Exploring the barriers and enablers experienced by people with Cystic Fibrosis and their healthcare professionals in accessing, utilising and delivering maternity and Cystic Fibrosis care during the pre-conception to post-partum period: A mixed methods systematic review protocol.

Background Cystic Fibrosis (CF) is an autosomal recessive inherited multi-system disease that primarily affects the lungs and digestive system. New drug therapies and treatments are improving the lives of many people with CF. With improved life expectancy and increased quality of life, many people with CF are now contemplating parenthood and becoming pregnant, an aspiration that decades ago was almost unheard of. Given this quickly evolving and more positive health landscape, it is vital to understand how people with CF experience the care they receive whilst accessing and utilising fertility and maternity services. It is also important to explore the experiences of healthcare professionals involved in providing care during this period. The overall aim of the mixed-methods systematic review will be to explore the barriers and enablers experienced by people with CF and the healthcare professionals involved in their care in the pre-conception to post-partum period. Methods The proposed review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for convergent integrated mixed methods systematic reviews. A systematic search of Medline (Ebsco), Cinahl, Embase, APA PsychINFO and Cochrane Library from inception to February 2022 will be conducted. Quantitative, qualitative and mixed methods studies pertaining to the experience of pre-conception to post-partum care for people with CF and their healthcare professionals will be included. Two independent reviewers will screen titles, abstracts and full texts with disagreements being resolved by a third reviewer. Conclusion This review will help to determine the potential barriers and facilitators experienced by people with Cystic Fibrosis and the health care professionals involved in their care during the pre-conception to post-partum period. The results will be of benefit specifically to the CF population and their healthcare providers when planning further studies in the area of fertility and pregnancy for this population and when delivering care.


Introduction
Cystic Fibrosis (CF) is an autosomal recessive, inherited multi-system disease that primarily affects the lungs and digestive system. Once considered a disease of childhood, improved therapies and better management has led to a changed demographic in the CF population, and many adults with CF are now experiencing improved quality and quantity of life 1,2 .
The first reported incident of pregnancy in a person with Cystic Fibrosis (CF) was in 1960 3 . The deterioration of the patient two months before delivery and her death soon after, established pregnancy as an undesirable and dangerous path for patients with CF. At a time where treatment options were limited and CF was primarily seen as a paediatric illness, the concept of pregnancy within this context as being an unfavourable complication is unsurprising. Much of the discourse in the following decades has focused on the maternal outcomes in pregnancies of people with CF (pwCF), the potential risks and complications of pregnancy in CF as well as guidelines for the management of patients with CF in pregnancy 4-6 .
With improved care and the advent of Cystic Fibrosis transmembrane conductance regulator (CFTR) modulator therapies, the landscape for many pwCF has changed dramatically, meaning that pregnancy and parenthood are now achievable aspirations. In a survey of 188 young women with CF in the US, seventy-eight percent expressed a desire to have children in the future 7 . This is in fact evidenced in recent years as many countries have seen increases in the numbers of pregnancies being recorded in international CF registries 1,2 .
Recent data suggest that pregnancy is now a considered choice for women with CF and they give consideration to the multi-factorial impacts the decision to conceive may have on their health status and wellbeing 8 , even before addressing it with their healthcare providers 9 . It is therefore essential to assess how this relatively recent phenomenon is experienced by people with CF and the healthcare professionals involved in their care in order to best provide care in the future.
Much of the literature that exists on pregnancy and CF is weighted in terms of outcomes and guidelines and is focused on the physiological and medical implications that CF has on maternal and foetal outcomes, or in terms of the effects pregnancy has on CF baseline parameters -such as pulmonary function 5,6,10-12 . While these studies often highlight how pregnancy in the main is well tolerated by pwCF, analysis of the experience of pregnancy by this population needs further investigation.
With a changing reality, more people with CF are navigating this new terrain and desire open communication around issues of sexual and reproductive health and pregnancy decision making in CF. A study on contraceptive options in CF, notes the high rates of unintended pregnancy in women with CF 13 , and another on reproductive health in CF asserts the need for improved communication as means of facilitating better decision making pre-conception 14 . Hughan postulates that 'Reproductive health decision-making tools should be explored as a way to enhance patient-provider communication surrounding reproductive health topics' 15 . A number of studies highlight how women with CF seek up to date and reliable information when planning a pregnancy or whilst pregnant 10,11 especially in relation to the management and potential contra indications of their medications as well as advice on treatments and adherence 16 .
The importance of collaborative care between CF and highrisk obstetrical care teams was highlighted in a recent review 17 . The lack of detailed information, collected by the large CF registries on delivery and foetal outcomes was also highlighted in this study 17 .
Analysing and synthesising the lived and evolving experience of pwCF and their healthcare professionals of pre-conception to post-partum care and identifying the barriers both groups encounter during this period will help to elucidate areas which require attention and future planning. Identifying enablers that add to the experience in a positive and practical way will

