Tobacco Use Disorder
Public health campaigns, smoke-free policies, and community initiatives have contributed to a decline in cigarette smoking over the last 20 years and have helped to disseminate information regarding the harms of smoking in pregnancy. However, over 7% of pregnant persons in the United States continue to smoke cigarettes during pregnancy, with the prevalence varying widely by state of residence and demographics such as race, age, and education.1–3 The demographic of young adults with the highest rates and rise in tobacco use correlates with the population shown to be at greatest risk of unintended pregnancy, which still accounts for ∼45% of pregnancies.4 Pregnancy remains a highly motivating period for tobacco cessation, but even with targeted interventions, more than half of individuals who were able to discontinue tobacco use during pregnancy resume in the postpartum period.5,6
Tobacco products have evolved significantly with combustible, noncombustible, and electronic products available on the market and are commonly used by young adults, which challenges accurate quantification of tobacco usage during the perinatal period. Since their introduction in 2007, e-cigarette use among youth and people of childbearing age has become a public health concern with 1 in 5 high school students reporting current e-cigarette use.7 Up to 23% of adult current e-cigarette users were never cigarette smokers, with the majority of this population <35 years old.8 A 2016 report from the Behavioral Risk Factor Surveillance System survey found that 44.3% of young adult current e-cigarette users were never smokers before trying e-cigarettes.9 The inconspicuous product designs, pleasing flavors, and low perceived harm appeal to individuals and have contributed to the rapid rise in use.
Tobacco use disorder can be diagnosed based on the diagnostic and statistical manual of mental disorders, 5th edition (DSM-5) diagnostic criteria for substance use disorder (Table 1) and the severity of the use disorder (mild, moderate, or severe) determined by the number of diagnostic criteria met.10 A key difference between tobacco use and tobacco use disorder remains the compulsive use of a tobacco product that continues despite harmful consequences.
TABLE 1 -
DSM-5 Diagnostic Criteria for Substance Use Disorder10
|A problematic pattern of use leading to clinically significant impairment or distress manifested by two or more of the following within a 12-month period
||Often taken in larger amounts or over a longer period than was intended
||A persistent desire or unsuccessful efforts to cut down or control use
||A great deal of time is spent in activities necessary to obtain, use, or recover from the substance’s effects
||Craving or a strong desire or urge to use the substance
||Recurrent use resulting in a failure to fulfill major role obligations at work, school or home
||Continued use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by its effects
||Important social, occupational or recreational activities are given up or reduced because of use
||Recurrent use in situations in which it is physically hazardous
||Continued use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been cause or exacerbated by the substance
|Severity (based on number of diagnostic criteria met by the patient at the time of diagnosis): Mild—two to three criteria; Moderate—four to five criteria; Severe—Six or more criteria
DSM-5 indicates diagnostic and statistical manual of mental disorders, 5th edition.
Tobacco can be smoked (cigarettes, cigars, cigarillos, bidis, kreteks, pipes, and hookah), chewed (chewing tobacco, snuff, dip, and snus) or sniffed (Table 2). Nicotine alternatives offered as interventions, also known as nicotine replacement therapy (NRT), include patches, gums, lozenges, inhalers, and nasal sprays are often used in combination with other tobacco products. Among current adult tobacco users, 19% use ≥2 tobacco products. One-third of current cigarette smokers also use little cigars and cigarillos.14
TABLE 2 -
||Forms or Alternate Names
||Additives and Exposures
||Cig, ciggies, smokes, butts, rollies, cancer sticks, darts, durries
||Cut tobacco rolled in paper with or without a filter and smoked
||Acetone, ammonia, arsenic, benzene, butane, carbon monoxide, formaldehyde, Lear, tar and 7000 other breakdown products13
||Varies by brand; range of 6-28 mg of nicotine per cigarette (median 10-12 mg); inhale around 1.1-1.8 mg per smoked13
||Little cigars, cigarillos (LCC), large cigars
||Roll of dried tobacco wrapped in leaf tobacco or in a substance that contains tobacco
||13.3-15.4 mg (large cigars)
|Electronic nicotine delivery systems (ENDS)
||e-cigs, e-cigarettes, cigalikes, vapes, vape pens, mods, pods, JUUL, Suorin, SMPO, tank systems
||First generation: replacement cartridges or disposable
||Flavorants; diacytyl and acetyl propionate; chromium, nickel, cadmium, lead and arsenic through aerosolization by the heating element of the devices
||Variable: 0-36 mg/mL of e-liquid
||Second generation: refillable reservoir
||Third generation: adjustable heating elements
||Fourth generation: various shape devices
||Chewing, nsuff, snus, pellets, strips, sticks
||Chewing tobacco: long strands of tobacco
||Chewing tobacco: 144 mg (entire can)
||Snuff: processed fine grain moist blend
||Snus: Variable (4-43 mg/g of tobacco)
||Snus: packets of heat cured, fine grain tobacco “parked” between the cheek and gums.
||Dissolvable: Variable (0.6-3.1 mg of nicotine per piece)
||Dissolvable: intraorally for varying durations (3 minutes for dissolvable strips and 30 for sticks)
||Narghile, waterpipe, hubble-bubble, or shisha
||Head, body, and water bowl attached to a mouthpiece with a hose
||Flavors, tobacco, charcoal carbon monoxide (CO), nitrosamines, polyaromatic hydrocarbons, and other volatile chemicals
||Variable: 1 hour session equal to 10 cigarettes
||Flavored tobacco burned over a charcoal briquette and filtered through water
Electronic nicotine delivery systems [ENDS: vapes, vaporizers, vape pens, hookah pens, electronic cigarettes (e-cigarettes or e-cigs), and e-pipes] are battery-powered devices that uses an e-liquid to provide nicotine and other additives and flavors in an aerosolized form. They generally contain three chemicals: a humectant, nicotine, and flavoring. The nicotine concentration varies widely in devices, but the nicotine emission is also dependent on the voltage of the device and duration of inhalation (ie, the greater the inhalation duration and voltage the higher the nicotine emission). Most solutions are advertised as having 0 to 24 mg/mL of nicotine but the third-generation pods may contain concentrations as high as 35 to 59 mg/mL. Generally, nicotine absorption from a cigarette is 1 mg (0.3 to 2 mg) with blood nicotine levels ranging from an average of 15 to 30 ng/mL.
