What barriers and facilitators to self-management are experienced by mothers who wish to breastfeed but require concurrent pharmacotherapy in the first two years postpartum? A mixed-methods systematic review protocol.

Many thanks for taking the time to review this protocol and for providing valuable feedback to improve the quality of our systematic review. We have revised our protocol following this and have individually addressed each comment below. Changes to the text are outlined in bold.

Reviewer comment 1:
This mixed-methods systematic review protocol aims to explore the barriers and facilitators to self-management for women who consider breastfeeding during pharmacotherapy within the first two years postpartum. The rationale for this review is sufficiently detailed, as well as the gap in the evidence it aims to address.
Response:
Thank you.

Reviewer comment 2:
Background: When mentioning two previous reviews about the topic of breastfeeding and pharmacotherapy, I advise the authors to mention that none of these articles follow a systematic review methodology. Therefore, the proposed review would contribute to improving the quality of existing evidence.
Response:
We have revised the final paragraph in the background to acknowledge this. Additionally, another systematic review on a similar topic has since been published (1), and thus has been discussed for further background and context to our review. The publication of this review has not indicated any changes to our methodological approach:
‘Neither of these literature reviews have applied a systematic review methodology, which further emphasises the need for the proposed study. A recently published systematic review however (35), did explore one possible outcome for women who face concurrent breastfeeding and medication needs. This review aimed to identify the percentage of women who discontinue breastfeeding due to pharmacotherapy, which medications may trigger this, and other influencing factors. Authors of this review highlight the need for future research to explore women’s perspectives and experiences in these situations, their contact with healthcare professionals and services, and broader social or cultural contexts which may influence outcomes. Pilgrim and colleagues also suggest that future research use mixed methods designs and a theoretical framework to understand the determinants of women’s decision-making when faced with the need for medication while breastfeeding. The proposed review seeks to address this gap in the literature, and to address all possible outcomes and self-management decisions for women who face the simultaneous need for breastfeeding and medication, including avoidance or discontinuation of medication, or methods aiming to reduce infant exposure to medication through breastmilk.’

Reviewer comment 3:
Research question: The authors have followed the PICO framework, but seem to have struggled to fit their research question into such a framework. Since this review does not consider a comparison, a PIO (population-intervention-outcome) or PEO (population-exposure-outcome) framework seems more appropriate. Furthermore, as no specific intervention is under study, the term “exposure” may be more fitting than “intervention”. I advise the authors to explore alternative frameworks for structuring their research question.
Response:
Thank you for this feedback. The use of the PICO question framework without identified comparators has been identified by both reviewers.  We have revised the paragraph regarding the research question framework in the methods section:
‘The PEO (Population, Exposure, Outcome) tool is used to frame the research question (41)

• Population: Studies which focus on the perspectives of mothers who breastfed their child(ren) at any point in the first two years of life, or women who considered breastfeeding. Studies which exclusively focus on the perspectives of healthcare professionals or other individuals will be excluded.
• Exposure: Studies which address the need for simultaneous breastfeeding and pharmacotherapy. This may be understood as breastfeeding women who considered taking medication, or women who were undergoing pharmacotherapy and then considered breastfeeding. Medication in this context may be prescription-only medication, over-the-counter medication, or dietary supplements.
• Outcome: The barriers and facilitators (or related concepts) to safe and effective self-management of medication use and breastfeeding, as experienced by mothers who face the need for these actions to be done concurrently.’

Reviewer comment 4:
Search strategy: I suggest including the Global Index Medicus database, which is free to consult and covers data from peripheral countries often underrepresented in mainstream databases. Also, authors should consider searching gray literature sources. I am aware that this decision might significantly increase the workload for the authors, but gray literature does provide valuable data for systematic reviews.
Paez, A. (2017). Gray literature: An important resource in systematic reviews. Journal of Evidence‐Based Medicine, 10(3), 233-240.
Response:
Thank you for the suggestions for how we can improve the search strategy of this review.
A search was conducted using the Global Index Medicus database following this recommendation with guidance from a subject librarian to ensure this was done effectively. The following section in the search strategy was updated accordingly:
‘Six electronic databases will be systematically searched: CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE (Excerpta Medica Database), PsycINFO, Medline (Ovid), Maternity and Infant Care, and Global Index Medicus. Databases will be searched using terms related to medication, breastfeeding, women, experience, barriers, and facilitators. Searches will be limited to peer reviewed, empirical studies published in the English language, and not limited by year. Other literature reviews will be excluded. The search strategies used for all six databases are available (39).’
When designing the search strategy for this review, preliminary grey literature searches were carried out, with input from a subject librarian. Available grey literature sources returned hundreds of thousands of papers to be screened, which is unsurprising given the broad population and exposure. Considering the apparent abundance of published literature on the topic, it was decided to limit our literature search to peer-review published papers. Should our current search strategy reveal gaps in the published literature, this could then serve as a guide for a focussed search of grey literature to investigate these further.
These decisions will be acknowledged as possible limitations in the final review if appropriate.

