Learning Objectives:After participating in this continuing education activity, the provider should be better able to:
1. Explain the 5A approach to nicotine use and how it can be applied during pregnancy.
2. Describe current pharmacologic and nonpharmacologic treatments for nicotine use as applicable to pregnant and nonpregnant women.
3. Differentiate among nicotine delivery products.
This article is the second of 2 parts.
Nicotine use, particularly cigarette smoking, during pregnancy continues to be a leading preventable cause of poor maternal and birth outcomes.1 Cigarettes are still the dominant form of nicotine products, although emerging products like electronic nicotine delivery systems (ENDSs) are quickly gaining popularity. Among women, nicotine use is most common between ages 18 and 45 years, and cigarette smoking is especially prominent among women living in rural areas and women with substance use disorders. Because the age range overlaps with a woman's reproductive years, it is highly likely that obstetricians and gynecologists will have contacts with women who use nicotine and should be encouraged to support reduction or cessation of nicotine use for these individuals. This review describes terminology about nicotine use, describes means for screening for nicotine use and providing brief interventions to support reduction of cessation attempts, and describes other intensive interventions that may be incorporated into practice or for which a person may be referred. Lastly, some new frontiers and potential upcoming federal regulations about nicotine products have been explored.
This review has at least 3 applications to practice. First, practitioners will be better equipped to screen and provide brief interventions for nicotine use. Second, a practitioner will be better able to counsel patients about more intensive treatments when patients are seeking additional help. Finally, practitioners will be able to converse more confidently and completely with a firmer knowledge of emerging products and upcoming federal regulations.
Important Definitions and Consistent Language
It is important to delineate between nicotine/tobacco use and tobacco use disorder. Nicotine or tobacco use refers to the use of products, whereas tobacco use disorder is the diagnostic term used when official criteria are met as defined by the Diagnostic and Statistical Manual of Mental Disorders.2 Like all other substance use disorders, simply using a nicotine product does not mean a person can be diagnosed with tobacco use disorder. Tobacco use disorder criteria include inability to control nicotine or tobacco use, use despite negative impacts on work or social functioning, and use despite knowledge that continuing to use is imminently dangerous or is exacerbating a physical or psychological harm associated with use. Generally, people who use tobacco or nicotine products daily meet criteria for tobacco use disorder. Others may engage in more sporadic nicotine use, like only in certain social situations, which is sometimes called "chipping." People who use nicotine products infrequently tend to not meet criteria for tobacco use disorder.
Tobacco or nicotine tolerance refers to the reduction in effect derived from consistent use of the same dose and the need to increase intake to achieve the desired effect. Tobacco or nicotine withdrawal refers to unpleasant effects that occur when bioavailable nicotine levels fall. Tobacco or nicotine withdrawal includes psychological symptoms like anxiety, depressed mood, and irritability, motor symptoms like restlessness, insomnia, and cognitive symptoms like difficulty concentrating. Increased appetite also occurs in tobacco or nicotine withdrawal, which can lead to weight gain.
Screening for Nicotine Use
Universal screening for nicotine use among pregnant and reproductive-aged women is recommended by the American College of Obstetricians and Gynecologists.3 Questions about nicotine use should specifically name products other than cigarettes, like ENDSs (eg, e-cigs, vapes, and vape pens) and noncombustible products like mints, candies, and gums, as individuals may not consider these as problematic products. Further, comprehensive screening for use of all drugs is recommended because smoking is often associated with use of other legal and illegal drugs. Screening means asking questions about use, not testing urine or blood samples for the presence of drugs or their metabolites.
Screening should be nonjudgmental, brief, and direct. Screening should also be repeated at subsequent visits, as growing rapport with the provider may lead to more disclosure of use. Using a structured question, like in Table 1, can also detect changes in use that can be celebrated. People who respond that they have never smoked, smoked fewer than 100 cigarettes, used nicotine products only a few times in their lifetime, or have stopped smoking or using nicotine products should be congratulated on their success and encouraged to remain abstinent from nicotine. Individuals who report continuing to use nicotine should not be scolded or sanctioned, as this may deteriorate rapport and undermine further behavior change. A strategy for responding to recalcitrant nicotine use is described below.
Treatments for Nicotine Use in Pregnancy
Many treatments for tobacco use disorder in the general population are applicable in pregnancy. Treatments often include a combination of pharmacotherapy, psychotherapy, and behavioral interventions. Combining pharmacotherapy with a behavioral intervention increases the likelihood of successful quitting by 10% to 20%.4 A framework for approaching nicotine use that is easily implemented into clinical practice is called the "5As"-Ask, Advise, Assess, Assist, and Arrange (Table 1).
