomised controlled trials (RCT) and systematic reviews published 2018–2019 as well as study protocols for RCT (no time limit) was undertaken (search strategy presented in Appendix 2).

Inclusion criteria

Population

Pregnant women, or their partners suffering from depression
New mothers or their partners suffering from depressions

Intervention

Any intervention given for depression

Control

Any type of control was accepted

Outcome

Outcomes relating to the effect of the treatment given

Study design

Randomised controlled trials or systematic reviews. Both protocols and published studies were included.

Limitations

Conference abstracts, studies investigating prevention of depression and studies investigating treatments given to persons suffering from a combination of depression and other chronic conditions such as HIV infection, were excluded.

Language

No language restriction applied to the search strategy, but the final inclusion was only for studies in English or Scandinavian languages

Search period

From 2018 to 2019 (clinicaltrials.gov no time restriction). Final search September-October 2019 (full search strategy presented in Appendix 2)

Databases searched

Medline (OVID), Cochrane library (Wiley), PsycINFO (EBSCO), Cinahl (EBSCO) and ClinicalTrials.gov

Client/patient involvement

Yes

All identified studies were screened for relevance independently by two members of the study management. Data were extracted by one review author and checked by another review author.

Following data were extracted from the studies:

Reference
Study design
Year for publication
Intervention/s used
Outcomes, with notification if outcomes are stated as primary or secondary
Toll for outcome measure
Time for outcome measure

After extraction, the identified outcomes were analysed and all outcomes that are unique were listed. Some of very similar outcomes in that list were brought together, for example outcomes measuring different hormonal or pharmaceutical levels were combined as under biological parameters.

Development of a Core Outcome Set

This process comprises a two-round Delphi survey and a consensus meeting. Relevant stakeholders (the working group) participated in the entire process, giving their perspectives on which outcomes are so important that they should be included in the COS. To allow international participation, all material was translated into English and information about the project was disseminated both within Sweden and internationally. In all, 222 people expressed an interest in participating, of whom 24 were international participants (Table 3). All participants belonged to one of the following four stakeholder group:

Patient- or relative
Researcher within the field
Health professional
HTA-agencies policy makers and others

In the Delphi study, all participants independently ranked the various outcomes in terms of importance and relevance, in two consecutive surveys. The information sent to the participants are presented in Appendix 3. Before they answered the second survey, they were shown how the different stakeholder groups, had ranked the outcomes in the first survey. In the first survey there was also an opportunity to suggest additional outcomes which were not identified in the actual research. The results of the surveys were analysed according to previously determined criteria, as to whether the outcome should be included in the COS. One exception from the pre-set protocol was made after the Delphi process. This to enable all outcomes included in the consensus meeting to be properly discussed. In total 23 outcomes were passed forward to the consensus meeting. Based on the results from the second survey three outcomes (marked with * in Table 1) were classified as consensus in, and thereby included in the COS. In addition, outcomes fulfilling the below specified criteria where discussed during the meeting:

Any outcome for which at least 70% of participants in either one of the stakeholder group scored as critically important (7–9)
The ten outcomes given the highest scores by each stakeholder group

The entire process concluded with a meeting at which a selection of the participants who had been in the Delphi study reached consensus about which further outcomes, over and above those which had already met the inclusion criteria, should be included in the COS. After the consensus meeting, all those who had completed the second questionnaire were given access to, and the option of making comments on, the final COS.

Results

Identifying outcomes in research

A total of 165 studies (Figure 3) were included and are described in further detail in Appendix 4. Excluded studies with reason for exclusion are presented in Appendix 5. On the basis of the included studies, a list was made of 93 different outcomes which were used in the research. As well, a further 13 outcomes were added by the project participants. Thus, in all, 105 outcomes were included in the consensus process. On average, the RCT: s contained six outcomes and the systematic reviews four outcomes (Table 2). The three most common outcomes in the included studies were self-assessed symptoms of depression, clinical diagnosis of depression and self-assessed symptoms of anxiety.

Table 2 Summary of results from the systematic overview of outcomes.

	Number of studies	Antenatal depression	Postpartum depression	Both antenatal samt postpartum depression	Number of outcomes in the studies, Median; Mean (min–max)
RCT-protocol	104	33	60	11	5; 6 (1–24)
RCT-published (2018–2019)	27	12	12	3	5; 6 (1–19)
Systematic reviews published (2018–2019)	34	8	16	10	2; 3 (1–13)
Total	165	53	88	24	5; 6 (1–24

Figure 3 Flow Chart.

Of 1772 records identified through database searching there were 165 studies included: 34 systematic reviews (2018–2019), 27 published RCTs (2018–2019) and 104 RCT protocols. Flödesschema

Development of a Core Outcome Set

A flow chart describing the different steps of the development of the COS are presented in Figure 4.

Figure 4 Flow chart of the different steps in the development of the Core outcome set.

From 945 outcomes who was identified in the studies became 9 outcomes in COS (Core Outcome Set) after a consensus meeting. Illustration

Out of the 222 people who expressed an interest to partake in the project, 151 completed survey 1 and 123 completed survey 2 (Table 3). All outcomes included in the survey and a summary of the results are presented in Table 4. A more detailed presentation of the results from survey 1 and survey 2 are available in Appendix 6 and Appendix 7).

Table 3 Characteristics of participants in the Delphi online survey.

* Brazil (n=1), Norway (n=1), United kingdom (n=4), Ireland (n=7), Finland (n=1), Germany (n=2), China (n=2), Nigeria (n=1), France (n=1), Holland (n=1), Portugal (n=1), India (n=1), Israel (n=1).
	Signed up for participation	Completed survey 1	Completed survey 2	Participated in consensus-meeting
Researcher within the field	41	30	31	3
HTA-agencies, policy makers and others	13	11	9	2
Patient- or relative	69	43	33	4
Health professional	99	67	50	4
Total (from countries other than Sweden)	222 (24*)	151 (20)	123 (18)	13 (0)

After analysing the result of both surveys, three outcomes met the criteria for inclusion in the COS (marked * in Table 1). As well as these three outcomes, a further 20 were discussed during the consensus meeting.

Table 4 Summary of results from survey 1 and 2. Highlighted in Bold are outcomes discussed during the consensus meeting.