The safety of the over 8000 flavorants used in e-liquid is controversial. E-liquids require much higher concentrations of flavorants than in foods. Diacetyl and acetyl propionyl have been found in the majority of e-liquids tested and are associated with bronchiolitis obliterans (ie, popcorn lung).15 ENDS devices made with nichrome alloys are significant sources of metal exposures (ie, chromium, nickel, cadmium, lead, and arsenic) through aerosolization by the heating element of the devices. These metals are associated with higher risks of cancer, respiratory, and central nervous system health problems.16
ADVERSE PERINATAL OUTCOMES
Although there are many chemicals present in tobacco smoke that could potentially harm the fetus, nicotine and carbon monoxide are the main tobacco derivatives that are thought to negatively impact pregnancy. Carbon monoxide readily crosses the placenta and can bind to fetal hemoglobin, contributing to fetal hypoxia. Nicotine and cotinine (the predominant metabolite of nicotine) are neurotoxins that also cross the placenta, with amniotic fluid and umbilical cord levels found to be similar to maternal plasma levels.17 Exposure during the third trimester appears to be more harmful to the fetus than at earlier gestational ages, potentially from the negative effects on the developing lung, cardiac, and neurological tissue. The harms of tobacco use during pregnancy and for offspring long-term extend to second-hand and third-hand exposures as well.18,19
The maternal, perinatal, and long-term offspring adverse effects of smoking have been well-characterized (Table 3; Fig. 1).21 A reduction in risk is achievable with cessation earlier in pregnancy, with studies showing that cessation before 15 weeks correlates with the greatest benefit.22–25 However, cessation efforts at any stage are important as evidence suggests that the positive benefits from tobacco cessation even late in pregnancy last until 18 months postpartum.26 Children of parents who smoke have been shown to have altered arousability, decreased hypoxic arousal, and autonomic dysfunction.27 In addition, there appears to be a dose-dependent relationship of smoking and increased risk for sudden infant death syndrome in the postnatal period. The perinatal risks using alternative forms of nicotine, electronic delivery products, and other noncombustible tobacco products are not as well described, but the growing literature suggests the risks are greater than public and provider perceptions of these alternative products.
TABLE 3 -
Adverse Effects of Tobacco Use20
|Autoimmune disorders cancer
||Poorer lung function
|Lung disease (COPD, bronchitis, emphysema)
||Fetal growth restriction
||Respiratory symptoms (wheezing, coughing, shortness of breath)
||Poor fetal head growth
||Premature rupture of membranes
||Behavioral and cognitive
||Intrauterine fetal demise
||Elevated blood pressure
||Preterm-related infant deaths
||Sudden infant death syndrome
COPD indicates chronic obstructive pulmonary disease.
American College of Obstetricians and Gynecologists (ACOG) guidelines for tobacco and nicotine cessation during pregnancy were updated in 2020 and are summarized below.21 They recommend that health care providers should screen for any type of tobacco or nicotine use, including vaping or e-cigarette use, hookah, chewing tobacco, snus, second-hand nicotine exposure and NRT, as well as concurrent alcohol or illicit substance use. All pregnant persons should be offered individualized treatment if they use nicotine products. The postpartum period is associated with stressors that can trigger relapse, so ongoing screening and support in the fourth trimester remains crucial for individuals with a history of tobacco use disorder. The US Preventive Services Task Force (USPSTF) provides similar recommendations. Both ACOG and the American Society of Addiction Medicine (ASAM) oppose the criminalization of substance use in pregnancy and other punitive measures that dissuade access to prenatal care, instead supporting collaborative approaches aimed at reduction of use or complete cessation of substance use in pregnancy.28
Prenatal care providers play a critical role in screening for tobacco use in pregnancy, providing brief interventions and appropriate referrals for treatment. Preconception cessation is the optimal period to reduce adverse perinatal outcomes and promote long-term tobacco cessation, but any reduction or discontinuation of tobacco use during pregnancy should be encouraged. Barriers for health care providers to routinely screen for substance use in pregnancy include but are not limited to time constraints, competing priorities, lack of adequate screening skills or clear protocols, under-reporting or false disclosure of substance use, provider perceptions of clinical utility and likelihood of successful cessation or abstinence, lack of knowledge, desire to avoid potential harm to patient-provider relationship or family unit because of some mandatory state reporting requirements and inconclusive evidence regarding some risks of use.29,30 Following screening, it has been estimated that only 49% of obstetricians routinely provide smoking cessation advice and only 28% discuss actual strategies for cessation, demonstrating room for improvement amongst health care providers.31
Motivational interviewing (MI) and trauma-informed care are effective approaches when inquiring about tobacco and nicotine use, as well as patient interest in cessation. Co-morbid mental health conditions are common in individuals who use tobacco products and routine anxiety and depression screening remains crucial during pregnancy. A recent study of the link between depression and tobacco use in a sample of low-income patients showed prevalence rates of positive depression screening in 30.31% during early pregnancy, 20.46% in late pregnancy, and 18.08% at 12 weeks postpartum, respectively.32
Both ACOG and the USPSTF recommend using SBIRT (Screening, Brief Intervention, and Referral to Treatment) for substance use screening in pregnancy.33 Universal screening remains best practice to reduce potential bias and stigma associated with targeted screening, as substance use disorders impact individuals from all socioeconomic backgrounds and demographics.
