The Relationship Between Reported Daily Nicotine Dose from NRT and Daily Cigarette Consumption in Pregnant Women Who Smoke in an Observational Cohort Study.

INTRODUCTION: For nonpregnant people unable to quit smoking, the NHS recommends nicotine replacement therapy (NRT) for smoking reduction. This is not recommended during pregnancy due to concerns about higher nicotine intake than smoking alone. We investigated the relationship between daily nicotine dose from NRT and cigarette consumption reported by pregnant women receiving smoking cessation support. METHODS: We conducted secondary analysis of data from currently smoking pregnant women, recruited from antenatal clinics (Nottingham University Hospitals, UK) or online between June 2019-September 2020. Participants set a quit date, received a prototype NRT adherence intervention, and reported cigarettes per day (CPD) and daily NRT dose (mg) via smartphone app for 28 days. RESULTS: 388 women were screened, 32 (8%) were eligible and joined the study. 24 (75%) submitted 510 app reports in total. 17 (71%) reported smoking and using NRT concurrently on at least one day, with concurrent use reported on 109 (21%) of app reports.The relationship between daily NRT dose and CPD followed an exponential decay curve of approximately 7%. In multilevel repeated measures modelling using 4 linear splines (knots 17, 40, and 85 mg/NRT), significant fixed effects of daily NRT dose on CPD were observed for splines 1, 3, and 4. The strongest association was spline 1 (0-17 mg/NRT), where each 10 mg NRT increase was associated with a 0.6 CPD reduction (24% on average). CONCLUSIONS: Among women in a cessation study, many smoked and used NRT concurrently; within these women, daily nicotine dose and heaviness of smoking were inversely related. IMPLICATIONS: Findings have implications for the design of future interventions intended to reduce harm associated with smoking in pregnancy. They suggest using NRT alongside smoking in pregnancy could help some women reduce the number of cigarettes they smoke per day.

Digitalising Specialist Smoking Cessation Support in Pregnancy: Views of Pregnant Smokers.

INTRODUCTION: Unsupported attempts to quit smoking during pregnancy have a low success rate. Chances of quitting successfully are higher with an interpersonal treatment programme but there is low uptake of this in the United Kingdom (UK). Delivering a pregnancy-specific treatment programme digitally may provide an alternative treatment route. This study explored pregnant smokers' perceptions of barriers and facilitators to using digital cessation support, along with identifying modes of delivery and engagement enhancers. METHODS: Semi-structured interviews were carried out with an ethnically and socioeconomically diverse sample of 25 participants with recent experience of attempting to quit smoking in pregnancy, aged 20 - 40, from the UK. An inductive thematic analysis approach was used. RESULTS: Digital smoking cessation support, particularly a smartphone app, for pregnancy was felt to overcome many barriers to engaging with interpersonal support, being viewed as more convenient and non-judgemental, providing better consistency of advice, and enhancing privacy and autonomy. However, some participants felt that removing access to a human could undermine a digital support package and reduce engagement. Popular engagement enhancers included self-monitoring (e.g. digital recording of smoking; smartphone-linked carbon monoxide monitoring), online communities, and remote access to nicotine substitution options. Digital support was viewed as having potential as a stand-alone intervention or working in conjunction with standard interpersonal treatment. CONCLUSIONS: The findings support the investigation of a digital support package as both a stand-alone and adjunct to standard interpersonal cessation support in pregnancy to increase the proportion of pregnant smokers who make a supported quit attempt. IMPLICATIONS: In many countries like the UK, there are few smoking cessation options routinely available that provide effective support for smoking cessation in pregnancy. To maximise impact, health services need an effective range of strategies to engage with and support quit attempts made by all pregnant smokers, particularly as interpersonal support options are not often well engaged with. Development of a pregnancy-specific digital support package for smoking cessation in pregnancy may represent a means to help address this gap.

The Effectiveness of Text Support for Stopping Smoking in Pregnancy (MiQuit): Multi-Trial Pooled Analysis Investigating Effect Moderators and Mechanisms of Action.