^a Indicates that the outcome has been listed as primary in at least one study. ^b The outcome has only been identified in studies on antenatal depression. ^c The outcome has only been identified in studies on postpartum depression. ^d The outcome has been added by the project management. ^e The outcome has been added by participants in the delphi survey.
	Survey 1		Survey 2		Number of studies including this outcome (of 165)
Outcome	Number of replys	Median (IQR1-IQR3)	Number of replys	Median (IQR1-IQR3)	Number of studies including this outcome (of 165)
Depressive symptoms	149	7 (6–9)	123	8 (7–9)	133^a
Depression in partner	144	6 (4–7)	123	5 (4–6,5)	1
Psychiatric diagnosis of depression	147	7 (6–8)	119	8 (6–9)	57^a
Recovery from depression (remission)	146	7 (6–8)	121	7 (5–8)	17^a
Depression relapse	144	7 (6–8)	121	7 (6–8)	4^a
Time to remission from depression	143	6 (5–8)	122	6 (5–7)	1^a,c
Was depression treatment initiated	145	7 (6–9)	122	7 (6–9)	6^a
Change in antidepressant medication	141	6 (4–7)	120	6 (4–7)	3
Expert rating of overall disease burden	137	6 (4–8)	118	6 (4–7)	17^a
Anxiety symptoms	141	7 (6–8)	119	7 (5–8)	51^a
Fear of childbirth	142	6 (4,25–8)	119	6 (4,5–8)	0^d
Psychiatric diagnosis of anxiety	141	7 (5–8)	118	6 (5–7)	8^a
Other psychiatric or neuropsychiatric diagnoses	138	6 (5–7)	117	6 (5–8)	2^b
Mood	139	6 (5–8)	119	6 (5–8)	5
Self-harm	141	7 (6–8)	118	7 (6–9)	0^d
Suicidal thoughts or attempts or completed suicide	140	9 (7–9)	114	9 (8–9)	10^a
Cognitive ability	143	6 (4–7)	117	5 (4–7)	4
Eating disorder symptoms	138	6 (4–7)	118	5 (4–6)	2
Visit to clinic for fear of childbirth	141	6 (4–8)	118	5 (4–7)	0^d
Post-traumatic stress symptoms	141	7 (6–8)	119	7 (4,5–8)	1^b
Psychiatric diagnosis of postpartum stress syndrome in relation with childbirth	141	7 (5–9)	117	7 (5–8)	0^d
Psychiatric diagnosis of postpartum psychosis	138	7 (6–9)	115	7 (6–9)	0^d
Domestic/ intimate partner violence	136	8 (5–9)	118	7 (6–9)	1^c
Family functioning	137	6 (5–8)	119	6 (5–7)	4
Quality of relationship	139	5 (4–7)	119	5 (4–6)	9^a
Parent to infant bonding	140	7 (6–9)	119	7 (6–8)	18
Attachment	139	8 (6–9)	118	7 (5,25–8)	2^a,c
Parenting Sense of Competency	139	6 (5–8)	119	6 (5–8)	13^a
Parental stress	139	6 (5–7)	118	6 (5–7)	15^a
General stress	139	6 (4–7)	118	6 (4–6)	5
Parent-infant interaction	138	7 (6–9)	116	7 (5–8)	11^a
Attitudes about parenting	137	6 (4–7)	117	5 (3–6)	4
Family planning	141	5 (4–7)	118	4 (3–6)	1^b
Daily functioning level/ activities of daily living	137	6 (5–8)	119	6 (5–7)	23
Sleep	138	7 (6–9)	119	7 (5,5–8)	8^a
Fatigue	137	6 (5–8)	119	6 (5–8)	2^c
Quality of life	140	6 (5–8)	117	6 (5–8)	26^a
Sexual desire/function	135	5 (3–6)	119	4 (3–6)	1^c
Stigma	138	6 (4–8)	117	6 (4–7)	2^b
Social relationships	138	6 (5–7)	119	6 (4–7)	9
Perceived ability to cope with life challenges	136	6 (4,75–7)	117	6 (4–7)	1^c
Effort-based decision-making	135	6 (4–7)	118	5 (4–6)	4^b
Self-compassion	135	5 (4–7)	117	5 (3–6)	1^b
Lifestyle	134	6 (4–7)	116	5 (4–6)	1^b
Verbal fluency	122	3 (2–4)	108	3 (2–5)	1
Personality	128	4 (3–6)	112	3 (3–5)	2
Perceived social support / Help-Seeking	137	7 (5–8)	117	6 (5–7)	12
Socio-emotional competence	131	6 (4–7)	117	5 (4–6)	4
Confidence to self-help	133	6 (4–7)	116	5 (3–7)	3
Mentalizing, reflective functioning and level of mindfulness	133	5 (4–7)	116	5 (3–6,25)	5^a,c
Self-esteem	135	6 (4–8)	117	6 (4–7)	3
Adverse event	133	7 (5–8)	116	6 (5–8)	29^a
Spontaneous abortion or stillbirth	127	7 (6–9)	112	8 (5–9)	1^b
Perinatal mortality	126	8 (6–9)	111	8 (6–9)	1^b
Infections during pregnancy	119	5 (3–6)	108	4 (3–6)	1^b
Residual physical problems after delivery	133	7 (6–9)	115	7 (5–8)	4^a,b
Birth injury	130	6 (5–9)	115	7 (5–8)	5
Pain	131	6 (4–7)	115	6 (4–8)	1^b
Gestational hypertension or preeclampsia	124	6 (4–7)	103	5 (4–7)	3^b
Gestational age at delivery	130	6 (5–8)	111	6 (4–7)	5^b
Gestational diabetes	121	5 (3–7)	107	5 (3–7)	1^b
Estimated blood loss	121	6 (4–7)	105	5 (3–7)	2^b
Induction of labour	126	6 (4–7)	110	5 (4–7)	1^b
Mode of delivery	132	6 (5–8)	114	6 (4–8)	6^a
Fetal growth assessment by ultrasound	124	5 (4–7)	108	5 (3–6)	1^b
Complications associated with the placenta	117	5 (3–7)	108	5 (3–7)	1^b
Vaginal and/or faecal microbiota	107	3 (3–6)	102	3 (3–5)	1^b
Transition of care from pregnancy to postpartum	133	7 (6–9)	115	7 (5–9)	1^a,b
Breastfeeding	131	6 (4–8)	114	6 (4–7)	8
Child attention	126	5 (4–7)	109	5 (4–6)	3^c
Duration of crying episodes	127	6 (4–7)	109	5 (3–6)	1^b
Child development	133	7 (5–8)	112	6 (5–8)	19^a
Neurodevelopmental and neurobehavioral outcomes	128	7 (5,75–8)	111	7 (5–8)	2^a,c
Infant sleep	131	6 (5–7)	112	6 (4–8)	1^b
Vaccinations received/ Immunization status	123	4 (2–6)	109	3 (2–6)	4
Infant or child’s temperament	132	5 (4–7)	112	4 (3–6)	6^a
Biological parameters in the infant	110	5 (3–7)	96	4 (3–6)	6
Well-baby check-up status	132	6 (4–7)	111	5 (3–7)	2
Congenital malformations	125	6 (4–8)	104	6 (4–7)	1^b
Infant antibiotic use	117	4 (3–6)	100	3 (3–5,25)	1^b
Birth weight, height and head circumference	126	5,5 (4–6)	106	5 (3–6)	8^a
Small for gestational age (SGA)	123	6 (4–7)	105	5 (4–7)	3^b
Apgar score	123	5 (4–7)	106	5 (3–7)	4^a
Neonatal intensive care unit admission	126	6 (5–8)	106	6 (5–8)	4
Cost-effectiveness	130	6 (4–7)	106	5 (4–7)	9^a
Use of health services	131	6 (4–7)	110	5 (4–6)	16
Engagement and retention with health services	133	6 (4–7)	109	5 (4–6)	3
Sick-leave	133	6 (4–7)	113	6 (4–7)	3
Satisfaction with intervention	136	7 (6–8)	114	7 (6–8)	31^a
Therapeutic alliance	135	7 (6–9)	113	7 (6–9)	2
Quality of care	136	6 (5–8)	114	7 (5–8)	5
Parent experience	133	7 (6–8)	114	7 (5–8)	2^a
Pregnancy/ delivery experience	135	7 (5–9)	114	7 (6–9)	2^a,b
Biological parameters	112	5 (4–7)	99	4 (3–6)	15^a
Maternal vital signs/ physical examination	116	4 (3–6)	101	4 (3–6)	6^a
Knowledge about anti-depressant treatment in pregnancy	128	5 (4–7)	110	5 (4–7)	2^b
Partner’s attendance	135	6 (5–7)	114	6 (4–7)	2
Coping strategies among relatives	126	5,5 (4–7)	112	5 (4–6,25)	1^b
Separation or divorce	-	-	112	5 (3–7)	0^e
Ability to return to work/ change of work	-	-	113	5 (4–7)	0^e
Obsessive thoughts or intrusive thoughts	-	-	110	6 (4–7)	0^e
Fear of something bad happening to the baby	-	-	113	6 (4–8)	0^e
Thoughts of harming the baby, (including thoughts of extended suicide)	-	-	113	8 (7–9)	0^e
Level of compliance with the given treatment	-	-	112	7 (6–8)	0^e
Mental health literacy	-	-	113	6 (4–8)	0^e

Thirteen people participated in the consensus meeting: all four stakeholder groups were represented. During the meeting the group agreed on inclusion of a further six outcomes in the COS and also to amend the formulation of some of the included outcomes. No further comments were received from other participants with respect to the COS which was developed during the consensus meeting. The outcomes which are included in the final COS are described in Table 1.

Discussion

The aim is that the outcomes included in this COS are to be measured in future studies and systematic reviews of treatment of antenatal and postnatal depression (intervention studies). If this is achieved it will result in improved potential to synthesise the results from different studies. In the long term this will lead to a stronger evidence. This can be important for some of the outcomes which occur less frequently, for example suicide, and where a large patient material is necessary in order to discern differences between various treatment methods. Most of the outcomes in the agreed COS are currently used in research (Figure 5). However, only one of the selected outcomes, self-assessed symptoms of depression, is used in more than 50% of the identified studies. The second most commonly used outcome, diagnosis of depression as assessed by a clinician only occurred in 33%.

Figure 5 Frequency of the COS included outcomes in the identified studies.

Number of outcomes who is included in COS: Self-assessed symptoms of depression, Diagnosis of depression as assessed by a clinician, Parent to infant bonding, Self-assessed symptoms of anxiety, Quality of life, Satisfaction with the study intervention, Suicidal thoughts, attempts or completed suicide, Thoughts of harming the baby, including thoughts of extended suicide, Adverse events

In the protocol for the present study the maximum number of outcomes to be included in the COS had already been limited to ten. We believe that a greater number is not practical. After going thru the actual studies in this field, we can state that generally they contain around six outcomes, i.e. fewer than the number included in this COS. Thus, despite our ambition to try to limit the number of outcomes, the nine outcomes included in this COS, may be to many. This might lead to difficulties for researchers to include further outcomes specific to the research question. This project has not addressed how and when these outcomes should be measured, directives that should be included in a comprehensive COS. We intend, however, to pursue these questions in a future project.

This COS included an outcome which has not been identified in any study, namely ”thoughts about harming the child”. This highlights the need to involve patients, healthcare personnel and researchers in the process of selecting which outcome to include in a COS, and also to encourage the project participants to suggest outcomes over and above those which are already used in research.

SBU would like to thank all those who have been involved in, or assisted in dissemination of information about, the project, especially all those who participated in the development of the COS.

Project group

Experts

Maria Jonsson, Associate professor and senior consultant at the Department of Obstetrics and Gynecology, Uppsala university hospital, Sweden.
Alkistis Skalkidou, Professor of Obstetrics and Gynecology, Dept. of Women’s and Children’s Health, Uppsala University and senior consultant at the Gynecologic Department, Uppsala university hospital
Frida Trönnberg, Patient representative

SBU

Christel Hellberg (Project Manager)
Marie Österberg (Project Manager)
Ann-Kristine Jonsson (Information Specialist)
Sara Fundell (Project Administrator)

External reviewers

Erik Forsell, PhD, Research and Development-Psychologist
Ann Josefsson, Professor, Senior consultant in Obstetrics and Gynecology
Sverker Svensjö, PhD, Senior Consultant, Surgery

References

SBU. Core outcome sets inom förlossningsvård. Sammanställning och analys av studier. Stockholm: Statens beredning för medicinsk och social utvärdering (SBU); 2020. SBU-rapport nr 309. ISBN 978-91-88437-51-8.
COMET Initiative. COMET Database. Treatment of perinatal depression: protocol for a systematic review of outcomes in the literature and identification of a core outcome set using a Delphi survey. [cited 2020 April 1]. Available from: http://www.comet-initiative.org/Studies/Details/1421.
Kirkham JJ, Davis K, Altman DG, Blazeby JM, Clarke M, Tunis S, et al. Core Outcome Set-STAndards for Development: The COS-STAD recommendations. PLOS Medicine 2017;14:e1002447.

Appendix 1 Protocol

Treatment of perinatal depression: protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey

Abstract

Background

Perinatal depression is depression experienced during pregnancy (known as ante or prenatal depression) or after childbirth (known as postnatal depression). To date no ongoing or available core outcome set is available for this condition.

Methods/Design

This study will include a systematic review of the literature to identify a list of outcomes that have previously been reported. This list of outcomes will be used in a Delphi survey with different stakeholder, for example patients, relatives, clinicians and researcher within the field. The Delphi survey will consist of two rounds. In the first round we will ask panel members to score the outcome list using a 9-point Likert scale. They will also be given the opportunity to add any outcomes they think are missing from the list. The second round involves presentation of scores according to stakeholder groups and the opportunity for participants to rescore outcomes. A final consensus meeting will be held with some representatives from all stakeholder groups, to agree on a final set of core outcomes.

Discussion

A core outcome set represents the minimum that should be measured in a clinical trial for a particular condition. This study will aim to identify a core outcome set that can be used in future trials of the treatment of perinatal depression, improving the consistency of research in this clinical area. To facilitate the implementation and use of the COS we aim to include a maximum of 10 different outcomes in the final COS.

Background

Clinical trials evaluate the safety and effect of interventions, treatments or care procedures. To enable this, one intervention is compared against a comparative intervention, for example placebo, in a trial. The effect of the intervention is seen as the difference between the groups when measuring different outcomes. It is crucial that these outcomes have a therapeutic importance to relevant stakeholders, such as patients and clinicians. To enable the best clinical evidence, all clinical trials within a field are often systematically collected, assessed and synthesized in systematic reviews.

