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.

Pharmacological interventions for promoting smoking cessation during pregnancy.

BACKGROUND: Tobacco smoking in pregnancy causes serious health problems for the developing fetus and mother. When used by non-pregnant smokers, pharmacotherapies (nicotine replacement therapy (NRT), bupropion, and varenicline) are effective for increasing smoking cessation, however their efficacy and safety in pregnancy remains unknown. Electronic cigarettes (ECs) are becoming widely used, but their efficacy and safety when used for smoking cessation in pregnancy are also unknown. OBJECTIVES: To determine the efficacy and safety of smoking cessation pharmacotherapies and ECs used during pregnancy for smoking cessation in later pregnancy and after childbirth, and to determine adherence to smoking cessation pharmacotherapies and ECs for smoking cessation during pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 May 2019), trial registers, and grey literature, and checked references of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) conducted in pregnant women, comparing smoking cessation pharmacotherapy or EC use with either placebo or no pharmacotherapy/EC control. We excluded quasi-randomised, cross-over, and within-participant designs, and RCTs with additional intervention components not matched between trial arms. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. The primary efficacy outcome was smoking cessation in later pregnancy; safety was assessed by 11 outcomes (principally birth outcomes) that indicated neonatal and infant well-being. We also collated data on adherence to trial treatments. We calculated the risk ratio (RR) or mean difference (MD) and the 95% confidence intervals (CI) for each outcome for each study, where possible. We grouped eligible studies according to the type of comparison. We carried out meta-analyses where appropriate. MAIN RESULTS: We included 11 trials that enrolled a total of 2412 pregnant women who smoked at enrolment, nine trials of NRT and two trials of bupropion as adjuncts to behavioural support, with comparable behavioural support provided in the control arms. No trials investigated varenicline or ECs. We assessed four trials as at low risk of bias overall. The overall certainty of the evidence was low across outcomes and comparisons as assessed using GRADE, with reductions in confidence due to risk of bias, imprecision, and inconsistency. Compared to placebo and non-placebo (behavioural support only) controls, there was low-certainty evidence that NRT increased the likelihood of smoking abstinence in later pregnancy (RR 1.37, 95% CI 1.08 to 1.74; I² = 34%, 9 studies, 2336 women). However, in subgroup analysis by comparator type, there was a subgroup difference between placebo-controlled and non-placebo controlled RCTs (test for subgroup differences P = 0.008). There was unclear evidence of an effect in placebo-controlled RCTs (RR 1.21, 95% CI 0.95 to 1.55; I² = 0%, 6 studies, 2063 women), whereas non-placebo-controlled trials showed clearer evidence of a benefit (RR 8.55, 95% CI 2.05 to 35.71; I² = 0%, 3 studies, 273 women). An additional subgroup analysis in which studies were grouped by the type of NRT used found no difference in the effectiveness of NRT in those using patches or fast-acting NRT (test for subgroup differences P = 0.08). There was no evidence of a difference between NRT and control groups in rates of miscarriage, stillbirth, premature birth, birthweight, low birthweight, admissions to neonatal intensive care, caesarean section, congenital abnormalities, or neonatal death. In one study infants born to women who had been randomised to NRT had higher rates of 'survival without developmental impairment' at two years of age compared to the placebo group. Non-serious adverse effects observed with NRT included headache, nausea, and local reactions (e.g. skin irritation from patches or foul taste from gum), but data could not be pooled. Adherence to NRT treatment regimens was generally low. We identified low-certainty evidence that there was no difference in smoking abstinence rates observed in later pregnancy in women using bupropion when compared to placebo control (RR 0.74, 95% CI 0.21 to 2.64; I² = 0%, 2 studies, 76 women). Evidence investigating the safety outcomes of bupropion use was sparse, but the existing evidence showed no difference between the bupropion and control group. AUTHORS' CONCLUSIONS: NRT used for smoking cessation in pregnancy may increase smoking cessation rates in late pregnancy. However, this evidence is of low certainty, as the effect was not evident when potentially biased, non-placebo-controlled RCTs were excluded from the analysis. Future studies may therefore change this conclusion. We found no evidence that NRT has either positive or negative impacts on birth outcomes; however, the evidence for some of these outcomes was also judged to be of low certainty due to imprecision and inconsistency. We found no evidence that bupropion may be an effective aid for smoking cessation during pregnancy, and there was little evidence evaluating its safety in this population. Further research evidence on the efficacy and safety of pharmacotherapy and EC use for smoking cessation in pregnancy is needed, ideally from placebo-controlled RCTs that achieve higher adherence rates and that monitor infants' outcomes into childhood. Future RCTs of NRT should investigate higher doses than those tested in the studies included in this review.

