A standardised individual unsupervised water exercise intervention for healthy pregnant women. A qualitative feasibility study

A standardised individual unsupervised water exercise intervention for healthy pregnant women. A qualitative feasibility study

Sexual & Reproductive Healthcare 5 (2014) 176–181 Contents lists available at ScienceDirect Sexual & Reproductive Healthcare j o u r n a l h o m e p...

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Sexual & Reproductive Healthcare 5 (2014) 176–181

Contents lists available at ScienceDirect

Sexual & Reproductive Healthcare j o u r n a l h o m e p a g e : w w w. s r h c j o u r n a l . o r g

A standardised individual unsupervised water exercise intervention for healthy pregnant women. A qualitative feasibility study Mette G. Backhausen a,b,*, Malene Katballe a, Helena Hansson a, Ann Tabor c,d, Peter Damm d,e, Hanne K. Hegaard a,d a Department of Obstetrics, The Juliane Marie Centre for Women, Children and Reproduction, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark b Department of Gynecology and Obstetrics, Roskilde University Hospital, Køgevej, 4000 Roskilde, Denmark c Center of Fetal Medicine, Department of Obstetrics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark d The Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen, Denmark e Center for Pregnant Women with Diabetes, Department of Obstetrics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

A R T I C L E

I N F O

Article history: Received 19 May 2014 Revised 15 September 2014 Accepted 19 September 2014 Keywords: Feasibility Intervention Pregnancy Water exercise Experience

A B S T R A C T

Introduction: Low back pain during pregnancy is common and associated with sick leave. Studies suggest that exercise may reduce low back pain during pregnancy. Before carrying out a randomised controlled trail with individual water exercise as intervention a qualitative feasibility study was done. Objective: To explore women’s views and experiences of the acceptability and benefits of and possible barriers to the standardised individual unsupervised water exercise intervention. Materials and Methods: Eleven women were interviewed after participating in a water exercise intervention. Content analysis was used. Results: Four main categories emerged: motivation to participate, attitudes towards the exercise programme, perception of benefits, and acceptability of supportive components. The women had a desire to stay physically active during pregnancy and found water exercise a suitable, type of exercise to perform during pregnancy. The intervention was experienced to have benefits on both their physical health and their mental well-being. Crowded swimming pools were perceived as the greatest barrier. Conclusion: It is feasible to perform a RCT using the described intervention. The intervention was accepted by the participants because it supported their desire to be physically active during pregnancy. The main barrier was crowded swimming pools and this issue must be addressed in a future RCT. © 2014 Elsevier B.V. All rights reserved.

Introduction Low back pain occurs frequently during pregnancy. Studies on the topic have been conducted on three different continents, and depending on the method and definition used, the prevalence varies from 50 to 70% of all pregnant women, indicating a general problem [1–3]. The prevalence of low back pain increases with gestational age and has been shown to be an important contributing factor to sick leave during pregnancy [4,5]. Back pain also has a negative impact on the ability to perform daily chores [6–8]. It is therefore important to focus on how to prevent or reduce low back pain in pregnant women.

* Corresponding author. The Research Unit Women’s and Children’s Health, Section 7821, The Juliane Marie Centre for Women, Children and Reproduction, Rigshospitalet, DK-2100 Copenhagen, Denmark. Tel.: +45 21 64 11 20. E-mail address: [email protected] (M.G. Backhausen). http://dx.doi.org/10.1016/j.srhc.2014.09.005 1877-5756/© 2014 Elsevier B.V. All rights reserved.

Some studies suggest that exercise decreases the pain intensity of low back pain during pregnancy [1,9–11]. However, most women reduce the intensity of exercise and time spent exercising during pregnancy, and many women do not exercise [12–14] despite both national and international recommendations advising pregnant women to be physically active at a moderate intensity level for at least 30 minutes per day [15,16]. The reason for this reduction in physical exercise level can be attributed to the growing body, pregnancy complications or a sense of insecurity while exercising [17,18]. Exercise methods such as swimming and exercising in water have been shown to be increasingly used during pregnancy, because pregnant women feel comfortable and safe performing exercises in water [19]. Two Swedish randomised intervention studies found that water exercise during pregnancy can diminish low back pain and reduce the number of days spent on sick leave [9,10]. In both studies, the intervention was supervised in groups and took place during the day at a scheduled time. Neither of the studies explored the participants’ views and experiences with the intervention. These results