The Centers for Disease Control and Prevention’s (CDC) Expert Meeting on Perinatal Illicit Drug Use in 2012 proposed key guidelines for screening for substance use in pregnancy. They recommend annual substance use and family planning screening during well-woman visits, and in pregnancy, they recommend screening at the initial prenatal visit and then at least every trimester for anyone who screens positive for past use.30 Different approaches to screening include a validated screening tool that the patient fills out and returns to the provider for review, computer-administered instruments or direct provider questioning using a standardized checklist, and medical interviews using open-ended and nonjudgmental questions. Urine drug testing should not be substituted in place of screening questions.
Validated Screening Tools
A variety of validated screening tools can be used to screen for tobacco use. The “5 A’s” intervention model is an evidence-based model, often used in obstetrics, to address patient smoking habits (Table 4).34 Inquiring about all types of nicotine exposures, products, and formulations is important to avoid missing patients who use other forms of tobacco products that they may not attribute similarly to cigarette smoking. Alternatively, the Ask, Advise, Refer approach is an effective and quicker approach to the 5A model. For patients who are ready to commit to cessation, using the STAR method can be beneficial (Table 5).35
TABLE 4 -
The 5 A’s Screening Tool
||Ask about tobacco use in any form, the amount of use, and document this in the patient record
||Advise patients who smoke to quit in a clear, strong, and personalized manner
||Assess the patient’s willingness to make a quit attempt
||Assist in the quit attempt for those who are willing
TABLE 5 -
The STAR Method
||Set a quit date (ideally within 2 wk)
||Tell family, friends and coworkers about your plan and elicit support
||Remove tobacco products from the home and lifestyle
MI is a widely researched and effective core communication style developed by William R. Miller and Stephen Rollnick that can be used within the context of SBIRT to assist individuals with strengthening personal motivation for and commitment to making challenging behavioral changes.36 The goal of MI is to enhance intrinsic motivation in a nonjudgmental, patient-centered, and compassionate way to resolve ambivalence about changing substance use and other health risk behaviors. The spirit of MI is collaborative, with the goal of the provider to draw out personal priorities, values, and wisdom in order to empower individuals to employ the resources and skills they have within themselves for change.37 The 5 principles of MI include expressing empathy, developing discrepancy, avoiding argument, rolling with resistance, and supporting self-efficacy.38 OARS is a mnemonic that describes the core counseling skills involved in MI: open-ended questions, using affirming language, reflective listening, and summarizing the discussion and goals (Fig. 2).36,37,42 Motivation theory posits that the drive to change depends on three key components: importance of the change to the patient, their readiness to change, and their confidence that they can be successful.
Prochaska and DiClemente’s Transtheoretical Model for the Stages to Change is an overarching psychological framework that allows providers and counselors to tailor counseling and interventions to a patient’s level of motivation to change their substance use behavior (Fig. 3).37 It considers why people do or do not make behavioral changes and acknowledges that motivation is dynamic, with people commonly going in and out of the different stages of change (Fig. 2).43,44 The stages are fluid, with an anticipation that individuals will both make progress and suffer setbacks.
For patients who are not yet ready to quit, the 5R’s model is a useful tool that focuses on the relevance of why quitting is of importance to that patient. Providers should highlight the individual’s risks or negative consequences of tobacco use, identify the rewards that will be gained by quitting and the roadblocks and anticipated barriers that the patient may face, and remember the importance of repetition and revisiting the discussion at future visits.34
PREVENTION AND RISK REDUCTION
Prevention of Tobacco Use or the Consequences of Use
Prevention efforts to ameliorate consequences of tobacco use can start at any level, including the individual, familial, community, state or national (Chapter 2). Clean indoor air laws and cigarette excise taxes are the tobacco control policies most consistently linked with reductions in tobacco/nicotine use. In 2010 to 2011, each $1.00 elevation in excise tax was associated with a 10% higher odds of recent smoking cessation.45 Twenty-eight US states have passed comprehensive smoke-free air policies, which prohibit smoking and address second-hand smoke exposure in government buildings, private workplaces, schools, childcare facilities, health care facilities, restaurants, and bars. Sixteen states and the District of Columbia have added e-cigarettes/ENDs devices to these smoke-free laws since 2016.46 The odds of attempting to quit and successful smoking cessation were increased for individuals who resided in states with comprehensive smoke-free air laws compared with those who lived in states without these laws.47
The Affordable Care Act (ACA) and many private insurers have improved insurance coverage for screening and treatment of tobacco use. The ACA mandates include that all patients be screened for tobacco use and for provision of at least two tobacco cessation attempts annually, which include telephone, group, and individual counseling and a 90-day coverage of FDA-approved prescription or over-the-counter tobacco cessation medications.48 Although pregnancy is an excellent opportunity to capture a motivated audience for cessation, prevention should be a priority for any age range. Tobacco use established in adolescence commonly carries into adulthood. The USPSTF recommends that primary care clinicians provide interventions, including education and counseling to school-aged children and adolescents to prevent tobacco initiation (Level B).49
Risk Reduction in Setting of Ongoing Tobacco Use
Given the dose-dependent relationship between perinatal tobacco exposure and adverse maternal and fetal effects, any reduction in use should be encouraged and contributes to improved short-term and long-term outcomes. Providers therefore have a responsibility to partner with all pregnant individuals to provide consistent messaging on the benefits of cessation and alternative forms of tobacco use, pursue risk reduction strategies, address barriers to cessation, and to continue efforts to reduce the overall use of tobacco products in the perinatal period (Fig. 1).
