Amber Shaikh
Critically Appraised Topic
Scenario:
patient is a 35 year old pregnant woman with a 10 pack smoking history. She is looking to quit smoking for the safety of her baby, but is not sure what the best way to go about it is. She wants to know if using pharmacotherapy such as Nicotine replacement therapy would be safe and effective in helping her quit smoking.
PICO question:
For a woman who is pregnant, is the use of Nicotine replacement therapy for smoking cessation a safe and effective option?
PICO elements:
P Patient, population, or problem: Pregnant woman looking to stop smoking
I Intervention: Nicotine replacement therapy
C Comparison: Not using any medication
O Outcome: ease and efficacy of smoking cessation and risk of birth defects
What type of scenario is this and what type of study would best answer the question:
Therapy/prevention
Systematic review, meta analysis, Randomized control trail,
Databases-Search:1278
Resources used with relevant filters/limits: 358
JAMA network, Cochrane library, Medical Journal of Australia, Science Direct, Canadian Family Physician, NCBI – smoking cessation, efficacy of pharmacotherapy, nicotine replacement therapy, pregnancy, safety, past 10 years
| Author; reference | Level of Evidence | Patient group/
Data collection |
Primary and Secondary outcomes | Key findings | Limitations/Bias |
| Claire et al. 2020
Pharmacological interventions for promoting smoking cessation during pregnancy
|
Systematic Review | 11 Randomized controlled trails of 2412 pregnant women who smoked at enrollment: 9 trails of NRT and 2 trails of Bupropion as adjuncts to smoking cessation with behavioral therapy
|
Risk ration, mean difference, and confidence interval for each study was done
Certainty of evidence and outcomes was assessed using GRADE method
Looked at rate of smoking cessation as well as any harm caused to the newborn baby |
There was low certainty evidence that the NRT group showed greater smoking cessation in later pregnancy then the placebo group. There was clear evidence that the non placebo group showed benefit. When comparing NRT patches vs fast acting NRTs, there was no difference in effectiveness found. | NRTs may improve smoking cessation, but there is low certainty for this conclusion. As it is difficult to enroll pregnant women in such randomized trails, due to potential risk to baby, the evidence it found to be judged of low certainty value due to inconsistency and imprecision. |
| Ioakeimidis et al. 2018
Smoking cessation strategies in pregnancy; current concepts and controversies
|
Informative review/ meta analysis | Analysis of 200 articles using randomized controlled studies
Exact number of sample size unknown |
Broke down those at low risk for continuing smoking vs high risk. Low risk was referred to just counseling, high risk was advised to use NRTs in addition to counseling
-assessed the number of cigarettes smoked each day, and if that reduced
-assessed the birth weight of the baby (NRTs vs placebo) |
In the RCT trail of the NRT gum effectiveness; those in the NRT group smoked fewer cigarettes and had higher baby birth weights then the placebo group.
In terms of efficacy and safety, those using NRT (patch or gum, increased their chances of smoking cessation by 48% when compared to the placebo group that used no pharmacotherapy |
Due to the sensitive nature of the study, there was not enough sample size to create a confident high certainty conclusion. Meta-analysis comparing birth weight of babies was not conducted due to limitation in these trails: low subject number, lack of affirmation that the subjects stuck to the trail plan, publication bias, and lack of follow up. |
| Bar-Zeev et al. 2018
Nicotine Replacement Therapy for smoking cessation during pregnancy
|
Narrative/ observational review | Multiple studies were analyized:
1.) UK population based cohort study: NRT group (n=2677) vs smokers not using NRT (n=9980)
2.)Randomized control studies: 8 studies (5 double blind placebo controlled, 3 nonplacebo controlled studies) n= 2199 |
UK study used the odds ration and confidence interval to compare smoking cessation and major congenital anomalies.
UK cohort study also tested the difference of using both NRT patch and oral form, or just one form alone
Meta analysis of the RCTs looked at smoking cessation rates, congenital anomalies and cesarean births. |
UK study found no significant increase in risk of congenital anomalies, expect for slight increase in respiratory anomalies in those not using NRT.