Amendments from Version 1
We would like to extend our thanks to the reviewers for taking the time to provide suggestions and commentary and for their positive and constructive feedback. We have made some minor changes to the manuscript and address them on a point by point basis in the responses section.
We have addressed both the reviewers' comments to the manuscript and the following changes were made to the paper since the previous version:

Introduction:
• We have further detailed and clarified our intent to adapt the definitions of barriers and enablers and include our intent to use the framework employed by Smith et al. when considering the outcomes at micro, ,meso and macro levels. This is now detailed in the introduction section.

Methods:
• We added our intent to use MMAT, a mixed methods critical appraisal tool for the critical appraisal of studies which are mixed methods in design.
• We have added more detail on the data extraction process. This includes the addition of certain categories of data such as main results, recommendations and evidence gaps.
• We have also given more specific detail on the process of piloting the data extraction template.

Patient and Public Involvement:
• We have added some detail in this section to reflect the fact that this review is part of a larger research project which will involve an empirical study which will explore the experiences of pwCF and their healthcare teams in Ireland as they access, utilise and deliver pre-conception to post-partum care. This includes details on how PPI has been and will be embedded in the empirical study.
Any further responses from the reviewers can be found at the end of the article also add to the growing bank of recommendations for health service provision in the future 18 . Comparing the experiences of both groups will also serve to highlight any gaps that may exist in how each group experiences accessing, utilising or delivering care in the pre-conception to post-partum period.

Review question
The mixed methods systematic review will seek to answer what are the barriers and enablers encountered by people with CF and the healthcare professionals involved in their care in accessing, utilising and delivering pre-conception, antenatal, intra-partum and post-partum care (pre-conception to post-partum care)? This will be addressed through two objectives; i) to explore the experiences of people with Cystic Fibrosis while accessing and utilising pre-conception to post-partum care; ii) to explore the experiences of healthcare professionals involved in providing fertility, obstetric and Cystic Fibrosis care to people with CF in the pre-conception to post-partum period.

Inclusion criteria Population
The review will consider studies that include people with CF who have experienced any or all stages of maternity care which we define as including, pre-conception, antenatal, intra-partum and post-partum care. The review will also consider studies that include healthcare professionals involved in delivering care, be that CF specific care or fertility and obstetric care to people with CF during this time.

Phenomena of interest
The experience under study for this review will be that of fertility, pregnancy, delivery and postnatal care in people with Cystic Fibrosis. The review will consider studies that investigate the pre-conception experience to post-partum experience for people with CF and health professionals that provide care to people with CF during this time.
Barriers will be identified as any perceived or experienced construct, attitude, or challenge, either systemically, internally or otherwise that impedes the experience of accessing, utilising or delivering, pre-conception to post-partum care. Enablers will be identified as any perceived or experienced facilitator of positive experience in accessing, utilising or delivering pre-partum to post-partum care. Approaching the concepts of barriers and enablers through a macro, meso and micro lens will also enable the identification of challenges and facilitators as they arise at different levels. This strategy was employed by Smith et al in an Australian study which sought to identify barriers and enablers which affected extended scopes of practice in rural Australia in relation to nurse practitioners. As such this lens may prove a suitable approach in identifying barriers and enablers as experienced by pwCF and healthcare professionals (HCPs) 19 . Although focusing on the HCP perspective the authors provide an adaptable and employable set of definitions for the three stages that will be addressed in this study and barriers and enablers will be identified and adapted using the framework employed by Smith et al..