As described previously, universally screening for nicotine use is the first step, "Ask," in the 5As framework. For people who report continuing nicotine use, the next step is to briefly advise the person of the importance of quitting and assess a person's readiness to stop nicotine use. Assessing readiness to quit can be done with brief questions, such as "On a scale of 1 to 10, how confident are you that you could stop nicotine use in the near future?" A follow-up question could be "Why did you say that and not a lower number?" This prompts the person to think about what strengths they can leverage for quitting.
For people who do not express a readiness to stop nicotine use, motivational interviewing techniques are recommended for enhancing motivation to stop nicotine use.5 Motivational interviewing is a client-centered approach, which involves facilitating self-exploration to identify a person's own goals, barriers to achieving goals, and strengths that will aid their success. A key component of motivational interviewing is reflective listening on the part of the provider. Rather than providing reasons why nicotine use is harmful in pregnancy and listing potential treatments, a motivational interviewing approach involves demonstrating empathy and acknowledging the difficulty of stopping nicotine use. Most people who use nicotine products have tried to quit or reduce use in the past. Asking about past attempts, and then asking questions that build upon past success, like asking what factors motivated them at that time to change their nicotine use behavior, what things made them successful, and what was a barrier, can help the person connect to that past success. The person may then be able to determine whether these past factors are still present or may be different. By listening to the person's responses, gently identifying discrepancies between behaviors and goals, providing personalized feedback based on what the person reports, and using positive language to support a person's strengths can then help the person build their self-motivation. Although this may sound like a lengthy process, this brief form of counseling adds only 3 minutes to encounters.6
To assist people who are ready to stop nicotine use, a brief treatment plan must be developed. These plans are individualized but have some common components. First, people should be encouraged to set a target quit date within the next 2 weeks. It is also helpful for the person to tell their family and social contacts that they are making a quit attempt, brainstorm some barriers and solutions to quitting, and to remove nicotine products from their regular environment. Another resource is the quitline, 1-800-QUIT-NOW, which provides people with confidential telephone counseling, self-help materials, and connects people to free quitting resources and free supplies of nicotine replacement therapy. Physicians should offer people seeking to quit nicotine use the FDA-approved medications for tobacco use disorder.
The FDA-approved medications for tobacco use disorder include nicotine replacement therapy, bupropion, and varenicline. Nicotine replacement therapy, which involves transdermal patches, inhalers, nasal sprays, gums, and lozenges, are the most used medications. These medications provide nicotine to alleviate withdrawal symptoms, ideally preventing the need to use a nicotine product. These products come in multiple dose levels, and a typical regimen involves using gradually lower doses over time. The starting dose is based on the frequency of nicotine use (typically a number of cigarettes smoked per day), with dose reductions every 2 to 4 weeks.
Nicotine replacement therapy has been the most widely studied pharmacotherapy for use in pregnancy. Its use is controversial, given the potential for nicotine to affect fetal development and marginal evidence of effectiveness at achieving cessation of cigarette smoking in pregnancy. The FDA classifies the nicotine patch in pregnancy category D (known fetal risk with benefits outweighing risk), with the other nicotine products in pregnancy category C (adverse fetal effects in animal studies but insufficient data in humans). In a meta-analysis of randomized controlled trials of nicotine replacement therapy, placebo-controlled trials revealed no significant benefit of nicotine replacement therapy achieving abstinence from smoking [relative risk (RR), 1.21; 95% confidence interval (CI), 0.95-1.55], whereas non-placebo-controlled trials revealed higher abstinence rates (RR, 8.55; 95% CI, 2.05-35.71).7 Overall, the trials that used nicotine patches revealed a slight, but statistically significant effect on smoking cessation (RR, 1.52; 95% CI, 1.16-2.01) and the 2 studies that used nicotine gum and nasal spray revealed no significant effects on cessation. There were no consistent significant effects of nicotine replacement therapy on any secondary measures, including miscarriage, stillbirth, birth weight, preterm birth, neonatal intensive care unit admissions, neonatal death, or congenital abnormalities. Despite the marginal evidence in controlled trials, nicotine replacement therapy using nicotine patches is a common intervention to address cigarette smoking in pregnancy.