UK cohort study showed that those who used combination of NRT oral and patch had a increased rate of smoking cessation vs those that used oral alone
RCT found that use of NRTs increased the rate of smoking cessation by 40% |
Limitations include a lot of women having low adherence to the NRT, not having the correct dose, NRTs dosages were not adjusted according to the increased metabolism during pregnancy, and withdrawal symptoms were not taken into consideration. |
| Cooper et al. 2014
The SNAP trial: a randomized placebo-controlled trial of nicotine replacement therapy in pregnancy–clinical effectiveness and safety until 2 years after delivery, with economic evaluation.
|
Randomized controlled trail | Total n=1,050 pregnant women
NRT: 521 Placebo: 529 |
Assessing clinical effectiveness of NRTs on development and behavior during pregnancy, at delivery, and at 2 years of age.
Self reported nicotine abstinence was reported along with CO level measurements.
Development impairments of the child were assessed at birth and at 2 years. |
NRT patches had no significant effect on smoking cessation during pregnancy, but 2 years olds of women who used NRTs had less developmental and cognitive impairments. | Higher doses of the NRT patch should be used in further studies to see if there is a significant difference, as in this study a 15mg NRT patch was used for a 16 hour period.
Also since a lot of the data is done by subjects self reporting, there is potential for data bias and inconsistency in results . |
| Cressman et al. 2012
Smoking cessation therapy during pregnancy
|
Systemic review/ meta analysis | Review of 5 different types of studies
Exact sample sizes not mentioned |
New born child’s birth weight was assessed as well as any major congenital malformations.
Rate of smoking cessation assessed |
Not enough significant information to show a change in smoking cessation with use of NRTs.
In those mothers using NRTs: safety hazards, low birth weights, congenital abnormalities and ICU admissions were all less in those using NRTs. NRTs should be used in addition to cognitive behavioral therapy for best results. A nicotine patch should be used and removed at night for increased safety. |
Lack on information on how NRTs affect pregnancy and smoking cessation
Inconclusive evidence due to lack of large sample sizes and concrete findings. |
Conclusion:
Article 1:
This article found low certainity of evidence of the benefit of NRTs for smoking cessation. It also compared the use of gum and patch forms of NRTs, and found no difference in the functionality of either. It also found no significant difference in the positive or negative effect of NRTs on birth defects. Research was limited due to lack of literature and publication bias.
Article 2:
This article highlighted the harms of smoking and nicotine on the baby, and that smoking cessation is crucial for the safety of the child. It highlighted the differences in high risk (>10 cigarettes) and low risk smokers and found that adjunct pharmocotherapy with NRTs is beneficial in high risk smokers. Further literature is required on the long term effects of NRTs and propensity for relapse.
Article 3:
This article highlighted the use of NRTs in a timely manner for smoking cessation. And if given properly and at the proper dose, it could provide overall benefit. Over all studies found that use of NRTs has a beneficial impact on limiting respiratory anomalies in children as well as it found that using combination forms such as oral and patch NRT has the most favorable outcome.
Article 4:
This study focused on the effect of NRT patches in smoking pregnant woman, as well as the lasting effecting it had on 2 year olds who were born to mothers who used NRTs. It found that the patch themselves had no lasting impact, and should be used as a higher dose, but did find that the 2 year olds whose mothers were on NRTs had fewer developmental abnormalities then those who did not use pharmacotherapy
Article 5:
This article is a systematic review looking at multiple different studies and their findings with the use of pharmacotherapy such as NRTs and bupropion for smoking cessation. Overall it found that the use of behavioral therapy and patient education should be the first line approach. However, if needed, NRTs can be added as an adjunct for helping with smoking cessation.
Bottom Line/Clinical Relevance:
When it comes to using pharmacotherapy such as Nicotine replacement therapy during pregnancy, several factors need to be considered: rate of smoking cessation, safety hazards during pregnancy, baby’s birth weight, and any congenital abnormalities. Currently, there is limited literature available assessing the affect of using NRTs during pregnancy to make a solid conclusion. This is due to the limitations of sample size (concerns of harming the baby), and lack of adherence to the therapy. However, over all it was found that the use of NRTs should be advised for this who are at high risk for continuing smoking during pregnancy (those who smoking more then 10 cigarettes a day), as an adjunct to cognitive behavioral therapy (which should always be used first). There is literature that supports that due to the harmful affects of nicotine on the growing fetus, the use of NRTs has shown a significant decrease in children born with congenital anomalies. Increased smoking cessation was also seen in those using NRTs, but is dependent on the subjects adherence to the proper dose based on their increased metabolism during pregnancy. Overall, NRTs seem to have a positive affect in those looking to stop smoking during pregnancy, but further research and literature is needed.