SBU, Swedish Agency for Health Technology Assessment and Assessment of Social Services, was founded in 1987 and is one of the oldest HTA (Health Technology Assessment) organisations in the world. SBU evaluates methods used by medical and social services based on systematic reviews and HTA reports of published research. Often these reviews are unable to synthesize results of individual studies because different outcomes were measured. This, in turn, lowers the certainty of the evidence for the specific intervention. One strategy that has been suggested to overcome issues of different outcomes being used in different clinical trials is the development of a Core outcome sets (COS). A COS consist of a minimum of outcomes which should be measured and reported in all future clinical trials of a specific condition. As a result, the potential for carrying out a meta-analysis for key outcomes and thereby increasing the certainty of the evidence in future systematic reviews is increased.

SBU was tasked by the government to analyse and develop COS within obstetric care in collaboration with relevant stakeholders like patients, researchers and caregivers.

To decide on a topic were to develop a COS we performed a review of the literature (unpublished data) [1]. We searched the Comet database and EMBASE, Medline, PsycINFO, Academic Search Elite, CINAHL with Full Text and SocINDEX with Full Text for existing or ongoing core outcome sets. Based on the result of this search, the input from SBU´s Scientific Advisory Committee and the result from a survey, were we asked relevant stakeholders for their opinion, we decided to develop a COS for treatment for perinatal depression. This decision was based upon the fact that no ongoing or existing COS for this common condition exists.

Some existing and ongoing COS regarding depression were found. The available COS will be checked for outcomes that also are relevant to perinatal depression and may then be included in the list of outcomes used in our Delphi survey:

Standardization of health outcomes assessment for depression and anxiety: recommendations from the ICHOM Depression and Anxiety Working Group [2]
ICF Core Sets for depression [3]
ICHOM Depression and anxiety for children and young people (ongoing) [4]
Core set of outcomes for adolescents with major depressive disorder: A tool of standardized outcomes for clinical research (ongoing) [5]
New methods for the development of Core Outcome Set: the example of depression (ongoing) [6]

Aims and objectives

Aim

The aim of this study is to develop a Core outcome set, with no more than 10 outcomes, relevant to the treatment of perinatal depression.

Objectives

The specific study objectives are:

To identify a list of outcomes used in studies (clinical trials and systematic reviews) of the treatment of perinatal depression from a systematic review of the literature;
To prioritise among the outcomes into a combined COS with up to 10 different outcomes.

Methods

Systematic review of outcomes

The systematic review will be carried out using different sources. We will identify outcomes reported in studies that are currently ongoing or completed and that have protocols available in Clinical Trials database. In addition, we will review outcomes measured in studies by reviewing relevant systematic reviews and randomised controlled trials (RCT) published within the last two years (2018 or 2019).

Types of studies

Studies will include published systematic reviews and randomised controlled trials as well as protocols for systematic reviews and randomised controlled trials.

Types of intervention

Any type of intervention for perinatal depression.

Types of participants

Persons suffering from perinatal depression (postnatal depression or postnatal depression). There will be no restriction to gender or age.

Exclusion criteria

Interventions directed to prevent postpartum depression.
Comorbidity where the depression can be related to living with other existing diagnosis, for example HIV, in combination with pregnancy is excluded.
Studies with a strict focus on developing countries, not transferable to a Swedish context. For example, studies focusing on proper food intake and the effect on depression.
Conference abstracts

Search methods for identification of studies

We will search PubMed, Psychinfo, Cochrane Database of Systematic Review, Central (Cochrane Central Register of Controlled Trials) and the Cumulative Index to Nursing & Allied Health Literature (CINAHL) for relevant systematic reviews and randomised controlled trials (January 2018 to present). In addition, we will search Clinical Trials and for ongoing and completed randomised clinical trials without any time restriction. Multiple databases will be utilised to maximise the sensitivity of a search.

In addition, we will review the outcomes listed in the available COS regarding to depression.

Eligibility of studies

Two review authors will independently assess the abstracts of studies resulting from the searches. Full copies of all potentially relevant studies and those appearing to meet the inclusion criteria, or for which there were insufficient data in the title and abstract to make a clear decision, will then be obtained.

The full-text papers will be assessed independently by two review authors and any disagreement on the eligibility of included studies resolved through discussion. Where resolution is not possible, a third review author will be consulted.

Assessment of methodological quality

For the purpose of this study there will be no synthesis of outcome data from the randomised control trials, and hence a critique of the overall methodological quality of the studies themselves is not necessary.

Data extraction

Data will be extracted by one review author and checked by another review author. Any disagreement will be resolved through discussion; where resolution is not possible, a third review author will be consulted.

The following data will be extracted from each study:

Reference
Study design
Year of publication;
Intervention(s) under investigation
Outcomes that were measured (if stated, the designated primary outcome; and the designated secondary outcome)
The method of measurement
The time points at which they were measured

The extracted outcomes will be classified according to the taxonomy developed by Dodd et al available at thru the COMET initiative webpage [7].

Data analysis and presentation

For analysis purposes, the data will be initially tabulated so that each study is listed, and the outcomes measured in the trial are displayed. Outcomes will then be grouped under appropriate outcome domains. The outcome domains will be determined following the extraction of outcomes by the authors. The outcome domains and included outcomes will be reviewed by members of the study team with clinical expertise to assess suitability of the domain name and grouping of outcomes.

Within each domain we will be able to evaluate how many different outcomes were used to reflect that domain and the frequency of selection for each individual outcome.

Identification of outcomes of importance to patients

To identify outcomes not currently used in clinical trial but of importance to patients, there will be an option to add outcomes not already listed in the first Delphi round survey.

Development of the Core outcome set

Overview

To investigate which outcomes are of most importance, a Delphi study will be used so that the opinions of the participants can be obtained in a way that gives equal influence of different groups of stakeholders, and avoids an individual participant being overtly influenced by the opinions of any other participant.

Identification of potential outcomes

An initial list of potential outcomes for use in the Delphi study will be obtained from the systematic review described above. To aid interpretation of the outcomes all outcomes will be listed individually but also grouped under a relevant domain.

Members of the study team will be asked to review the list of outcomes for comprehension.

This review process will produce a final list of outcomes identified from the systematic review.

Owing to their involvement in the study design and contribution to the project, no members of the study team will be invited to participate in the Delphi study.

Participants

The Delphi study will be conducted with different groups of stakeholders. The Survey will be available in Swedish and English. We will include the following stakeholder groups in the Delphi study:

People with personal experience of the condition (mothers and partners), for example, patients, caregivers and user organisations
Health professionals with expertise in treating and caring for people with the condition (Key clinicians are midwife´s, psychologists, obstetricians, psychiatrists and general physicians)
Researchers within the field and research funders
HTA-agencies and policy makers
Others (including payers and industry)

Identified clinical leads and organisations active within this field will be approached by email. Participants will also be sought using social media (Twitter, Facebook and LinkedIn) and an open invitation on SBU´s website.

Upon registration, participants will be asked to specify their role to allow identification of stakeholder groups. Participants will not be able to identify any individual responses. Participant will be informed that participation is voluntary, and that participation can be cancelled at any time.

The National Research Ethics Committee were consulted to see whether the Delphi study with clinicians and patients require ethical approval or not.

Delphi study

Delphi round 1

Individual participants will then be emailed directly and asked to complete an online Delphi survey via an embedded link. Participants will be asked to complete each round of the Delphi study within 3–4 weeks of receipt of the email and will be reminded of this at the start of each survey.

The number of participants invited to participate will be documented and the number of participants completing subsequent rounds. Reminder emails will also be sent to aid completion of each round.

Round 1 survey format

Round 1 content includes: the respondent’s role; a list of outcomes to be scored, ordered by domain; and an option for a participant to add any additional outcomes.

At the beginning of the survey, participants will be presented with the information about the study. They will then be asked the key question: “What outcomes should be measured in clinical trials investigating treatment of perinatal depression”.

Participants will be asked to score each of the outcomes listed using a Likert scale. In the Delphi study the scale will be presented in the format 1 to 9, with 1 to 3 labelled ‘not important’, 4 to 6 labelled ‘important but not critical’ and 7 to 9 labelled ‘critical importance’.

Analysis of round 1

Additional outcomes listed by participants will be reviewed and coded by two members of the study team to ensure they represent new outcomes. If uncertainty occurs, all members of the study team will be consulted. For each outcome, the distribution of scores will be summarised for all participants combined and by stakeholder group. Outcomes scored as consensus out in round 1 will not be taken forward to round 2.

The number of participants in each stakeholder group who respond to round 1 will be assessed following round 1 closure. Results will be presented as: the total number and percentage of respondents who completed the round; the total number and percentage of respondents in each stakeholder group. Those who have not provided any scores in round 1 will not be invited to participate in round 2.

Delphi round 2

In round 2, each participant will be presented with the distribution of scores for each outcome for the different stakeholder groups. Participants will be asked to consider responses from the others and asked to review the score provided in round 1 for each of the outcomes.

Consensus definitions:

Consensus in: Consensus that outcome should be included in the core outcome set: 70% or more of each stakeholder group scoring as 7 to 9 AND <15% participants scoring as 1 to 3. If more than 10 outcomes are scored as consensus in, a prioritisation of which to include in the final core outcome set will be done during the consensus meeting.
Consensus out: Consensus that outcome should not be included in the core outcomes set: 70% or more of each stakeholder group scoring as 1 to 3 AND <15% of participants scoring as 7 to 9.
No consensus: Uncertainty about importance of outcome: Anything else.

Analysis of round 2

The total number of participants invited to take part in round 2 will be recorded. For each outcome, the distribution of scores will be summarised for all participants combined and by stakeholder group.

Consensus meeting

The final phase of the study will be a face-to-face consensus meeting with a smaller group of persons representing all the different groups of stakeholders. The goal of the consensus meeting is to agree on a COS including no more than 10 outcomes. This is to facilitate the implementation and use of the COS.

In the beginning of the meeting the results from each round of the Delphi survey will be presented. The responses from round 2 of the Delphi study will be used to inform the structure and content of the consensus meeting as follow.

If more than 10 outcomes were scored as consensus in, the main task at the consensus meeting will be to reach an agreement on which of these outcomes should remain in the COS to keep the final COS to a number. The outcomes scored as no consensus will also be discussed to some extent but with limited chance of being included in the final COS. In the meeting there will also be a chance of discussing if some of the outcomes should be combined or further specified.
If less than 10 outcomes were scored as consensus in, the main task at the consensus meeting will be to review the outcomes scored as no consensus and to see if any of those should be added to the final COS to a number. In the meeting there will also be a chance of discussing if some of the outcomes should be combined or further specified.

After the consensus meeting all persons in the panel, that have finished both surveys, will be sent a draft of the final COS and will be given a chance to comment on them. After reviewing any comments from the panel, the project team will then finalize the COS in a report. The report will be available in full in Swedish and as a summary in English at the SBU webpage. The team will also seek to publish the result of the project in a scientific journal.

