Developing a taxonomy to describe offspring outcomes in studies involving pregnant mammals' exposure to non-tobacco nicotine: A systematic scoping review.

INTRODUCTION: Many countries recommend Nicotine Replacement Therapy (NRT) for smoking cessation in pregnancy. Preclinical studies of nicotine exposure to pregnant mammals could indicate how nicotine may adversely affect the developing fetus. As a first step towards summarising this literature, we undertook a systematic scoping review to determine the number and nature of offspring outcomes studied. METHODS: We searched MEDLINE and EMBASE databases for papers reporting empirical data on offspring outcomes following nicotine exposure to pregnant non-human mammals. We excluded studies that investigated exposure to only smoking, e-cigarettes, nicotine vaccines, or studies with no 'nicotine only' group. We developed a draft taxonomy and using this, described and quantified outcomes reported. RESULTS: We identified 476 studies, which reported 729 offspring outcomes. The draft taxonomy classified outcomes as being measured in i) whole animals, ii) body systems and iii) 'other'. Body system outcomes were further categorised as being functional changes, or changes at macroscopic or cellular levels. The most frequently used outcomes were those detecting changes in the brain (n = 265), physical parameters measured in whole animals (n = 122) and any respiratory system changes (n = 97). CONCLUSIONS: This scoping review quantifies the nature and frequency of outcomes used in preclinical studies investigating the potential impacts of nicotine administration in pregnancy on offspring. Systematic reviews of studies investigating outcomes involving animal brains, respiratory system, or 'whole animal' outcomes may have greatest potential for further advancing knowledge regarding impacts of gestational nicotine exposure on offspring. PROTOCOL AND REGISTRATION: Protocol for this review can be found on Open Science Framework (https://osf.io/ptmzc/).

Fetal safety of nicotine replacement therapy in pregnancy: systematic review and meta-analysis.

BACKGROUND AND AIMS: Smoking in pregnancy causes substantial avoidable harm to mothers and offspring; nicotine replacement therapy (NRT) may prevent this, and is used to help women to quit. A recently updated Cochrane Review of randomized controlled trials (RCTs) investigating impacts of NRT in pregnancy focuses primarily on efficacy data, but also reports adverse impacts from NRT. Here we identify and summarize NRT impacts on adverse pregnancy outcomes reported in non-randomized controlled trials (non-RCTs). METHODS: Systematic reviews and meta-analyses of RCTs and non-RCT studies of NRT in pregnancy, with design-specific risk of bias assessment and grading of recommendations, assessment, development and evaluations (GRADE) criteria applied to selected outcomes. FINDINGS: Relevant Cochrane Review findings are reported alongside those from this new review. Seven RCTs were included; n = 2340. Nine meta-analyses were performed; non-statistically significant estimates indicated potentially reduced risk from NRT compared with smoking for mean birth weight, low birth weight, preterm birth, intensive care admissions, neonatal death, congenital anomalies and caesarean section and potentially increased risks for miscarriage and stillbirth. GRADE assessment for mean birth weight and miscarriage outcomes indicated 'low' confidence in findings. Twenty-three non-RCTs were included; n = 931 163. Eleven large studies from five routine health-care cohorts reported clinical outcomes; 12 small studies investigated mainly physiological outcomes within in-patient women given NRT. Findings from meta-analyses for congenital anomalies, stillbirth and preterm birth were underpowered and not in a consistent direction; GRADE assessment of confidence in findings was 'very low'. Routine health-care studies were of higher quality, but implications of reported findings were unclear as there was inadequate measurement and reporting of women's smoking. CONCLUSIONS: Available evidence from randomized controlled trials and non-randomized comparative studies does not currently provide clear evidence as to whether maternal use of nicotine replacement therapy during pregnancy is harmful to the fetus.

Stop smoking practitioner consensus on barriers and facilitators to smoking cessation in pregnancy and how to address these: A modified Delphi survey.

