The effectiveness of nicotine replacement therapy during pregnancy: investigating the role of nicotine substitution, nicotine metabolism and pregnant smokers’ experiences

Nicotine replacement therapy (NRT) is effective in non-pregnant populations at assisting smoking cessation, but there is no evidence that NRT can help pregnant smokers to stop. Nicotine metabolism increases during pregnancy, and so the nicotine dose delivered by NRT could be insufficient for ameliorating withdrawal symptoms. However, little is known about the level of nicotine substitution provided by NRT or the pattern of nicotine metabolism during pregnancy. Also low adherence to NRT may explain why NRT does not appear to be effective. The overall aim of this thesis was to increase understanding as to why NRT does not appear to be effective during pregnancy. The thesis consists of three studies. The first study involved analysing data on 33 pregnant participants from the NRT arm of a randomised control trial who had stopped smoking and were still using 15mg/16hr nicotine patches 1 month after quitting. Salivary cotinine levels when smoking at baseline were compared with levels on NRT at 1 month. Cotinine levels were lower than those achieved from smoking (median 98.5ng/ml while smoking and 62.8ng/ml while using NRT and remaining abstinent, p = 0.045). The second study involved 101 pregnant smokers, who were asked to provide saliva samples to measure NMR at 8-14 weeks, 18-22 weeks , 32-36 weeks gestation, 4 weeks postpartum and 12 weeks postpartum . Compared with NMR at 12 weeks postpartum, NMR was significantly higher at 18-22 weeks (26% higher, 95% CI 12% to 38%) and 32-36 weeks (23% higher, 95% CI 9% to 35%). There was no difference between the 8-14 weeks gestation or 4 weeks postpartum NMR and 12 weeks postpartum. The third study was a qualitative study that involved semi-structured telephone interviews with 14 pregnant smokers who had recently been prescribed NRT, but self-reported low NRT adherence or discontinuing treatment prematurely. Thematic analysis was used to analyse data. Most smoked regularly while using NRT and many used NRT to cut down their cigarette intake rather than to quit abruptly. Some were concerned that using NRT instead of smoking could actually increase their nicotine dependency or cause greater harm to the fetus, and consequently often underutilised NRT. This thesis supports the hypothesis that NRT at standard doses may be ineffective in pregnancy due to increased metabolism. The effectiveness of NRT may be hindered by the way in which NRT is used in pregnancy

Understanding pregnant smokers’ adherence to nicotine replacement therapy during a quit attempt: a qualitative study

Background: Pregnant smokers may be offered nicotine replacement therapy (NRT) alongside behavioral support to assist with a quit attempt. Yet trials of NRT have found adherence to be low among pregnant women, and this has made it difficult to determine the efficacy of NRT. The aim of this study is to understand the experience of pregnant women who use NRT but discontinue this early or do not use the medication as recommended. Methods: Semi-structured telephone interviews were conducted with 14 pregnant smokers who had recently been prescribed NRT, but self-reported poor NRT adherence or discontinuing treatment prematurely. Data were transcribed and analyzed using inductive thematic analysis. Results: There were four main themes identified; expectations of NRT, experience of using NRT, safety concerns and experience of using e-cigarettes. Some women intentionally used NRT to substitute a proportion of their cigarette intake and smoked alongside. Most women smoked while using NRT. Women who underutilized NRT did so as they experienced side effects, or were concerned that using NRT instead of smoking could actually increase their nicotine exposure and potential for increased nicotine dependence or fetal harm. Most women spoke about the use of e-cigarettes as a smoking cessation method but only a few had actually experienced using them during pregnancy. Conclusion: Many women underused NRT but simultaneously smoked. Challenging negative perceptions about NRT and educating women further about the risks of smoking may encourage them to use NRT products as recommended.Implications: These findings add to the research surrounding the efficacy of NRT during pregnancy by providing insight into how pregnant women use NRT during a quit attempt and how this may influence adherence. It may assist health professionals to support pregnant smokers by increasing their understanding about the differing ways in which women use NRT and help them address concerns women may have about the safety of NRT