Vitamin C supplementation. Vitamin C supplementation (500 mg daily) is a risk reduction strategy that can be used during pregnancy to reduce the potential for fetal lung insult from tobacco use. Maternal smoking negatively impacts fetal lung development as demonstrated by decreased pulmonary function and increased asthma rates in children. A handful of small randomized controlled trials (RCTs) have demonstrated potential benefit for the reduction of childhood lung disease with vitamin C use in pregnancy. McEvoy et al50 studied 159 newborns of randomized pregnant individuals who smoked; 76 randomized to 500 mg of vitamin C daily and 83 placebo controls. Infants of women randomized to vitamin C supplementation had significantly decreased wheezing through 1 year of age (relative risk: 0.56; 95% confidence interval: 0.33-0.95; P=0.03) although no differences were noted in the 1-year PFTs. A second larger RCT randomized 251 pregnant women between 13 and 23 weeks gestation who smoked to either placebo or 500 mg oral vitamin C daily.51 Infants in the vitamin C group were found to have improved forced expiratory flows over the first year. Continued follow-up on these populations are ongoing.
Other dose reduction strategies. Many individuals respond positively to a tobacco dose-tapering approach, using a gradual reduction in the number of cigarettes smoked, daily vape sessions, or other repetitive alternative forms of tobacco over the course of weeks to months. Given the dose-dependent relationship between perinatal tobacco exposure and adverse maternal and fetal effects, any reduction in use should be encouraged and contributes to improved short and long-term outcomes. NRT functions as both a risk reduction strategy as well as a treatment modality. It will be reviewed below under the section on pharmacologic treatment. ENDS are not currently recommended as tools to help patients achieve abstinence given inconsistent evidence of greater tobacco cessation with use and concern for other potential health risks previously reviewed. Expansion and support of treatment services for partners of pregnant or parenting persons likely reduces exposure to second-hand smoke with an associated decrease in maternal/child adverse health effects, stabilizes the family unit and decreases risk of relapse postpartum.52
Prevention of Withdrawal Symptoms and Relapse
Nicotine has a half-life of ∼2 hours, accumulates in tissues throughout the day and continues to be released for 6 to 8 hours after last use. Tobacco withdrawal symptoms can occur hours after the last cigarette and can last for up to 4 weeks after cessation. Withdrawal symptoms include anxiety, irritability, restlessness, stress, difficulty concentrating, insomnia, increased appetite, and depression. In a small RCT of pregnant women who smoked, 20 minutes of moderate intensity treadmill walking was an effective method to moderate cravings and, to a lesser extent, withdrawal symptoms.39 Identifying personal triggers, developing diverse coping strategies and initiation of NRT are all strategies that can be used to minimize withdrawal symptoms and decrease risk of relapse.
Addiction includes periods of relapse and remission for most individuals. Substance use disorders, including tobacco use disorder, require a lifelong management plan in order to achieve continued cessation and quality of life. General triggers that contribute to risk of relapse include concerns about weight and postcessation weight gain, exposure to alcohol or caffeine, poor coping skills, having a partner or close friends and family who use tobacco products, sleep issues, financial stress, and relationship tensions. The pregnancy and postpartum periods are complicated by life transitions, family expansions, and unexpected stressors that can act as triggers and predispose an individual to relapse. Proactive discussions about pregnancy and postpartum expectations, management of triggers and relapse risk, and managing triggers are important for cessation continuation.
Supportive Resources and Behavioral Counseling
Supportive resources. Numerous helpful resources are available for providers (Table 6, Fig. 4). Providing a multidimensional treatment approach individualized to the patient remains important. The National Cancer Institute (NCI) operates a toll-free multilingual quitline that will connect you directly to your state’s tobacco quitline (1-800-QUIT-NOW). In the primary care setting, patients who use quit lines have a 2 to 3 times greater chance of success with cessation compared with counseling alone.53 The Centers for Disease Control has developed a free smartphone App (quickSTART App) that provides additional resources for making a quit plan, recognizing withdrawal symptoms and exploring cessation medications options. Educating patients on common triggers may include ways to curb the hand/oral fixation (eg, sucking candy or chewing on a straw), financial benefits of cessation, and coping strategies to overcome the urge to smoke.
TABLE 6 -
Provider-based Counseling and Interventions5
||Areas of Counseling Points
|2-3 minutes of physician advice regarding tobacco or nicotine-related risks
||Educate on the negative health effects, including effects of second-hand and third-hand smoke exposure, for the patient and fetus
|A videotape with information on risks, barriers to quitting, and helpful tips followed by one 10-minute counseling session, self-help manual, and follow-up letters
||Help patients identify barriers and trigger factors to avoid relapse and withdrawals
|10-minute counseling session with health educator plus pregnancy-specific self-help manual
||Encourage the patient to identify and develop a supportive nontobacco social network
|One 90-minute counseling session plus twice monthly phone calls while pregnant and then monthly in the postpartum period
||Encourage the patient to involve other support persons who use tobacco in the process of cessation
||Provide information and strategies to focus on body positivity and limiting excessive weight gain
||Training on behavioral and mental coping skills or referral to experts on cognitive behavioral and/or mindfulness therapy
||Shift the focus on to responsibilities of parenting and motivating on intrinsic sources
||Support with positive encouragement and not judging or shaming
||Reaffirm her commitment to abstinence
||Pharmacotherapy options and safety in pregnancy
||Discuss the risks of relapse throughout the cessation process but most commonly immediately after delivery
Leveraging technology through the internet, smartphone, and apps is becoming increasingly used for tobacco cessation. These platforms expand access to prevention, education, and treatment resources and may reduce adverse health effects among reproductive-aged persons who smoke and their offspring.54 Online “serious games” often used for educational purposes have been shown to enhance tobacco abstinence in pregnant women over 18 years of age with at least three months of use compared with nonusers (57% vs. 14%, P=0.001).40
Behavioral counseling. Counseling and behavioral modification interventions that are individualized to the patient are considered first line treatment for tobacco use. The USPSTF reported that behavioral interventions are more effective than usual care or minimal support for smoking cessation in late pregnancy based on pooled data from trials including over 26,000 pregnant women (relative risk: 1.35; 95% confidence interval: 1.23-1.48).26 In addition, a 2017 Cochrane meta-analysis of 88 RCTs that included over 28,000 pregnant women demonstrated no adverse effects with behavioral interventions. Counseling interventions, including MI, cognitive behavioral therapy (CBT), psychotherapy, relaxation, and facilitating problem solving, had a clear benefit on tobacco cessation compared with usual care. Moderate to high-quality evidence demonstrated that these interventions were associated with a 35% increase in women who stopped smoking in late pregnancy, an increase in mean birthweight of 56 g, a 17% decrease in low birthweight infants, and a 22% decrease in NICU admissions.55 CBT has been found to be particularly useful for dependency challenges. It is a form of counseling that encourages individuals to recognize distortions and maladaptive thoughts associated with tobacco use in order to gain a deeper understanding of their behaviors and motivations for tobacco use and subsequently make changes to behavior patterns.