INTRODUCTION: Pregnant women can experience barriers and facilitators towards achieving smoking cessation. We sought consensus from smoking cessation practitioners on how influential pre-identified barriers and facilitators can be on pregnant women's smoking behaviour, and how difficult these might be to manage. Suggestions for techniques that could help overcome the barriers or enhance the facilitators were elicited and consensus sought on the appropriateness for their use in practice. METHODS: Forty-four practitioners who provided cessation support to pregnant women completed a three-round modified Delphi survey. Round one sought consensus on the 'influence' and 'difficulty' of the barriers and facilitators, and gathered respondents' suggestions on ways to address these. Rounds two and three sought further consensus on the barriers and facilitators and on 'appropriateness' of the respondent-suggested techniques. The techniques were coded for behaviour change techniques (BCTs) content using existing taxonomies. RESULTS: Barriers and facilitators considered to be the most important mainly related to the influence of significant others and the women's motivation & self-efficacy. Having a supportive partner was considered the most influential, whereas lack of support from partner was the only barrier that reached consensus as being difficult to manage. Barriers relating to social norms were also considered influential, however these received poor coverage of respondent-suggested techniques. Those considered the easiest to address mainly related to aspects of cessation support, including misconceptions surrounding the use of nicotine replacement therapy (NRT). Barriers and facilitators relating to the women's motivation & self-efficacy, such as the want to protect the baby, were also considered as being particularly easy to address. Fifty of the 54 respondent-suggested techniques reached consensus as being appropriate. Those considered the most appropriate ranged from providing support early, giving correct information on NRT, highlighting risks and benefits and reinforcing motivating beliefs. Thirty-three BCTs were identified from the respondent-suggested techniques. 'Social support (unspecified)', 'Tailor interactions appropriately' and 'Problem solving' were the most frequently coded BCTs. CONCLUSIONS: Involving partners in quit attempts was advocated. Existing support could be potentially improved by establishing appropriate ways to address barriers relating to pregnant smokers' 'social norms'. In general, providing consistent and motivating support seemed favourable.

Comparison of nicotine exposure during pregnancy when smoking and abstinent with nicotine replacement therapy: systematic review and meta-analysis.

BACKGROUND AND AIMS: Smoking during pregnancy is strongly associated with negative pregnancy and perinatal outcomes. Some guidelines recommend nicotine replacement therapy (NRT) for smoking cessation during pregnancy, but adherence with NRT is generally poor and could be partially explained by nicotine-related safety concerns. We compared pregnant women's cotinine and nicotine exposures from smoking with those when they were abstinent from smoking and using NRT. DESIGN: Systematic review with meta-analysis and narrative reporting. Twelve studies were included: in most, only one type of NRT was used. Seven were quality-assessed and judge of variable quality. SETTING: Studies from any setting that reported nicotine or cotinine levels when smoking and later when abstinent and using NRT. PARTICIPANTS: Pregnant women who smoked and became abstinent but used NRT either in a cessation study or in a study investigating other impacts of NRT. MEASUREMENTS: We quality-assessed longitudinal cohort studies using a modified version of the Newcastle-Ottawa scale. For meta-analysis, we used mean within-person differences in cotinine or nicotine levels when smoking and at later follow-up when abstinent and using NRT. Where such data were not available, we calculated differences in group mean levels and reported these narratively, indicating where data were not completely longitudinal. FINDINGS: Of the 12 included studies, four cotinine-measuring studies (n = 83) were combined in a random effects meta-analysis; the pooled estimate for the mean difference (95% confidence intervals) in cotinine levels between when women were smoking and abstinent but using NRT was 75.3 (57.1 to 93.4) ng/ml (I2  = 42.1%, P = 0.11). Of eight narratively-described studies, six reported lower cotinine and/or nicotine levels when abstinent and using NRT; two had mixed findings, with higher levels when abstinent but using NRT reported from at least one assay time-point. CONCLUSIONS: Pregnant women who use nicotine replacement therapy instead of smoking reduce their nicotine exposure.

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.

Improving Behavioral Support for Smoking Cessation in Pregnancy: What Are the Barriers to Stopping and Which Behavior Change Techniques Can Influence These? Application of Theoretical Domains Framework.

Behavioral support interventions are used to help pregnant smokers stop; however, of those tested, few are proven effective. Systematic research developing effective pregnancy-specific behavior change techniques (BCTs) is ongoing. This paper reports contributory work identifying potentially-effective BCTs relative to known important barriers and facilitators (B&Fs) to smoking cessation in pregnancy; to detect priority areas for BCTs development. A Nominal Group Technique with cessation experts (n = 12) elicited an expert consensus on B&Fs most influencing women's smoking cessation and those most modifiable through behavioral support. Effective cessation interventions in randomized trials from a recent Cochrane review were coded into component BCTs using existing taxonomies. B&Fs were categorized using Theoretical Domains Framework (TDF) domains. Matrices, mapping BCT taxonomies against TDF domains, were consulted to investigate the extent to which BCTs in existing interventions target key B&Fs. Experts ranked "smoking a social norm" and "quitting not a priority" as most important barriers and "desire to protect baby" an important facilitator to quitting. From 14 trials, 23 potentially-effective BCTs were identified (e.g., information about consequences). Most B&Fs fell into "Social Influences", "Knowledge", "Emotions" and "Intentions" TDF domains; few potentially-effective BCTs mapped onto every TDF domain. B&Fs identified by experts as important to cessation, are not sufficiently targeted by BCT's currently within interventions for smoking cessation in pregnancy.

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.