Bupropion is a mild dopamine and norepinephrine reuptake inhibitor that is commonly used to treat depression, including during pregnancy. Its actions with dopamine and norepinephrine may reduce nicotine withdrawal by producing mild nicotine-stimulant effects. In the nonpregnant population, bupropion combined with cognitive-behavioral therapy achieved abstinence among 44% of women at the end of 7 weeks of treatment compared with 18% of women who received bupropion combined with standard therapy.8 Bupropion is in the FDA's pregnancy category B and is currently being studied for smoking cessation in pregnancy. The one published randomized trial demonstrated abstinence rates of 19% versus 2% in bupropion versus placebo groups, respectively, during treatment, but no significant difference in 7-day point-prevalence abstinence at the end of the 12-week treatment period.9
Varenicline is a partial agonist of nicotinic acetylcholine receptors. This means that varenicline produces mild nicotine-like effects, and it prevents nicotine from binding to these receptors. The mild nicotine-like effects can reduce withdrawal symptoms, and the blockade of receptors reduces the effects of additional nicotine use. Varenicline is the most effective pharmacotherapy, more than doubling the likelihood of abstinence at 6 or more months compared with placebo.10 Varenicline may also be more effective at helping women meet short-term smoking cessation goals compared with men. In a systematic review of 16 studies, women were 46% more likely than men to have 7 days of continuous abstinence after 12 weeks of treatment with varenicline, and over 30% more likely than men to be continuously abstinent at the end of treatment and at 6 months.11 Although the FDA removed varenicline's "black box" warning in 2016, patients taking varenicline should be monitored for increased depression and suicidal ideation. Varenicline is in FDA's pregnancy category C and has not been experimentally evaluated for smoking cessation during pregnancy. Meta-analyses of incidental varenicline exposure (eg, by a nonpregnant person who becomes pregnant during use of varenicline) suggest low risk of adverse outcomes due to exposure.12
One of the most effective behavioral therapies for nicotine use among pregnant and reproductive-aged women is contingency management, with 13% to 45% of participants with confirmed abstinence in randomized trials.13 In contingency management for nicotine use, incentives are provided contingent upon the patient providing a biospecimen that tests negative for evidence of nicotine use. Incentives are usually financial, either cash or vouchers redeemable for goods or services. Several biomarkers of nicotine use can be tested, but the most common are expired carbon monoxide and urinary or salivary cotinine. For patients who smoke cigarettes, expired carbon monoxide can be measured through a portable carbon monoxide detector. A reading of less than 6 to 8 parts per million is generally accepted as indicative of several hours of abstinence from cigarette smoking. Expired carbon monoxide is sensitive to short bouts of abstinence, which makes it ideal for initiating abstinence or reinforcing longer times between cigarettes. However, people could still smoke and provide negative carbon monoxide samples if enough time lapses between smoking and the test. Also, carbon monoxide is only effective for combustible tobacco products. Nicotine's primary metabolite, cotinine, can be detected in saliva or urine for several days. This makes cotinine testing less sensitive to short bouts of abstinence but more sensitive to long bouts of abstinence. Cotinine is also a biomarker of both combustible and noncombustible tobacco product use. Point-of-care test strips are available to rapidly test both saliva and urine for cotinine.
Contingency management is underutilized despite its effectiveness. In the past, practitioner effort and cost have been viewed as barriers to implementation. To maximize effectiveness, patients need to provide biospecimens multiple times per week, and someone need to quickly perform the tests and deliver the incentives. New technologies and methods have been developed to mitigate these barriers, such as internet and smartphone applications and devices. Rather than visiting the physician's office, patients may engage with remote providers, provide biospecimens that are tested at home with internet-connected devices, and receive incentives electronically. In some services, the patient deposits an amount of money to be repaid as incentives, which alleviates the cost barrier. Hopefully, these innovations will increase implementation of this highly effective intervention.
Mindfulness-based treatments for nicotine use have received growing interest in research and practice. In general, mindfulness involves attending to the present moment, internal and external sensations, in a nonjudgmental manner. Applied to nicotine use, this involves attending to physiological cues related to nicotine use or withdrawal and learning that these sensations are temporary, and do not require an impulsive reaction (ie, nicotine use) to remove. A mindfulness approach also involves a detachment from narrative storylines around nicotine use, or failed quit attempts, through attending to just what is happening in a present moment. There have been a few randomized controlled trials of mindfulness-based approaches to smoking cessation, and many have taken different forms through blending with other methodology. One of the largest randomized trials (n = 419) compared mindfulness-based stress reduction techniques combined with cognitive-behavioral therapy to traditional cognitive behavioral therapy and to brief counseling.14 There were no significant differences between the 3 groups in smoking abstinence after 4 or 26 weeks of treatment, with 24% to 34% and 11% to 15% abstinent, respectively. Participants who received the mindfulness-based approach were significantly more likely to return to abstinence after a lapse, with 28% becoming abstinent again within 1 week of completing treatment compared with less than 15% in the other groups. Meta-analysis of the relatively small literature of randomized controlled trials suggests mindfulness-based approaches are not superior to control groups for smoking cessation.15 That said, most trials used active control groups, so at the very least mindfulness-based approaches are not ineffective compared with other interventions. There are promising data that mindfulness-based approaches can be highly effective, so this is an area both worthy and in need of further research.