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indicate that supervised water exercise may have a beneficial effect on healthy pregnant women, and in Denmark, an unsupervised water exercise programme for healthy pregnant women, AquaMama, was implemented in public swimming pools in 2011 [20]. However, there is no evidence on the effect of unsupervised water exercise programmes on the intensity of low back pain and the number of days spent on sick leave. We therefore developed an unsupervised individual water exercise programme on the basis of AquaMama supplemented with supportive components to be tested in a randomised controlled trial (RCT). We have performed a pilot-test of the intervention to examine its feasibility before initiating a large RCT [21]. The aim of this qualitative feasibility study was to explore women’s views and experiences of the acceptability and benefits of and possible barriers to the standardised individual unsupervised water exercise intervention. Materials and methods A descriptive qualitative study was conducted. The results from the quantitative part of the pilot study will be published elsewhere. Setting Pregnant women were recruited to the water exercise intervention from the Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark between 10 January and 10 February 2013. The women were selected on the basis of their due date to time the water exercise intervention from the 20th to 32nd week of gestation. Healthy, pregnant women, with a single foetus who were ≥ 18 years old and between gestational weeks 16 and 17 were eligible for recruitment. The exclusion criteria were as follows: women with medical or obstetrical conditions contraindicating physical activity, women who were diagnosed in the present pregnancy or had formerly been diagnosed with pelvic girdle pain, BMI > 29 kg/m2, non-Danish speaking women and women with substance abuse problems. In all, 57 pregnant women were invited to participate in this pilot intervention, and 30 chose to participate. Of these 30 women, 11 were selected for the qualitative interview. The women completed a questionnaire at the baseline interview and informed consent was obtained. Another questionnaire was completed at follow-up at 32 weeks. Intervention We chose the AquaMama concept developed by the Danish Arthritis Association for healthy pregnant women as our intervention [20]. The six standardised exercises are available in 130 public swimming pools distributed throughout the country and can be performed during normal opening hours. The exercises are developed to strengthen the larger muscle groups (legs, abdominals, back, hips, buttocks, arms and shoulders) during pregnancy. Before starting the training, the participants were invited to attend an instruction session at an indoor swimming pool. The session was led by MB and HKH and a specially trained coach. At this session, the participants were given theoretical counselling about general exercise recommendations during pregnancy and shown short movie clips of the six AquaMama water exercises. Subsequently, the women were given practical instructions by the coach while performing the exercises in water. The participants were encouraged to keep a training logbook that was handed out during the introduction session. At the end of the session, the participants received food and beverages. During the 12 week training period, women received weekly emails with questions on how the training worked for them and

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whether they had any problems with any of the exercises. These emails were meant to have a motivating and supportive effect. One training session consisted of four laps (100 m) of swimming as a warm up followed by the six AquaMama exercises. Each exercise was illustrated on a board with the number of repetitions for the specific exercise. There were usually between 15 and 20 repetitions of each exercise, which were all performed twice. After completing the exercises, the participants swam another four laps. The six exercises required two dumbbells, a belt and a kickboard. (A video of the exercises is available at www.youtube.com) search for AquaMama. The exercises were performed at a moderate pace corresponding to Borg scale 11–13 and 14–15 [22]. Each training session was estimated to last approximately 45 min. The participants were asked to exercise twice a week for a period of 12 weeks. No limitations were placed on other physical exercises outside the water exercise programme. The study protocol was approved by the Ethics Committee (H-3–2012-132) and by the Danish Data Protection Agency (j.nr.:2007-58-0015). Participants Of the 30 participating women, a purposeful sample of 11 women was selected. We selected information-rich cases for in depth interviews to ensure a wide range of experiences with the intervention [23,24].This included participants with high and low compliance with the training intervention, primiparous and multiparous women, and participants with and without low back pain. Sample size was chosen due to the study purpose and available time and recourses. The women were invited by email to participate in an interview and a separate informed consent was obtained from the women participating in the interviews. A thematic semi-structured interview guide was used to explore the participants’ views and experiences on the following topics: motivation for participation, acceptability of the training intervention, possible benefits or barriers of the training, and practical issues. Data were collected through individual telephone interviews [25]. Each interview began by requesting informants to answer the same introductory question and following the open ended questions in the interview guide. The interviews were conducted one to two weeks following completion of the intervention and were undertaken by MK in May 2013. All interviews were audiotaped. The interviews varied from 15 to 35 minutes and were transcribed verbatim by a person with no other connection to the project. Data analysis The transcribed text was analysed within each topic of the interview guide, using content analysis according to Burnard’s 14 steps [26] with the exception of step 11, which concerns informant checking. The analysis process involves identifying, coding and categorising the primary patterns emerging from the collected data [26]. The transcripts were read trough to become familiar with the data and to get a sense of the experiences of the participants. The first transcript was analysed by MB, XX and HKH to ensure a similar analytical approach. The analysis of the remaining transcripts was divided between MB and MK, and each was independently analysed. Transcripts were read through again, and meaningful units were put into a coding scheme. MB and MK met several times to ensure similarity of the coding, and disagreements were discussed and necessary adjustments made. The coding resulted in a list of higherorder headings. These higher-order headings were grouped by removing repetitious or very similar categories and merging categories and subcategories, and a new list of categories was thereby generated.