Although counseling was the most common intervention studied, trials of financial incentives, feedback, and health education also showed a consistent benefit. Feedback interventions are cessation tools to provide objective evidence on the potential impact on the fetus, including fetal ultrasound or measurement of tobacco metabolites in the pregnant individual (ie, carbon dioxide or urine cotinine levels). Financial incentives for smoking cessation remains an effective method when compared with noncontingent, incentive-based interventions, health education, or social support alone.
Pharmacologic treatment for tobacco/nicotine cessation in pregnancy is challenging because of the lack of evidence, paucity of RCTs, and heterogeneity and bias in studies.
NRT. For the general (nonpregnant) population, NRT is commonly used for smoking cessation and is often considered first line treatment. NRT can be used as a means of treatment to taper an individual’s tobacco use and exposure over time or as a risk-reducing measure to decrease overall tobacco exposure to the fetus. Abstinence within the first 2 weeks of use is highly predictive of long-term abstinence and alterations in therapy at follow-up should be based on relief of withdrawal symptoms and maintenance of abstinence.56 ACOG recommends that pregnant women who have not been able to quit smoking can use NRT to support cessation provided that patients are counseled on both benefits and risks.21 In addition, the National Institute for Health and Care Excellence (NICE) recommends NRT for women who are unable to stop smoking with nonpharmacologic interventions.57 However, initiation of NRT in pregnant women and adherence to NRT once started has been found to be lower when compared with nonpregnant individuals who smoke.58–60 Concern about safety may play a role in these findings.
NRT is absorbed through oral/nasal mucosa or the skin to reduce the intensity of cravings and withdrawal symptoms, facilitating a reduction or cessation of tobacco use. In the United States, nicotine patches, gum, and lozenges are available over the counter, while the nasal spray and inhaler require a prescription. NRT comes in long-acting (eg, patches) and short-acting formulations (eg, lozenges and gum) at different doses, intended to deliver a range of plasma nicotine levels over the course of a 24-hour period similar to the trough levels seen between cigarettes. Nicotine patch therapy has been shown to nearly double abstinence rates compared with placebo and patches are available in 7, 14, and 21 mg.61 The standard 21 mg/24 hour patch has been found to achieve a medium serum cotinine level of 54% of the cotinine concentrations achieved with cigarette smoking and has been found to be more effective among lighter smokers compared with heavier smokers (Table 7). Heavier smokers (>20 cigarettes per day) are likely underdosed with standard-dose patches and may experience persistent nicotine withdrawal symptoms. Although high-dose nicotine patch therapy (>21 mg/day) has been shown to be safe and well-tolerated for individuals who smoke more than 20 cigarettes per day, rates of abstinence have been inconsistently demonstrated.63
TABLE 7 -
Recommended Initial Dosing of Nicotine Patch Based on Number of Cigarettes Smoked in Nonpregnant Population62
|Cigarettes Per Day
||Patch Dose (mg/d)
Short-acting NRT is most effective for acute management of nicotine withdrawal symptoms and cravings, and for individuals with evidence of “high” physical dependence (ie, time to first cigarette of the day <30 minutes after awakening).64 Individualizing NRT doses remains crucial because of interindividual variability of baseline nicotine and cotinine concentrations among patients who smoke a similar number of cigarettes. In the nonpregnant population, combination therapy with a long and short-acting formulation is preferred to monotherapy with a short-acting formulation given increased odds ratio of smoking abstinence compared with placebo at 6 months. Beginning NRT before quitting may improve success as compared with beginning NRT on the quit day.65
A Cochrane review of 11 randomized trials investigating NRT and pregnancy included 2412 pregnant women.66 Low-quality evidence supports that NRT combined with behavioral support is more effective for cessation in later pregnancy than just behavioral support alone. Higher-quality placebo-controlled trials suggested that NRT is more effective than placebo, without a specific form of NRT found to be more effective than another (ie, patches vs. fast-acting gum or lozenges). Because cessation rates, compliance with pharmacologic agents, and the path to cessation is variable both clinically and in trials, it does not come as a surprise that there is insufficient evidence to determine whether NRT impacts immediate pregnancy outcomes (ie, miscarriage rates, stillbirth, delivery before 37 weeks, birthweight <2500 g, mean birthweight, neonatal intensive care admission or neonatal death). However, one trial that followed infants until 2 years of age did find that infants born to women randomized to the NRT group were more likely to have healthy development.67 A recent systematic review and meta-analysis of RCTs and non-RCT studies of NRT use in pregnancy found that NRT is unlikely to have adverse impacts nor be more harmful than smoking in pregnancy. In addition, there was a nonstatistical trend towards a risk reduction of low birthweight, preterm birth, intensive care admissions, neonatal death, and congenital anomalies when comparing smoking in pregnancy to NRT in pregnancy.68
Until recently, clinical guidelines for NRT use in pregnancy have tended to be conservative. Short-acting, lower dose NRT such as gum was favored over nicotine patches, which provide a higher dose and duration of nicotine exposure. With the recent studies in the nonpregnant population suggesting that success is better with higher NRT doses and the increased physiologic metabolism of nicotine in pregnancy, longer acting formulations of NRT (ie, patches) at higher doses may be needed to show a benefit for NRT. While more studies involving pregnant persons are required, enough data does currently exist for expert opinion to consider NRT in pregnancy both safe and effective.