New Frontiers
Products
New nicotine products and devices have emerged, as the use of combustible tobacco products has decreased. ENDSs, sometimes called e-cigarettes, vaporizers, "vapes," or "vape pens," are currently the most widely used noncombustible alternatives to traditional combustible tobacco products. Rather than burning tobacco, ENDS use an "e-liquid" that is heated and vaporized, and then the user inhales the vapor. E-liquids primarily contain propylene glycol and/or glycerin into which flavorings and nicotine are suspended. Additional e-liquid contents are possible, but ingredients are not required to be listed on packaging. E-liquids may be prepared by a manufacturer, though many are mixed and sold in retail stores. As a result, the nicotine content of e-liquids is variable and may not match the products' labels.
The general thought is that the harms associated with ENDS use are less than combustible tobacco products, but the data are not conclusive. There are also many unanswered questions about the short- and long-term effects of inhaling e-liquid vapors. In the context of pregnancy, concerns remain that exposure to nicotine through ENDS may be associated with the same poor infant outcomes as maternal cigarette smoking. The public, including pregnant and postpartum women, views ENDS as less harmful than combustible tobacco products, and there is interest in using ENDS to help people reduce or abstain from cigarette smoking. Several randomized controlled trials have demonstrated that ENDS can facilitate smoking reductions or cessation similar to nicotine replacement therapy,16 but the evidence remains limited.
Although ENDSs are the most used noncombustible tobacco product, dissolvable nicotine products and novel preparations of powdered tobacco have grown in popularity, especially among those who use more mainstream tobacco products like cigarettes. Snus is a nonfermented, moistened tobacco powder that is placed against the gums, usually in the top lip. Unlike chewing tobacco, snus use requires no spitting, making it easier to use. In the United States, snus is often sweetened and flavored, further increasing its appeal. Snus may be sold loose in a tin, or in portioned pouches that look somewhat like teabags. Dissolvable products like mints, orbs, and strips that contain nicotine, or toothpicks coated in dissolvable tobacco are also available and are typically used by people who also use combustible tobacco products. The safety of these products is debatable, but may carry less cancer risk than combustible and chewing tobacco products. There have been few studies of the safety of these products in pregnancy, but among those which control for maternal smoking, noncombustible products are associated with low birth weight, small for gestational age, stillbirth, and prematurity.17
Federal Regulations
In 2009, the Family Smoking Prevention and Tobacco Control Act granted the FDA the authority to more closely regulate the manufacturing, marketing, and distribution of tobacco products. Of key importance, this act enabled the FDA to regulate the nicotine content in tobacco products. Past attempts at reducing the harms associated with smoking included ventilated cigarettes, where small holes in the cigarette allowed smoke to escape before inhalation. Although this could effectively reduce the dose of nicotine and tar inhaled by the user, it was easily thwarted through compensatory behaviors, like covering the ventilation holes. Cigarettes with lower nicotine content in the tobacco have been shown to produce less smoking with minimal compensatory smoking behaviors in randomized trials.18 There is optimism that reducing the nicotine content in tobacco products will help people quit smoking and prevent new users. In 2018, the FDA published an advance notice of proposed rule-making containing an intent to set a maximum nicotine content in tobacco products to reduce the number of new users and to help current users reduce or stop smoking. The FDA has not yet released a plan for regulating nicotine content in tobacco products as of this writing.
Conclusion
In summary, tobacco product use continues to be a leading cause of preventable health problems for pregnant women and women of reproductive age. Cigarette smoking continues to occur at a high rate, especially among women in vulnerable populations, such as the socioeconomically disadvantaged and those with substance use disorders. Plans for recognizing tobacco product use among pregnant and reproductive-aged women, along with providing support for reducing or stopping use, should be part of every provider's toolkit, and especially those who practice in rural areas or those who serve populations with substance use disorders.
Nicotine's pharmacokinetics and pharmacodynamics that impact multiple behaviors make it particularly difficult for people to stop using tobacco products. Understanding these complexities underscores the importance of multicomponent interventions, inclusive of pharmacotherapy and counseling, to assist with reduction or cessation. Further, understanding how interwoven nicotine use can be in a person's life enables a practitioner to provide compassionate and positive support.
New nicotine products pose a growing concern for increases in nicotine use with many unanswered questions of their safety and effects on pregnancy. Although new products have been advertised, and are viewed by consumers and others, as safer than cigarettes, substantial further research is necessary to assess whether these products can be used as smoking cessation aids or to avoid the harms of cigarette smoking. Finally, forthcoming regulation of the nicotine content in tobacco products may help to reduce the number of new people who use nicotine and help those who use nicotine reduce or stop their use.
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