Context
Given the incidence of pregnancy is rising in this population internationally 1,2 , all geographical locations and settings will be considered. Settings may include but are not limited to; hospitals, clinics, community care or primary healthcare settings. Settings will be included if they are identified as providing fertility, obstetric, maternity or Cystic Fibrosis care to pwCF in the pre-conception to post-partum period.

Types of studies
The review will consider quantitative, qualitative and mixedmethods studies (if it is possible to clearly extract the quantitative and qualitative components of such studies).
Qualitative studies will include designs such as descriptive qualitative design, phenomenology, grounded theory, ethnography, participatory and action research, and feminist research. This will include interviews, focus group discussions, ethnographic data and journaling that explore the experiences of pwCF and their HCPs during the pre-conception to post-partum period.
Quantitative studies will include observational studies (e.g. cohort studies, cross-sectional studies and case-control studies). The quantitative component of this review will consider studies that include questionnaires that are aimed at ascertaining the experience of pwCF or HCPs in accessing, utilising or providing care during the pre-conception to post-partum period. Such studies may report sociodemographic data which may help to provide a broader picture about how sociodemographic factors can influence the experience of accessing, utilising or delivering care in pwCF during the pre-conception to post-partum period.
The qualitative and quantitative components of this review will consider studies that investigate how the barriers and enablers perceived or encountered by people with CF and their healthcare professionals during the pre-conception to post-partum period, contribute to their experience of accessing, utilising and delivering care.
To correspond with the first reporting of a case of pregnancy in a person with CF in 1960, studies published from this year to the present will be included.

Methods
The review will be conducted in accordance with the JBI methodology for mixed methods systematic reviews, following a convergent integrated approach 20 . This approach suggests that when a review question is answerable by both quantitative and qualitative data that 'an integrated approach to synthesis is undertaken' and data transformation should be employed 20 .
Quantitative and qualitative data which presents or explores the experiences of pwCF and healthcare professionals in accessing, utilising and delivering fertility, maternity and CF care during the pre-conception to post-partum period will be examined in order to ascertain any perceived or experienced barriers and enablers relating to the above mentioned period.
A preliminary search of Medline and Cinahl has been undertaken and to the best of our knowledge no existing or ongoing mixed method or individual systematic reviews on the topic have been identified.

Search strategy and Information Sources
An initial limited search of MEDLINE and CINAHL will be undertaken to identify articles on the topic and to inform the search strategy. A librarian from the Royal College of Surgeons in Ireland has assisted in the development of the search strategy. The text words contained in the titles and abstracts of relevant articles, and the index terms used to describe the articles will be used to develop a full search strategy for Medline, Cinahl, Embase, APA PsycInfo and Cochrane Library. The search strategy, including all identified keywords, and index terms relating to barriers and enablers in accessing, utilising and delivering pre-conception to post-partum care for pwCF will be adapted for each included information source. The reference list of all studies selected for critical appraisal will be screened for additional studies.

Study selection
Following the search, all identified citations will be loaded into EndNote X9 and duplicates removed. Titles and abstracts will then be screened by two independent reviewers for assessment against the inclusion criteria for the review using Covidence software. Potentially relevant studies will be retrieved in full and their citation details imported into Covidence. The full text of selected citations will be assessed against the inclusion criteria by two independent reviewers. Reasons for exclusion of full text studies that do not meet the inclusion criteria will be recorded and reported in the systematic review. Any disagreements that arise between the reviewers at each stage of the study selection process will be resolved through discussion, or with a third reviewer. The results of the search will be reported in full in the final report and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram 21 .

