Factors influencing the uptake and use of nicotine replacement therapy and e-cigarettes in pregnant women who smoke: a qualitative evidence synthesis

Background Nicotine replacement therapy (NRT) delivers nicotine without the toxic chemicals present in tobacco smoke. It is an effective smoking cessation aid in non-pregnant smokers, but there is less evidence of effectiveness in pregnancy. Systematic review evidence suggests that pregnant women do not adhere to NRT as prescribed, which might undermine effectiveness. Electronic cigarettes (e-cigarettes) have grown in popularity, but effectiveness and safety in pregnancy are not yet established. The determinants of uptake and use of NRT and e-cigarettes in pregnancy are unknown. Objectives To explore factors affecting uptake and use of NRT and e-cigarettes in pregnancy. Search methods We searched MEDLINE(R), CINAHL and PsycINFO on 1 February 2019. We manually searched OpenGrey database and screened references of included studies and relevant reviews. We also conducted forward citation searches of included studies. Selection criteria We selected studies that used qualitative methods of data collection and analysis, included women who had smoked in pregnancy, and elicited participants' views about using NRT/e-cigarettes for smoking cessation or harm reduction (i.e. to smoke fewer cigarettes) during pregnancy. Data collection and analysis We identified determinants of uptake and use of NRT/e-cigarettes in pregnancy using a thematic synthesis approach. Two review authors assessed the quality of included studies with the Wallace tool. Two review authors used the CERQual approach to assess confidence in review findings. The contexts of studies from this review and the relevant Cochrane effectiveness review were not similar enough to fully integrate findings; however, we created a matrix to juxtapose findings from this review with the descriptions of behavioural support from trials in the effectiveness review. Main results We included 21 studies: 15 focused on NRT, 3 on e-cigarettes, and 3 on both. Studies took place in five high-income countries. Most studies contributed few relevant data; substantially fewer data were available on determinants of e-cigarettes. Many studies focused predominantly on issues relating to smoking cessation, and determinants of NRT/e-cigarette use was often presented as one of the themes. We identified six descriptive themes and 18 findings within those themes; from these we developed three overarching analytical themes representing key determinants of uptake and adherence to NRT and/or e-cigarettes in pregnancy. The analytical themes show that women's desire to protect their unborn babies from harm is one of the main reasons they use these products. Furthermore, women consider advice from health professionals when deciding whether to use NRT or e-cigarettes; when health professionals tell women that NRT or e-cigarettes are safer than smoking and that it is okay for them to use these in pregnancy, women report feeling more confident about using them. Conversely, women who are told that NRT or e-cigarettes are as dangerous or more dangerous than smoking and that they should not use them during pregnancy feel less confident about using them. Women's past experiences with NRT can also affect their willingness to use NRT in pregnancy; women who feel that NRT had worked for them (or someone they know) in the past were more confident about using it again. However, women who had negative experiences were more reluctant to use NRT. No trials on e-cigarette use in pregnancy were included in the Cochrane effectiveness review, so we considered only NRT findings when integrating results from this review and the effectiveness review. No qualitative studies were conducted alongside trials, making full integration of the findings challenging. Women enrolled in trials would have agreed to being allocated to NRT or control group and would have received standardised information on NRT at the start of the trial. Overall, the findings of this synthesis are less relevant to women's decisions about starting NRT in trials and more likely to help explain trial participants' adherence to NRT after starting it. We considered most findings to be of moderate certainty; we assessed findings on NRT use as being of higher certainty than those on e-cigarette use. This was mainly due to the limited data from fewer studies (only in the UK and USA) that contributed to e-cigarette findings. Overall, we judged studies to be of acceptable quality with only minor methodological issues. Authors' conclusions Consistent messages from health professionals, based on high-quality evidence and clearly explaining the safety of NRT and e-cigarettes compared to smoking in pregnancy, could help women use NRT and e-cigarettes more consistently/as recommended. This may improve their attitudes towards NRT or e-cigarettes, increase their willingness to use these in their attempt to quit, and subsequently encourage them to stay smoke-free.


B A C K G R O U N D
Smoking in pregnancy remains an important public health issue. Europe and regions of the Americas have the highest prevalence in the world (Lange 2018), and in the UK around 1 in 10 women are smoking at the time of childbirth (NHS Digital 2019). Smoking is potentially preventable and associated with negative outcomes for both the woman and the unborn child. Compared with pregnant women who do not smoke, smokers face heightened risks of placental abruption, miscarriage, still birth, ectopic pregnancy, preterm labour, and low birthweight (Cnattingius 2004). Furthermore, a systematic review of randomised clinical trials (RCTs) shows that stopping smoking in pregnancy improves birth outcomes (Chamberlain 2017). There are also strong intergenerational associations, with children of smokers more likely to become smokers (Leonardi-Bee 2011). Tobacco smoking is also a major risk factor for six of the eight leading causes of death globally (WHO 2008). Encouraging greater use of NRT in pregnancy is logical and ethical provided this promotes smoking cessation without causing additional harm to the developing fetus. There is no biological rationale for suspecting that NRT used in pregnancy could be more harmful than smoking; it is more likely that NRT will be better for pregnant women and their babies than smoking. NRT produces none of the harmful products of combustion from tobacco smoke, and nicotine and cotinine levels are lower when women use NRT compared to smoking (Hickson 2018). There is no evidence that NRT has any impact on birth outcomes (Chamberlain 2017). Evidence from the largest trial of NRT used for smoking cessation in pregnancy found that infants born to women in the NRT group were more likely to have impairment-free development at two years of age than those born to women in the placebo group (Cooper 2014).

Description of the topic
In recent years, smokers wanting to reduce or stop smoking have increasingly used electronic cigarettes (e-cigarettes); like NRT, ecigarettes deliver nicotine without the tobacco smoke. They work by heating a solution that contains nicotine, propylene glycol or glycerine, and flavourings to produce a vapour, without the release of combustion products (McNeill 2015). Internationally, non-pregnant smokers' use of e-cigarettes is increasing (Filippidis 2016; Gravely 2014; Mirbolouk 2018); in the European Union use has risen from about 7.2% (95% CI 6.7% to 7.7%) in 2012 to 11.6% (95% CI 10.9% to 12.3%) in 2014 (Filippidis 2016). In England, e-cigarettes are the most popular aid to smoking cessation and are used in 37% of quit attempts (West 2019).
Comparisons of toxic chemicals in the urine and saliva of nonpregnant e-cigarette users versus smokers show significantly lower levels of harmful chemicals among e-cigarette users (Shahab 2017). In 2018, Public Health England issued a report concluding that e-cigarettes are considerably safer than continuing to smoke (McNeill 2018). Furthermore, a systematic review of RCT data shows that e-cigarettes were twice as e ective as placebo in helping non-pregnant smokers stop smoking for at least six months (risk ratio (RR) 2.29, 95% confidence interval (CI) 1.05 to 4.96, placebo 4% vs e-cigarettes 9%) (Hartmann-Boyce 2016). Since the above systematic review was published, another trial assessing behavioural support plus either e-cigarettes or NRT for smoking cessation in non-pregnant smokers found that nearly double the people using e-cigarettes were able to quit (RR 1.83, 95% CI 1.30 to 2.58, NRT 9.9% vs e-cigarettes 18%) (Hajek 2019a). Unlike NRT, in the UK e-cigarettes are a consumer product and not available on prescription; users purchase them from designated vendors, including specialist vaping shops, supermarkets, and newsagents. However, some countries such as Canada and Australia have more restrictive policies on their use (Yong 2017).
There are no published trials of e-cigarette use in pregnancy. Cross-sectional studies from the USA indicate that prevalence of e-cigarette use in all pregnant women ranges from 0.6% to 4.9% (Kapaya 2019; Kurti 2017; Liu 2019; Mark 2015), but it is considerably higher amongst pregnant women who smoke. For example, in a nationally representative sample of women in the USA who smoke, 38.9% of pregnant women reported using e-cigarettes (Liu 2019). To our knowledge, there is currently no published data on prevalence of e-cigarette use in pregnancy available from other countries. A narrative review of literature suggests that pregnant women perceive e-cigarettes as less harmful than smoking and believe these can aid smoking cessation (Breland 2019). These were also the key reasons given by pregnant women for initiating the use of e-cigarettes around the time of pregnancy (Kapaya 2019); however, the determinants of sustained e-cigarette use are not known.