Due to lack of consistent literature on the use of NRTs during pregnancy for smoking cessation, I would always recommend the women to talk to the primary care provider before starting something that can potentially harm they baby. However, with the literature I found, I believe the use of dose monitored NRTs as an adjunct to behavioral therapy and counseling for high risk patients (those who smoke more then 10 cigarettes a day) will allow for increased rates of smoking cessation without causing harm to the baby. More information and studies need to be done however, correcting for the limitations such as publication bias, limited sample size, and dosage inconsistencies.
References:
Claire R, Chamberlain C, Davey MA, Cooper SE, Berlin I, Leonardi‐Bee J, Coleman T. Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database of Systematic Reviews 2020, Issue 3. Art. No.: CD010078. DOI: 10.1002/14651858.CD010078.pub3.
Abstract:
BackgroundTobacco 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 efficacyand safety when used for smoking cessation in pregnancy are also unknown.ObjectivesTo determine the efficacy and safety of smoking cessation pharmacotherapies and ECs used during pregnancy for smoking cessation inlater pregnancy and aCer childbirth, and to determine adherence to smoking cessation pharmacotherapies and ECs for smoking cessationduring pregnancy.Search methodsWe searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (20 May 2019), trial registers, and grey literature, and checkedreferences of retrieved studies.Selection criteriaRandomised controlled trials (RCTs) conducted in pregnant women, comparing smoking cessation pharmacotherapy or EC use with eitherplacebo or no pharmacotherapy/EC control. We excluded quasi-randomised, cross-over, and within-participant designs, and RCTs withadditional intervention components not matched between trial arms.Data collection and analysisWe followed standard Cochrane methods. The primary efficacy outcome was smoking cessation in later pregnancy; safety was assessedby 11 outcomes (principally birth outcomes) that indicated neonatal and infant well-being. We also collated data on adherence to trialtreatments. We calculated the risk ratio (RR) or mean difference (MD) and the 95% confidence intervals (CI) for each outcome for eachstudy, where possible. We grouped eligible studies according to the type of comparison. We carried out meta-analyses where appropriate.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010078.pub3/full
Ioakeimidis, Nikolaos, et al. “Smoking Cessation Strategies in Pregnancy: Current Concepts and Controversies.” Hellenic Journal of Cardiology, Elsevier, 5 Oct. 2018
Abstract:
Smoking during pregnancy is a risk factor associated with adverse pregnancy outcomes. Despite the fact that these outcomes are well known, a considerable proportion of pregnant women continue to smoke during this critical period. This paper evaluates critically smoking cessation interventions targeting pregnant women. We describe the findings of key published studies, review papers and expert statements to report the efficacy and safety of strategies for smoking cessation in pregnancy, including counselling and pharmacotherapy. Counselling appears to improve quit rates but mainly when used in combination with pharmacological therapy. Pharmacotherapy is recommended for women who are heavy smokers and are unable to quit smoking on their own. Nicotine replacement therapy is a reasonable first-line drug option. It is recommended that women who are pregnant, or planning to become pregnant, should be informed of potential risks for the foetus before considering smoking cessation therapy with bupropion or varenicline. Pregnant women view electronic nicotine delivery systems as being safer than combustible cigarettes, and this indeed may be the case; however, further evidence is required to assess their effectiveness as a smoking cessation aid and their safety for the mother and the child. Postpartum relapse is a significant problem, with approximately one out of two quitters relapsing in the first 2 months after delivery. These women should be considered ‘at risk’ and provided with ongoing support.