INTRODUCTION: Digital cessation support appeals to pregnant smokers. In two pooled RCTs, MiQuit, a pregnancy-specific tailored text messaging intervention, did not show effectiveness for validated prolonged abstinence. However, secondary outcomes and potential moderators and mediators have not been investigated. We aimed to determine, using pooled RCT data: (1) MiQuit effectiveness on a range of smoking outcomes; (2) whether baseline tobacco dependence or quit motivation moderate effectiveness; (3) whether hypothesized mechanisms of action (quitting determination, self-efficacy, baby harm beliefs, lapse prevention strategies) mediate effectiveness. METHODS: Pooled data analysis from two procedurally identical RCTs comparing MiQuit (N = 704) to usual care (N = 705). Participants were smokers, <25 weeks pregnant, recruited from 40 English antenatal clinics. Outcomes included self-reported 7-day abstinence at 4 weeks post-baseline and late pregnancy, and prolonged abstinence. Late pregnancy outcomes were also biochemically validated. We used hierarchical regression and structural equation modeling. RESULTS: MiQuit increased self-reported, 7-day abstinence at 4 weeks (OR = 1.73 [95% CI 1.10-2.74]) and was borderline significant at late pregnancy (OR = 1.34 [0.99-1.82]) but not for prolonged or validated outcomes. Effectiveness was not moderated by baseline dependence (heaviness of smoking "low" vs. "moderate-high") or motivation (planning to quit ≤30 days [high] vs. >30 days [low]), but effects on self-reported outcomes were larger for the high motivation sub-group. MiQuit had a small effect on mean lapse prevention strategies (MiQuit 8.6 [SE 0.17], UC 8.1 [SE 0.17]; P = .030) but not other mechanisms. CONCLUSIONS: MiQuit increased short-term but not prolonged or validated abstinence and may be most effective for those motivated to quit sooner. IMPLICATIONS: Digital cessation support appeals to pregnant smokers. MiQuit, a tailored, theory-guided text messaging program for quitting smoking in pregnancy, has not shown effectiveness for validated prolonged abstinence in two previous RCTs but its impact on other smoking outcomes and potential mechanisms of action are unknown. When pooling trial data, MiQuit increased self-reported short-term abstinence, including making a quit attempt and abstinence at 4-week follow-up, but not late pregnancy, sustained, or validated abstinence. MiQuit appeared effective at late pregnancy for participants with high quitting motivation, but its mechanisms of action remain uncertain. Additional support components are likely required to enhance effectiveness.

Development of "Baby, Me, & NRT": A Behavioral Intervention to Improve the Effectiveness of Nicotine Replacement Therapy in Pregnancy.

BACKGROUND: The effectiveness of Nicotine Replacement Therapy (NRT) for smoking cessation in pregnancy is limited by inconsistent and incorrect use. This paper describes the development process for "Baby, Me, & NRT", a novel pregnancy-specific intervention aimed at enhancing adherence to NRT. METHODS: An integrated approach to intervention development was used, combining evidence, theory, stakeholders' feedback, and tailoring principles. The process involved six iterative steps: (1) synthesizing relevant published evidence and guidance, (2) collecting primary qualitative data on barriers and facilitators to NRT adherence along with potential intervention design features, (3) identifying relevant behavioral theories and mapping the evidence against these, (4) prioritizing behavioral determinants identified in steps 1 and 2, generating intervention objectives, and identifying behavior change techniques which target the prioritized determinants, (5) consulting with stakeholders on intervention components, key content and tailoring features, and (6) producing a prototype intervention along with implementation guidance. RESULTS: The prototype intervention comprises of a multi-component, 1-month cessation programme, which includes six enhanced behavioral support sessions delivered by a trained advisor, tailored text messages, a website, and an illustrated booklet. It promotes the uptake of high-dose and combination NRT, emphasizes the importance of adherence, addresses motivation to use NRT, proactively helps problem solve NRT use issues, and provides guidance on preventing and managing smoking lapses. CONCLUSION: The development process generated an evidence- and theory-guided intervention, designed with stakeholder input, aimed at improving NRT effectiveness for smoking cessation in pregnancy. The prototype intervention has since been optimized and is being evaluated in a randomized controlled trial.

Development and Content Validation of a Questionnaire for Measuring Beliefs About Using Nicotine Replacement Therapy for Smoking Cessation in Pregnancy.