References

The COMET (Core Outcome Measures in Effectiveness Trials) Initiative. A systematic review over core outcome sets in obstetric care; cited [2019 October 21]. Available from http://www.comet-initiative.org/studies/details/1370.
Obbarius A, van Maasakkers L, Baer L, Clark DM, Crocker AG, de Beurs E, et al. Standardization of health outcomes assessment for depression and anxiety: recommendations from the ICHOM Depression and Anxiety Working Group. Qual Life Res 2017;26:3211-25.
Cieza A, Chatterji S, Andersen C, Cantista P, Herceg M, Melvin J, et al. ICF Core Sets for depression. J Rehabil Med 2004:128-34.
International Consortium for Health Outcomes Measurement (ICHOM). Anxiety, Depression, OCD and PTSD in Children and Young People; cited [2019 October 21]. Available from https://www.ichom.org/portfolio/anxiety-depression-ocd-and-ptsd-in-children-and-young-people/.
The COMET (Core Outcome Measures in Effectiveness Trials) Initiative. Core set of outcomes for adolescents with major depressive disorder: A tool of standardized outcomes for clinical research; cited [2019 October 21]. Available from http://www.comet-initiative.org/studies/details/1122#.
The COMET (Core Outcome Measures in Effectiveness Trials) Initiative. New methods for the development of Core Outcome Set: the example of depression; cited [2019 October 21]. Available from http://www.comet-initiative.org/studies/details/1105.
Dodd S, Clarke M, Becker L, Mavergames C, Fish R, Williamson PR. A taxonomy has been developed for outcomes in medical research to help improve knowledge discovery. J Clin Epidemiol 2018;96:84-92.

Appendix 2 Search strategies

Cinahl via EBSCO 24 September 2019
Title: Development of a core outcome set for treatment of depression during pregnancy or after birth
The search result, usually found at the end of the documentation, forms the list of abstracts.; AB = Abstract; AU = Author; DE = Term from the thesaurus; MM = Major Concept; TI = Title; TX = All Text. Performs a keyword search of all the  database's searchable fields; ZC = Methodology Index; * = Truncation; “ “ = Citation Marks; searches for an exact phrase
Search terms		Items found
Population:
1.	(MH "Depression, Postpartum")	5205
2.	(MH "Depression+") AND ((MH "Postnatal Period+") OR (MH "Pregnancy+") OR (MH "Childbirth+") OR (MH "Postnatal Care+") )	6258
3.	TI ( ((postpartum or post-partum or postnatal or post-natal or perinatal or peri-natal or prenatal or pre-natal or antenatal or ante-natal or matern) N2 depressi) ) OR AB ( ((postpartum or post-partum or postnatal or post-natal or perinatal or peri-natal or prenatal or pre-natal or antenatal or ante-natal or matern) N2 depressi) )	6656
4	1-3 (OR)	10676
Study types:
5.	MH "Systematic Review" OR ZT "systematic review" OR MH "Meta Analysis" OR ZT "meta analysis"	113132
6.	(TI (systematic* n3 review)) or (AB (systematic n3 review)) or (TI (systematic n3 bibliographic)) or (AB (systematic n3 bibliographic)) or (TI (systematic n3 literature)) or (AB (systematic* n3 literature)) or (TI (comprehensive* n3 literature)) or (AB (comprehensive* n3 literature)) or (TI (comprehensive* n3 bibliographic)) or (AB (comprehensive n3 bibliographic)) or (TI (integrative n3 review)) or (AB (integrative n3 review)) or (JN "Cochrane Database of Systematic Reviews") or (TI (information n2 synthesis)) or (TI (data n2 synthesis)) or (AB (information n2 synthesis)) or (AB (data n2 synthesis)) or (TI (data n2 extract)) or (AB (data n2 extract)) or (TI (medline or pubmed or psyclit or cinahl or (psycinfo not "psycinfo database") or "web of science" or scopus or embase)) or (AB (medline or pubmed or psyclit or cinahl or (psycinfo not "psycinfo database") or "web of science" or scopus or embase)) or (TI (meta-analy or metaanaly)) or (AB (meta-analy or metaanaly*))	154507
7.	5 OR 6	182125
Combined sets/Study types/Limits
8.	4 AND 7 Limiters - Published Date: 20180101-20191231	137
9.	4 AND Limiters - Published Date: 20180101-20191231; Clinical Queries: Therapy - Best Balance	122

Clinical trials.gov: 03 Oct 2019
Title: Development of a core outcome set for treatment of depression during pregnancy or after birth
The search result, usually found at the end of the documentation, forms the list of abstracts.
Search terms		Items found
Population/Limits
1.	"postpartum depression" OR "post-partum depression" OR "postnatal depression" OR "post-natal depression" OR "perinatal depression" OR "prenatal depression" OR "antenatal depression" [Condition or Disease]	260
2.	"postpartum depression" OR "post-partum depression" OR "postnatal depression" OR "post-natal depression" OR "perinatal depression" OR "prenatal depression" OR "antenatal depression" [Other terms]	517

Cochrane Library via Wiley 03 October 2019 (CDSR & CENTRAL)
Title: Development of a core outcome set for treatment of depression during pregnancy or after birth
The search result, usually found at the end of the documentation, forms the list of abstracts.; :au = Author; MeSH = Term from the Medline controlled vocabulary, including terms found below this term in the MeSH hierarchy; this term only = Does not include terms found below this term in the MeSH hierarchy; :ti = title; :ab = abstract; :kw = keyword; * = Truncation; “ “ = Citation Marks; searches for an exact phrase; CDSR = Cochrane Database of Systematic Review; CENTRAL = Cochrane Central Register of Controlled Trials, “trials”; CRM = Method Studies; DARE = Database Abstracts of Reviews of Effects, “other reviews”; EED = Economic Evaluations; HTA = Health Technology Assessments
Search terms		Items found
Population:
1.	[mh "Depression, Postpartum"]	494
2.	([mh "Depression"] OR [mh "Depressive Disorder"]) AND ([mh "Pregnancy"] OR [mh "Delivery, Obstetric"] OR [mh "Pregnancy Complications"])	681
3.	(((postpartum or post-partum or postnatal or post-natal or perinatal or peri-natal or prenatal or pre-natal or antenatal or ante-natal or matern) NEAR/2 depressi)):ti,ab,kw	1928
Combined sets
	1-3 (OR)	CDSR/9 Central/843

Medline via OvidSP 24 September 2019
Title: Development of a core outcome set for treatment of depression during pregnancy or after birth
The search result, usually found at the end of the documentation, forms the list of abstracts.; .ab. =Abstract; .ab,ti. = Abstract or title; .af. = All fields; Exp = Term from the Medline controlled vocabulary, including terms found below this term in the MeSH hierarchy; .sh. = Term from the Medline controlled vocabulary; .ti. = Title; / = Term from the Medline controlled vocabulary, but does not include terms found below this term in the MeSH hierarchy; * = Focus (if found in front of a MeSH-term); * or $ = Truncation (if found at the end of a free text term); .mp = text, heading word, subject area node, title
Search terms		Items found
Population:
1.	exp Depression, Postpartum/	5144
2.	(exp Depression/ OR Depressive Disorder/) AND (exp Pregnancy/ OR exp Delivery, Obstetric/ OR exp Pregnancy Complications/ )	6175
3.	((postpartum or post-partum or postnatal or post-natal or perinatal or peri-natal or prenatal or pre-natal or antenatal or ante-natal or matern) adj2 depressi).ti,ab.	9531
4.	1-3 (OR)	14600
Study types: Subject Subsets
5.	(systematic reviews pre 2019 or systematic reviews)
Study types: Publication types
6.	(clinical study or clinical trial, all or clinical trial or controlled clinical trial or randomized controlled trial)
Combined sets /Limits/
7.	4 AND 5 limit to (yr="2018 - 2019")	180
8.	4 AND 6 limit to (yr="2018 - 2019")	66

PsycInfo via EBSCO 23 September 2019
Title: Development of a core outcome set for treatment of depression during pregnancy or after birth
The search result, usually found at the end of the documentation, forms the list of abstracts.; AB = Abstract; AU = Author; DE = Term from the thesaurus; MM = Major Concept; TI = Title; TX = All Text. Performs a keyword search of all the  database's searchable fields; ZC = Methodology Index; * = Truncation; “ “ = Citation Marks; searches for an exact phrase
Search terms		Items found
Population:
1.	DE "Postpartum Depression"	4463
2.	(DE "Major Depression" AND (DE "Antepartum Period" OR DE "Intrapartum Period" OR DE "Perinatal Period" OR DE "Postnatal Period" OR DE "Birth" OR DE "Pregnancy Outcomes" OR DE "Caesarean Birth" OR DE "Labor (Childbirth)" OR DE "Natural Childbirth" OR DE "Birth Injuries" OR DE "Birth Trauma" OR DE "Obstetrical Complications" OR DE "Pregnancy" DE "Postnatal Period"))	694
3.	TI ( ((postpartum or post-partum or postnatal or post-natal or perinatal or peri-natal or prenatal or pre-natal or antenatal or ante-natal or matern) N2 depressi) ) OR AB ( ((postpartum or post-partum or postnatal or post-natal or perinatal or peri-natal or prenatal or pre-natal or antenatal or ante-natal or matern) N2 depressi) )	9015
4.	1-3 (OR)	10170
Study types:
5.	( DE "Meta Analysis" OR ZC "systematic review" OR ZC "meta analysis" OR DE "Systematic Review" ) OR ( TX (systematic* N3 review) OR TX (metaanaly OR meta-analy* OR "meta analy" ) ) OR ( TX ((systematic n3 bibliographic) OR (systematic n3 literature) OR (comprehensive* n3 literature) OR (comprehensive* n3 bibliographic) OR (integrative n3 review) OR (information n2 synthesis) OR (data n2 synthesis) OR (data n2 extract)) OR JN ("Cochrane Database of Systematic Reviews") )	70915
Combined sets/Limits
6.	4 AND 5	349
7.	6 Limiters - Published Date: 20180101-20191231	81
8.	4 Limiters - Publication Year: 2018-2019; Methodology: CLINICAL TRIAL	30

Appendix 3 Information to the participants

Information about participation in the development of a core outcome set for treatment of perinatal depression

Project aim

The goal of the project is to determine a core set of outcomes (not more than 10) to be measured in future clinical studies on different treatments for perinatal depression.

Definitions

The following definitions are adapted from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. The COMET Initiative brings together researchers interested in the development and application of core outcome sets¹.

^1. http://www.comet-initiative.org/

Core outcome set – an agreed standardized collection of outcomes which should be measured and reported, as a minimum, in all trials of a specific clinical area or of a specific condition.