Non-nicotine medications. Bupropion sustained release and varenicline are effective smoking cessation medications commonly used in the nonpregnant population. Bupropion is a monocyclic antidepressant that inhibits reuptake of both norepinephrine and dopamine and is hypothesized to be effective for patients through its dopaminergic activity on the pleasure and reward pathways in the mesolimbic system and nucleus accumbens. Dopamine release in these brain structures has been hypothesized to reinforce the use of nicotine and other drugs. Varenicline has an antagonist effect on nicotinic acetylcholine receptors by blocking nicotine binding and also stimulates receptor-mediated activity that leads to the release of dopamine. These medications can be used as monotherapy or in combination with a short-acting formulation of NRT. A recent meta-analysis of pregnancy outcomes after exposure to either drug included studies of variable quality, which demonstrated insufficient data to determine risk with varenicline use in pregnancy and inconclusive impacts on infant birthweight, premature birth, or congenital anomalies with bupropion use in pregnancy.69 Existing evidence does not suggest that either treatment is immediately harmful with use during pregnancy. However, because of the paucity of safety data, limited quality studies, and unknown long-term offspring health risks, neither bupropion nor varenicline is recommended for primary prevention of tobacco use during pregnancy or lactation at this time.
Cannabis Use Disorder
Cannabis (also called marijuana, weed, grass, green, hash, pot, reefer, dope, ganja, bong, kush, sativa, and Mary Jane) is the most commonly used illicit substance in pregnancy under US federal law. It can be smoked, vaped, or taken orally [eaten in a resin or solid form (hash oil, honey oil, or shatter) or mixed with food or beverages]. Since 2012 when Colorado legalized the recreational use and sale of cannabis, marijuana use or possession is fully illegal in only 5 US states.70 The rapid legalization of cannabis by states has been adopted for financial and social justice reasons, as well as growing evidence of nonpregnant therapeutic benefits of cannabinoids found in the marijuana plant. The health effects of legalization have been challenging to quantify due in part to the heterogeneity of legalization policies and their implementation, the impact on different populations (eg, youth vs. adults, light vs. heavy use), and the lack of uniformity across marijuana products.71
Like tobacco products, cannabis markets have evolved to include a wider diversity of products at greater potencies. While the average delta-9-tetrahydrocannabinol (THC; main psychoactive compound in cannabis) content was less than 2% in the 1960s to 1980s, it now has steadily climbed to 17% to 28% as of 2017 with high potency concentrated products such as oils, shatter, dab, and edibles with THC content as high as 95%.72 Particularly among teenagers, the prevalence of more potent categories of cannabis (vapes/oils) has significantly increased over the last 5 years.73 The DSM-5 criteria for substance use disorder is used to diagnose a cannabis use disorder, with severity of the disorder characterized by the number of fulfilled criteria (Table 1). In general, ∼9% of individuals who use marijuana will develop a use disorder, with the risk increasing to 17% for those who start using marijuana in adolescence and up to 25% to 50% in individuals who use daily.74
Cannabis use in pregnancy has increased, with ∼10% of people reporting use before pregnancy and 4% to 7% continuing use during pregnancy and in the postpartum period.75–77 Data regarding use in pregnancy is impacted by the historical reliance on self-reporting and medical records, which can be influenced by social stigma, provider reporting bias, punitive state laws, and fear of intervention by child protection or social services.78 Cannabis use in pregnancy is highest in the first trimester compared with second and third trimesters, but rates of recreational use in all periods of gestation have increased over the last 5 to 10 years. Among pregnant persons who continue to use cannabis in pregnancy, the general perception is that it is more “natural” and safer as compared with other illicit substances or pharmacologic interventions, with an overall low or no risk of harm with use.79 The National Survey on Drug Use and Health, a nationally representative survey on substance use, performed from 2005 through 2015, noted that 17% of pregnant nonusers and 65% of pregnant marijuana users reported no anticipated health risk with marijuana.80 Moreover, provider education and communication with patients regarding the potential harms with use in pregnancy are widely variable and contribute to notions of perceived safety.81 These limitations highlight the critical need for (1) more robust screening and accurate reporting of cannabis use in pregnancy (frequency, mode, and indications of use); (2) more research on perinatal and postpartum cannabis use and associated outcomes; and (3) provider training and education to clearly message the potential benefits and harms of general and perinatal cannabis use.