Changes in the rate of nicotine metabolism across pregnancy: a longitudinal study

Aims: Increased nicotine metabolism during pregnancy could explain why nicotine replacement therapy (NRT) appears to be less effective on smoking cessation in pregnancy than in non-pregnant smokers, but little is known about nicotine metabolism across pregnancy. This study was conducted to determine when changes in nicotine metabolism occur during pregnancy and to describe the magnitude of these changes. Design: Longitudinal cohort study of pregnant smokers' nicotine metabolite ratio (NMR). Setting and Participants: 101 pregnant smokers recruited from hospital antenatal clinics in Nottingham, UK were asked to provide saliva samples at 8–14 weeks (n = 98), 18–22 weeks (n = 65), 32–36 weeks gestation (n = 47), 4 weeks postpartum (n = 44) and 12 weeks postpartum (n = 47). Measurements: Nicotine metabolite ratio (NMR) was measured using the ratio of cotinine to its primary metabolite trans-3'-hydroxycotinine. Multi-level modelling was used to detect any overall difference in NMR between time points. The 12 week postpartum NMR was compared with the NMRs collected antenatally and 4 weeks postpartum. Findings: NMR changed over time (p = 0.0006). Compared with NMR at 12 weeks postpartum, NMR was significantly higher at 18–22 weeks (26% higher, 95% CI 12% to 38%) and 32–36 weeks (23% higher, 95% CI 9% to 35%). There was no significant difference between the 8-14 weeks gestation or 4 weeks postpartum NMR and 12 weeks postpartum. Conclusions: Nicotine metabolism appears to be faster during pregnancy; this faster metabolism is apparent from 18 to 22 weeks of pregnancy and appears to fall by 4 weeks after childbirth

Understanding Pregnant Smokers’ Adherence to Nicotine Replacement Therapy During a Quit Attempt: A Qualitative Study

This is the author accepted manuscript. The final version is available from Oxford University Press via http://dx.doi.org/10.1093/ntr/ntv205Background: Pregnant smokers may be offered nicotine replacement therapy (NRT) alongside behavioral support to assist with a quit attempt. Yet trials of NRT have found adherence to be low among pregnant women, and this has made it difficult to determine the efficacy of NRT. The aim of this study is to understand the experience of pregnant women who use NRT but discontinue this early or do not use the medication as recommended. Methods: Semi-structured telephone interviews were conducted with 14 pregnant smokers who had recently been prescribed NRT, but self-reported poor NRT adherence or discontinuing treatment prematurely. Data were transcribed and analyzed using inductive thematic analysis Results: There were four main themes identified; expectations of NRT, experience of using NRT, safety concerns and experience of using e-cigarettes. Some women intentionally used NRT to substitute a proportion of their cigarette intake and smoked alongside. Most women smoked while using NRT. Women who underutilized NRT did so as they experienced side effects, or were concerned that using NRT instead of smoking could actually increase their nicotine exposure and potential for increased nicotine dependence or fetal harm. Most women spoke about the use of e-cigarettes as a smoking cessation method but only a few had actually experienced using them during pregnancy. Conclusion: Many women underused NRT but simultaneously smoked. Challenging negative perceptions about NRT and educating women further about the risks of smoking may encourage them to use NRT products as recommended. Implications: These findings add to the research surrounding the efficacy of NRT during pregnancy by providing insight into how pregnant women use NRT during a quit attempt and how this may influence adherence. It may assist health professionals to support pregnant smokers by increasing their understanding about the differing ways in which women use NRT and help them address concerns women may have about the safety of NRT

Antenatal Clinic and Stop Smoking Services Staff Views on "Opt-Out" Referrals for Smoking Cessation in Pregnancy: A Framework Analysis.