INTRODUCTION: Improving adherence to nicotine replacement therapy (NRT) in pregnancy may result in higher smoking cessation rates. Informed by the Necessities and Concerns Framework, we developed an intervention targeting pregnancy NRT adherence. To evaluate this, we derived the NRT in pregnancy necessities and concerns questionnaire (NiP-NCQ), which measures perceived need for NRT and concerns about potential consequences. AIMS AND METHODS: Here we describe the development and content validation of NiP-NCQ. From qualitative work, we identified potentially modifiable determinants of pregnancy NRT adherence and classed these as necessity beliefs or concerns. We translated these into draft self-report items and piloted items on 39 pregnant women offered NRT and a prototype NRT adherence intervention, assessing distributions and sensitivity to change. After removing poorly performing items, smoking cessation experts (N = 16) completed an online discriminant content validation (DCV) task to determine whether retained items measure a necessity belief, concern, both, or neither construct. RESULTS: Draft NRT concern items encompassed safety for the baby, side effects, too much or insufficient nicotine, and addictiveness. Draft necessity belief items included perceived need for NRT for short- and longer-term abstinence, and desire to minimize or cope without NRT. Of 22 out of 29 items retained after piloting, four were removed following the DCV task: three were judged to measure neither construct and one possibly both. The final NiP-NCQ comprised nine items per construct (18 total). CONCLUSIONS: The NiP-NCQ measures potentially modifiable determinants of pregnancy NRT adherence within two distinct constructs and may have research and clinical utility for evaluating interventions targeting these. IMPLICATIONS: Poor adherence to NRT in pregnancy may result from low perceived need and concerns about consequences; interventions challenging these beliefs may yield higher smoking cessation rates. To evaluate an NRT adherence intervention informed by the Necessities and Concerns Framework, we developed the NiP-NCQ. Through the content development and refinement processes described in this paper, we derived an evidence-based, 18-item questionnaire measuring two distinct constructs within two nine-item subscales. Higher concerns and lower necessity beliefs indicate more negative NRT beliefs; NiP-NCQ may have research and clinical utility for interventions targeting these.

An Automated, Online Feasibility Randomized Controlled Trial of a Just-In-Time Adaptive Intervention for Smoking Cessation (Quit Sense).

INTRODUCTION: Learned smoking cues from a smoker's environment are a major cause of lapse and relapse. Quit Sense, a theory-guided Just-In-Time Adaptive Intervention smartphone app, aims to help smokers learn about their situational smoking cues and provide in-the-moment support to help manage these when quitting. METHODS: A two-arm feasibility randomized controlled trial (N = 209) to estimate parameters to inform a definitive evaluation. Smoker's willing to make a quit attempt were recruited using online paid-for adverts and randomized to "usual care" (text message referral to NHS SmokeFree website) or "usual care" plus a text message invitation to install Quit Sense. Procedures, excluding manual follow-up for nonresponders, were automated. Follow-up at 6 weeks and 6 months included feasibility, intervention engagement, smoking-related, and economic outcomes. Abstinence was verified using cotinine assessment from posted saliva samples. RESULTS: Self-reported smoking outcome completion rates at 6 months were 77% (95% CI 71%, 82%), viable saliva sample return rate was 39% (95% CI 24%, 54%), and health economic data 70% (95% CI 64%, 77%). Among Quit Sense participants, 75% (95% CI 67%, 83%) installed the app and set a quit date and, of those, 51% engaged for more than one week. The 6-month biochemically verified sustained abstinence rate (anticipated primary outcome for definitive trial), was 11.5% (12/104) among Quit Sense participants and 2.9% (3/105) for usual care (adjusted odds ratio = 4.57, 95% CIs 1.23, 16.94). No evidence of between-group differences in hypothesized mechanisms of action was found. CONCLUSIONS: Evaluation feasibility was demonstrated alongside evidence supporting the effectiveness potential of Quit Sense. IMPLICATIONS: Running a primarily automated trial to initially evaluate Quit Sense was feasible, resulting in modest recruitment costs and researcher time, and high trial engagement. When invited, as part of trial participation, to install a smoking cessation app, most participants are likely to do so, and, for those using Quit Sense, an estimated one-half will engage with it for more than 1 week. Evidence that Quit Sense may increase verified abstinence at 6-month follow-up, relative to usual care, was generated, although low saliva return rates to verify smoking status contributed to considerable imprecision in the effect size estimate.

Promoting and Maintaining Changes in Smoking Behavior for Patients Following Discharge from a Smoke-free Mental Health Inpatient Stay: Development of a Complex Intervention Using the Behavior Change Wheel.

