Smoking Cessation in Pregnant Women

1. Smoking Cessation in Pregnant Women Cheryl Oncken, M.D., MPH University of Connecticut School of Medicine

2. Risks of Smoking During Pregnancy(Surgeon General’s Report 2004) • Maternal smoking is responsible for a number of poor pregnancy outcomes • spontaneous abortion (RR=1.2-1.3 ) • preterm delivery (OR=1.3) • placenta previa (RR=1.3-4.4) • placental abruption (RR=1.4-2.4) • low birth weight (RR=1.5-2.5) • Perinatal mortality (RR=1.2-1.3) • SIDS (OR=1.4-3.0)

3. Effect of Prenatal and Postnatal Tobacco Exposure on Children • Prenatal tobacco exposure • Attention deficit disorder (Romano et al., 2008) • Deficits in attention and auditory processing (Fried et al., 1997; Fried et al 2003) • Increased risk of becoming a smoker (Kendell et al., 1994; Buka et al., 2003) • Childhood obesity (Wideroe et. al., 2003) • Postnatal tobacco exposure • Increased risk of otitis media, pneumonia, asthma (DiFranza et al., 2004)

4. Public Health Implications of Smoking During Pregnancy • In US, maternal smoking is estimated to be responsible for: • 30% of small for gestational age babies, • 10% of preterm babies, and • 5% of infant deaths (Salihu et al, MCH Journal 2003)

5. Benefits of Cessation • Early cessation is best: • Women quit quit smoking by 16 weeks gestation have normal birth weight infants (MaCarther et al, 1988) • Women who quit smoking by 30-36 weeks have near normal birth weight infants (Ahlsten et al., 1993) • Smoking Reduction may also be beneficial: • 50% reduction in cotinine has been shown to improve birth weight (Li et al., 1993)

6. Objectives • Discuss natural history of smoking behavior during pregnancy • Discuss treatment strategies • Psychosocial • Pharmacotherapy • Discuss areas of future research

7. Natural History of Smoking During Pregnancy 25% spontaneously quit smoking after learning of pregnancy (Floyd et al., 1993; LeClere & Wilson, 1997; Severson et al., 1995) Another 12% quit later on; however, the majority of pregnant smokers cut down, but do not quit(Fingerhut et al., 1991) Of women who quit during pregnancy, about 70% relapse within 1 year following delivery(Fingerhut et al., 1991)

8. Continued Smokers vs. Spontaneous Quitters (DiClemente et al., 2000; Phares TM et al., 2004) • Less educated, lower SES, white, unemployed women are less likely to quit • Heavier smokers are less likely to quit smoking • Partner smoking is an independent risk factor for continued smoking during pregnancy

9. Mental Health and Smoking during Pregnancy • Nicotine dependence during pregnancy significantly predicted any mental disorder (OR 3.3), any mood disorder (OR 2.5), major depression (OR 2.07), dysthymia (OR 6.2), panic disorder (OR 3.1) ( Goodwin et al., 2007) • Pregnant smokers report more daily stressors and higher depressive symptoms than nonsmokers (Paarlberg et al., 1999; Zhu 2002) • Women with current depressive disorders (i.e., dysthymia, sub-threshold depression) may be less likely to quit (Blalock et al., 2006)

10. Behavioral Interventions • Two meta-analyses have shown that behavioral interventions have a consistent, although modest, impact on quit rates (Fiore, et al., 2008, Cochrane reviews 2004) • In the USPHS guidelines, augmented behavioral interventions were at least 3 minutes and usually included discussion of risks and benefits and self-help materials (http://www.surgeongeneral.gov/tobacco)

11. Meta-analysis: Effectiveness of Psychosocial Interventions Fiore et al., 2008

12. Examples: Psychosocial Interventions • Physician advice regarding smoking-related risks (2-3 minutes); videotape with information on risks, barriers and tips for quitting; midwife counseling 10 minutes; self-help manual with follow-up letters • Pregnancy-specific materials (Pregnant Woman’s Guide To Quit Smoking) and one 10 minute counseling session • Counselor provided one 90 minute counseling session with bi-monthly telephone calls