https://www.sciencedirect.com/science/article/pii/S1109966618302057
Bar-Zeev, Yael, et al. “Nicotine Replacement Therapy for Smoking Cessation during Pregnancy.” Medical Journal of Australia, Elsevier, 15 Jan. 2018
Abstract
Smoking during pregnancy is the most important preventable risk factor for poor maternal and infant health outcomes. In 2014, 11% of women who gave birth in Australia smoked at some point of their pregnancy, and smoking rates during pregnancy were higher for specific vulnerable populations, such as Aboriginal and Torres Strait Islander women (45%).1 Behavioural counselling combined with medication is the most effective smoking cessation strategy.2 In pregnant women who smoke, studies have shown counselling alone to be effective.3 Medications such as varenicline and bupropion are not recommended during pregnancy,4 and the use of nicotine replacement therapy (NRT), while well supported and safe for the general population,5 remains controversial for use during pregnancy because nicotine crosses the placenta and may accumulate in the amniotic fluid.6 Thus, it is important to gather evidence regarding the benefits and potential harms of NRT for pregnant women. In a recent survey of Australian general practitioners and obstetricians, 25% of participants stated that they never prescribe NRT during pregnancy.7 These findings mirror surveys from the United Kingdom,8 New Zealand9 and the United States.10 The most frequently cited barriers are low confidence in the ability to prescribe NRT and safety concerns.8,10 The aim of this narrative review is to provide an overview of current guidelines regarding NRT use in pregnancy, considering the existing evidence base on safety, efficacy and effectiveness. In addition, we outline pragmatic suggestions for clinical practice and implications for policy and future research.
https://www.mja.com.au/system/files/issues/208_01/10.5694mja17.00446.pdf
Cooper, Sue, et al. “The SNAP Trial: a Randomised Placebo-Controlled Trial of Nicotine Replacement Therapy in Pregnancy–Clinical Effectiveness and Safety until 2 Years after Delivery, with Economic Evaluation.” Health Technology Assessment (Winchester, England), NIHR Journals Library, Aug. 2014
Abstract
BACKGROUND: Smoking during pregnancy causes many adverse pregnancy and birth outcomes. Nicotine replacement therapy (NRT) is effective for cessation outside pregnancy but efficacy and safety in pregnancy are unknown. We hypothesised that NRT would increase smoking cessation in pregnancy without adversely affecting infants.
OBJECTIVES: To compare (1) at delivery, the clinical effectiveness and cost-effectiveness for achieving biochemically validated smoking cessation of NRT patches with placebo patches in pregnancy and (2) in infants at 2 years of age, the effects of maternal NRT patch use with placebo patch use in pregnancy on behaviour, development and disability.
DESIGN: Randomised, placebo-controlled, parallel-group trial and economic evaluation with follow-up at 4 weeks after randomisation, delivery and until infants were 2 years old. Randomisation was stratified by centre and a computer-generated sequence was used to allocate participants using a 1 : 1 ratio. Participants, site pharmacies and all study staff were blind to treatment allocation.
SETTING: Seven antenatal hospitals in the Midlands and north-west England.
PARTICIPANTS: Women between 12 and 24 weeks’ gestation who smoked ≥ 10 cigarettes a day before and ≥ 5 during pregnancy, with an exhaled carbon monoxide (CO) reading of ≥ 8 parts per million (p.p.m.).
INTERVENTIONS: NRT patches (15 mg per 16 hours) or matched placebo as an 8-week course issued in two equal batches. A second batch was dispensed at 4 weeks to those abstinent from smoking.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782812/
Cressman, Alex M., et al. “Smoking Cessation Therapy during Pregnancy.” The College of Family Physicians of Canada, The College of Family Physicians of Canada, 1 May 2012
Abstract
Question Despite being highly motivated to quit, many of my patients struggle with smoking cessation during pregnancy. Can you comment on the current treatment options and discuss their safety and efficacy during pregnancy?
Answer Given the considerable and well-documented adverse effects of antenatal smoking on mother and fetus, pharmacotherapy for smoking cessation should be considered. Available medications include nicotine replacement therapy, sustained-release bupropion, and varenicline. Nicotine replacement therapy and bupropion do not appear to increase the risk of major malformations; however, there is currently limited evidence on the use of varenicline during pregnancy. Given that these agents are only marginally successful in smoking cessation, their use should always be accompanied by behavioural counseling and education to maximize quit rates.
The risks of smoking during pregnancy are well known.1 Cigarette smoke contains thousands of compounds, many of which are well-documented reproductive toxins and carcinogens. Since the last Motherisk update on nicotine replacement therapy (NRT),2 new medications have been released that show improved efficacy in smoking cessation among nonpregnant populations compared with standard NRT or placebo.