Assessment of methodological quality
Quantitative studies selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardised critical appraisal instruments from JBI 22 .
Qualitative studies selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using the standardised critical appraisal instrument from JBI 23 .
Mixed methods studies will be appraised using MMAT, a mixed methods critical appraisal tool 24 .
Authors of papers will be contacted to request missing or extra data for clarification purposes, where required. If disagreements arise between the reviewers, they will be resolved through discussion, or with a third reviewer. To capture the experience of both people with CF and HCPs, all studies, regardless of the results of their methodological quality, will undergo data extraction and synthesis (where possible). The results of the critical appraisal will be reported in narrative form and in a table.

Data extraction
Quantitative and qualitative data will be extracted from studies included in the review by two independent reviewers, using Covidence software.
The data extracted will include details on both populations identified in the study. In the case of HCPs, details on the specific area of care they are associated with, i.e. CF specific care or obstetric care etc. Further data on the specific role within the care team will also be identified, i.e. Consultant, CF Nurse, Midwife, Psychologist etc. In terms of the data regarding pwCF, details on age, gender and service accessed or utilised will be included where available. Details on study methods and design, and results relating to experience of accessing/utilising or providing pre-conception to post-partum care will be recorded. Details on barriers/enablers as experienced/perceived by pwCF or HCPs will also be recorded. Details on specific settings will be noted, including but not limited to; fertility clinic, maternity hospital, primary care centre, CF centre, and acute hospital. Details on the particular stage of care (pre-conception, ante-natal, intra-partum and postpartum), and geographical location will also be recorded. Main results, recommendations and evidence gaps will also be extracted.
Data extracted from quantitative studies will include any data-based outcomes relating to the experience of pwCF and the HCPs involved in the care of pwCF during the specified period. Qualitative data will be assessed and categorised by theme and sub-theme relating to the review question and a quotation from the direct quote or observation from the study in question will be provided. The sample data extraction chart is included and will be refined following piloting in 2023. A sample of five articles which have progressed to full text screening will be piloted by two reviewers.
The lead author will review all articles and two other reviewers will sample half the texts each. The data extraction template will be completed by two reviewers. The piloted extraction sheets will be reviewed by the two reviewers and any conflicts will be resolved by consensus or by decision of a third reviewer.

Data synthesis and integration
The review will follow a convergent integrated approach according to the JBI methodology for mixed methods systematic reviews using JBI SUMARI 20 .
Once data extraction is complete the quantitative data will be transformed into 'qualitised' data, whereby textual descriptions and narrative interpretation will be used to transform the quantitative data. This will enable integration with data extracted from the qualitative studies and the qualitative components of mixed methods studies 20 . This particular approach involves gathering the qualitised data with the qualitative data. This assembled data will then be categorised and pooled together to create a set of integrated findings.

Study status
At the time of publication of this mixed method systematic review protocol, search terms have been piloted and are currently being refined. Full database searches will be run in February 2022.

Discussion
The changing landscape of maternal health in the context of Cystic Fibrosis care is worthy of exploration. Though now not an uncommon experience as once it was, it is vital that we understand how the experience of accessing, utilising and delivering all aspects of maternal care is experienced by pwCF and their HCPs. A systematic review of the literature pertaining to the lived experiences of pwCF and their HCPs will illuminate the current barriers and enablers as experienced by both groups and will serve to inform future policy and practice in this dynamic area. It may also illuminate experiences of barriers and facilitators experienced by patients and healthcare professionals in other similar populations as there is potentially areas of convergence between pwCF and other patient populations living with physical impairments who utilise pre-conception to post-partum care.