INTRODUCTION: Evidence suggests that smokers can successfully quit, remain abstinent or reduce smoking during a smoke-free mental health inpatient stay, provided behavioral/pharmacological support are offered. However, few evidence-based strategies to prevent the return to prehospital smoking behaviors post-discharge exist. AIMS AND METHODS: We report the development of an intervention designed to support smoking-related behavior change following discharge from a smoke-free mental health stay. We followed the Behavior Change Wheel (BCW) intervention development process. The target behavior was supporting patients to change their smoking behaviors following discharge from a smoke-free mental health stay. Using systematic reviews, we identified the barriers and enablers, classified according to the Theoretical Domains Framework (TDF). Potential intervention functions to address key influences were identified by consulting the BCW and Behavior Change Technique (BCT) taxonomy. Another systematic review identified effectiveness of BCTs in this context. Stakeholder consultations were conducted to prioritize and refine intervention content. RESULTS: Barriers and enablers to supporting smoking cessation were identified within the domains of environmental context and resources (lack of staff time); knowledge (ill-informed interactions about smoking); social influences, and intentions (lack of intention to deliver support). Potential strategies to address these influences included goal setting, problem-solving, feedback, social support, and information on health consequences. A strategy for operationalizing these techniques into intervention components was agreed upon: Pre-discharge evaluation sessions, a personalized resource folder, tailored behavioral and text message support post-discharge, and a peer interaction group, delivered by a trained mental health worker. CONCLUSIONS: The intervention includes targeted resources to support smoking-related behavior change in patients following discharge from a smoke-free mental health setting. IMPLICATIONS: Using the BCW and TDF supported a theoretically and empirically informed process to define and develop a tailored intervention that acknowledges barriers and enablers to supporting smoking cessation in mental health settings. The result is a novel complex theory- and evidence-based intervention that will be formally tested in a randomized controlled feasibility study.

Trends in Prescribing of Nicotine Replacement Therapy to Pregnant Women in Primary Care in England.

INTRODUCTION: Smoking during pregnancy remains common, and the English National Health Service (NHS) has recently been directed to prioritize providing cessation support for pregnant women. We investigated the impact on prescribing of stop smoking treatments to pregnant women of the 2013 transfer of public health budgets from the NHS to administrative authorities responsible for local social care and other nonhealth services (local authorities). METHODS: We used data from the Clinical Practice Research Datalink and Hospital Episode Statistics to determine annual proportions (2005-2017) of women who smoked during pregnancy and who were prescribed, at least once before childbirth, (1) any NRT and (2) long- and short-acting NRT together (dual NRT). Segmented regression was used to quantify the impact of the 2013 transfer of smoking cessation budgets to local authorities, assessing changes in the level and the trend of the proportions post-2013 compared with pre-2013. RESULTS: We identified 84 539 pregnancies in which women were recorded as smoking; any NRT was prescribed in 7.9% (n = 6704) and dual NRT in 1.7% (n = 1466). Prescribing of any NRT was declining prior to 2013 at an absolute decrease of -0.25% per year, but the rate of decline significantly increased from 2013 onwards to -1.37% per year. Prescribing of dual NRT was increasing prior to 2013 but also decreased post-2013. CONCLUSIONS: These findings suggest that transferring responsibility for English Smoking Cessation Services from the NHS to local authorities adversely affected provision of cessation support in pregnancy. Consequently, some women may have been denied access to effective cessation treatments. IMPLICATIONS: Women who smoke during pregnancy may be being denied potentially effective means to help them quit, contrary to NICE guidance, at what can be a teachable moment with substantial immediate and longer-term health benefits for woman and their unborn child, and economic benefits for the NHS. When the organizations responsible for offering smoking cessation support are changed, health systems should consider potential adverse effects on the delivery of support and deploy strategies for mitigating these.

Using Trial Sequential Analysis for estimating the sample sizes of further trials: example using smoking cessation intervention.