Why it is important to do this qualitative evidence synthesis
It is important to understand why pregnant women choose to use or not use NRT or e-cigarettes, the nature of any concerns they might have about NRT or e-cigarette use, and how to address these concerns. For NRT, such knowledge could help improve pregnant women's adherence to NRT and could likely also improve their chances of successfully quitting smoking (Raupach 2014). Ecigarettes appear to have potential as a cessation aid (Hartmann-Boyce 2016), and in some countries, such as the UK, expert health professionals recommend supporting pregnant women who use e-cigarettes in this way, especially if behavioural support and/ or NRT are ine ective or inappropriate (Smoking in Pregnancy Challenge Group 2019). It is therefore also important to understand the factors that influence pregnant women's use of e-cigarettes. This qualitative evidence synthesis aims to provide an enhanced understanding of pregnant women's perceptions around using NRT or e-cigarettes.

O B J E C T I V E S
To describe factors that influence pregnant women's uptake and use of NRT or e-cigarettes for smoking cessation or harm reduction, including barriers and facilitators; and to describe women's views on and experiences of using NRT or e-cigarettes during pregnancy.

Types of studies
We included empirical, non-review, qualitative studies, either conducted alongside e icacy trials or as 'stand-alone' studies, using any qualitative design and appropriate methods of data collection and data analysis. Mixed-methods studies were eligible if they had a distinct section dedicated to qualitative data collection and analysis and reported qualitative data.
Included studies explored views, opinions, and experiences of pregnant women who smoke(d) in pregnancy on the use of any type of NRT or e-cigarettes in pregnancy for smoking cessation or harm reduction (i.e. using NRT or e-cigarettes to smoke fewer cigarettes).

Types of participants
Participants were either pregnant women who smoked at any point during their pregnancy or women in the postpartum period who had smoked in pregnancy. As we were interested in determinants of use rather than just women's views a er using NRT or e-cigarettes, participants were not required to have previous experience using NRT or e-cigarettes.

Settings
We included studies from any setting.

Phenomenon of interest
Factors influencing the uptake and subsequent use of NRT and e-cigarettes during pregnancy, from the perspectives of pregnant women.

Search strategy
We adopted a broad search strategy to include all relevant qualitative studies. As a scoping exercise, we tried di erent search strategies in varied bibliographic databases to test the ability of these to identify a selection of known research papers, which would be appropriate for inclusion in the review. This exercise informed the final selection of databases and of search terms, including MeSH terms and key words used. Using database-appropriate strategies based on the MEDLINE one, we searched MEDLINE Ovid (1946 to 1 February 2019), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 1 February 2019) and PsycINFO Ovid (1967 to 1 February 2019). All database strategies presented in Appendix 1. Additionally, we manually searched the OpenGrey database (http://www.opengrey.eu/ searched 1 February 2019) using terms 'pregnancy' AND 'smoking cessation' and 'pregnancy' AND 'nicotine replacement' and screened references of included studies and literature reviews identified by searching. Finally, we conducted forward citation searches of included studies.

Data collection and analysis Selection of studies
We entered the identified studies into one Endnote database and removed duplicates (EndNote X8), then we exported them to Covidence, a screening and data extraction tool. Each title and abstract was screened by two of the review authors (KB, KAC, TCH, SLC, and SC), using a priori inclusion criteria (see Appendix 2). We resolved conflicts through discussion where possible, involving a third review author if necessary. For all potentially relevant studies, two review authors independently assessed the full text, again involving a third review author to resolve conflicts.
We recorded the following study characteristics on a specially designed form.
• First study author.
• Date of publication.
• Country and context of study (urban/rural).
• Key participant characteristics (pregnancy status, smoking status, NRT/e-cigarette user status, age, gestation, ethnicity, socioeconomic data). • Theoretical/conceptual perspective of the study.
• Data collection methods.
• Data analysis methods.
• Key themes reported by the authors.
We also screened the full text of manuscripts to identify and extract any other data that might be of relevance to this review.

Appraisal of study quality
We used the Wallace quality appraisal criteria (Croucher 2003; Wallace 2004; Appendix 3). Previous Cochrane qualitative evidence syntheses, like Husk 2016, have used this tool. With it, the review author assesses 13 criteria as being met ('yes'), not met ('no') or uncertain ('cannot tell') (Husk 2016). For this study, eight criteria relating to the research question were considered essential: clarity of research question, appropriateness of study design, adequacy of sample, adequacy of the population from which sample was drawn, description of data collection, rigour of data collection, rigour of analysis, and extent to which the data substantiated the findings. The remaining five criteria were considered desirable: clarity of theoretical perspective, adequacy of study context description, reflexivity, claims regarding generalisability, and adequately addressed ethical issues. Two review authors (KAC and SLC) independently undertook the quality assessment and met to discuss their ratings. Any disagreements were resolved through discussion. Following recent guidance, which suggests that overall ratings should not be assigned to qualitative studies (Munthe-Kaas 2018), we present specific methodological issues identified in each study in Table 1.
In addition, we assessed studies for data richness (i.e. the amount and depth of qualitative data that are relevant to the current review), using a tool devised by Ames 2019. This tool uses a scale of 1 to 5, where 1 indicates 'very few qualitative data which are relevant to the review, and those presented are fairly descriptive' and 5 indicates 'a large amount and depth of qualitative data Library Trusted evidence. Informed decisions. Better health.
Cochrane Database of Systematic Reviews relevant to the review'. See Appendix 4 for more details. We assessed only the richness of data relevant to the review. For example, a study focusing broadly on smoking cessation and presenting large amounts of data on that topic might only present one theme or part of a theme relating to NRT or e-cigarettes; we would rate such a study 1 or 2, as there would be few qualitative data relevant to this review. Richness of the data relevant to the review did not a ect the quality assessment, as it did not reflect the quality of the primary study, only how much it contributed to the review.