13. Self-help Interventions ( Ershoff et al., 1989; Hjalmarson AI et al., 1991)

14. Clinical Practice Guidelines: suggestions to improve disclosure (Fiore et al., 2008) • Multiple choice format • I smoke regularly now, about the same as when I found out I was pregnant • I smoke regularly now, but I’ve cut down since I found out I was pregnant • I smoke every once and awhile • I quit when I found out I was pregnant • I wasn’t smoking when I found out I was pregnant and I am not smoking now

15. Clinical practice suggestions to assist women in stopping smoking (Fiore et al., 2008) • Congratulate those who have quit • Motivate quit attempts by providing educational messages • Use problem-solving methods • Arrange Follow-up assessments • Assess for relapse in early postpartum period

16. Recommended Counseling for pregnant smokers (Melvin et al., 2000) • Ask (multiple choice format--document smoking status) • Advise (<1 minute) • Provide clear, strong messages about risks and benefits • Assess (willingness to quit) • Assist (>3 minutes) • Pregnancy specific, self-help materials • Suggest and encourage problem solving -review previous methods • Arrange social support • Provide social support • Arrange Follow-up • Reassess at every visit

17. Cochrane review (Lumley et al., 2004) • Randomized and quasi-randomized trials • 64 trials (approximately 28,000 subjects) • Significant reduction in smoking in the intervention versus control groups (RR).94 95% CI .93 to .95. • Absolute difference was 6 in 100 women continuing to smoke

18. Cochrane Review (Lumley, 2004)

19. Rewards for smoking cessation • Low income women were randomized to voucher condition ($50/month contingent on abstinence or to a control condition) (Donatelle et al., 2000) • 32% vs 9% abstinence at the end of pregnancy • 21% vs 6% postpartum • 87 Pregnant smokers randomized to a contingent vs non contingent condition (Heil et al., 2008) • 41% vs 9% abstinence at the end of pregnancy • 24% vs 3% postpartum

20. Considerations in the Use of Pharmacotherapy • Pregnancy quit rates in meta-analyses average 13.3% • Pharmacotherapies double quit rates in non-pregnant smokers • However, the benefit/risk ratio is unknown among pregnant smokers

22. Pharmacotherapies in Non-pregnant Smokers Fiore et al., 2008 (Table 6.26)

23. Clinical Practice GuidelinesFiore et al. Clinical Practice Guidelines, 2008 “ Safety is not categorical… Although the use of NRT exposes pregnant women to nicotine, smoking exposes them to nicotine plus numerous other chemical that are injurious to the woman and the fetus. These concerns must be considered in the context of inconclusive evidence that cessation medications boost abstinence rates in pregnant smokers.”

24. Expert opinions regarding Pharmacotherapy (Dempsey and Benowitz, 2000) Research is needed to better determine the risk/benefit profile Intermittent vs. continuous delivery system may deliver a lower total dose Pregnancy registries (prospective) would be useful to better determine the risk/benefit profile

25. Pharmacotherapy in Practice • 30% of physicians reported that they would discuss and/or prescribe pharmacotherapy to highly dependent smokers (Oncken et al., 2003) • In a recent survey, 30% of pregnant smokers discussed pharmacotherapy with their health care provider; 10% utilized either nicotine replacement or bupropion (Rigotti et al., 2008) • Older age, more education, living with a partner, having an ob who discussed medication, private insurance

26. Study of Nicotine Gum for Short- Term Smoking Cessation in Pregnant Women • Between-subjects design • Compared the effects of 5 days of 2-mg nicotine gum use versus a wait-list control group on: • Plasma nicotine and cotinine concentrations • maternal and fetal hemodynamics Oncken CA, Hatsukami DK, Lupo VR, et al. Effects of short term nicotine gum use in pregnant smokers Clin Pharmacol ther 1996;59:654-1.