The Cannabis sativa plant is comprised of pharmacologically active chemicals and compounds known as phytocannabinoids. Marijuana chemotypes are determined by the concentrations of the two most studied cannabinoids found within marijuana, THC and cannabidiol (CBD). Cannabinoid products contain THC or CBD, often in different relative concentrations. THC is the psychoactive compound responsible for the euphoria associated with marijuana use and has the ability to alter mood-perception and consciousness. CBD is pharmacologically but not psychologically active. Although widely available in retail locations, CBD products remain highly unregulated, are not always accurately labeled and may still contain low levels of THC.82,83
Cannabis can enter the systemic circulation by different routes, which impacts the timing of onset and duration of symptomatic effects. Inhaled marijuana through smoking, vaporizing or dabbing is the fastest method for THC to enter into the systemic circulation (1 to 3 min) but has a shorter duration of symptoms (1 to 3 h). Smoking marijuana destroys some of the medicinal compounds, while concurrently releasing carcinogens and other particulate matter.84 Oral mucosal absorption through use of drops, tinctures, sprays, lollipops, or breath strips takes ∼20 minutes before symptoms occur and duration of effect is usually 1 to 3 hours. Suppositories, inserted vaginally or rectally, have similar properties to oral administration and are made from oils and waxes.85 The onset of symptoms with oral consumption and gastrointestinal absorption (edibles, candy, drinks, snacks, capsules) is generally longer (30 to 90 min) but has a longer duration of effect (6 to 8 h).85
Transdermal (patches and gels) and topical (lotions, salves, balms, and bath soaks) products depend on skin absorption. Transdermal formulations are absorbed into the bloodstream with time to effect in 15 to 30 minutes with a duration of action of ∼6 to 8 hours. Topicals are not psychoactive and less likely to result in a positive urine drug screen because they generally will not enter the bloodstream. They have a similar onset of action to transdermal products but a slightly shorter duration of effect (3 to 6 h).85 Any product with a longer delay in symptom onset can risk overconsumption, and caution must be utilized when consuming.
ADVERSE PERINATAL OUTCOMES
Endocannabinoids and phytocannabinoids (the active chemicals and compounds found in the cannabis plant) act upon type 1 (CB1) and type 2 (CB2) cannabinoid receptors that are expressed throughout the central nervous system, immunologic system, and peripheral tissues, including reproductive tissues and the placenta.86,87 While THC and CBD (phytocannabinoids) are lipophilic and readily cross the placenta, the impact of these compounds on the reproductive system and pregnancy have not been fully delineated. The transfer of THC through the placenta and breastmilk is likely dependent on route of administration, maternal dose, and frequency of use.88 Fetal blood THC concentrations have been reported to be ∼10% of maternal concentrations.89
Cannabis use in pregnancy has been associated with low birthweight (<2500 g) and increased NICU admissions.90,91 The association of cannabis use and miscarriage, congenital anomalies, placental abruption, preterm birth, SGA infants, lower 5-minute Apgar score, and intrauterine fetal demise has been inconsistently reported but data supports that, similarly to tobacco, the risk of adverse outcomes increases in a dose-dependent manner.92–94 Offspring exposure to cannabis has been associated with cognitive and behavior sequelae including attention deficit disorders and behavioral problems.89,95 Despite common reports of cannabis use to treat nausea symptoms during pregnancy, cannabinoid hyperemesis syndrome should also be considered among persons using cannabis during pregnancy that present with significant nausea and vomiting. Cannabinoid hyperemesis syndrome is characterized by daily cannabis use, abdominal discomfort, and cyclical vomiting that is attenuated with frequent hot water bathing. Limitations of current studies to understand the risks of perinatal cannabis use include: insufficient rigor to quantify the type, mode, and frequency of consumption; potential for concurrent polysubstance or paternal cannabis use; and inadequately addressing socioeconomic disparities, postnatal environmental, nutritional, and psychosocial stressors.
The CDC currently recommends against the use of marijuana in pregnancy because it can potentially result in adverse fetal development.96 ACOG has published guidelines recommending that obstetrician-gynecologists counsel persons against using marijuana while trying to get pregnant, during pregnancy, and while they are breastfeeding.93 In the absence of sufficient evidence investigating the effects of marijuana use on infants during lactation, both ACOG and the American Academy of Pediatrics (AAP) discourage marijuana use during lactation and breastfeeding.88,93 However, due the multitude of maternal and neonatal benefits associated with breastfeeding, marijuana consumption during the postpartum period should not be a contraindication to breastfeeding.
ACOG recommends universal substance use screening in pregnancy given that screening alone can lead to behavior change, but no validated screening tools exist for the evaluation of cannabis use or cannabis use disorder in pregnancy.37,97 Despite marijuana being the most commonly used substance in pregnancy, there are currently no evidence-based interventions for cannabis cessation.
The Cannabis Use Disorders Identification Test (CUDIT) was modified from the Alcohol Use Disorders Identification Test (AUDIT) to identify individuals in the preceding 6 months who were using cannabis in a potentially problematic or harmful way. CUDIT-R is an effective revision of the screening tool, which also assesses the severity of cannabis use.98 ACOG, USPSTF, and SAMHSA recommend the use of SBIRT as a screening tool for hazardous use of a substance and for substance use disorders for all pregnant persons as a routine part of prenatal care. Screening can be done with the use of a single question or a validated screening tool. Preliminary screening instruments for pregnant individuals include the validated 4 P’s Plus and the 5 P’s screening tools (Table 8).99–101
TABLE 8 -
The 5 P’s Screening Tool99
||Did any of your parents have a problem with alcohol or drugs?
||Do any of your friends (peers) have problems with alcohol or drug use?
||Does your partner have a problem with alcohol or drug use?
||Before you knew you were pregnant (past), how often did you drink beer, wine, wine coolers or liquor?
||Not at all
||In the past month, did you drink beer, wine or liquor, or use other drugs? (Pregnancy)
||Not at all
*High risk for substance use should be assessed for opioid use.
Even without a specific diagnosis of cannabis use disorder, it is critical for providers to screen and identify any use in pregnancy to educate patients and provide opportunities for cessation and treatment. Providers can use MI principles when a patient is found to engage in cannabis or other substance use. If the pregnant individual is diagnosed with a substance use disorder and is amenable to treatment, a referral can be made for treatment services if available.