BACKGROUND: Assessing benefits and harms of health interventions is resource-intensive and often requires feasibility and pilot trials followed by adequately powered randomised clinical trials. Data from feasibility and pilot trials are used to inform the design and sample size of the adequately powered randomised clinical trials. When a randomised clinical trial is conducted, results from feasibility and pilot trials may be disregarded in terms of benefits and harms. METHODS: We describe using feasibility and pilot trial data in the Trial Sequential Analysis software to estimate the required sample size for one or more trials investigating a behavioural smoking cessation intervention. We show how data from a new, planned trial can be combined with data from the earlier trials using trial sequential analysis methods to assess the intervention's effects. RESULTS: We provide a worked example to illustrate how we successfully used the Trial Sequential Analysis software to arrive at a sensible sample size for a new randomised clinical trial and use it in the argumentation for research funds for the trial. CONCLUSIONS: Trial Sequential Analysis can utilise data from feasibility and pilot trials as well as other trials, to estimate a sample size for one or more, similarly designed, future randomised clinical trials. As this method uses available data, estimated sample sizes may be smaller than they would have been using conventional sample size estimation methods.

Interest in and Use of Smoking Cessation Support Across Pregnancy and Postpartum.

BACKGROUND: Limited research exists on interest in and use of smoking cessation support in pregnancy and postpartum. METHODS: A longitudinal cohort of pregnant smokers and recent ex-smokers were recruited in Nottinghamshire, United Kingdom (N = 850). Data were collected at 8-26 weeks gestation, 34-36 weeks gestation, and 3 months postpartum and used as three cross-sectional surveys. Interest and use of cessation support and belief and behavior measures were collected at all waves. Key data were adjusted for nonresponse and analyzed descriptively, and multiple regression was used to identify associations. RESULTS: In early and late pregnancy, 44% (95% CI 40% to 48%) and 43% (95% CI 37% to 49%) of smokers, respectively, were interested in cessation support with 33% (95% CI 27% to 39%) interested postpartum. In early pregnancy, 43% of smokers reported discussing cessation with a midwife and, in late pregnancy, 27% did so. Over one-third (38%) did not report discussing quitting with a health professional during pregnancy. Twenty-seven percent of smokers reported using any National Health Service (NHS) cessation support and 12% accessed NHS Stop Smoking Services during pregnancy. Lower quitting confidence (self-efficacy), higher confidence in stopping with support, higher quitting motivation, and higher age were associated with higher interest in support (ps ≤ .001). A recent quit attempt and greater interest in support was associated with speaking to a health professional about quitting and use of NHS cessation support (ps ≤ .001). CONCLUSIONS: When asked in early or late pregnancy, about half of pregnant smokers were interested in cessation support, though most did not engage. Cessation support should be offered throughout pregnancy and after delivery. IMPLICATIONS: There is relatively high interest in cessation support in early and late pregnancy and postpartum among smokers; however, a much smaller proportion of pregnant or postpartum women access any cessation support, highlighting a gap between interest and engagement. Reflecting women's interest, offers of cessation support should be provided throughout pregnancy and after delivery. Increasing motivation to quit and confidence in quitting with assistance may enhance interest in support, and promoting the discussion of stopping smoking between women and health practitioners may contribute to higher support engagement rates.

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.

Identifying Effective Behavior Change Techniques for Alcohol and Illicit Substance Use During Pregnancy: A Systematic Review.

BACKGROUND: During pregnancy, consuming alcohol and using illicit drugs can have serious health implications for both mother and child. Behavioral change interventions, especially those underpinned by theoretical constructs, can be effective in reducing harmful substance use among pregnant women. PURPOSE: To understand what type of behavior change mechanisms could be useful in reducing alcohol consumption or achieving abstinence from illicit drug use during pregnancy, this review aimed to identify behavior change techniques (BCTs), the smallest, active components of interventions that may be effective. It also aimed to establish the extent that psychosocial-based theories were used to inform intervention design. METHODS: To identify eligible randomized controlled trials (RCTs), five databases were searched electronically from the end search dates of the most recent Cochrane systematic reviews on behavioral interventions for each behavior, until March 2018. Within the RCTs, intervention descriptions were analyzed for BCT content and extent of theory use in the intervention design process and outcome measurements, in each trial, was established. "Effectiveness percentages," the number of times a BCT had been a component of an effective intervention divided by the total number of interventions it had been used in, were calculated for BCTs used in two or more trials. RESULTS: Including all RCTs from the Cochrane reviews, and those published subsequently, nine alcohol and six illicit drug trials were identified. Interventions tested in four alcohol RCTs and no illicit drugs RCTs showed positive results. Subsequent data were extracted for alcohol consumption trials only. Thirteen BCTs showed "potential effectiveness" for alcohol consumption. Six of nine included alcohol trials reported using theory but not extensively. CONCLUSIONS: Action planning, behavioral contract, prompts/cues, self-talk, offer/direct toward written material, problem solving, feedback on behavior, social support (unspecified), information about health consequences, behavior substitution, assess current readiness and ability to reduce excess alcohol consumption, goal setting (behavior), and tailor interactions appropriately are BCTs that could be useful in helping reduce alcohol consumption among pregnant women.