Domain – broad categories (for example, adverse events, resource use, function).

Outcomes – the “what” we want to measure. Each domain contains one or more outcomes.

Intervention – Intervention is any kind of treatment that can be given to a person with perinatal depression,for example anti-depressive drugs, cognitive behavioural therapy, acupuncture, psychotherapy, digital aids, decisional aids, transcranial magnetic stimulation or exercise.

Population – persons included in the research study, in this case individuals with depression during pregnancy or after giving birth, both parents included.

How the outcomes were collected

The outcomes in the survey have been identified through a review of ongoing or recently published (2018-2019) research (104 RCT protocols, 27 published RCT, and 34 systematic reviews). Also, experts included in the project management were given the opportunity to add outcomes they thought of as important.

Except for outcomes relating to study feasibility and study quality all identified outcomes are included in the survey. Some of the outcomes included may be more commonly collected as background factors or demographic information rather outcomes in research studies in this field. However, to avoid subjectivity from our side we have decided to keep them in the survey. If you feel that an outcome is of no importance you give it a low score.

Instructions for participating in the survey

In the Delphi survey², we will ask you to rate the importance of the listed OUTCOMES, which are grouped by DOMAINS as to whether they should be included as core outcomes in treatment for perinatal depression.

^2. An explanation for the different steps in a Delphi study is summarised in the document “Delphi plain language summary” developed by the comet initiative at: http://www.comet-initiative.org/assets/downloads/Delphi%20plain%20language%20summary%20for%20COMET%20website.pdf

Your assessment should be based on what you believe will be the most valuable information for decisions, that could be care decisions by patients and providers, regulatory approval, or coverage and reimbursement decisions.

You do not need to consider weather adequate and well-validated measures currently exist when rating the different outcomes.

Some of the listed outcomes may be mainly relevant for studies investigating treatments for individuals experiencing depression during pregnancy or treatments of individuals with postpartum depression. Please include outcomes you think are important, regardless of if they apply to both populations or just one of the two. In the last section of the survey you have an opportunity to specify any such outcomes and to which population you think they are of most importance. This will also be further discussed on the consensus meeting and clearly stated in the final report.

The outcomes included in the final core set should be useful for future clinical studies within the field, regardless of the type of interventions being investigated. The Core outcome set should be considered a minimum of what is to be measured. This means that there might be outcomes, that are important mainly for specific interventions, but not all (or most) intervention, which will not be included in the final core outcome set.

Outcomes which are only important in relation to specific interventions can always be used in future clinical trials in addition to those included in the core outcome set.

Please try to give as many outcomes as possible a priority score based on your personal perspective.

In the final page of the first survey, you will have the opportunity to suggest additional outcomes you feel should be included.

In this project the task is to prioritise what to measure, but not on how (which instruments to use) to measure the outcomes.

How to score

You will score the outcomes using a 9-point Likert scale.

1–3 The outcome is not important to be included in the core outcome set with 1 being the less important

4–6 The outcome is important but not critical to include in a core outcome set

7 –9 The outcome is critical to include in a core outcome set with 9 being the most important

Unable to score – You are uncertain about the meaning of the outcome.

Please try to use as many scoring options as possible, since this will make it easier to differentiate the importance between different outcomes. Remember that the goal is to include up to ten outcomes in the core outcome set, so try to limit the number of outcomes scored as critical.

When you have finished the survey, you will receive an e-mail with your answers. Please save this e-mail, you may want to have a look at it when you fill in the second survey.

Next step

Then staff at SBU are going to summarise the scores from all surveys at group level and remove outcomes that are scored as not important by all groups. We will also go through all suggestions about outcomes to add that you suggested in the survey. Thereafter all participants that finished the first survey will receive the second one.

If you have any questions during the process you can always contact any of us from project management.

This reference document provides further detail about the outcomes included in the Round 1 survey. As you work through the survey, you may refer to this document for descriptions of the outcomes that are listed.

Outcomes to measure depression

Outcome	Explanation
Depressive symptoms	Self-assessed symptoms of depression
Depression in partner	Self-assessed symptoms of depression in the partner of an individual with antenatal /postpartum depression
Psychiatric diagnosis of depression	Diagnosis of depression as assessed by a clinician
Recovery from depression (remission)	Rate of recovery from depression
Depression relapse	Relapse into a new depressive episode
Time to remission from depression	Time to recovery from depressive episode
Was depression treatment initiated	Was any type of treatment initiated?
Change in Antidepressant Medication	Was there any change regarding dosage or choice of drug
Expert rating of overall disease burden

Other psychiatric outcomes

Outcome	Explanation
Anxiety symptoms	Self-assessed symptoms of anxiety
Fear of childbirth	Self-assessed symptoms of fear of childbirth
Psychiatric diagnosis of anxiety	Diagnosis of anxiety assessed by a clinician
Other psychiatric or neuropsychiatric diagnoses	The presence of other psychiatric diagnosis
Mood	Assessment of the mood
Self-harm	The extent a person thinks about self-harm or acts on it
Suicidal thoughts or attempts	Prevalence of suicidal thoughts or attempts
Cognitive ability	The ability of an individual to perform the various mental activities most closely associated with learning and problem solving
Eating disorder symptoms	Eating disorders are a group of conditions marked by an unhealthy relationship with food.
Visit to clinic for fear of childbirth	Treatment for fear of childbirth during pregnancy
Post-traumatic stress symptoms	Self-assessed symptoms of post-traumatic stress syndrome or severe stress- crisis reaction postpartum
Psychiatric diagnosis of postpartum stress syndrome in relation with childbirth	Diagnosis of postpartum stress syndrome related to childbirth, as assessed by a clinician
Psychiatric diagnosis of postpartum psychosis	Diagnosis of postpartum psychosis assessed by a clinician

Outcomes relating to family circumstances

Outcome	Explanation
Domestic/ intimate partner violence
Family functioning	The social and structural properties of the global family environment. It includes interactions and relationships within the family, particularly levels of conflict, adaptability, organization, and quality of communication
Quality of relationship	Assessment of the quality of a relationship between adults
Parent to infant bonding	Parent to infant bonding. Bonding refers only to the feeling of the parent, the surge of love and tenderness she/he feels for the baby. Includes feeling felt during pregnancy.
Attachment	The feelings between the parent and the baby (different from bonding which only refers to the feeling of the parent)
Parenting Sense of Competency	The parents’ anxiety, motivation frustration, competence, capability levels, and problem-solving abilities in their parental role.
Parental stress	Parental stress can be defined as anything related to caring for and rearing a child that causes frustration and interferes with how a parent relates to a child
General stress	Stress symptoms that do not have to do with the parental role
Parent-infant interaction	Assessment of the level and quality of the interaction between parent and child
Attitudes about parenting	Expectations of the self as a parent
Family planning	the number of children someone wishes to have, including the choice to have no children, as well as the age at which she wishes to have them and if this was affected by the depression

Outcomes relating to function

Outcome	Explanation
Daily functioning level/ activities of daily living	Assessment of level of function when considering routine activities people do every day without assistance, such as eating, bathing, getting dressed, preparing meals, work, participating in activities
Sleep	Different parameters on sleep measured by self-report questionnaire or wrist actigraphy. Examples, duration, time for and quality of sleep
Fatigue	Extreme tiredness resulting from mental or physical exertion or illness
Quality of life	An individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns
Sexual desire/function
Stigma	Feeling of depression related stigma
Self-esteem	Describes a person's overall sense of self-worth
Social relationships	Interpersonal relationships
Effort-based decision-making
Perceived ability to cope with life challenges

Outcomes relating to characteristics

Outcome	Explanation
Self-compassion	Extending compassion to one's self in instances of perceived inadequacy, failure, or general suffering.
Lifestyle	Lifestyle factors such as use of tobacco, alcohol, sleep and exercise
Verbal fluency	Verbal ability, using test that measures spontaneous production of words belonging to the same category or beginning with some designated letter
Personality	Personality assessment self-reported or completed by clinicians
Perceived social support / Help-Seeking	The feeling that one has people around that can offer support. The feeling of being valued, respected, cared about, and loved by others who are present in one's life
Socio-emotional competence	Ability to interact with others, regulate one's own emotions and behaviour, solve problems, and communicate effectively
Confidence to self-help
Mentalizing, reflective functioning and level of mindfulness	Ability to understand mental states such as feelings, desires, and attitudes and level of mindfulness
Self-esteem	Describes a person's overall sense of self-worth

Outcomes relating to adverse events

Outcome	Explanation
Adverse event	Unwanted effect of the treatment
Spontaneous abortion or stillbirth	Rate of spontaneous abortion or stillbirth.
Perinatal mortality	Stillbirths and death during the first week after birth

Obstetric outcomes

Outcome	Explanation
Infections during pregnancy	Infection occurring during pregnancy
Residual physical problems after delivery	Such as incontinence, dyspareunia or prolapse
Birth injury	Such as perinatal tear and injuries to the levator ani muscle
Pain	Level of pain associated with pregnancy or birth related complications
Gestational hypertension or preeclampsia	Having a blood pressure higher than 140/90 with/without the presence of protein in the urine and diagnosed after 20 weeks of gestation
Gestational age at delivery	Preterm, at term or post term
Gestational diabetes
Estimated blood loss
Induction of labour
Mode of delivery	Delivery mode, vaginal, operative vaginal or by caesarean section (elective or emergency)
Fetal growth assessment by Ultrasound
Complications associated with the placenta	Such as placental abruption or placenta previa
Vaginal and/or faecal microbiota	Analyses of bacteria (microbiota) from vagina and/or faeces
Transition of care from pregnancy to postpartum	Patient continuity of care for depression, or other care, across the transition of care from pregnancy to postpartum

Outcomes relating to the child

Outcome	Explanation
Breastfeeding	Proportion of participants with exclusive breastfeeding and partial breastfeeding at a predefined timepoint after childbirth, time and/or place of initiation of breastfeeding
Child attention
Duration of crying episodes
Child development	Cognitive, motor, social and language development
Neurodevelopmental and neurobehavioral outcomes	Neurodevelopmental and neurobehavioral diagnoses, specified
Sleep	Length of sleep periods and duration of sleep in the child, problems with sleep
Vaccinations received/ immunization status
Infant or child’s temperament	The way in which the child approaches and reacts to the world
Biological parameters in the infant	Such as estradiol, cortisol, oxytocin, omega-3 fatty acid, brain-derived neurotrophic factor, glucose
Well-baby check-up status	To which extent appointments are carried out as planned
Congenital malformations
Infant antibiotic use
Birth weight, height and head circumference	Birth weight, percent low birth weight, or percent small for gestational age, infant weight-for-age, infant height-for-age and head circumference for age
Small for gestational age (SGA)	Small for gestational age (SGA), defined as weight for gestation < 10th (or 5th) percentile or birth weight is lower than 2 standard deviations below the mean value for the gestational age
Apgar score	The Apgar score is a method to quickly summarize the health of new born children
Neonatal intensive care unit admission

Outcomes relating to resource use

Outcome	Explanation
Cost-effectiveness	Measure of the amount of resources required to achieve a predefined goal
Use of health services	Use of health care service in different populations, change over time, hospitalization
Engagement and retention with health services	The extent which the patient engages with other health care services other than the specific intervention
Sick-leave	Number of days unable to work (on sick-leave)

Outcomes relating to experiences and level of satisfaction

Outcome	Explanation
Satisfaction with intervention	Patient satisfaction with the treatment
Therapeutic alliance	Level of therapeutic alliance between the therapist and patient.
Quality of care	Quality of care in general not limited to the specific intervention
Parent experience	Parental experience of a situation, condition, incident, treatment
Pregnancy / delivery experience

Other outcomes

Outcome	Explanation
Biological parameters	Levels of cortisol, inflammatory markers hormone levels and other factors measured in the blood or saliva
Maternal vital signs/physical examination	Physical parameter as temperature, pulse, blood pressure, etc.
Knowledge about antidepressant treatment in pregnancy	Self-rated knowledge of medication for depression
Partner’s attendance	To what extent the partner is involved in and attends care visits
Coping strategies among relatives

Information sent out in prior to survey 2.