Data extraction and analysis/synthesis
One review author (KAC) extracted data from included studies, and another (SLC) checked them. This process acknowledged that identifying the data or findings in qualitative studies can be challenging (Noyes 2018). We followed the guidance from Thomas 2008 and extracted study data reported as quotes from participants, as well as key concepts, that is, summaries of findings or any other relevant data presented in primary studies. We assessed the whole text of each paper when searching for relevant data. These data were extracted verbatim into NVivo so ware.
We used thematic synthesis described by Thomas 2008; this allows inductive data coding and flexible data exploration to identify concepts and constructs from within the data, which may not have been predefined. We were also sensitive to the fact that derived themes should relate to factors influencing uptake and use of NRT and e-cigarettes and their acceptability as cessation aids. Synthesis was conducted in three steps.

Steps one and two: line-by-line data coding and development of descriptive themes
Initially KAC read all included studies to ascertain which ones provided the potentially richest or most substantial data relevant to the study questions. At this point it was clear that very few studies of either NRT or e-cigarettes specifically investigated either the barriers or facilitators for women using these (i.e. the determinants of NRT or e-cigarette use). We decided therefore, that in order to develop descriptive themes, we should carefully consider all data for inferences about potential determinants of product use, including data describing women's general views on or attitudes to e-cigarettes and NRT.
A er the initial read-through, 6/21 studies were considered likely to provide the richest and most relevant data; we selected these for initial detailed reading and sought to extract key concepts and assign codes to the data (Ashwin 2010; Bowker 2016; Bowker 2018; Fallin 2016b; Hotham 2002; Taylor 2010). Next, two review authors (KAC and KB) independently read these six primary studies and inductively coded concepts arising from the data on a line-by-line basis. Researchers first derived codes from Taylor 2010 and subsequently applied them to other studies whilst simultaneously seeking new concepts and coding these, where appropriate. However, once the initial 6 studies had been coded, no new concepts were identified from the remaining 15 studies. A er independently coding all studies, the two researchers met, discussed each other's emerging findings, refined coding and agreed on new definitions and descriptions for each.
The researchers then looked for similarities and di erences between codes, grouped these into broader, descriptive themes, and organised them hierarchically (Table 2). KAC recoded the entire   data set with the final, agreed codes. A third review author (TC)  then reviewed a document comprising all code definitions and  descriptive themes with definitions and discussed it with KAC and  KB in order to agree on a final version. This process showed that data from the 15 primary studies were limited, as all original concepts arising from the data had already been identified from the six studies with richer data.
Step three: developing analytical themes In the third step of the synthesis, we organised descriptive themes into more abstract, analytical ones to help findings, as far as possible, answer review questions. Two review authors (KAC and KB) discussed descriptive themes and considered their relevance to study questions. Through discussion, we identified further analytical, overarching themes that encompassed the descriptive ones and suggested barriers, facilitators, and other implications. We then synthesised descriptive codes and themes to generate analytical themes that directly answered review questions posed. A third review author (TC) considered descriptions and definitions of the derived analytical themes and discussed them with KAC and KB prior to finalisation. We considered implications for future research and practice in the context of the analytical themes.
The authors' perspective during the synthesis process, as described in the reflexive note, is that we believe it is better for pregnant women to use NRT or e-cigarettes than it is for them to smoke. This belief is based on current evidence and guidance, which suggests that: • NRT is e ective for smoking cessation in the general population (Hartmann-Boyce 2018); • NRT used in pregnancy has no e ects on the birth outcomes (Coleman 2015); • NRT is recommended as a smoking cessation aid during pregnancy (NICE 2010); • New evidence suggests that e-cigarettes might be e ective for smoking cessation in the general population (Hajek 2019a); • E-cigarettes are likely to be significantly less harmful than tobacco cigarettes, but are not without risk (McNeill 2018)

Assessment of confidence in the review findings
To assess the confidence in the findings of this review, we applied the Confidence in Evidence from Reviews of Qualitative research method (CERQual) (Lewin 2015). This approach, developed by GRADE-CERQual Project Group 2004, uses four components to evaluate confidence in the review findings. These include the methodological limitations of included studies, the relevance of the included studies to review questions, the coherence of the review findings, and the adequacy of the data that contributes to each review finding. In the first instance, KAC evaluated each finding using the four components of CERQual and a four-point scoring system ranging from 'no or very minor concerns' to 'substantial concerns'; TCH then checked the evaluation. The review authors met and discussed the scores and assigned each finding an overall CERQual assessment score. Each finding started with a 'high confidence' score which could be downgraded to

Reflexive note
The review has been conducted from the epistemological stance of critical realism, which assumes that our understanding of reality is mediated by our beliefs and perceptions (Barnett-Page 2009). It is therefore important to consider the characteristics of the review authors, their beliefs and experiences, and how these might have a ected the interpretation of the data throughout the synthesis process. All review authors are researchers with backgrounds in either primary health care, public health, psychology, sociology and/or midwifery and have extensive experience conducting research in the field of smoking cessation in pregnancy; none are smokers or NRT or e-cigarette users. The review team is UKbased, and this review was partially funded by National Institute for Health and Care Excellence (NICE), a funder with a particular interest in the UK context. In the UK, health authorities and/or expert health professionals recommend use of NRT in pregnancy (NICE 2010,Smoking in Pregnancy Challenge Group 2019), and they support use of e-cigarettes as smoking cessation aids in pregnancy (Smoking in Pregnancy Challenge Group 2019), which may have had impact on the authors' views. To ensure rigour, the authors considered the funder's interest as well as their own views and beliefs about NRT and e-cigarettes and how these views could a ect study conduct. At the outset, all authors viewed NRT and ecigarettes in pregnancy to be potentially valuable tools for smoking cessation but were also aware of some of the issues pregnant women experience in relation to using these and in particular women's safety concerns. The review authors remained aware of their views throughout the process of screening, data extraction, and synthesis and attempted to treat all data equally and ensure that contradictory findings were given equal place in the review.

Description of studies
The details of included studies appear in the Characteristics of included studies tables. The Characteristics of excluded studies tables show excluded studies and reasons for exclusion.

Study focus
Fi een studies presented data relating to women's views on NRT

Study context
All included studies were conducted in high-income countries: Studies were inconsistent in their collection and reporting of socioeconomic status indicators; overall, the presented data suggested that participants were from lower socioeconomic groups. However, 10 studies did not report any data on this variable (

Support and funding for studies
None of the studies received funding from commercial sources, and just one study declared conflicts of interest (Herbec 2014), with the last author stating "RW undertakes consultancy and research for and receives travel funds and hospitality from manufacturers of medications for smoking cessation. He also undertakes training for smoking cessation advisors and has a share of a patent for a novel nicotine delivery device." Table 1 presents the outcomes of the quality appraisal (Wallace 2004). In all studies, the research question was clearly presented, and the design was appropriate to the research question. All studies except England 2016 drew the sample from an appropriate population of pregnant women with some history of smoking in pregnancy. In England 2016, the sample was drawn from a marketing company database, and the characteristics of the wider population were unclear. Several studies had some methodological issues relating to insu icient descriptions of the study sample  Cochrane Database of Systematic Reviews