Systematic Review and Meta-Analysis to Assess the Safety of Bupropion and Varenicline in Pregnancy.

INTRODUCTION: Smoking in pregnancy is a substantial public health issue, but, apart from nicotine replacement therapy (NRT), pharmacological therapies are not generally used to promote cessation. Bupropion and varenicline are effective cessation methods in nonpregnant smokers and this systematic review investigates their safety in pregnancy. METHODS: We searched MEDLINE, EMBASE, CINAHL, and PsychINFO databases for studies of any design reporting pregnancy outcomes after bupropion or varenicline exposure. We included studies of bupropion used for smoking cessation, depression, or where the indication was unspecified. Depending on study design, quality was assessed using the Newcastle-Ottawa Scale or Cochrane Risk of Bias Tool. Most findings are reported narratively but meta-analyses were used to produce pooled estimates for the proportion of live births with congenital malformations and of the mean birthweight and gestational age at delivery following bupropion exposure. RESULTS: In total, 18 studies were included: 2 randomized controlled trials, 11 cohorts, 2 case- control studies, and 3 case reports. Study quality was variable. Gestational safety outcomes were reported in 14 bupropion and 4 varenicline studies. Meaningful meta-analysis was only possible for bupropion exposure, for which the pooled estimated proportion of congenital malformations amongst live-born infants was 1.0% (95% CI = 0.0%-3.0%, I2 = 80.9%, 4 studies) and the mean birthweight and mean gestational age at delivery was 3305.9 g (95% CI = 3173.2-3438.7 g, I2 = 77.6%, 5 studies) and 39.2 weeks (95% CI = 38.8-39.6 weeks, I2 = 69.9%, 5 studies), respectively. CONCLUSIONS: There was no strong evidence that either major positive or negative outcomes were associated with gestational use of bupropion or varenicline. PROSPERO registration number CRD42017067064. IMPLICATIONS: We believe this to be the first systematic review investigating the safety of bupropion and varenicline in pregnancy. Meta-analysis of outcomes following bupropion exposure in pregnancy suggests that there are no major positive or negative impacts on the rate of congenital abnormalities, birthweight, or premature birth. Overall, we found no evidence that either of these treatments might be harmful in pregnancy, and no strong evidence to suggest safety, but available evidence is of poor quality.

Stillbirth Among Women Prescribed Nicotine Replacement Therapy in Pregnancy: Analysis of a Large UK Pregnancy Cohort.

INTRODUCTION: We aimed to compare risk of stillbirth between maternal smokers and those prescribed nicotine replacement therapy (NRT) during pregnancy. AIMS AND METHODS: We conducted a cross-sectional analysis on a pregnancy cohort of 220,630 singleton pregnancies ending in live or stillbirth between 2001 and 2012 from The Health Improvement Network UK general practice database. Women were categorized into three groups: NRT (prescribed during pregnancy or 1 month before conception); smokers; and controls (nonsmokers without a pregnancy NRT prescription). We calculated Odds ratios (OR) and corresponding 95% confidence intervals (CI) for stillbirth in the NRT group and smokers compared to controls. RESULTS: A total of 805 pregnancies ended in stillbirth (3.6/1000 births). Absolute risks of stillbirth in NRT and smoker groups were both 5/1000 births compared with 3.5/1000 births in the control group. Compared with the control group, the adjusted odds of stillbirth in the NRT group was not statistically significant (OR = 1.35, 95% CI 0.91 to 2.00), although it was similar in magnitude to that in the smokers group (OR = 1.41, 95% CI 1.13 to 1.77). CONCLUSIONS: We found no evidence of a statistically significant association between being prescribed NRT during pregnancy and odds of stillbirth compared with nonsmoking women. Although our study had much larger numbers than any previously, an even larger study with biochemically validated smoking outcome data and close monitoring of NRT use throughout pregnancy is required to exclude effects on findings of potential exposure misclassification.