Thank you for your participation in the first survey. Please find a file with the summarised results attached to this e-mail. You will get access to the second (and last) survey in a separate e-mail very soon.

Aim of the project

The aim of this project is to develop a core outcome set (COS) from the long list of outcomes extracted from ongoing or recently published research. The final COS will include a limited number of outcomes (maximum 10) based upon your scoring and discussion during the workshop. The PICO (population, intervention, control, outcome) for the COS is treatment of depression during or after pregnancy. No restrictions regarding treatment options is set.

How to use the result from the first survey when filling in the second survey

The result is presented as distribution of scores given by all participants as well the distribution for the different perspectives (patient, profession, researcher, others). No outcome fulfilled the prespecified criteria for consensus out, meaning all outcomes found in the first survey are also present in the second one. One outcome, Suicidal thoughts or attempts, was scored as consensus in (scored as critical important by 70% or more by all perspectives). Based on suggestions in the first survey seven new outcomes have been added. They are presented at the end of the survey.

The second survey will be sent to you soon, it will be open for approximately three weeks.

We now ask you to re-score the outcomes, this time after assessing the information regarding how others have scored the different outcomes. With this information you can decide to change your score or keep it the same, it is up to you. You should have received a e-mail with your personal score after filling in the first survey. Please e-mail us if you, for any reason, need us to send you this information again.

It is of great importance that as many as possible participate in this second round in order to develop a robust COS. We are very grateful that you are willing to take the time to do this survey.

What happens next

The outcomes given the highest scores, as well as those scored as consensus in, will be passed forward to the workshop. During this workshop a proposal for which outcomes to be included in the final COS will be made. All participants will have the opportunity to address the final COS after the workshop.

If you have any questions, please do not hesitate to contact us.

Thanks’ for your contribution to this project!

Information to participants sent out after the consensus meeting

Dear XXX!

Firstly, we would like to thank you for participating in the development of a Core Outcome Set regarding treatment for perinatal depression.

Secondly, we would like to share information regarding the results of the final consensus meeting and provide you with an opportunity to comment on the results. We will not be able to make any major changes to the final core (for example adding additional outcomes), but smaller adjustments can be made, and important remarks will be included in the discussion.

As previously informed, the outcomes given the highest scores in the second survey, as well as those scored consensus in, were passed forward to the final consensus meeting. During this meeting a proposal for which outcomes to include in the final COS was made. Please see the attached document for more details.

If you have any comments, please send them to us no later than the 15.:th of March.

The information included should be considered working material and we ask you not to share it until the report is published. We are hoping to be able to publish the report in Swedish during May 2020. We will then continue to work on the English summary as well as a scientific article.

Information regarding the consensus meeting and result from the second survey

In total 23 outcomes were passed forward to the consensus meeting (listed on page 3-6). Based on the results from the second survey three outcomes (marked with * in the list below) were classified as consensus in³, and thereby included in the COS. In addition, outcomes fulfilling the below specified criteria were discussed during the meeting.

Any outcome for which at least 70% of participants in either one of the stakeholder group scored as critically important (7-9)
The ten outcomes given the highest scores by each stakeholder group

In the consensus meeting a total of 13 persons participated. Participants were representatives from all four different stakeholder groups. Persons from the project management facilitated the meeting but took no active part in the discussion.

^3. At least 70% of participants in each stakeholder group to score the outcome as critically important (7-9) and <15% to score the outcome as not important (1-3).

The core outcome set

In total 9 outcomes where included in the COS.

Self-assessed symptoms of depression. (Including measurement of sleep quality) *
Diagnosis of depression as assessed by a clinician, should include a structured interview
Parent to infant bonding
Self-assessed symptoms of anxiety
Quality of life
Satisfaction with intervention
Suicidal thoughts, attempts or completed suicide *
Thoughts of harming the baby, (including thoughts of extended suicide) *
Adverse event. Includes spontaneous or induced abortion, miscarriage, fetal death and death during the first week of life.

The group did some rearrangements of the outcomes during the discussions, those were;
Adding information regarding sleep in the self-rated depression instruments, the importance of using structured interviews when doing a clinical diagnosis and pointing out spontaneous or induced abortion, miscarriage, fetal death and death during the first week of life as important adverse events.

Other remarks from the meeting that will be discussed in the report.

During the meeting the group agreed on highlighting the following factors/mediators as important in the discussion section of the report.

Transition of care from pregnancy to postpartum
Pregnancy / delivery experience

During the discussions the group agreed that these are not to be considered important outcomes, but important background factors or mediators. They argued that they are to be considered important to take into consideration. The group also agreed that continuity of care was a very important area and that the organization of care is an important research area.

The group also wanted to stress following:

Few of the selected outcomes included in the COS involving the child. It is important to include the interaction between parent-child and the development of the child. It is not sure that recovery from a depression is correlated with a better interaction with the child. However, to enable this, studies with long follow up are needed.
It is important to do a clinical psychiatric assessment, including a structured interview, at study start. This enables identification of other conditions or comorbidity. This can be important for inclusion or exclusion in the study population, or to make sure that the population is described accurately.