Pharmacological interventions for promoting smoking cessation during pregnancy.

BACKGROUND: Smoking in pregnancy is a public health problem. When used by non-pregnant smokers, pharmacotherapies (nicotine replacement therapy (NRT), bupropion and varenicline) are effective for smoking cessation, however, their efficacy and safety in pregnancy remains unknown. Electronic Nicotine Delivery Systems (ENDS), or e-cigarettes, are becoming widely used but their efficacy and safety when used for smoking cessation in pregnancy are also unknown. OBJECTIVES: To determine the efficacy and safety of smoking cessation pharmacotherapies (including NRT, varenicline and bupropion), other medications, or ENDS when used for smoking cessation in pregnancy. SEARCH METHODS: We searched the Pregnancy and Childbirth Group's Trials Register (11 July 2015), checked references of retrieved studies, and contacted authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) conducted in pregnant women with designs that permit the independent effects of any type of pharmacotherapy or ENDS on smoking cessation to be ascertained were eligible for inclusion.The following RCT designs are included.Placebo-RCTs: any form of NRT, other pharmacotherapy, or ENDS, with or without behavioural support/cognitive behaviour therapy (CBT), or brief advice, compared with an identical placebo and behavioural support of similar intensity.RCTs providing a comparison between i) any form of NRT, other pharmacotherapy, or ENDS added to behavioural support/CBT, or brief advice and ii) behavioural support of similar (ideally identical) intensity.Parallel- or cluster-randomised trials were eligible for inclusion. Quasi-randomised, cross-over and within-participant designs were not, due to the potential biases associated with these designs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias and also independently extracted data and cross checked individual outcomes of this process to ensure accuracy. The primary efficacy outcome was smoking cessation in later pregnancy (in all but one trial, at or around delivery); safety was assessed by 11 outcomes (principally birth outcomes) that indicated neonatal and infant well-being; and we also collated data on adherence with trial treatments. MAIN RESULTS: This review includes a total of nine trials which enrolled 2210 pregnant smokers: eight trials of NRT and one trial of bupropion as adjuncts to behavioural support/CBT. The risk of bias was generally low across trials with virtually all domains of the 'Risk of bias' assessment tool being satisfied for the majority of studies. We found no trials investigating varenicline or ENDS. Compared to placebo and non-placebo controls, there was a difference in smoking rates observed in later pregnancy favouring use of NRT (risk ratio (RR) 1.41, 95% confidence interval (CI) 1.03 to 1.93, eight studies, 2199 women).  However, subgroup analysis of placebo-RCTs provided a lower RR in favour of NRT (RR 1.28, 95% CI 0.99 to 1.66, five studies, 1926 women), whereas within the two non-placebo RCTs there was a strong positive effect of NRT, (RR 8.51, 95% CI 2.05 to 35.28, three studies, 273 women; P value for random-effects subgroup interaction test = 0.01). There were no differences between NRT and control groups in rates of miscarriage, stillbirth, premature birth, birthweight, low birthweight, admissions to neonatal intensive care, caesarean section, congenital abnormalities or neonatal death. Compared to placebo group infants, at two years of age, infants born to women who had been randomised to NRT had higher rates of 'survival without developmental impairment' (one trial). Generally, adherence with trial NRT regimens was low. Non-serious side effects observed with NRT included headache, nausea and local reactions (e.g. skin irritation from patches or foul taste from gum), but these data could not be pooled. AUTHORS' CONCLUSIONS: NRT used in pregnancy for smoking cessation increases smoking cessation rates measured in late pregnancy by approximately 40%. There is evidence, suggesting that when potentially-biased, non-placebo RCTs are excluded from analyses, NRT is no more effective than placebo. There is no evidence that NRT used for smoking cessation in pregnancy has either positive or negative impacts on birth outcomes. However, evidence from the only trial to have followed up infants after birth, suggests use of NRT promotes healthy developmental outcomes in infants. Further research evidence on NRT efficacy and safety is needed, ideally from placebo-controlled RCTs which achieve higher adherence rates and which monitor infants' outcomes into childhood. Accruing data suggests that it would be ethical for future RCTs to investigate higher doses of NRT than those tested in the included studies.