PREVENTION AND RISK REDUCTION
Prevention of Cannabis Use or the Consequences of Use
Legislative policies have reduced the initiation of harmful substance use, especially amongst the adolescent population. Many individuals initiate their marijuana use during adolescence and continue through their reproductive years. Therefore, one key strategy for preventing marijuana use in pregnancy is preventing marijuana use during adolescence.102 Furthermore, cannabis use during adolescence while the brain is still developing can alter brain structure and function, contributing to developmental changes in memory, cognition, and executive functioning.103 Many of the evidence-based interventions focusing on reducing substance use in adolescents pertain to alcohol use but similar policies targeting cannabis may limit or discourage cannabis use in adolescence as well. Policies such as increasing the price of alcohol, restricting use or sale of alcohol at youth and community events, restricting advertising to minors and consequences such as driver’s license suspension following an offense correlate with reductions in underage consumption of alcohol, among other adverse outcomes. In addition, minimum age of purchase, seller, and server laws, as well as efforts aimed at preventing minors from using false identification to purchase alcohol have also been shown to limit minors’ access to alcohol, therefore aiding in the reduction of alcohol initiation and consumption in adolescence.102 Some barriers to implementing prevention programs include ongoing discrimination; stigma and potential punitive practices that prevent pregnant and parenting persons from disclosing substance use or seeking regular prenatal care; lack of adequate provider knowledge or time; and differing local, state and federal marijuana laws.
Another method for preventing marijuana use in the perinatal period is to employ prevention efforts that have been shown to be generally effective in reducing substance use in pregnancy. Integrated clinics for pregnant and parenting persons that provide prenatal care, primary care, substance use and mental health care, and address other social supports (ie, housing, transportation, etc.) have been shown to (1) reduce substance misuse before, during and after pregnancy; (2) increase engagement in treatment and prenatal care for persons who use marijuana; (3) improve general infant and child wellbeing; (4) decrease rates of breastfeeding discontinuation; and (5) increase use of effective postpartum contraception, including LARCs.102 Similarly, postpartum home visits by health professionals have been shown to improve maternal and family health by providing medical and social support at a time where increased stressors contribute to risk of relapse, postpartum mood disorders and less positive parenting practices.102
Risk Reduction in Setting of Ongoing Cannabis Use
Individuals who use marijuana in pregnancy are more likely to use tobacco, alcohol or other drugs in pregnancy, experience nausea or vomiting in pregnancy, and receive limited or disrupted prenatal care compared with pregnant persons who do not use cannabis. Therefore, while harm reduction approaches specifically targeting cannabis use in pregnancy are sparse, any harm reduction approach that contributes to decreased hazardous use of other substances or improves access to prenatal care likely remains beneficial. Exploration of underlying symptoms that a patient may be attempting to self-medicate, education, and proactive medical or psychological management of individual symptoms may also contribute to prevention and risk reduction of substance use. Reducing use (ie, amount and/or frequency) and avoiding high potency THC strains may also help ameliorate some cannabis-associated adverse effects. Further research specifically about cannabis use is needed to develop more targeted approaches, systematic changes, and evidenced-based interventions.
Management of Withdrawal Symptoms
It is now well-recognized that regular cannabis use leads to a physical dependence and that abrupt reduction or termination of long term, frequent use is associated with a withdrawal syndrome.104 This withdrawal syndrome consists of behavioral, emotional and physical symptoms, such as anxiety, irritability, insomnia, unpleasant dreams, depressed mood, decreased appetite or weight loss, restlessness, abdominal pain, tremors, sweating, fever, chills, and headache. Withdrawal contributes to ongoing use. These symptoms can last from 2 weeks to greater than a month after reduction or cessation of use. Cannabis withdrawal syndrome was added to the DSM-5 and also as one of the criteria for diagnosing a cannabis use disorder.10 Physical exercise, meditation or prayer, relaxation techniques, herbal preparations, over-the-counter analgesics, and other medications can be successful interventions for many individuals with mild cannabis withdrawal.105,106 Treatment of withdrawal symptoms is an important aspect of relapse prevention. Gabapentin has been demonstrated to help reduce cannabis withdrawal symptoms compared with a placebo and its utility and appropriateness can be considered.107
Treatment of cannabis use disorder remains challenging secondary to limited evidence-based approaches with only modest rates of abstinence and high rates of relapse. Furthermore, there are no FDA-approved medications for the treatment of cannabis use disorder. As with other substance use disorders, identification and treatment of underlying factors contributing to use, such as anxiety, mental health disorders, nausea or reduced appetite, are important aspects of care.
Several psychosocial treatments of cannabis use disorder, including motivational enhancement therapy (MET), CBT and contingency management, have been shown to be beneficial. MET is a counseling approach aimed at resolving ambivalence about engaging in treatment and supporting internal motivation to make a behavioral change. MI techniques are often used in conjunction with guidance on coping strategies. CBT has the most robust data for reduction of cannabis use and rates of abstinence. However, overall rates of continued abstinence remain low and decline after completion or cessation of treatment.108 For cannabis use disorder, MET in combination with CBT has been found to be a more comprehensive treatment approach.109 Incentive-based interventions have been shown to be highly effective in treatment retention and promoting abstinence from substances. While contingency management has mixed data as a standalone psychosocial intervention for cannabis use disorder, either MET or CBT or combined MET/CBT programs may be potentially augmented by contingency management to optimize successful cessation or reduction.110
- Tolerance: refers to the need to take higher doses of a substance to get the same effect.
- Physical dependence: occurs as a result of adaptations by the body as a result of regular exposure to a substance, legal or illegal, even when taken as prescribed.
- Addiction: a treatable, chronic medical disease involving complex interactions among brain circuits, genetics, the environment, and an individual’s life experiences. People with addiction use substances or engage in behaviors that become compulsive and often continue despite harmful consequences. Prevention efforts and treatment approaches for addiction are generally as successful as those for other chronic diseases (adopted by the ASAM Board of Directors September 15, 2019).
- Tobacco or cannabis use disorder: DSM-5 diagnostic criteria for substance use disorder are fulfilled, where tobacco or cannabis is substance of use.
- Withdrawal: condition that occurs when that substance is taken away or frequency of use is decreased and cravings can emerge in order to relieve negative symptoms.
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