Appendix 4 Included studies

Appendix 5 Excluded studies

Studies considered not relevant

Reference	Main reason for exclusion
Kanes S, Colquhoun H, Riesenberg R, Rubinow D, Maximos B, Meltzer-Brody S. Phase 3 Study Evaluating Brexanolone, a GABAA Receptor Modulator, in Moderate Postpartum Depression [25H]. Obstet Gynecol 2018;131.	Conference abstract
Lee SH, Huang LS, Lee MC, Lee MS. Effects of family centered postpartum care for postpartum depression among previously infertile couples. Human reproduction. Conference: 34th annual meeting of the european society of human reproduction and embryology. ESHRE. Barcelona, Spain. 2018;33:i396‐i397.	Conference abstract
Meltzer-Brody S, Kanes S, Riesenberg R, Epperson CN, Deligiannidis K, Rubinow D, et al. Efficacy and safety of brexanolone IV across phase 2/3 studies: a first-in-class gabaa receptor positive allosteric modulator for postpartum depression. Biological Psychiatry 2018;83:S385‐S386.	Conference abstract
Ngai FW. Telephone-based cognitive-behavioral therapy on postnatal depression and quality of life. BJOG 2018;125:18.	Conference abstract
Adams V, Volo J, Burnside A, Cross J, Kalafut M, Figuers C. Effects of Exercise on Women With Postpartum Depression: A Systematic Review of the Literature. J Womens Health Phys Therap 2018;42:38-9.	Conference abstract
Simonds AH, Cortes J, D'Antico T, Hood BL, Rebilas M, Richards A, et al. Effectiveness of Physical Activity to Reduce Symptoms of Depression and Fatigue in the Postpartum Population. J Womens Health Phys Therap 2018;42:52-52.	Conference abstract
Wang C, Bayes S. Effectiveness of acupuncture as an add-on treatment for women with postnatal depression: a systematic review. Women Birth 2018;31:S27-S27.	Conference abstract
Clemson C. S.08.01 Development of brexanolone iv, a GABA-A receptor positive allosteric modulator, for postpartum depression. Eur Neuropsychopharmacol 2019;29:S10‐S11.	Conference abstract
Clemson C, Meltzer-Brody S, Colquhoun H, Riesenberg R, Epperson CN, Deligiannidis K, et al. 86: brexanolone iv efficacy in postpartum depression in three pivotal trials: montgomery-åsberg depression rating scale assessment. Am J Obstet Gynecol 2019;220:S69‐S70.	Conference abstract
Brexanolone iv, a GABA-A receptor modulator, in postpartum depression: pooled analysis of HAM-D sub-items. Eur Neuropsychopharmacol 2019;29:S63.	Conference abstract
Burger H, Verbeek T, Meijer J, Beijers C, Mol B, Ormel J, et al. 80: effects of cognitive behavioural therapy for antenatal anxiety and depression on mother and offspring. Am J Obstet Gynecol 2019;220:S65.	Conference abstract
Wang CC, Zhu R, Ge L, Tufanaru C, Bayes S, De Jong G. Effectiveness of acupuncture as an adjunct treatment for women with postnatal depression: a systematic review protocol. JBI Database System Rev Implement Rep 2018;16:2080-4.	Duplicate
Meltzer-Brody S, Colquhoun H, Riesenberg R, Epperson CN, Deligiannidis KM, Rubinow DR, et al. Brexanolone Injection in Postpartum Depression: Two Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 3 Trials. Obstet Gynecol Surv 2019;74:219-20.	Duplicate
Li S, Zhong W, Peng W, Jiang G. Effectiveness of acupuncture in postpartum depression: a systematic review and meta-analysis. Acupunct Med 2018;36:295-301.	Not able to retrive full text
Roman M, Constantin T, Bostan CM. The efficiency of online cognitive-behavioral therapy for postpartum depressive symptomatology: a systematic review and meta-analysis. Women Health 2019:1-14.	Not able to retrive full text
Ctri. Study the effect of two health and wellness therapies during and after pregnancy. http://www.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2018/02/012121 2018.	Not able to retrive full text
Sebela A, Hanka J, Mohr P. Diagnostics and modern trends in therapy of postpartum depression. Ceska Gynekol 2019;84:68-72.	Not able to retrive full text
Meltzer-Brody S, Colquhoun H, Riesenberg R, Epperson CN, Deligiannidis KM, Rubinow DR, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet 2018;392:1058-70.	Not able to retrive full text
Ekrami F, Mohammad-Alizadeh Charandabi S, Babapour Kheiroddin J, Mirghafourvand M. The Effect of counselling on depression and anxiety of women with unplanned pregnancy: A randomized controlled trial. Community Ment Health J 2019;55:1047-56.	Not relevant population
Drks. Efficacy of Parent Infant Psychotherapy by mothers with postpartum psychopathological disorders as part of the SKKIPPI study. http://www.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00016353 2019.	Not relevant population
Goldsmiths UoL. Prenatal Listening to Songs Composed for Pregnancy and Symptoms of Anxiety and Depression: a Pilot Study. In; 2015.	Not relevant population
Karolinska Institutet. Mindfulness Based Childbirth and Parenting Education - RCT of Effects on Parent and Child Health. In; 2017.	Not relevant population
Irct20170423033609N. Effect of Melissa Officinalis on postpartum blues. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20170423033609N7 2018.	Not relevant population
Irct20170726035328N. Postpartum depression and stress of mothers with preterm infants. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20170726035328N2 2018.	Not relevant population
Nikoomazhab S, Abedi P, Honarmandpour A, Haghdoust MR. The effect of evening primrose oil on the intensity of postpartum blues among primiparous females: a double-blind, randomized, controlled, clinical trial. Iran Red Crescent Med J 2018;20.	Not relevant population
Spiro-Levitt C, Gallop R, Young JF. Trajectories of change in maternal and adolescent depressive symptoms in the depression prevention initiative. J Affect Disord 2019;253:176‐83.	Not relevant population
Icahn School of Medicine at Mount Sinai, National Institute of Mental Health. Using a Preparation and Education Intervention to Reduce Postpartum Depression Among New Mothers (The MADE IT 2 Study). In; 2010.	Not relevant population
Icahn School of Medicine at Mount Sinai, National Institute on Minority Health Disparities. Mothers Avoiding Depression Through Empowerment Intervention Trial. In; 2010.	Not relevant population
Bayrampour H, Trieu J, Tharmaratnam T. Effectiveness of eHealth Interventions to Reduce Perinatal Anxiety: A Systematic Review and Meta-Analysis. J Clin Psychiatry 2019;80.	Not relevant population
Scime NV, Gavarkovs AG, Chaput KH. The effect of skin-to-skin care on postpartum depression among mothers of preterm or low birthweight infants: A systematic review and meta-analysis. J Affect Disord 2019;253:376-84.	Not relevant population
Haga SM, Drozd F, Lisøy C, Wentzel-Larsen T, Slinning K. Mamma Mia – A randomized controlled trial of an internet-based intervention for perinatal depression. Psychol Med 2019;49:1850-8.	Not relevant population
Daley A, Riaz M, Lewis S, Aveyard P, Coleman T, Manyonda I, et al. Physical activity for antenatal and postnatal depression in women attempting to quit smoking: randomised controlled trial. BMC Pregnancy Childbirth 2018;18:156.	Not relevant population
Mihelic M, Morawska A, Filus A. Does at perinatal parenting intervention work for fathers? A randomized controlled trial. Infant Ment Health J 2018;39:687-98.	Not relevant population
Lowndes TA, Egan SJ, McEvoy PM. Efficacy of brief guided self-help cognitive behavioral treatment for perfectionism in reducing perinatal depression and anxiety: a randomized controlled trial. Cogn Behav Ther 2019;48:106-20.	Not relevant population
St. Joseph's Healthcare, Hamilton. Cognitive Behavioural Group Therapy for Perinatal Anxiety. In; 2019.	Not relevant population
University of Calgary, Alberta Centre for Child, Family Community Research, Alberta Family Wellness Initiative. Mindfulness Based Cognitive Therapy for Psychological Distress in Pregnancy. In; 2017.	Not relevant population
University of Glasgow, Scottish Collaboration for Public Health Research Policy. Mellow Bumps RCT - Antenatal Intervention for Vulnerable Women. In; 2013.	Not relevant population
Nct. Happy Mother-Healthy Baby: an Anxiety-focused Early Prenatal Intervention. https://clinicaltrials.gov/show/NCT03880032 2019.	Not relevant population
University of North Carolina, Chapel Hill, National Institute of Mental Helath. A Pilot Trial of Perinatal Depression Treatment in HIV Infected Women. In; 2020.	Not relevant population
Harvard Medical School, National Institute of Mental Health. Healthy Options: Group Psychotherapy for HIV-positive Depressed Perinatal Women. In; 2017.	Not relevant population
Seeley JR, Sheeber LB, Feil EG, Leve C, Davis B, Sorensen E, et al. Mediation analyses of Internet-facilitated cognitive behavioral intervention for maternal depression. Cogn Behav Ther 2018;48:1‐16.	Not relevant population
National University Singapore, Ministry of Education Singapore. MoodUP in Improving Psychological Outcomes Among Perinatal Women. In; 2021.	Not relevant population
Northwestern University. Comparing the Effectiveness of Clinicians and Paraprofessionals to Reduce Disparities in Perinatal Depression. In; 2019.	Not relevant population
Saint Anselm College, Catholic Medical Center. Effectiveness of a Web-based Nursing Intervention in the Reduction of Postpartum Depression and Parenting Stress. In; 2018.	Not relevant population
The Jones Institute. Oral Contraceptive Ethinyl Estradiol Dose Effect on Postpartum Depression and Sexual Functioning Scales. In; 2015.	Not relevant population
University of Melbourne. Effect of the 'Mother and Baby' Program on Well-Being. In; 2006.	Not relevant population
University of Pittsburgh, National Institute of Mental Health. Sertraline for the Prevention of Recurrent Postpartum Depression. In; 2006.	Not relevant population
University of the Incarnate World Joint Program. Mentors Offering Maternal Support (M-O-M-S™): A Prenatal Program for Decreasing Maternal Anxiety and Depression. In; 2020.	Not relevant population
K. K. Women's Children's Hospital,. CODEPAD (Collaborative Outcomes of DEpression and Pain Associated With Delivery). In; 2020.	Not relevant population
University of Roma La, Sapienza. MAMA NO STRESS Project. The Effects of the "HAPPY MAMA" Intervention. In; 2019.	Not relevant population
Actrn. Mums on the Move Study: a pilot randomised controlled trial to evaluate the effectiveness of a physical activity program for women at risk of post-natal depression. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12618001453279 2018.	Not relevant population
Irct20180118038424N. Effect of acceptance and commitment therapy counseling on postpartum depression in unwanted pregnancies. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20180118038424N1 2018.	Not relevant population
Irct20180618040135N. The effect of infant massage on maternal depression and fatigue in mothers referred to selected clinics of Iranshahr University of Medical Sciences. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20180618040135N1 2018.	Not relevant population
Irct20180912041009N. Investigating the effectiveness of Dialectical Behavior Therapy skills on postpartum depression, anxiety symptoms and Hematocrit Level. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20180912041009N1 2019.	Not relevant population
Irct20181231042192N. The Effect of Floor Foot Therapy on Anxiety and Depression in Newborns. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20181231042192N1 2019.	Not relevant population
Nct. RCT of Automated Conversational Agent vs. Treatment as Usual for the Management of Perinatal Mood. https://clinicaltrials.gov/show/NCT03646539 2018.	Not relevant population
Nct. Impact of Mothers Touch Program to Improve Maternal Health After Birth. https://clinicaltrials.gov/show/NCT03715218 2018.	Not relevant population
Nct. Couple-based Interpersonal Psychotherapy on Postnatal Depression and Family Sense of Coherence. https://clinicaltrials.gov/show/NCT03499756 2018.	Not relevant population
Nct. Proactive, Personalized Postpartum Mental Healthcare. https://clinicaltrials.gov/show/NCT03803189 2019.	Not relevant population
Nct. Northwell Health Visits: a Family Connects Pilot Implementation at Northwell Health. https://clinicaltrials.gov/show/NCT03887910 2019.	Not relevant population
Nct. Mindfulness Based Cognitive Therapy (MBCT) During Pregnancy. https://clinicaltrials.gov/show/NCT03809572 2019.	Not relevant population