Confidence in the findings
We identified six descriptive themes that related to factors influencing women's decisions about using or continuing to use NRT and/or e-cigarettes. These were: safety concerns about nicotine, concerns about the addictiveness of nicotine, beliefs about the e ectiveness of nicotine-containing products, perceived side e ects, influence of others, and characteristics of nicotine products. Within these themes, we identified 18 unique findings relating to the review questions. Table 2 presents a short overview of these themes and the 18 related findings; Table 3 , a summary of qualitative findings with overall CERQual assessments for each finding; and Table 4, the matrix of qualitative findings. In Table  2, where there is no key finding within a theme, this is because there were insu icient data reported on the issue in empirical studies. Hence, for findings 7 and 11, there were enough data reported on concerns about addictiveness of nicotine and on side e ects in the NRT studies to formulate key findings relating to NRT, but insu icient data for similar findings to arise in relation to ecigarettes. Table 3 presents the assessment of confidence in review findings, and Appendix 5 shows individual CERQual evidence profiles. We also present an overall CERQual rating for each finding. Confidence in findings ranged from 'high' to 'low', with most being ranked as 'moderate' confidence. Findings were most o en downgraded where studies contributed thin/very thin data or data from few participants, or because most studies contributing data to a finding were from only one country, similar contexts, or the context of data report was di icult to establish. Findings were also downgraded due to methodological issues with the primary studies, relating to sample, data collection and analysis.

Factors influencing use of NRT and e-cigarettes in pregnancy
Eighteen

Finding 1: women believe that NRT is safer than smoking
Six studies found that women perceived NRT as safer than smoking, as it only delivers nicotine and not the many harmful chemicals present in cigarette smoke ( In two studies, some women felt that NRT was as harmful as smoking (England 2016; Naughton 2013).

Finding 2: women are concerned that NRT can deliver an unsafe amount of nicotine
Seven studies reported that women were worried about the amount of nicotine delivered via NRT compared to smoking There was a common concern that women would receive more nicotine from NRT than they would from a cigarette, especially from higher dose patches or when using NRT and smoking at the same time.

"The patch can give you a nicotine overdose, so it's scary, smoking and wearing it." Pregnant smoker (England 2016)
The constant delivery of nicotine from the patch was also problematic for some women; they believed that the increased amount of nicotine supplied via NRT could be dangerous to their health.
"But with the patch you would wear it all day and there's going to be a constant kind of supply of nicotine going to the body, and I just don't like the thought of that." Pregnant woman 14, smoker (Taylor 2010)

Finding 3: women are concerned that using NRT during pregnancy can harm their baby
Participants most commonly expressed concerns about the potential harms NRT could cause to their unborn baby; in 12 studies participants expressed uncertainty regarding the safety of NRT while pregnant, which in many cases was a barrier to NRT use (

Finding 4: women believe that e-cigarettes are safer than smoking
Women's views on the safety of e-cigarettes varied depending on whether they concerned general use or in pregnancy. Women in five studies indicated that they thought e-cigarettes to be less harmful than smoking traditional cigarettes, for both the vapour and in terms of second-hand smoke (Bauld 2017; Bowker 2018; England 2016; Fallin 2016b; Grant 2020). Study participants referred to ecigarettes as being 'cleaner' and 'safer' because they believed these contained fewer chemicals than traditional cigarettes and no tar. In some cases, e-cigarettes were perceived as a harm reduction strategy.

"It [e-cigarette] doesn't pass on second-hand smoke, because even if the baby was close by, which I wouldn't have a baby close by, it wouldn't be dangerous." 19 antenatal ex-smoker and current ecigarette user (Bowker 2018)
"I think the idea behind it-is that because it's water vapour you're not getting some of the tar and some of the other things you get out of a regular cigarette." Pregnant smoker (England 2016) "It's just vapour, like you have nothing to lose by using their product." (Fallin 2016b) Three of these studies also mentioned that some women feel uncertain about e-cigarette safety due to lack of evidence on this (Bauld 2017; Bowker 2018; Fallin 2016b).

Finding 5: women are concerned that e-cigarettes can deliver an unsafe amount of nicotine
In two studies some women were concerned about the amount of nicotine and the potentially harmful properties of other chemicals delivered via the e-cigarette (Bowker 2018; England 2016). Women were also concerned that an e-cigarette could be used for as long as they wanted.
"Obviously with a cigarette you can only smoke it for so long till it's finished, but with an e-cigarette you can smoke for as long as you want to. So sometimes, I guess, I was taking in more than the usual nicotine intake that I would have done with a cigarette." 01 antenatal ex-smoker and ex-e-cigarette user (Bowker 2018) On the other hand, one study suggested that women found the opportunity to choose the concentration of nicotine in their e-liquid beneficial (Fallin 2016b).

Finding 6: women are concerned that using e-cigarettes during pregnancy can harm their baby
Women in three studies reported some uncertainty about the safety of using e-cigarettes during pregnancy and believed there was insu icient available information about the e ects of vaping on the baby to make an informed decision about using these in pregnancy (Bauld 2017; Bowker 2016; Fallin 2016b). Women viewed e-cigarettes as a new and untested product.
"I wasn't allowed anything like that during pregnancy because they have not tested things like that properly yet." Area A, pregnant woman 18, non-smoker (Bauld 2017)

Finding 7: women report concerns that NRT is as addictive as smoking
Four studies briefly reported women's concern about the addictive potential of NRT (Ashwin 2010; Bowker 2016; England 2016; Taylor 2010). Data were relatively thin, however, with few participant quotes.
Some women felt that using nicotine products of any kind constituted 'not actually quitting' or replacing one addiction with another (Ashwin 2010; Bowker 2016; Taylor 2010).
"Well, all they keep saying is you know it gets rid of the toxins, you still get the nicotine but it gets rid of the toxins, this, that and the other and it's just in that the nicotine you take it in. The nicotine itself is what makes it addictive, so to me the more nicotine that you're taking in anyway, the more you're going to want to smoke or you know you're going to need that nicotine." Respondent 6; inhalator (Bowker 2016) There was also a belief that becoming addicted to NRT would prolong the quitting process and would give women 'something else they would have to quit a er quitting smoking', and therefore  In one study women noted that NRT might be better than ecigarettes with regards to weaning o nicotine (Bowker 2018).   Additionally, one study reported that some women who struggled with cravings independently decided to wear NRT patches for longer than recommended to help cope with these (Bowker 2016).
In other studies, some women who had used lower dose patches found these ine ective (Bauld 2017; Mantzari 2012).
"She did say to put them on and take them o before bedtime to give you and baby a rest. I was finding I was waking up and wanting a cigarette so I took it upon myself to leave them on for 24 hours." Respondent 9; patches (Bowker 2016) Women treated for opioid dependency found NRT to be less e ective in treating their smoking addiction than medication for opioid dependency (Fallin 2016a).

Finding 10: women present mixed views on e ectiveness of ecigarettes
Four studies contributed data on women's views on e ectiveness of e-cigarettes, although these were very sparse, with mixed opinions reported and minimal insight into how these might a ect readiness to use e-cigarettes (Bauld 2017; Bowker 2016; Bowker 2018; Grant 2020). One study concluded that women did not find e-cigarettes helpful in a quit attempt (Bowker 2016), but in two others, women perceived e-cigarettes could potentially help them to quit (Bauld 2017; Bowker 2018). An interviewee in one study reported that while she successfully used an e-cigarette to quit before pregnancy, she started craving regular cigarettes when pregnant and had to supplement her e-cigarette use with smoking to manage cravings (Grant 2020).