Introduction: UK guidance recommends routine exhaled carbon monoxide (CO) screening for pregnant women and "opt-out" referrals to stop smoking services (SSS) of those with CO ≥ 4 ppm. We explored staff views on this referral pathway when implemented in one UK hospital Trust. Methods: Seventeen semi-structured interviews with staff involved in the implementation of the new referral pathway: six antenatal clinic staff (before and after implementation); five SSS staff (after). Data were analyzed using framework analysis. Results: Two themes were identified: (1) views on implementation of the pathway and (2) impact of the pathway on the women. Generally, staff felt that following training, referrals were less arduous to implement and better received than expected. The majority believed this pathway helped engage women motivated to quit and offered a unique chance to impart smoking cessation knowledge to hard-to-reach women, who might not otherwise contact SSS. An unexpected issue arose during implementation-dealing with non-smokers with high CO readings. Conclusions: According to staff, the "opt-out" referral pathway is an acceptable addition to routine antenatal care. It can help engage hard-to-reach women and educate them about the dangers of smoking in pregnancy. Incorporating advice on dealing with non-smokers with high CO into routine staff training could help future implementations.This work was supported by the NIHR under its Programme Grants for Applied Research (RP-PG 0109-10020). The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors are members of the UK Centre for Tobacco and Alcohol Studies. Funding to UKCTAS from the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Medical Research Council and the National Institute of Health Research, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged.This is the final version of the article. It first appeared from the Molecular Diversity Preservation International via https://doi.org/10.3390/ijerph1310100

Pregnant Women’s Experiences and Views on an “Opt-Out” Referral Pathway to Specialist Smoking Cessation Support: A Qualitative Evaluation

Introduction: Smoking in pregnancy remains an important and costly public health concern with policy makers worldwide researching methods to aid cessation. UK government guidelines recommend implementation of an ‘opt-out’ (i.e. whether requested or not) referral pathway for pregnant smokers to specialist smoking cessation support using carbon monoxide (CO) screening. This study explores the views of pregnant smokers who experienced this new pathway in one UK hospital trust. Methods Eighteen semi-structured telephone interviews with women who experienced the ‘opt-out’ pathway were undertaken. Data were analysed thematically. Results Three themes were identified relating to expectations, acceptability and impact of the pathway. Women were generally very accepting of the CO testing especially when it met their prior expectations and was perceived as being a routine component of antenatal care. They considered the visual feedback from the CO monitoring improved their motivation to quit. Views on the automatic referral for cessation support were divided with questions raised as to the removal of choice, with many women also expressing dissatisfaction about perceived lack of contact by Stop Smoking Services (SSS) following referral. Conclusion The ‘opt-out’ pathway is potentially an acceptable addition to current practice. The women considered CO monitoring to be the most valuable element of the pathway. Women keen to engage with SSS desired a more efficient system of contact.This article presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-0109-10020). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.This is the author accepted manuscript. The final version is available from Oxford University Press via http://dx.doi.org/10.1093/ntr/ntv27

Understanding pregnant smokers’ adherence to nicotine replacement therapy during a quit attempt: a qualitative study

Background: Pregnant smokers may be offered nicotine replacement therapy (NRT) alongside behavioral support to assist with a quit attempt. Yet trials of NRT have found adherence to be low among pregnant women, and this has made it difficult to determine the efficacy of NRT. The aim of this study is to understand the experience of pregnant women who use NRT but discontinue this early or do not use the medication as recommended.Methods: Semi-structured telephone interviews were conducted with 14 pregnant smokers who had recently been prescribed NRT, but self-reported poor NRT adherence or discontinuing treatment prematurely. Data were transcribed and analyzed using inductive thematic analysis.Results: There were four main themes identified; expectations of NRT, experience of using NRT, safety concerns and experience of using e-cigarettes. Some women intentionally used NRT to substitute a proportion of their cigarette intake and smoked alongside. Most women smoked while using NRT. Women who underutilized NRT did so as they experienced side effects, or were concerned that using NRT instead of smoking could actually increase their nicotine exposure and potential for increased nicotine dependence or fetal harm. Most women spoke about the use of e-cigarettes as a smoking cessation method but only a few had actually experienced using them during pregnancy.Conclusion: Many women underused NRT but simultaneously smoked. Challenging negative perceptions about NRT and educating women further about the risks of smoking may encourage them to use NRT products as recommended.Implications: These findings add to the research surrounding the efficacy of NRT during pregnancy by providing insight into how pregnant women use NRT during a quit attempt and how this may influence adherence. It may assist health professionals to support pregnant smokers by increasing their understanding about the differing ways in which women use NRT and help them address concerns women may have about the safety of NRT