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Table 1 Overview of analyses, examples. Quotes

Codes

Sub-categories

Categories

I thought that when I become pregnant, it will become more difficult to be physically active, it would be nice with another type of exercise (I:1) On the days where I exercise in water I feel happier and have more energy (I:3) Sometimes you feel that you are in the way, if you are the only one doing the exercises, you get the sense that the other swimmers become annoyed (I:6) It was a good feeling to be able to talk to someone in person rather than writing emails (I:9)

When I become pregnant I would like to perform another type of exercise Feel happier and have more energy Sometimes you feel that you are in the way

Desire to continue physical activity

Motivation to participate

Sense of mental wellbeing

Perception of benefits

Barriers

Attitudes towards the exercise programme

Satisfaction with personal contact

Acceptability of supportive components

Good feeling to talk to someone in person

The final main categories and sub-categories were generated within the topics of the interview guide in cooperation with author HKH. During the entire process, MB, MK and HKH repeatedly reread the original transcript to avoid misinterpretation and to ensure that the context of the coded sections was maintained and to make sure that the list covered all aspects of the interviews (see Table 1). Pre-understanding Before initiating the study, the authors’ (MB, MK and HKH) preunderstanding was described. The authors’ experience came from years of clinical practice in midwifery, and was generated based on a joint interest in the role of physical activity during pregnancy in general. HKH has conducted research on pregnancy and physical activity and also has experience with qualitative research. This preunderstanding was discussed during the study period to decrease the risk of subjectively influencing the study. Results The following four main categories emerged: motivation to participate, perception of benefits, attitudes towards the exercise programme, and acceptability of supportive components. The 11 subcategories are listed under the main categories. Motivation to participate When the women were asked what motivated them to participate, the following three sub-categories emerged: desire to continue physical activity, availability and expecting health benefits. Desire to continue physical activity The women were motivated to participate because they wanted to continue being physically active during pregnancy. Several women expressed that it was important for them to be able to continue an active lifestyle during their pregnancy. Most of the women were already physically active and had been on the lookout for a different type of exercise suitable for pregnant women as they did not find activities such as jogging manageable longer. Some women had already begun swimming because this type of exercise could be performed during pregnancy. The fact that the intervention consisted of water exercises was appreciated by the women even though they did not normally exercise in water. “I have always been a physically active person before I became pregnant. I thought that this was a good way for me to continue to be so, as I become bigger” (I:8) “I thought that I would find it more difficult to exercise during pregnancy and that a new kind of exercise would be a good idea” (I:1)