28. Peak Nicotine Concentrations (ng/mL) 25 Smokers Gum chewers 20 15 Trough Nicotine Concentrations (ng/mL) 10 14 5 Smokers 12 Gum chewers NS p<.0001 10 0 Follow-up Baseline 8 6 4 2 NS p<.0025 0 Follow-up Baseline

30. Short-Term Use of Nicotine Gum • May be useful for smoking cessation • Nicotine gum results in a significant reduction in overall tobacco and nicotine exposure compared to continued smoking • Favorable effect versus smoking on hemodynamic parameters (e.g., maternal BP and pulse)

31. Efficacy of Nicotine Patch • A large randomized trial found no overall efficacy of nicotine vs placebo patch, but did show an increase in birth weight (Wisborg et al., 2000) • A smaller randomized trial (n=30) of women who smoked at least 15 cigs per day found that 4/17 (23.5%) women quit with the nicotine patch , whereas 0/13 in placebo group quit smoking (p=0.11) (Kapur et al., 2001)

32. Nicotine Patch for Pregnant Smokers • 250 pregnant smokers who smoked 10 cigarettes/day • Random assignment to 15 mg patches for 8 weeks, then 10 mg patches for 3 weeks versus placebo • Overall 26% quit smoking- no advantage for TDN • Compliance low in both groups • Birth weights 186 gram increase in intervention vs. control group Wisborg K, Henrikson TB, Jesperson LB, Secher N. Nicotine patches for Pregnant smokers. Obstet Gynecol 2000;96:967-71.

33. Quit rates

34. NRT Effectiveness Studies • NRT as part of a multi-modal intervention resulted in higher cessation rates (14%) vs usual care (5.0%) (Hegaard et al., 2003) • A large randomized open label found that addition of OTC NRT to counseling improved cessation rates over usual care (Pollack et al., 2007)

35. Nicotine Replacement and Behavioral Therapy Randomized open-label two-arm design: 2:1 randomization with more in NRT group • Arm 1, Cognitive Behavioral Treatment • Arm 2, Cognitive Behavioral Treatment + NRT • Choice of patch, gum, or lozenge (72 patch, 32 gum, 12 chose the lozenge, 6 CBT)

36. Results: Cessation Rates Adjusted for number of completed counseling sessions * indicates p<.05 Pollak KI, Oncken CA, Lipkus et al., AJPM 2007;33:297-305

37. Serious Adverse Events • 44/171 women had at least one SAE; 34/113 (30%) NRT vs. 10/58 (17%) CBT • RD=0.13, 95% CI: 0.00-0.26, p=0.07 • After controlling for hx preterm birth • RD=0.09, 95% CI: 0.05-0.21, p=0.26 • Data and Safety Monitoring Board suspended enrollment after interim AE report • Based on a priori stopping rule • Concluded AE’s likely not related to NRT use

38. Bupropion SR

39. Bupropion SR in pregnancy • Non-nicotine medication, category B in pregnancy (US) • Two prospective studies of bupropion SR in the first trimester did not find an increase in congential malformations or other adverse outcomes (Chun-Fai-Cahn B et al., 2005; Cole et al., 2006) • Efficacy for smoking cessation • One small study does not support an effect of bupropion SR on cessation rates (Miller et al., 2003) • Effectiveness for smoking cessation • In a controlled observational study, of 10/22 (45%) pregnant smokers receiving bupropion quit smoking, as compared to 3/22 (14%) of controls (P = 0.047) (Chan et al., 2005) • May be useful for pregnant smokers with co-existent mood problems

40. Bupropion SR for smoking cessation and reduction in pregnancy • Double-blind placebo controlled trial • 8 week intervention of Bupropion SR versus placebo • Examined point prevalence abstinence at 4 and 8 weeks Miller H, Ranger-Moore J, Hington M. et al. Bupropion SR for smoking cessation and reduction in pregnancy Am J Obstet Gynecol 2003:189: S133

41. Bupropion SR for Smoking Cessation or Reduction

42. Pharmacotherapy for Smoking Cessation During Pregnancy • Randomized placebo-controlled trials have not shown efficacy, but risk/benefit ratio seems favorable • Open-label, but not randomized controlled trials have shown effectiveness for NRT but have raised questions regarding safety • Limited studies on buproprion SR • More research is needed to better define the benefit/risk ratio

43. Summary • Pregnant smokers should be treated with known effective interventions (Fiore et al., 2008) • Person-to-person psychosocial interventions that exceed minimal advice to quit • Given the absence of definitive data on pharmacotherapy, individual decisions should be made between health care provider and pregnant smoker

44. Future Directions • Need to better understand risk factors for treatment failure • Development of novel behavioral interventions • Better understand the mechanisms by which treatments work • Better assessment of the risks/benefits of pharmacotherapy • Interventions are needed for heavier smokers • Treatment-matching studies • Studies to reduce postpartum relapse