Patient and Public Involvement
Adults with CF who have accessed and utilised pre-conception to post-partum care and healthcare professionals with experience in delivering care to pwCF in the pre-partum to post-partum period will be involved in the interpretation and dissemination of the findings of the review. While there has been no Public and Patient Involvement in the development of this protocol, the lead author is a person with Cystic Fibrosis who has accessed and utilised pre-conception to post-partum care.
This review is one part of a larger research project. This mixed methods study will involve an empirical study exploring the experience of pre-conception to post-partum care for pwCF and the HCPs involved in their care in Ireland.
To date the author and lead researcher has established an expert panel including pwCF from Ireland to inform the study from the protocol stages. PPI will be embedded in the study from protocol development, interview and survey guides, interpretation of findings through to dissemination stages.

Data availability
Underlying data No underlying data are associated with this article.

Open Peer Review
review. Generally speaking its pretty rare for authors who published a study (sometimes years ago) to respond to request for missing or extra data. What will the authors of this systematic review do if data is not acquired from authors whom they try to contact?
Otherwise, I have no further comments and wish the authors the best success in completing this systematic review.

Competing Interests:
No competing interests were disclosed.
Reviewer Expertise: Sexual and reproductive health in cystic fibrosis, patient engagement research methods, systematic reviews I think the authors could better justify their rationale for and define their broad outcomes under barriers and enablers. They mention looking at these outcomes at macro, mesa and micro levels, but what is meant by that is unclear. It seems that if barriers include constructs, attitudes, perceived challenge that such outcomes represent more of a micro level, as opposed to something more macro, like the health system or how care is paid for?
I appreciate that the authors have patient and public involvement. I encourage participants that represent different health systems globally, as access to care differs from country to country. The authors should also be aware that there are initiatives coming from pwCF who have done work in this area and whose publications may not show up under the proposed search strategy. Here is an initiative by pwCF: https://cfreshc.org/srh-guide/ Is there an opportunity to also include reports from the grey literature (such as CF Roundtable) -pwCF-driven newsletter whereby pwCF report their experiences (with stories over the past year that specifically include SRH stories) that may be enlightening in terms of fully understanding the barriers and enablers to care in this arena? Sufian S, Mentch L and Godfrey EM. Is the rationale for, and objectives of, the study clearly described? Partly

Are sufficient details of the methods provided to allow replication by others? Partly
Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Sexual and reproductive health in cystic fibrosis, contraception abortion, patient engagement methods, systematic reviews I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Author Response 24 Apr 2023

Jen Balfe
Thank you very much for taking the time to read and respond to our systematic review protocol. We appreciate your constructive and considered feedback. We have addressed your suggestions and advice in our revised manuscript.
1) Thank you for highlighting any lack of clarity here in terms of the outcomes relating to barriers and enablers. The authors were informed by the approach of Smith et al., (2019) who, although focusing on the Health Care Professional perspective provide an adaptable and employable set of definitions for the three stages that will be addressed in this study. Their definitions and our intent to adapt them accordingly for our study is outlined now on page 5 paragraph 4.
2) The authors are aware of the excellent and collaborative initiatives by CFRESHC and others and considered at the early stages of the protocol development including such resources.
From an initial scoping review, the lack of peer reviewed articles on experience in comparison to the amount of peer reviewed articles on outcomes and guidelines, highlighted the need to conduct this review.
This review is one part of a larger research project which was co-funded by the Irish Research Council and Cystic Fibrosis Ireland. Another arm of the project will involve an empirical study exploring the experience of pre-conception to post-partum care for pwCF and the HCPs involved in their care in Ireland.
To date the lead author and lead researcher has established an expert panel including pwCF from Ireland to inform the mixed-methods study from the protocol stage. Public and Patient Involvement(PPI) will be embedded in the study from protocol development, interview and survey guides, interpretation of findings through to dissemination stages.
This information is now included in the section referring to Public and Patient Involvement on page 9. In order to ensure that the scope of the review was not too broad as to make it unachievable within the time frame to feed into the empirical study, it was decided that the primary focus would be on peer reviewed empirical studies. When disseminating the results of the findings of the review, the authors will ensure they share their findings with the global CF community through social media and publications/presentations.
3) As outlined above it was felt that it was important to assess the peer reviewed and empirical literature first so as to establish the context of fertility and pregnancy in CF in this sphere. Following the JBI approach we will use critical appraisal tools to assess the current literature pertaining to the topic.