Theme 5: influence of others -women's readiness to use nicotine-containing products in pregnancy is influenced by the perceived views of and support from other people
In 14 studies, the influence of health professionals, but also family and friends, was found to be an

Finding 15: women's readiness to use e-cigarettes in pregnancy is influenced by the advice they report receiving from their health professionals
In four studies most women reported that their health professionals did not endorse the use of e-cigarettes in pregnancy (Bauld 2017; Bovill 2018; Fallin 2016b; Grant 2020). Media reports recalled by the women also tended to be negative, in particular highlighting product malfunctions and health scares, and women did not report verifying this information with their health professionals (Bowker 2018; Fallin 2016b).
Lack of information about safety and discouragement from health professionals o en led to pregnant women's reluctance to try ecigarettes or a desire to stop using them (Bauld 2017; Bowker 2016; Bowker 2018). Bowker 2018 reported that women felt more confident using NRT than e-cigarettes because they believed NRT was recommended by health professionals; women in this study were reluctant to start using e-cigarettes until safety of the product was established and clearly communicated. On the other hand, some pregnant women decided to continue using e-cigarettes (Bowker 2016), or they showed interest in using them despite discussing 'unknown risks' with their health professionals (Bauld 2017). One participant decided to continue using e-cigarettes based on her own 'online research', which satisfied her that vaping was safer than smoking (Grant 2020).

"The doctors and the health visitors all say: 'Are you going to cut down?' And I say: 'No, I don't think it's harming my child' so I am happy to stay on them and that's it really . . . it hasn't got any of the harmful chemicals like tar and all you know. . . it's my decision and I'm happy with this like you know?" Becky (Grant 2020)
Two studies reported that some women were encouraged to use ecigarettes by their health professional (Bowker 2018; Fallin 2016b).
"And then I completely just quit and picked up the e-cig and worked with it while I was kind of pregnant but I was kind of scared but I talked to my doctor about it and they said it was fine you know, so." (Fallin 2016b) Overall, there were mixed reports about women's experiences of health professionals' stance on e-cigarette safety, and, apart from a small number of participants in three studies (Bauld 2017; Bowker 2018; Grant 2020), women tended to consider their health professionals' advice when making a decision to use e-cigarettes in pregnancy.

Finding 16: women's readiness to use e-cigarettes in pregnancy is influenced by other people (non-health professionals)
There was limited evidence about the role of family and friends in the studies, but two studies mentioned that family and friends encouraged pregnant women to use e-cigarettes to quit smoking (Bauld 2017; Bowker 2018).

"They [family] were a lot happier about me using that [e-cigarette] than obviously smoking. My Mum actually bought me the e-cigarette and she never ever bought me cigarettes in my life." 08 antenatal smoker and current e-cigarette user (Bowker 2018)
In addition, two studies also noted that women felt judged by other members of the public when using e-cigarettes, which reduced their willingness to use e-cigarettes in public places (Bowker 2018; Grant 2020). Some women said they felt embarrassed and uncomfortable to be seen using an e-cigarette while pregnant or out with children, similar to when smoking.
"And I smoke my e-cig and some people might not, not that that bothers me at all, but they might look at me and like judge but it doesn't bother me but it's still a factor in the pregnancy." Becky (Grant 2020)

Finding 17: perceived characteristics of the NRT product, such as cost, convenience and ability to mimic a cigarette, can influence uptake and continuous use of NRT in pregnancy
Eleven studies contributed data to how the characteristics of NRT products can influence women's views and readiness to use Taylor 2010). One study mentioned that the appearance was one of the main reasons for discontinuing the use of inhalator (Butterworth 2014).
In one Australian study where women had to pay for NRT, some perceived the cost to be prohibitive (Hotham 2002). In two UK studies, authors reported that women were unaware that NRT would be provided free of charge (Bauld 2017; Taylor 2010).
Women o en chose their product based on its ability to mimic the traditional cigarette; some women found that inhalators helped manage the behavioural aspects of their addiction, such as the hand-to-mouth action (Ashwin 2010; Bauld 2017; Bowker 2016; Taylor 2010). Some also felt that inhalators allowed them to continue socialising with friends who smoked (Bowker 2016; Butterworth 2014; Taylor 2010).  Cost influenced women's decisions to use e-cigarettes. E-cigarettes were not free of charge to any of the women who participated in studies. Some women believed e-cigarettes were good value (Bowker 2018; England 2016), while others felt they were more expensive than smoking (Bauld 2017; Butterworth 2014).

"I had one of them e-cig[arette] things you know the ones with the oil, and it lasted 3 weeks and then I got rid of it because it was rubbish to be fair. It was, you had to charge it all the time and then you had to
Factors influencing the uptake and use of nicotine replacement therapy and e-cigarettes in pregnant women who smoke: a qualitative evidence synthesis (Review) Copyright  Some women, however, found these products not as satisfying as smoking, which was a source of frustration, while others found it too much like the cigarette or a cue to smoking (Bowker 2018; Fallin 2016b).
"I think not smoking at all was less frustrating than trying to get the satisfaction of a real cigarette from an e-cigarette." (Fallin 2016b) "One thing I missed when I have quit smoking is inhaling the smoke, so when I used an e-cigarette obviously you've got that kind of experience of inhaling the vapour. It was too much, it was too similar to having a cigarette, so it made me miss it even more." 01 antenatal ex-smoker and ex-e-cigarette user (Bowker 2018)

Analytical themes
We identified three analytical themes representing the key determinants explaining uptake of and adherence to NRT and e-cigarettes; each potentially acted as a barrier or facilitator to use. Similar descriptive themes emerged from NRT and e-cigarette studies, but some issues only appeared to relate to NRT. Overall, we felt that the determinants of e-cigarette and NRT use were relatively similar, and that even more similarities, and perhaps some di erences, might have been apparent had there been more data on e-cigarettes.

Women consider health professionals' advice when making decisions about NRT or e-cigarette use in pregnancy
Findings (F) contributing to this theme: F12 (moderate confidence), F13 (high confidence), F15 (high confidence).
When pregnant women perceive that health professionals endorse NRT or e-cigarettes as smoking cessation aids, they feel more confident about using them. Conversely, when health professionals provide inconsistent or unclear information about safety or appropriateness of using these products, women can be less willing to use them.
The degree to which women perceive NRT and e-cigarettes to be acceptable and safe cessation aids influences how much they use them. Women who believed that these were safer than smoking were more willing to use them in quit attempts. However, where women perceived that NRT or e-cigarettes were at least as harmful as smoking, their concern for the e ect these might have on their unborn babies hindered their acceptance of them as quit aids during pregnancy. Some women lacked understanding of which tobacco smoke components cause most harm, with many believing this to be nicotine. Many were concerned about the possible addictiveness of nicotine and worried that NRT and e-cigarettes could deliver higher, and therefore less safe, nicotine doses than cigarettes.
Nicotine-related fears can deter women from using NRT or ecigarettes. Such fears may stem from the perceived lack of evidence regarding safety of NRT and e-cigarettes and/or from negative opinions about NRT and e-cigarettes expressed by family and friends, and sometimes by health professionals. The belief that there is insu icient safety evidence was particularly apparent in relation to e-cigarettes. However, women in some NRT studies, including recent ones, expressed fears about nicotine and hence about NRT safety, despite NRT being increasingly recommended internationally as a cessation aid in pregnancy (
Past positive experiences with NRT, or those of their family and friends, can influence pregnant women's beliefs about likely e ectiveness of NRT, encouraging them to try it. Conversely, previous negative experiences of using NRT in unsuccessful quit attempts, ine ective management of withdrawal symptoms or experience of unpleasant side e ects, or family and friends' reports of similar issues can discourage pregnant women from trying NRT. A er initiating NRT, there are many reasons why women might find it unhelpful and discontinue it early. For example, they might use insu icient NRT to ameliorate nicotine cravings due to concerns about nicotine; when they subsequently continue to experience cravings, women may believe NRT is not helping them. For ecigarettes, there is less evidence on how past experience influences future use; available data suggests a similar relationship to that for NRT, but more research could confirm or refute this.