Safety of Electronic Cigarette Use During Breastfeeding: Qualitative Study Using Online Forum Discussions.

BACKGROUND: Electronic cigarettes (e-cigs) are an increasingly popular alternative to smoking, helping to prevent relapse in those trying to quit and with the potential to reduce harm as they are likely to be safer than standard cigarettes. Many women return to smoking in the postpartum period having stopped during pregnancy, and while this can affect their decisions about breastfeeding, little is known about women's opinions on using e-cigs during this period. OBJECTIVE: The aim of this study is to explore online forum users' current attitudes, motivations, and barriers to postpartum e-cig use, particularly as a breastfeeding mother. METHODS: Data were collected via publicly accessible (identified by Google search) online forum discussions, and a priori codes identified. All transcripts were entered into NVivo for analysis, with a template approach to thematic analysis being used to code all transcripts from which themes were derived. RESULTS: Four themes were identified: use, perceived risk, social support and evidence, with a number of subthemes identified within these. Women were using e-cigs to prevent postpartum return to smoking, but opinions on their safety were conflicting. They were concerned about possible transfer of harmful products from e-cigs via breastmilk and secondhand exposure, so they were actively seeking and sharing information on e-cigs from a variety of sources. Although some women were supportive of e-cig use, others provided harsh judgement for mothers who used them. CONCLUSIONS: E-cigs have the potential to reduce the number of women who return to smoking in the postpartum period and potentially improve breastfeeding rates, if breastfeeding mothers have access to relevant and reliable information. Health care providers should consider discussing e-cigs with mothers at risk of returning to smoking in the postpartum period.

Predictors of Postpartum Return to Smoking: A Systematic Review.

Background: Finding effective ways to help pregnant women quit smoking and remain abstinent is a major public health issue. Approximately half of UK women who smoke attempt cessation after conception; unfortunately, up to 75% return to smoking within 12 months postpartum. Interventions for preventing postpartum return to smoking (PPRS) have not been found to be effective. It is important to identify factors associated with PPRS, to inform development of alternative interventions. Aim: Identify by systematic review factors associated with PPRS. Methods: Systematic searches of electronic databases (MEDLINE, EMBASE, PsychINFO, CINAHL), trials registers, and conference proceedings were conducted to November 2016. Studies statistically examining factors associated with PPRS were included. Modified versions of the Newcastle Ottawa Quality Assessment Scale were used to assess studies' quality and a narrative synthesis focused on those judged of high quality. Results: Thirty-nine studies (12 trials, 27 observational studies) were included. Thirty-one (79.5%) studies were high-quality. Among these, the most common significant predictors of PPRS were being less well educated, younger, multiparous, living with a partner or household member who smoked, experiencing higher stress, depression or anxiety, not breastfeeding, intending to quit only for pregnancy and low confidence to remain abstinent postpartum. Conclusions: Of the factors found to be associated with PPRS, intending to quit smoking only for the duration of pregnancy, partner/household member smoking and confidence to remain abstinent are those most likely to have a direct, causal impact on smoking behavior after childbirth, and need to be considered when designing interventions to prevent PPRS. Implications: This is the first systematic review of factors that may facilitate or inhibit PPRS. Considering how having a partner or household member who smokes, intending to quit smoking only for pregnancy, having self-efficacy to quit long term, breastfeeding and depression exert direct or indirect impacts on women's relapse to smoking and how such impacts could successfully be manipulated will inform development of new interventions to prevent PPRS.

A randomised controlled trial of a complex intervention to reduce children's exposure to secondhand smoke in the home.