Lyndsay A. Alexander
School of Health Sciences, Robert Gordon University, Aberdeen, UK I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Author Response 24 Apr 2023

Jen Balfe
Thank you very much for taking the time to read and respond to our systematic review protocol. We appreciate your constructive and considered feedback. We have addressed your suggestions and advice in our revised manuscript.
1) Due to constraints on time and resources the review will focus only on English language studies. Given the sometimes complex and medical nature of the expected articles it was considered best not to rely on Google translate for accuracy purposes especially when quotes from participants in studies being reviewed are to be included. The JBI approach is to be as inclusive as possible and the authors recognise that not including languages will be a limitation of the study, and this will be highlighted when findings are being written up.
2) Covidence 2.0 software will be used. In keeping with the JBI approach to extracting findings, the data extraction will follow two phases. Study characteristics such as country, setting, stage of care and population will be included. To this we have added main results, evidence gaps and recommendations and this is included now on page 8, paragraph 1 under the heading Data Extraction.
In the second phase, findings will be extracted. Findings will be extracted alongside illustrations/quotes from the text that demonstrate where the finding originated. Findings will be coded, after which themes will be developed. As noted on page 8 under Data Extraction two independent reviewers will be involved in coding, with disputes being reached by consensus or with a third reviewer.
The findings and illustrations will be extracted verbatim from the paper completely unedited. Illustrations may include supporting data, fieldwork observations or verbatim words of participants.
On page 8 under 'Data Synthesis and Integration' the process of combining the qualitative data with the qualitized data into categories is detailed further.
3) Yes there are plans to pilot the data extraction sheet to establish reliability. A sample of five articles which have progressed to full text screening will be piloted by two reviewers. We have added this, page 8, paragraphs 2 and 3.
The lead author will review all articles and two other reviewers will sample half the texts each. The data extraction template will be completed by two reviewers. The piloted extraction sheets will be reviewed by the author and two reviewers and any conflicts will be resolved by consensus or by decision of a third reviewer. This is now added to page 8 paragraph 3.
Two authors will be involved in the synthesis of findings. Any conflicts will be involved by a consensus agreement or in consultation with a third reviewer.
4) The authors intend to use the Mixed Methods Appraisal Tool (MMAT) for the critical appraisal of this study design. This is now included in the section 'Assessment of methodological quality'.

5) A PPI panel of pwCF and
HCPs and other stakeholders will be consulted in the interpretation of the findings. CF Ireland will use their social media accounts to raise awareness and invite discussion on the findings.
One author on this study is a HCP with expertise in delivering care to pwCF during pregnancy, the lead author is a pwCF who has been pregnant twice. A third author is the senior research and policy coordinator with the charity and advocacy organisation Cystic Fibrosis Ireland. All three authors have informally consulted with other stakeholders in the field, including pwCF, HCPS and charity representative bodies.
As a pwCF the author is deeply aware of the importance of participation and collaboration between HCPs and pwCF to further the research aims of pwCF and hopes that in doing so she will elucidate the potential for co-creation and design of research in a way that is fully participatory and engaged and moves beyond the trope of tokenism.
6) As stipulated on the HRB Open Research guidelines pertaining to supplementary material, 'all materials associated with a manuscript are visible, FAIR, and subject to peer review, HRB Open Research does not accept supplementary material. Additional materials that support the key claims in the paper but are not absolutely required to follow the study design and analysis of the results, e.g. questionnaires, or supporting images or tables, can be included as extended data. Extended data should be deposited in an approved repository and listed as part of the data availability statement.' As such the search strategy and data extraction sheet are published on OSF.