Integrating the findings from this synthesis with the findings of the relevant Cochrane e ectiveness review
Here we consider how findings from this qualitative evidence synthesis (QES) might relate to those from a Cochrane Review that investigated e ectiveness of pharmacological treatments for smoking cessation in pregnancy (Coleman 2015, updated Claire 2020). The following issues from that review are relevant here.
• There were no completed trials of e-cigarettes in pregnancy.
• All participants in review trials agreed to being randomly allocated to NRT or control (placebo or behavioural support only), which implies that they did not hold strong negative beliefs about NRT. • Descriptions of counselling about NRT use were very brief.
• NRT was borderline e ective compared to control.
• Study design was the only factor found to influence NRT e ectiveness estimates. Trials that were not placebo-controlled produced higher e ectiveness estimates than those with Cochrane Database of Systematic Reviews placebo control; review authors concluded that this was due to bias. • Where studies reported adherence to NRT, this was universally low. However, as adherence reporting was inconsistent, intrastudy comparisons were not possible.
As there were no e-cigarette trials, this section only relates QES findings on NRT to the Cochrane e ectiveness review.
With respect to the determinants of women's decisions to start NRT, we consider that findings from the qualitative studies in this QES have limited transferability to the context of RCTs. All women enrolled in RCTs included in Coleman 2015 (updated Claire 2020) had to understand standardised information on NRT, received counselling about NRT from trained health professionals and, following this process, agree to use NRT, placebo or to only receive behavioural support. Conversely, women recruited to QES qualitative studies are less likely to have received any formal advice on NRT, and information from health professionals' may have been less comprehensive or consistent than that given in RCTs. In some QES studies, women reported inadequate or inaccurate advice from health professionals, and some health professionals were negative about NRT. While women in trials may have had similar previous experiences, any negative impressions of NRT as a result would have likely been addressed when they enrolled in the trial. In this QES, the influence of health professionals' advice was a key determinant of women's decisions about NRT use, so we feel the di erences outlined above are important and that QES studies' findings are not directly transferable to trial participants' decisions around the use of NRT.
Although we do not think it is appropriate to equate the initiation of NRT in an RCT versus routine health care, we consider that QES findings are relevant to why women decide to carry on or stop using this a er starting NRT. In smoking cessation RCTs, participants receive most behavioural support in initial consultations. A erward, trial participants who use NRT o en have relatively little contact with health professionals, so women are likely to make decisions on continuing or stopping NRT without further professional advice; this is similar to the conditions of routine health care (Bowker 2016). Hence, we believe that QES findings are much more transferable to, and likely to help explain, women's adherence to NRT in both routine care and RCTs, and we propose using QES findings to help understand why adherence to NRT in e ectiveness review trials was so low (Coleman 2015, updated Claire 2020). This is an important issue because when pregnant women adhere more strongly to NRT, they have a better chance of becoming abstinent (Raupach 2014). To facilitate investigation of how QES findings might explain trial participants' adherence to NRT, we created a matrix showing the extent to which key QES findings are represented within interventions used for each trial in the e ectiveness review (see Appendix 6). Across most e ectiveness review trials, this demonstrates the following key issues.
• All e ectiveness review trials included behavioural support, but trial reports gave little detail about the information on NRT included in this support (Coleman 2015, updated Claire 2020). • Initial and follow-up counselling in trials was usually delivered by the same health professionals, so it is likely to have been consistent. • Few trials o ered participants a choice of NRT types. QES findings show that pregnant women value health professionals' clear advice about NRT and are more likely to follow this when it addresses any concerns they may have about nicotine use in pregnancy. It is unclear if support delivered in the e ectiveness review trials included this specific advice, as details provided in trial reports were very scanty. However, as most studies finished recruiting over nine years ago and there was only limited literature on NRT safety then, this seems unlikely (Coleman 2015, updated Claire 2020). Another issue, which is unclear from trial descriptions, is the degree to which information about NRT might have been delivered consistently. Again, QES findings suggest that this is important to pregnant women. In most of the RCTs included in the e ectiveness reviews (Coleman 2015, updated Claire 2020), both initial and follow-up behavioural support was delivered by a single team of smoking cessation-trained health professionals. Although it is not explicitly stated or reported, it is highly likely that these teams delivered consistent messages about NRT. However, in two larger trials, routine healthcare sta provided follow-up counselling, whereas trial sta provided initial support; in these RCTs, messages given about NRT may have been less consistent (Berlin 2014; Coleman 2012). Appendix 6 also demonstrates the limited extent to which trial participants had a choice of NRT product (e.g. patch versus inhalator); the QES found that women reported product choice as being potentially influential in their decisions to start and subsequently continue using NRT. Only Pollak 2007 o ered women a choice of NRT types (i.e. gum, lozenge, or patch). Other RCTs restricted women to only one NRT type, and although four trials o ered varied NRT strengths, only one type of NRT was used in each study, and NRT selection was guided by the severity of women's nicotine dependence so they could not actually QES findings suggest that to maximise participants' adherence to NRT, and potentially their chances of stopping smoking, future trials of NRT in pregnancy should develop interventions that increase participants' chances of receiving consistent, positive advice on NRT safety and which counter any inaccurate beliefs about nicotine or NRT. Additionally, researchers designing trials should consider o ering participants a choice of NRT products.

Summary of main findings
This review included 21 studies that took place in five developed countries, predominantly the UK, followed by the USA, Australia, New Zealand, and Canada. We identified six descriptive themes and 18 individual findings situated within those themes, from which we developed three overarching analytical themes, representing the key determinants to uptake and adherence to NRT and/or ecigarettes in pregnancy. These analytical themes are related to the advice from health professionals on NRT or e-cigarette use in pregnancy, women's desire to protect their unborn baby from harm, and the role of past experiences with NRT on motivation to use it in pregnancy. Each of these determinants can either hinder or facilitate uptake and adherence to these products, depending on women's individual experiences. Women who perceive that the advice and support from health professionals endorses NRT or ecigarette use in pregnancy, who believe that NRT or e-cigarettes are less harmful for their developing baby than smoking, who have successfully used these products in the past, or who have received positive messages from peers about these, are likely to

Summary of integrating the findings from this synthesis with the findings from Cochrane e ectiveness review
The contexts of included studies in the QES and in Coleman 2015 (updated Claire 2020) were not su iciently similar to fully integrate the findings. QES findings are more relevant to RCT participants' adherence with NRT once this has been initiated than to RCT participants' decisions on whether to start using NRT. Although adherence with NRT is associated with cessation in pregnant women who are trying to stop smoking (Raupach 2014), the trials included in the e ectiveness review did not consistently or clearly report NRT adherence outcomes, so we have not attempted to relate QES findings to these. Instead, we have investigated the extent to which RCTs reported using interventions, which were consistent with the key qualitative issues experienced by women in relation to NRT use in pregnancy. We suggest that future RCTs might encourage women's adherence to NRT by providing consistent and clear advice on NRT, which addresses any fears about nicotine use in pregnancy and o ering a choice of NRT types.