Availability The availability of the exercise programme was mentioned by almost all of the interviewed women. They found it to be a great opportunity to start exercising during their pregnancy. Some women expressed that they chose to participate because the lessons were free of charge and furthermore the timing of the inclusion seemed to be perfect based on their pregnancy stage. Women were motivated by the opportunity to participate in a research project. They wanted to support the research and thought it would be fun to participate. Furthermore they felt that participating in a research project would encourage them to get the exercise done. “It was perfect timing, right at the point, where I wanted to start” (I:5) Expecting health benefits The majority of the women were motivated due to expectations of health benefits for both mother and child. These benefits include having a better pregnancy, feeling good and staying fit during pregnancy. Some women were focused on the prevention of certain common pregnancy complications and other women on already experienced discomforts. “I expected that it was beneficial for both me and the baby to participate in this kind of exercise” (I:7) “I would like to stay healthy during my pregnancy and hopefully prevent the low back pain I suffered from in my first pregnancy” (I:4) Furthermore, some women expressed being motivated due to earlier experienced anxiety, knee injury or low back pain and the hope of preventing or reducing these conditions. Perception of benefits The women were asked what they felt they had gained from the water exercise during the project period. The following two subcategories emerged: improving physical health and sense of mental well-being. Improving physical health The women described various physical and mental benefits experienced from the exercise. A feeling of doing something good for the body and the unborn child were often implied. Some felt that they could maintain body strength and felt a strengthening effect on the arms and pelvis. It was also important that the exercise was cardiovascular, because this increased the sense of benefit. The exercise was experienced as a way to loosen up muscles in the back. The women experienced less weight gain during pregnancy, were able to sleep better at night and having an easier pregnancy. Other pregnancy related discomforts such as less pain,

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fewer false contractions and less oedema on the days of the exercise session were also experienced. “Just getting in the water and use your body loosens up, I think” (I:10) “I experience less back pain, and I believe that it is due to the exercise” (I:2) Sense of mental well-being Some women found it very pleasant to be in the water; it gave them joy, a sense of wellness and an opportunity to spend some time for themselves. Experiences of a positive effect on the mood and mental resources in general, of an increased energy level and decreased anxiety were described. “I feel happier and have generally more energy on the days where I have exercised” (I:3) “I think, I felt extremely well after the exercise” (I:8) Attitudes towardss the exercise programmeme In the interview, the women were asked about their experiences with the exercise programme itself, and the following four sub-categories emerged: acceptability of the exercise; feeling safe in the water, a need to adjust the exercises, and barriers. Acceptability of the exercise The women felt that the requirement to exercise two times a week for 12 weeks was appropriate and realistic, but not all women ended up doing so. The reasons for not attending all sessions were described as follows: lack of time, crowded swimming pools, tiredness, low back pain, vacation, and prioritising other things. “Some weeks I have been working all week from 7.00 a.m. to 3.00 p.m. and having to spend two evenings every week has been too much, I think, when I have a small child and a husband who is also active with sports and social life” (I:4) In general, the women were satisfied with the six exercises which they found manageable, easy and safe to perform. They did, however, express that the exercises strengthened the arm and shoulder muscles more than the back and abdominal muscles. Furthermore, some women experienced problems with performing some of the exercises because of trouble balancing on the board and discomfort. The women found it flexible to be able to exercise individually but seemed ambivalent in this perception as they concurrently expressed a social benefit and an increased motivation when exercising together with other pregnant women. Some of the women even suggested that this type of exercise should be structured in teams scheduled two times a week. “I push myself harder if I exercise alone, so I have chosen to exercise mostly on my own even though it is nice to talk to the others” (I:2) “It would be kind of nice to have someone to do the exercises with” (I:1) The exercise was perceived by some women as being light and an individual adjustment was desired so that the exercises could be performed at different levels. Not feeling any physical tiredness after the exercise was perceived both as not having trained hard enough and not having overdone the training. Gaining less from the water exercise than from exercise in fitness center was also experienced.