Pharmacological interventions for promoting smoking cessation during pregnancy.

BACKGROUND: Smoking in pregnancy is a substantial public health problem. When used by non-pregnant smokers, pharmacotherapies [nicotine replacement therapy (NRT), bupropion and varenicline] are effective treatments for smoking cessation, however, their efficacy and safety in pregnancy remains unknown. OBJECTIVES: To determine the efficacy and safety of smoking cessation pharmacotherapies, including NRT, varenicline and bupropion (or any other medications) when used to support smoking cessation in pregnancy. SEARCH METHODS: We searched the Pregnancy and Childbirth Group's Trials Register (5 March 2012), checked references of retrieved studies and contacted authors in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) with designs that permit the independent effects of any type of NRT (e.g. patch, gum etc.) or any other pharmacotherapy on smoking cessation to be ascertained were eligible for inclusion. Trials must provide very similar (ideally identical) levels of behavioural support or cognitive behaviour therapy (CBT) to participants in active drug and comparator trial arms.The following RCT designs are considered acceptable.Placebo RCTs: any form of NRT or other pharmacotherapy, with or without behavioural support/CBT, or brief advice compared with placebo NRT and additional support of similar intensity.RCTs providing a comparison between i) behavioural support/CBT or brief advice and ii) any form of NRT or other pharmacotherapy added to behavioural support of similar (ideally identical) intensity.Parallel- or cluster-randomised design trials are eligible for inclusion. However, quasi-randomised, cross-over and within-participant designs are not eligible for inclusion due to the potential biases associated with these designs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias and extracted data. Two assessors independently extracted data and cross checked individual outcomes of this process to ensure accuracy. The primary efficacy outcome was smoking cessation in later pregnancy (in all but one trial, at or around delivery); safety was assessed by seven birth outcomes that indicated neonatal well being and we also collated data on adherence. MAIN RESULTS: Six trials of NRT enrolling 1745 pregnant smokers were included; we found no trials of varenicline or bupropion. No statistically significant difference was seen for smoking cessation in later pregnancy after using NRT as compared to control (risk ratio (RR) 1.33, 95% confidence interval (CI) 0.93 to 1.91, six studies, 1745 women). Subgroup analysis comparing placebo-RCTs with those which did not use placebos found that efficacy estimates for cessation varied with trial design (placebo RCTs, RR 1.20, 95% CI 0.93 to 1.56, four studies, 1524 women; non-placebo RCTs, RR 7.81, 95% CI 1.51 to 40.35, two studies, 221 women; P value for random-effects subgroup interaction test = 0.03). There were no statistically significant differences in rates of miscarriage, stillbirth, premature birth, birthweight, low birthweight, admissions to neonatal intensive care or neonatal death between NRT or control groups. AUTHORS' CONCLUSIONS: Nicotine replacement therapy is the only pharmacotherapy for smoking cessation that has been tested in RCTs conducted in pregnancy. There is insufficient evidence to determine whether or not NRT is effective or safe when used to promote smoking cessation in pregnancy or to determine whether or not using NRT has positive or negative impacts on birth outcomes. Further research evidence of efficacy and safety is needed, ideally from placebo-controlled RCTs that investigate higher doses of NRT than were tested in the included studies.