Overall completeness and applicability of the evidence Populations explored
All studies involved pregnant women who had experience smoking during pregnancy. Not all participants had experience using NRT or e-cigarettes, so some studies provided insight into how women who smoked, but had not used NRT or e-cigarettes, perceived these. Most studies did not mention the socioeconomic characteristics of study participants; however, when reported, participants were described as coming from disadvantaged backgrounds, which is consistent with smoking during pregnancy being strongly associated with maternal deprivation.

Geographical context
All identified studies were conducted in high-income, predominantly English-speaking countries, and there are gaps in perspectives of women living in low-and middle-income countries. Rates of smoking in pregnancy were around 10% in the included countries (Bar-Zeev 2018; Drake 2018; Lange 2018; NHS Digital 2019) which is higher than global prevalence of 1.7% (95% CI 0.0 to 4.5) (Lange 2018), so understanding barriers to using smoking cessation or harm reduction aids such as NRT and e-cigarettes in this context is important. All countries where studies took place had guidelines recommending use of NRT by pregnant women who were unable to quit without pharmacological support. However, for e-cigarettes they had environments of varying permissiveness. For example, UK health experts recommend that health professionals should support women who wish to use e-cigarettes to quit smoking, especially where other methods have failed (Smoking in Pregnancy Challenge Group 2019), while in some places, such as New South Wales (Australia), nicotine-containing e-cigarettes were illegal (NSW Government 2019). Studies investigating e-cigarette use were all set in either the UK or USA.

Time of data collection
NRT studies took place between 2002 and 2018, with most completed within the last five years of this period. These o er contemporary evidence whilst also providing an understanding of how views on NRT might have changed as the evidence base for using this in pregnancy has grown. For example, studies conducted before 2010 cited the lack of evidence for the safety of NRT in pregnancy as a barrier to NRT use more forcefully. Compared to NRT, e-cigarettes have been brought to market more recently, so studies included in the QES were also very recent and revealed that women's views on using e-cigarettes were less consistent, with much more uncertainty about safety.

Confidence in the findings
We used GRADE-CERQual to assess confidence in findings. Of the 11 findings related to NRT, we had high confidence in 4 and moderate confidence in 7. Of the seven findings related to e-cigarettes, one was of high confidence, four of moderate confidence, and two of low confidence. Lower confidence in e-cigarette findings was attributable to there being fewer studies and data. When studies contributing to a finding came from only one country or from a few very similar countries, we downgraded findings for relevance issues. We most frequently downgraded findings for adequacy when few studies contributed to the finding or those that did contributed only small amounts of data. We deemed the overall quality of the included studies acceptable, and while we detected some methodological issues, such as insu icient reporting of data collection or data analysis, we felt that these were rarely severe enough to significantly a ect confidence in findings. Consequently, we noted only minor/moderate concerns due to methodological issues. We noted issues with coherence when there were opposing cases within a theme; these were usually minor.

Agreements and disagreements with other studies or reviews
To our knowledge, there are no qualitative systematic reviews investigating determinants of NRT and e-cigarette uptake and use in pregnancy; however, there are some similarities between our study and others. A qualitative systematic review including 38 studies provided insights into the determinants of smoking cessation in pregnant women, and some findings are similar (Flemming 2015). For example, the authors of that review also found that health professionals' advice could be perceived as a barrier or facilitator to successful cessation in pregnancy. They noted that pregnant women perceived consistently supportive interactions with their health professionals to be a facilitator to smoking cessation and that negative or ambivalent attitudes, halfhearted support, and insu icient practical help served as barriers to successful quit attempts. Similar to QES findings, women in this review also reported their desire to protect their baby as a motivator to change their smoking behaviour (Flemming 2015).
Another qualitative systematic review investigated the barriers and facilitators to delivering e ective smoking advice from health professionals' perspective (Flemming 2016). Health professionals (predominantly midwives, health visitors and obstetricians) recognised that helping pregnant women quit smoking was a key part of their role. However, they also believed that their wishes to maintain positive relationships with women could make this task di icult. This and other barriers could lead to health professionals addressing women's smoking inconsistently or with mixed messages, such as advising women to cut down rather than stop smoking completely. Women's desire to protect their babies was also an identified facilitator to delivering support; Cochrane Database of Systematic Reviews health professionals felt more confident when delivering smoking cessation messages that included the benefits of quitting for the baby.
A recent qualitative study in 26 UK health professionals who deliver smoking cessation in pregnancy focused on how health professionals' believe their support and advice about using NRT can influence pregnant women's use of this (Thomson 2019). A reported barrier to women's NRT use was women receiving misinformation about NRT safety or appropriateness from friends, family, and health professionals. Similar to findings from this QES, participants also noted that pregnant women's past negative experiences with NRT could deter them from using this. Professionals reported a belief that when women overestimated the e ects of NRT and underestimated the importance of willpower, their quit attempts were more likely to fail.
There was only sparse literature on the determinants of e-cigarette use in pregnancy, presumably because these are relatively new products. There are no published e ectiveness trials of e-cigarettes in pregnancy, although one is underway (Hajek 2019b). One nonsystematic review of qualitative and quantitative studies from the USA investigating women's views on e-cigarette use in pregnancy included seven studies (McCubbin 2017): four qualitative (two included in this QES) and three cross-sectional surveys. The authors concluded that while participants believed e-cigarettes were generally safer than smoking, they were less certain about their safety in pregnancy, which echoes findings of this QES. The authors noted the scarcity of the evidence and highlighted the need for further research in this field.