Reviewer comment 5:
Screening and selection: I see your literature search has retrieved over 8000 articles. This volume is exceedingly large for only two reviewers to manage, particularly during the full-text screening and data extraction phases. I recommend involving additional reviewers at later stages of the process, especially if the authors intend to publish the final review in 2025. Also, a third reviewer could be added for conflict resolution during the screening of abstracts, to reduce the workload during the full text stage.
Response:
Thank you for these suggestions. The following has been revised in the screening and selection section:
‘Round 1 will comprise title and abstract screening. Dual independent screening will be carried out by two members of the research team to reduce bias and ensure high quality screening. Disagreements will be resolved by consensus between the two reviewers or following input from a third reviewer if required.
Round 2 will comprise full text screening. Again, results will undergo dual independent screening by two researchers. An additional reviewer may be added if necessary to facilitate screening in a timely manner. Any discordance regarding the inclusion of a paper at this stage will be resolved by consensus between the two reviewers or following input from a third reviewer from the research team if required.’

Reviewer comment 6:
Data extraction: I recommend using a bigger sample for piloting of the data extraction form.
Response:
Thank you for this feedback. This has been considered by the team and the data extraction form will now be piloted on five of the included studies. The following sentence in the protocol has been revised to reflect this:
‘This form will be piloted on five studies identified from the list of included studies in the review and refined following this if necessary.’

Reviewer comment 7:
Quality assessment: Does the MMAT checklist have cut-off points to categorize methodological quality? How are the authors planning to determine whether the quality of the studies is high or low? Moreover, the MMAT checklist is not comprehensive enough to determine risk of bias, which is necessary for a systematic review. Consider including other, more comprehensive tools, such as JBI’s (taking into account that the authors already use the JBI manual to guide their methodology).
Response:
Many thanks for your suggestions regarding this aspect of our review. Following your feedback, we (protocol authors) took time to re-examine both the MMAT and the JBI critical appraisal tools in detail, and this decision was the topic of several lengthy discussions within the research team. There is an acknowledgement in the literature that the terms ‘critical appraisal’, ‘quality assessment’ and ‘risk of bias’ are often used interchangeably (2, 3), with risk of bias used, mainly, in quantitative reviews (2). From an extensive review of the variety of tools/checklists used in other reviews, risk of bias appears be more applicable to quantitative, comparative reviews of effectiveness; given the purpose of our review, and the nature of the studies that we anticipate including, the risk of bias may not be as applicable. We considered the significant numbers of previously published systematic reviews which have used the MMAT effectively for critical appraisal (4-7). Alternative tools, such as the JBI critical appraisal tools, do not specifically account for mixed-methods research papers, which are likely to be included in our review. We considered the possibility of utilising both the JBI and MMAT tools – for example, using JBI critical appraisal tools for solely quantitative or qualitative papers, and using the MMAT for mixed-methods papers, as has been done in some published systematic reviews (8, 9). Additionally, we contemplated using the JBI critical appraisal tools alone, using a qualitative and quantitative assessment tool together to address the different aspects of any mixed-methods study included in our review. Considering the nature of our review, the need to ensure an appropriate tool for mixed-methods papers, and the desire to maintain consistency by appraising all papers with the same tool, the decision was reached that the best approach is to conduct critical appraisal using the MMAT.
The MMAT advises against the calculation of an overall methodological quality score and removed this from their tool (10). Rather, they encourage users to provide more detail on the performance of the study against each methodological quality criterion to inform the quality of each study included in the review.

Reviewer comment 8:
Data synthesis: Are the authors planning to conduct a meta-analysis of the quantitative data? If so, the methodology for this analysis should be clearly outlined.
Response:
The authors do not plan to conduct a meta-analysis of the included quantitative data.   

Reviewer comment 9:
Public and patient involvement: Please clarify the role of the PPI panel in the review process. The current wording only states that they will be “consulted” during several stages, which is vague. A more explicit explanation of their specific contributions is needed.
Response:
The PPI panel were invited to validate the research question and the need for this systematic review prior to publication of this protocol. During the review process, PPI contributors will be involved in research tasks of their choice, with support and training, where needed. For example, they may be involved with interpreting study findings through participation in workshops, or in outreach activities to share the study findings.

References:
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