OBJECTIVES: Exposing children to secondhand tobacco smoke (SHS) causes significant harm and occurs predominantly through smoking by caregivers in the family home. We report a trial of a complex intervention designed to reduce secondhand smoke exposure of children whose primary caregiver feels unable or unwilling to quit smoking. DESIGN: An open-label, parallel, randomised controlled trial. SETTING: Deprived communities in Nottingham City and County, England PARTICIPANTS: Caregivers resident in Nottingham City and County in England who were at least 18 years old, the main caregiver of a child aged under 5 years living in their household, and reported that they were smoking tobacco inside their home. INTERVENTIONS: We compared a complex intervention combining personalised feedback on home air quality, behavioural support and nicotine replacement therapy for temporary abstinence with usual care. MAIN OUTCOMES: The primary outcome was change in air quality in the home, measured as average 16-24 hours levels of particulate matter of < 2.5 µm diameter (PM2.5), between baseline and 12 weeks. Secondary outcomes included changes in maximum PM2.5, proportion of time PM2.5 exceeded WHO recommended levels of maximum exposure of 25 µg/mg3, child salivary cotinine, caregivers' cigarette consumption, nicotine dependence, determination to stop smoking, quit attempts and quitting altogether during the intervention. RESULTS: Arithmetic mean PM2.5 decreased significantly more (by 35.2 %; 95% CI 12.7% to 51.9 %) in intervention than in usual care households, as did the proportion of time PM2.5 exceeded 25 µg/mg3, child salivary cotinine concentrations, caregivers' cigarette consumption in the home, nicotine dependence, determination to quit and likelihood of having made a quit attempt. CONCLUSIONS: By reducing exposure to SHS in the homes of children who live with smokers unable or unwilling to quit, this intervention offers huge potential to reduce children's' tobacco-related harm. TRIAL REGISTRATION NUMBER: ISRCTN81701383.This trial was funded by the UK National Institute for Health Research (NIHR): RP-PG-0608-10020.

Physical activity for antenatal and postnatal depression in women attempting to quit smoking: randomised controlled trial.

BACKGROUND: Antenatal depression is associated with harmful consequences for both the mother and child. One intervention that might be effective is participation in regular physical activity although data on this question in pregnant smokers is currently lacking. METHODS: Women were randomised to six-weekly sessions of smoking cessation behavioural-support, or to the same support plus 14 sessions combining treadmill exercise and physical activity consultations. RESULTS: Among 784 participants (mean gestation 16-weeks), EPDS was significantly higher in the physical activity group versus usual care at end-of-pregnancy (mean group difference (95% confidence intervals (CIs)): 0.95 (0.08 to 1.83). There was no significant difference at six-months postpartum. CONCLUSION: A pragmatic intervention to increase physical activity in pregnant smokers did not prevent depression at end-of-pregnancy or at six-months postpartum. More effective physical activity interventions are needed in this population. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48600346 . The trial was prospectively registered on 21/07/2008.

Views on and experiences of electronic cigarettes: a qualitative study of women who are pregnant or have recently given birth.

BACKGROUND: Electronic cigarettes (ECs) are increasingly used for reducing or stopping smoking, with some studies showing positive outcomes. However, little is known about views on ECs during pregnancy or postpartum and previous studies have nearly all been conducted in the US and have methodological limitations, such as not distinguishing between smokers and ex/non-smokers. A greater understanding of this topic will help to inform both clinicians and EC interventions. We elicited views and experiences of ECs among UK pregnant or recently pregnant women. METHODS: We conducted semi-structured telephone interviews, using topic guides, with pregnant or recently pregnant women, who were current or recent ex-smokers. To ensure broad views of ECs were obtained, recruitment was from several geographical locations and via various avenues of recruitment. This included stop smoking services, antenatal and health visitor clinics, a pregnancy website and an informal network. Participants were 15 pregnant and 15 postpartum women, including nine current EC users, 11 ex-users, and 10 never-users. Five women who were interviewed in pregnancy were later interviewed in postpartum to explore if their views had changed. Audio data was transcribed verbatim and framework analysis was applied. RESULTS: Five main themes emerged: motivations for use (e.g., for stopping or reducing smoking), social stigma (e.g., avoiding use in public, preferring 'discrete' NRT), using the EC (e.g., mostly used at home); consumer aspects (e.g., limited advice available), and harm perceptions (e.g., viewed as less harmful than smoking; concerns about safety and addiction). CONCLUSIONS: ECs were viewed positively by some pregnant and postpartum women and seen as less harmful than smoking and useful as aids for reducing and stopping smoking. However, due to perceived social stigma, some women feel uncomfortable using ECs in public, especially during pregnancy, and had concerns about safety and nicotine dependence. Health professionals and designers of EC interventions need to provide women with up-to-date and consistent information and advice about safety and dependence, as well as considering the influence of social stigma.