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“I wasn’t totally busted in my body afterwards or felt that I couldn’t cope with it. It was I would say on the lighter end” (I:5) Feeling safe in the water A sense of safety, the feeling of not overloading the body or doing something damaging by exercising in water was experienced by the women. They felt that this resulted in fewer concerns while performing the exercises in the water. “I thought it was really good that it′s in the water, because you had a good sense of feeling safe in terms of doing it correctly” (I:11) Women who suffered from a knee injury, false contractions, anxiety or back pain also expressed feeling safe when exercising in a non-weight bearing environment without the usual strain experienced in other types of exercise. A need for adjusting the exercises Some women asked for more challenging exercises, while other women altered the exercises to fit their wish for greater intensity. The women expected greater benefits and expressed a need to individualise the exercises according to gestational week, discomforts, pain and effect. “I could have used some more strength or more weight or maybe just to increase the number of repetitions” (I:8) The majority of the women swam the recommended distance of 200 m, but some women felt a need to exercise more than the programme and therefore extended the distance. A few women needed to swim or take a break in between the exercises because they got cold. Barriers The experiences of trouble finding space to perform the exercise in the pool seem to be the main barrier in this intervention. It was even described as a barrier towards being motivated. One exercise in particular, MamaPendul, required a particularly large amount of space, which made it difficult to perform if the swimming pool was crowded; this was a reason for not completing the exercises. It was found uncomfortable for some women if they were the only one performing the exercises. “Sometimes you feel that you are in the way, if you are the only one doing the exercises, you got the sense that other swimmers became annoyed” (I:6) The feeling of being in the way was experienced as less significant if the training was done along with other participants. Acceptability of supportive components The women were asked about their experience of the supportive components. These included the introduction session, brush up sessions, Aqua coaches, the weekly emails and logbooks. The following two sub-categories emerged: satisfaction with personal contact and feeling of support. Satisfaction with personal contact The introduction session was perceived as satisfactory and was found fulfilling and informative. Very few felt the need for a brushup session. The women who participated in the brush-up sessions stated that the personal contact was important.

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“There are some midwives who can help guide you” (I:1) In general, the women were very satisfied with the instructions and support they received from the coaches at the swimming pools. The coaches often addressed the women by asking if they needed help and supplied them with equipment for the exercises. Feeling of support The women found the emails to be motivating and expressed that the emails were nice to receive and that they felt supported in a positive way. Women were encouraged to return emails to the research midwife with comments on how they were doing with regard to the exercise, and several appreciated this opportunity. The logbook did not motivate the participants, but gave an overview of the exercise activities. “There is somebody keeping an eye on you a little, which makes you pull yourself together to exercise” (I:6) The women also experienced the feeling of support as a motivating factor due to the presence of the research midwives and the coaches connected to the project. Some women asked for the promised Facebook group and thought that it might have had an influence on their ability to exercise together; to encourage each other in doing the exercises, to share experiences with others supplied them with a feeling of unity. Discussion The aim of this qualitative feasibility study was to explore women’s views and experiences of the acceptability and benefits of and possible barriers to the standardised individual unsupervised water exercise intervention. The women described several motivating factors for participating in the intervention. They also described experiencing barriers, which needs to be addressed in a future RCT. The intervention was experienced to have benefits to physical health as well as mental well-being. The participants had a desire to perform the exercises at a higher level to gain the maximum benefit from the exercise and altered some of the exercises to fit their needs. The amount of exercise was found to be realistically performable and the supporting elements were in general perceived as sufficient. The women described varied motivational factors for participation in the water exercise. There was a general acceptability of the intervention among the informants because it captured their own desires, such as a desire to continue being physically active and to perform exercises suited for pregnancy. This is supported by quantitative studies that found that pregnant women desire to be physically active during pregnancy and that pregnant women change the intensity of physical activities from high to low intensity activities as well as the type of activities during first or second trimester [12–14]. Furthermore, the women expressed that the timing of the invitation for this study was perfect – which is in line with the fact that pregnant women change the type of exercise they perform, and the prevalence of swimming has been shown to increase during pregnancy compared to prior to pregnancy whereas other types of physical activity decline [13,27]. Improved physical well-being was experienced as an important benefit. The women felt that the training increased and maintained body-strength, contributed to less weight gain during pregnancy and gave a feeling of undergoing an easier pregnancy. Another study investigated the effect of aquatic exercises and found significantly less discomfort, improved mobility and positive body image in the participants [28]. These findings can be useful for future participants.