Limitations of the qualitative evidence findings
Most studies contributed few relevant data to the findings of this review. Data from primary studies were relatively limited, with few studies contributing rich data to help answer study questions and some only contributing very small amounts. Very few studies of either NRT or e-cigarettes specifically investigated determinants of use. Furthermore, most did not state a theoretical perspective, and findings were mostly presented at the manifest level of the data. This made it challenging to move beyond primary studies' findings, so analytical themes remain close to descriptive ones. Most evidence came from UK-based studies, and two studies from the USA and Australia substantially supported their findings. Few studies reported findings on determinants of e-cigarette use, and therefore some identified determinants of NRT use (e.g. beliefs about addictiveness or side e ects) were not found within the available data to apply to e-cigarettes. It is possible that with more studies focusing specifically on determinants of NRT or e-cigarette use in pregnancy, additional determinants could be identified. Furthermore, the available evidence was insu icient to detect all di erences in determinants of NRT and e-cigarette use. Undescribed di erences may exist due to diverse ways of obtaining and/or accessing NRT and e-cigarettes, as well as varying social and cultural perceptions of these products. For example, in the UK, unusually, e-cigarette use is encouraged in non-pregnant people for harm reduction, but in pregnancy it is only encouraged to help women stop smoking when they cannot do so using other means (Smoking in Pregnancy Challenge Group 2019). In some other countries, for example Canada and Australia, nicotine-containing e-cigarettes are banned or restricted (Yong 2017). This division within the public health community regarding views on safety of ecigarettes as nicotine replacement/harm reduction products versus a product that may be harmful and addictive in its own right, may further contribute to the scarcity of the evidence base.
The included studies had some methodological limitations. Most did not use a theoretical perspective to guide the data collection and analysis, and findings were typically presented at the manifest level of the data. We also noted some issues with reporting of researchers' reflexivity, data collection, analysis, and sample characteristics. Overall, studies were of acceptable quality; however, these methodological issues could potentially pose a threat to the reliability and validity of the findings of included studies (Morse 2002).
We also note limitations relating to quality assessment in reviews of qualitative studies. There is still some controversy surrounding quality assessment tools for qualitative studies, and the methodology is developing (Noyes 2018; Santiago-Delefosse 2016). The current guidance suggests that scores for quality assessment in qualitative studies are meaningless (Munthe-Kaas 2018; Noyes 2018). Instead, review authors should report the methodological limitations of primary studies with an indication how these limitations can impact the interpretation of findings.

Implications for practice
Clear, consistent messages from health professionals about the relative safety and e ectiveness of NRT or e-cigarettes compared to smoking could potentially improve women's uptake and adherence to these products and may help some women to stop smoking. Furthermore, information on the most e ective ways of using these products could also potentially improve adherence and increase smoking cessation.

Implications for further research
To better understand pregnant women's decisions to use and adhere to NRT and e-cigarettes, future qualitative studies that specifically address determinants of use are needed. To understand more about pregnant trial participant's adherence to NRT and e-cigarettes, trials should be accompanied by qualitative studies that aim to understand factors influencing adherence to NRT and/ or e-cigarettes. Interview studies, focus groups, and case studies could help shed light on this issue. Furthermore, a strong evidence base for the safety of NRT and/or e-cigarettes in pregnancy could enable health professionals to more confidently deliver messages about their safety. Needed research includes rigorously conducted randomised control trials, with follow-up past childbirth in order to track pregnancy and infant outcomes. Care should also be taken to ensure that practitioners routinely collect data on exposure to NRT, e-cigarettes and smoking to enable accurate outcomes in studies using routine data. The findings of this QES point to an apparent gap in evidence, which should be addressed by more research in low-and middle-income countries, as well as countries where smoking prevalence in pregnancy is the highest, for example in Ireland or Bulgaria (Lange 2018).

FACTORS INFLUENCING USE OF NRT IN PREGNANCY FACTORS INFLUENCING E-CIGARETTE USE IN PREGNANCY
Theme 1: safety concerns about nicotine -women's beliefs about safety of nicotine-containing products influence their use in pregnancy Finding 1 : women believe that NRT is safer than smoking in general.
Finding 2 : women are concerned that NRT can deliver an unsafe amount of nicotine.
Finding 3 : women are concerned that using NRT during pregnancy can harm their baby.
Finding 4 : women believe that e-cigarettes are safer than smoking in general.
Finding 5 : women are concerned that e-cigarettes can deliver an unsafe amount of nicotine.
Finding 6 : women are concerned that using e-cigarettes during pregnancy can harm their baby.

Theme 2: concerns about addictiveness of nicotine -women's beliefs about addictiveness of nicotine influence their use of NRT in pregnancy
Finding 7 : women report concerns that NRT is as addictive as smoking.

Theme 3: effectiveness of nicotine-containing products -women's beliefs about the effectiveness of nicotine-containing products influence their use in pregnancy
Finding 8 : past positive experiences of NRT can facilitate NRT use in pregnancy.
Finding 9 : past negative experiences with NRT can be a barrier to NRT use in pregnancy.
Finding 10 : women present mixed views on effectiveness of e-cigarettes.

Theme 4: side effects -women's beliefs about and experiences with side effects of NRT influence their use in pregnancy
Finding 11 : women who report experiencing and feeling unable to deal with side effects of NRT, perceive these as a barrier to NRT use in pregnancy.

Theme 5: influence of others -women's readiness to use nicotine-containing products in pregnancy is influenced by the perceived views of and support from other people
Finding 12 : women who report receiving clear and consistent reassurance from health professionals about NRT safety in pregnancy feel this can facilitate NRT use.
Finding 13 : women who report experiencing lack of support towards NRT use from health professionals are reluctant to use NRT in pregnancy.
Finding 14 : women feel discouraged from using NRT in pregnancy by the perceived views and experiences of other people (non-health-professionals).
Finding 15 : women's readiness to use e-cigarettes in pregnancy is influenced by the advice they report receiving from their health professionals.
Finding 16 : women's readiness to use e-cigarettes in pregnancy is influenced by other people (non-professionals).

Theme 6: characteristics of nicotine-containing products can influence women's readiness to use them in pregnancy
Finding 17 : perceived characteristics of the NRT product, such as cost, convenience and ability to mimic a cigarette, can influence uptake and continuous use of NRT in pregnancy.
Finding 18 : perceived characteristics of e-cigarettes, such as cost, convenience and ability to mimic a cigarette, can influence uptake and continuous use of e-cigarettes in pregnancy.   Theme 6: characteristics of nicotine-containing products -women's views on characteristics of the nicotine-containing products can influence their readiness to use these in pregnancy Table 3. Summary of findings (Continued) Factors influencing the uptake and use of nicotine replacement therapy and e-cigarettes in pregnant women who smoke: a qualitative evidence synthesis (Review) Copyright Table 3. Summary of findings (Continued) NRT: nicotine replacement therapy.   Factors influencing the uptake and use of nicotine replacement therapy and e-cigarettes in pregnant women who smoke: a qualitative evidence synthesis (Review) Copyright   Cochrane Database of Systematic Reviews 32. 30 and 31 33. 32 not 29 NB: No filters for qualitative terms will be used, as these are not consistently e ective across databases.

Cochrane Database of Systematic Reviews
• Mixed-methods studies that include a distinct qualitative component, as described above tive methods) were used to analysed qualitative data

Phenomenon of interest
• Studies that explore experiences, views or opinions on NRT or e-cigarettes, of women who either smoked in pregnancy, and/or vaped/used NRT in pregnancy, as means to smoking cessation or harm reduction -Participants • Pregnant women who smoke or smoked at any point of their pregnancy or • Women in the postpartum period, who smoked at any point during their pregnancy • Study participants would not need to have experience of using NRT or e-cigarettes, as we are broadly interested in determinants of use/not use rather than just women's views formed after using NRT or e-cigarettes (but if they don't have experience of using NRT or e-cigs in pregnancy, they must have experience of smoking in pregnancy).
• For example, a typical qualitative research article in a journal with a smaller word limit and often using simple thematic analysis 4 A good amount and depth of qualitative data For example, a qualitative research article in a journal with a larger word count that includes more content and setting descriptors and a more indepth presentation of the findings 5 A large amount and depth of qualitative data For example, from a detailed ethnography or a published qualitative article