Nct. The Impact of a Newborn Behavioral Intervention on the Mental Health of Mothers With Late Pre-Term Infants. https://clinicaltrials.gov/show/NCT03836430 2019.	Not relevant population
Sanaati F, Charandabi S-A, Eslamlo HF, Mirghafourvand M. A randomized controlled trial on the effect of lifestyle education for Iranian women and their husbands on post-partum anxiety and depression. Health Educ Res 2018;33:416‐28.	Not relevant population
Thitipitchayanant K, Somrongthong R, Kumar R, Kanchanakharn N. Effectiveness of self-empowerment-affirmation-relaxation(Self-EAR) program for postpartum blues mothers: a randomize controlled trial. Pak J Med Sci 2018;34:1488‐93.	Not relevant population
Vaziri F, Sahebkaram Z, Bahrami R, Pourahmad S, Azima S. Lavender oil aromatherapy on infantile colic and maternal mood: a double blind randomized clinical trial. Pharm Sci 2018;24:38‐43.	Not relevant population
Yu HY, Wang SY, Quan CX, Fang C, Luo SC, Li DY, et al. Dexmedetomidine Alleviates Postpartum Depressive Symptoms following Cesarean Section in Chinese Women: a Randomized, Placebo-Controlled Study. Pharmacotherapy 2019;39:994-1004.	Not relevant population
University of Coimbra. Be a Mom: Effectiveness of a Web-based Preventive Intervention for Postpartum Depression. In; 2019.	Not relevant population
University of Minnesota Clinical Translational Science Institute. Effect of Exercise on Perinatal Depression. In; 2019.	Not relevant population
London School of Hygiene, Tropical Medicine, National Institute of Mental Health, University of Liverpol. Thinking Healthy Program - Peer Delivered, India (THPP-I). In; 2017.	Not relevant population
University of Washington, National Institute of Nursing Research. Online Prenatal Trial in Mindfulness Sleep Management. In; 2020.	Not relevant population
Influences of family-centered maternity care nursing on puerperal depression of delivery women during puerperal period. Biomedical research (india) 2018;29:654‐7.	Not relevant population
Isrctn. Can taking a zinc supplement during pregnancy reduce the symptoms of depression both before and after the baby is born? http://www.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN80468181 2018.	Not relevant population
Levine MD, Emery RL, Kolko Conlon RP, Marcus MD, Germeroth LJ, Salk RH, et al. Depressive Symptoms Assessed Near the End of Pregnancy Predict Differential Response to Postpartum Smoking Relapse Prevention Intervention. Ann Behav Med 2019;53:N.PAG-N.PAG.	Not relevant population
Silverstein M, Diaz-Linhart Y, Cabral H, Beardslee W, Broder-Fingert S, Kistin CJ, et al. Engaging Mothers With Depressive Symptoms in Care: Results of a Randomized Controlled Trial in Head Start. Psychiatr Serv 2018;69:1175-80.	Not relevant population
Townshend K, Caltabiano NJ, Powrie R, O’Grady H. A Preliminary Study Investigating the Effectiveness of the Caring for Body and Mind in Pregnancy (CBMP) in Reducing Perinatal Depression, Anxiety and Stress. J Child Fam Stud 2018;27:1556-66.	Not relevant population
Rezaie-Keikhaie K, Hastings-Tolsma M, Bouya S, Shad FS, Sari M, Shoorvazi M, et al. Effect of aromatherapy on post-partum complications: A systematic review. Complement Ther Clin Pract 2019;35:290-5.	Not relevant population
Felice E, Agius A, Sultana R, Felice EM, Calleja-Agius J. The effectiveness of psychosocial assessment in the detection and management of postpartum depression: a systematic review. Minerva Ginecol 2018;70:323-45.	Not relevant population
Nakamura A, van der Waerden J, Melchior M, Bolze C, El-Khoury F, Pryor L. Physical activity during pregnancy and postpartum depression: Systematic review and meta-analysis. J Affect Disord 2019;246:29-41.	Not relevant population
Jonson-Reid M, Drake B, Constantino JN, Tandon M, Pons L, Kohl P, et al. A Randomized Trial of Home Visitation for CPS-Involved Families: the Moderating Impact of Maternal Depression and CPS History. Child Maltreat 2018;23:281‐93.	Not relevant population
Ribeiro MKA, Alcantara-Silva TRM, Oliveira JCM, Paula TC, Dutra JBR, Pedrino GR, et al. Music therapy intervention in cardiac autonomic modulation, anxiety, and depression in mothers of preterms: randomized controlled trial. BMC Psychol 2018;6:57.	Not relevant population
Bledsoe SE, Killian-Farrell C, Lombardi B, Rizo C, Bellows A-MO, Sommers AR, et al. Feasibility of treating depression in pregnant adolescents using brief interpersonal psychotherapy. Soc Work Ment Health 2018;16:252-65.	Not relevant study design
Darius Tandon S, Leis JA, Ward EA, Snyder H, Mendelson T, Perry DF, et al. Adaptation of an evidence-based postpartum depression intervention: feasibility and acceptability of mothers and babies 1-on-1. BMC Pregnancy Childbirth 2018;18:93.	Not relevant study design
Cynthia Logsdon M, Myers J, Rushton J, Gregg JL, Josephson AM, Davis DW, et al. Efficacy of an Internet-based depression intervention to improve rates of treatment in adolescent mothers. Arch Womens Ment Health 2018;21:273-85.	Not relevant study design
Frieder A, Fersh M, Hainline R, Deligiannidis KM. Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development. CNS Drugs 2019;33:265-82.	Not relevant study design
Garcia SE, Lillehei NE, Valente ER, Grote NK, Hankin BL, Davis EP. Does Brief Psychotherapy With Distressed Pregnant Women Benefit Mother and Baby? Zero Three 2019;39:23-32.	Not relevant study design
Fagbemi F. Impact of social support on postnatal depression among adolescent mothers: a systematic literature review. MIDIRS Midwifery Digest 2019;29:20-26.	Not relevant study design
Kimmel MC, Bauer A, Meltzer-Brody S. Toward a framework for best practices and research guidelines for perinatal depression research. J Neurosci Res 2019.	Not relevant study design
Molenaar NM, Kamperman AM, Boyce P, Bergink V. Guidelines on treatment of perinatal depression with antidepressants: An international review. Aust N Z J Psychiatry 2018;52:320-27.	Not relevant study design
Giardinelli L, Lelli L, Ugolini V, Lazzeretti L, Burian I, Lino G, et al. Comparison of two different treatments in depressed pregnant women: fetal growth characteristics and neonatal outcomes. J Perinat Med 2019;47:134-7.	Not relevant study design
Rundgren S, Brus O, Bave U, Landen M, Lundberg J, Nordanskog P, et al. Improvement of postpartum depression and psychosis after electroconvulsive therapy: A population-based study with a matched comparison group. J Affect Disord 2018;235:258-64.	Not relevant study design
Ward HB, Fromson JA, Cooper JJ, De Oliveira G, Almeida M. Recommendations for the use of ECT in pregnancy: literature review and proposed clinical protocol. Arch Womens Ment Health 2018;21:715-22.	Not relevant study design
Cuomo A, Maina G, Neal SM, De Montis G, Rosso G, Scheggi S, et al. Using sertraline in postpartum and breastfeeding: balancing risks and benefits. Expert Opin Drug Saf 2018;17:719-25.	Not relevant study design
Dinwiddie KJ, Schillerstrom TL, Schillerstrom JE. Postpartum depression in adolescent mothers. J Psychosom Obstet Gynaecol 2018;39:168-175.	Not relevant study design
Reza N, Deligiannidis KM, Eustis EH, Battle CL. Complementary Health Practices for Treating Perinatal Depression. Obstet Gynecol Clin North Am 2018;45:441-54.	Not relevant study design
Cauli G, Iapichino E, Rucci P, Quartieri Bollani M, Marconi AM, Bassi M, et al. Promoting the well-being of mothers with multidisciplinary psychosocial interventions in the perinatal period. J Affect Disord 2019;246:148-56.	Not relevant study design
Nishi D, Su K-P, Usuda K, Chang JP-C, Chiang Y-JJ, Guu T-W, et al. Differences between Japan and Taiwan in the treatment of pregnant women with depressive symptoms by omega-3 fatty acids: An open-label pilot study. Nutr Neurosci 2019;22:63-71.	Not relevant study design
Clalit Health Services, Ben-Gurion University of the Negev. A Culturally Appropriate Intervention for Preventing and Reducing Postpartum Depression. In; 2018.	Not relevant study design
Medical University of South Carolina. Accelerated iTBS for Post Partum Depression. In; 2019.	Not relevant study design
National Institute on Aging, National Institutes of Health Clinical Center. A Prospective Study of Postpartum Depression in Women With Major Depression. In.	Not relevant study design
Neuronetics. Efficacy and Safety Study of NeuroStar TMS Therapy in Patients With Major Depressive Disorder With Postpartum Onset. In; 2015.	Not relevant study design
Sage T. Expanded Access Protocol of ZULRESSO™ (Brexanolone) Injection for Adult Patients With Postpartum Depression. In.	Not relevant study design
University of Calgary. rTMS for Peripartum Depression. In; 2023.	Not relevant study design
University of Edinburgh, Edinburgh and Lothians Health Foundation, Tommy´s Edinburgh Maternal and Fetal Health Centre, National Health Service Lothian, et al. Enjoy Your Bump : Online Cognitive Behavioural Therapy in Pregnancy. In; 2019.	Not relevant study design
Fallon PC-K, National Center for Advancing Translational S, Dartmouth-Hitchcock Medical C. Video-based Family Therapy for Peripartum Depression in Home Visited Mothers. In; 2018.	Not relevant study design
Tokyo Medical University, China Medical University Taiwan, Japan Society for the Promotion of Science, University of Toyama, Chiba University. The synchronized trial on expectant mothers with depressive symptoms by Omega-3 PUFAs (SYNCHRO): Open Trial. In; 2015.	Not relevant study design
Irct20171227038096N. Attention Training Technique in depression. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20171227038096N1 2018.	Not relevant study design
Kubota C, Inada T, Nakamura Y, Shiino T, Ando M, Aleksic B, et al. Stable factor structure of the Edinburgh Postnatal Depression Scale during the whole peripartum period: results from a Japanese prospective cohort study. Scientific reports 2018;8:17659‐.	Not relevant study design
Olmsted Medical C. Translating Research Into Practice for Postpartum Depression. In.	Not relevant study design
Lewis BA, Gjerdingen D, Schuver K, Avery M, Marcus BH. The effect of sleep pattern changes on postpartum depressive symptoms. BMC Womens Health 2018;18:12.	Not relevant study design
Smith-Nielsen J, Matthey S, Lange T, Væver MS. Validation of the Edinburgh Postnatal Depression Scale against both DSM-5 and ICD-10 diagnostic criteria for depression. BMC Psychiatry 2018;18.	Not relevant study design
Kraus MR, Simonovich SD, Tabb KM. An Integrative Review Examining the Manifestation and Trajectory of Depression from Pregnancy to Postpartum in Childbearing Women. Journal of Nursing Practice Applications & Reviews of Research 2019;9:32-39.	Not relevant study design
Virginia Commonwealth University, Eunice Kennedy Shriver National Institute of Child Health, Human Development. Self-Management of Chronic Depressive Symptoms in Pregnancy. In; 2019.	Not relevant study design
Holopainen A, Hakulinen T. New parents' experiences of postpartum depression: a systematic review of qualitative evidence. JBI Database System Rev Implement Rep 2019;17:1731-69.	Not relevant study design
Dickinson F, McCauley M, Smith H, van den Broek N. Patient reported outcome measures for use in pregnancy and childbirth: a systematic review. BMC Pregnancy Childbirth 2019;19:155.	Not relevant study design
International Centre for Diarrhoeal Disease Research B, Bangor U, Institute of Child H. Effect of Community Based Depression Management and Child Development. In; 2015.	Not transferreble to swedish context
Tomlinson M, Rotheram-Borus MJ, Scheffler A, le Roux I. Antenatal depressed mood and child cognitive and physical growth at 18-months in South Africa: A cluster randomised controlled trial of home visiting by community health workers. Epidemiology and Psychiatric Sciences 2018;27:601-10.	Not transferreble to swedish context
Martinez-Paredes JF, Jacome-Perez N. Depression in Pregnancy. Rev Colomb Psiquiatr 2019;48:58-65.	Other language than specified
Moschner SL, Achtergarde S, Ramsauer B. Treatment Satisfaction of Mothers with Postpartum Depression Concerning Circle of Security Intervention. Praxis der kinderpsychologie und kinderpsychiatrie 2018;67:351‐66.	Other language than specified
Effect of prayer on depression among mothers with premature infants in NICU. Journal of mazandaran university of medical sciences 2018;27:144‐56.	Other language than specified

Appendix 6 Results survey 1

Appendix 7 Results survey 2

Page published June 7, 2020

To top