The reduction of discomfort and pain related to low back pain during the intervention period was also described. Whether the intervention has a significant effect on low back pain will be investigated in a RCT. The women also experienced several mental health benefits. Being in the water gave the women a sense of wellness, which is in line with other studies [19,29]. This indicates that participating in the exercise gives a sense of mental wellbeing, a factor that might increase the willingness to complete the intervention. The women expressed that exercising twice a week for 12 weeks is a realistic goal for compliance, which confirms that the amount of exercise is feasible. Furthermore, the women found exercising individually flexible in relation to work and family. However, they also expressed a desire to do the training with other pregnant women because it gave them an opportunity to socialise. This ambivalence is useful information and reinforces our intentions of creating a platform such as a Facebook group that allows them to connect with each other and arrange to exercise with others. It was perceived as important that the exercise was cardiovascular to give the women a sense of benefit. Another qualitative study from Denmark found a similar desire for cardiovascular training among pregnant women [19]. In a future RCT study, it is therefore important to inform the participants that they should perform the exercise programme as recommended and that they have the opportunity to add more cardiovascular exercises if desired. Crowded swimming pools were described as the most consistent barrier by the women, resulting in extensive consequences. Initiatives will be introduced to ensure better space conditions. The participants will furthermore be encouraged to exercise together as this was suggested to reduce this barrier. The women stated that the supportive elements of emails, the log-book and the personal contact during the introduction and brushup sessions were positive. The close contact during the intervention seems to be important, which might be because that the exercise programme is unsupervised and women therefore feel supported in a positive way. The validity of the study may be affected by several aspects. We strategically selected the sample of 11 women with various backgrounds, characteristics and compliance to the water exercise was considered adequate to describe the variation in the women’s experiences and to answer the research question. We have tried to increase the validity in the interview process by asking informants the same introductory question and following up with questions within the same themes. Telephone interviews were used as a method of data collection because of its suitability to gather information quickly and relatively easily from the informants and due to the low costs. A limitation to this method is that data based on non-verbal communication cannot be obtained [26]. However we do not believe that it has any significant impact on the results in this study. During the interviews, the informants were often confronted with their replies and asked to confirm them once again. This was done to make sure that the correct meaning was stated, which ensures a mutual understanding between the researcher and the informant and increases the validity [23]. It is also relevant to reflect on whether the authors MB, MK and HKH’s great interest in exercising and pregnancy and MB and HKH’s involvement in the pilot water exercise study might have influenced the analysis and results of this study. To avoid this, efforts were made to ensure that the original transcript was re-read frequently by authors MB, MK and HKH to avoid misinterpretation. Furthermore the fact that MK carried out all the interviews and did not participate in the recruitment, introduction sessions and email corresponding with the informants, created a distance. We are aware that excluding non-Danish speaking women is a limitation of this study. The unsupervised water exercise

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intervention required that the women could communicate in Danish with the staff in the public swimming pool. In future studies, specific interventions should be developed to include pregnant women who do not speak the country’s language. It is important to discuss the transferability of the information produced in this study to other contexts beyond our setting [23]. We believe that it may be transferred to other settings of pregnant women with a wish to continue physical activity during pregnancy. The participants in this study were selected from the same population as the future study will be, and we believe that the results can be transferred to a larger RCT. Conclusion This qualitative study elucidated that it is feasible to perform a larger scale RCT using the described intervention. The intervention was acceptable by the participants because it supported their desire to be physically active during pregnancy, to change exercisetype to one suited for the pregnancy, and to maintain physical activity during pregnancy. Physical health as well as mental well-being was widely experienced. The main barrier was crowded swimming pools, and this must be addressed in a future RCT. The qualitative results were important in preparing the water exercise intervention for a future RCT testing its effect on low back pain and sick leave during pregnancy. Funding statement This study was supported by The Danish Association of Midwifes, The Lundbeck Foundation, TrygFonden (grant nr. 7-121088), The Danish Arthritis Association and The Augustinus Foundation. Contributors HKH, AT and PD participated in the initial planning phase. This qualitative study was designed by all authors. Recruitment was performed by MB and HKH. The interviews were undertaken by MK. All authors participated in the drafting and reviewing of the paper and approved the final draft. Conflict of interest All authors declare they had no support from any organization for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work. Reference [1] Gjestland K, Bo K, Owe KM, Eberhard-Gran M. Do pregnant women follow exercise guidelines? Prevalence data among 3482 women, and prediction of low-back pain, pelvic girdle pain and depression. Br J Sports Med 2013;47(8): 515–20.

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