Understanding pregnant smokers’ adherence to nicotine replacement therapy during a quit attempt: a qualitative study

Background: Pregnant smokers may be offered nicotine replacement therapy (NRT) alongside behavioral support to assist with a quit attempt. Yet trials of NRT have found adherence to be low among pregnant women, and this has made it difficult to determine the efficacy of NRT. The aim of this study is to understand the experience of pregnant women who use NRT but discontinue this early or do not use the medication as recommended. Methods: Semi-structured telephone interviews were conducted with 14 pregnant smokers who had recently been prescribed NRT, but self-reported poor NRT adherence or discontinuing treatment prematurely. Data were transcribed and analyzed using inductive thematic analysis. Results: There were four main themes identified; expectations of NRT, experience of using NRT, safety concerns and experience of using e-cigarettes. Some women intentionally used NRT to substitute a proportion of their cigarette intake and smoked alongside. Most women smoked while using NRT. Women who underutilized NRT did so as they experienced side effects, or were concerned that using NRT instead of smoking could actually increase their nicotine exposure and potential for increased nicotine dependence or fetal harm. Most women spoke about the use of e-cigarettes as a smoking cessation method but only a few had actually experienced using them during pregnancy. Conclusion: Many women underused NRT but simultaneously smoked. Challenging negative perceptions about NRT and educating women further about the risks of smoking may encourage them to use NRT products as recommended.Implications: These findings add to the research surrounding the efficacy of NRT during pregnancy by providing insight into how pregnant women use NRT during a quit attempt and how this may influence adherence. It may assist health professionals to support pregnant smokers by increasing their understanding about the differing ways in which women use NRT and help them address concerns women may have about the safety of NRT

Pregnant women’s experiences and views on an “opt-out” referral pathway to specialist smoking cessation support: a qualitative evaluation

Introduction: Smoking in pregnancy remains an important and costly public health concern with policy makers worldwide researching methods to aid cessation. UK government guidelines recommend implementation of an “opt-out” (ie, whether requested or not) referral pathway for pregnant smokers to specialist smoking cessation support using carbon monoxide (CO) screening. This study explores the views of pregnant smokers who experienced this new pathway in one UK hospital trust. Methods: Eighteen semi-structured telephone interviews with women who experienced the opt-out pathway were undertaken. Data were analyzed thematically. Results: Three themes were identified relating to expectations, acceptability and impact of the pathway. Women were generally very accepting of the CO testing especially when it met their prior expectations and was perceived as being a routine component of antenatal care. They considered the visual feedback from the CO monitoring improved their motivation to quit. Views on the automatic referral for cessation support were divided with questions raised as to the removal of choice, with many women also expressing dissatisfaction about perceived lack of contact by Stop Smoking Services (SSS) following referral. Conclusion: The opt-out pathway is potentially an acceptable addition to current practice. The women considered CO monitoring to be the most valuable element of the pathway. Women keen to engage with SSS desired a more efficient system of contact. Implications: This study presents a unique insight into pregnant women’s views on the implementation of opt-out referrals for smoking cessation. Introducing CO testing and opt-out referrals at the time of antenatal ultrasound examination can potentially increase motivation to stop smoking in pregnancy. The findings demonstrate that facilitating access to SSS was not always achieved, and further refinement is needed to ensure more effective contact procedures. Ensuring all women are fully informed prior to the CO testing may further improve both the impact of the opt-out referral pathway and the chance of successfully engaging with SSS