1. Real-world effectiveness of nicotine replacement therapy in pregnancy Leonie S. Brose, PhD Andy McEwen, PhD & Robert West, PhD University College London and National Centre for Smoking Cessation and Training

2. Background Smoking in pregnancy in UK 1 –26% immediately before or during pregnancy –12% throughout and at delivery –Underreporting likely Smoking in pregnancy increases risk of e.g. 2 –Preterm birth –Placental abruption –Low birth-weight –Sudden infant death syndrome –Adult morbidities such as obesity, diabetes, asthma, mental health problems Stopping smoking reduces increased risks 1 NHS Information Centre, 2011 2 USDHHS, 2004

3. Background In general population: Medication increases quit rates –Single nicotine replacement therapy (NRT) –Combination of two (or more) NRT products –Bupropion (Zyban) –Varenicline (Champix) Brose et al, 2011, Thorax

4. Background Pregnancy: NRT can be used Review of randomised controlled trials (RCTs) failed to find evidence for effectiveness 3 –Evaluated single NRT, mostly nicotine patch NHS Stop Smoking Services 4 –Behavioural support and medication –Different types of support and range of settings –More than 20,000 pregnant women per year –Many use combination NRT 3 Coleman et al, Cochrane, 2012 4 NHS Information Centre, 2011

5. Objective and research questions To assess the association of single and combination NRT with success of quit attempts of pregnant smokers in clinical practice while adjusting for smoker and treatment characteristics. –Are negative RCT findings for single NRT borne out in clinical practice? –Combination NRT has not been evaluated in RCTs; does it confer a benefit for smoking cessation in pregnant smokers?

6. Sample Identified as pregnant N=9,587 N=315,721 treatment episodes in 49 Services April 2009 – June 2011 Missing due date Main analysis N=3,880 N=8,999 (Sensitivity analysis) Missing age, sex, setting or support type (n=71) Varenicline or bupropion (n=79) Telephone support (n=438)

7. Methods Outcome CO-validated 4- week quit rates Russell Standard (Clinical) Clients lost to follow-up counted as smoking 5 Outcome CO-validated 4- week quit rates Russell Standard (Clinical) Clients lost to follow-up counted as smoking 5 Predictors Medication (none, single NRT, combination NRT) Treatment setting (specialist clinics, home visit, primary care, other) Type of support (group, 1-to-1, drop-in, other) Occupational grade (employed, not employed, student, unable to code) Age Months pregnant Ethnicity (white, other) Year of quit attempt 5 West et al, Addiction, 2005 Dependence: Heaviness of Smoking Index (HSI) completed for 29%. Differences between medications assessed separately. Dependence: Heaviness of Smoking Index (HSI) completed for 29%. Differences between medications assessed separately.

8. Methods Two-level logistic regression models to assess effect of predictors on quit rates Sensitivity analyses a.Including those without months pregnant, n=8,999 b.Excluding all lost to follow-up, remaining n=2,887

9. N=3,880 No medication n=588 (15.2%) Single NRT n=1166 (30.1%) Combination NRT n=2126 (54.8%) Age, Mean (SD)25.3 (6.0)25.7 (6.3)26.4 (6.1) Months pregnant, Mean (SD)3.5 (2.1)4.3 (1.9)4.3 (1.8) Ethnicity % (n) White73.388.290.3 Occupational grade % In employment24.138.641.6 Not in employment24.744.943.9 Unable to code48.511.110.1 Intervention setting % Specialist clinic71.851.149.2 Home visit a 16.329.436.0 Primary care9.712.38.5 Other2.27.26.4 Intervention type % One-to-one79.874.181.2 Group1.24.11.3 Other11.410.9 CO-validated 4-week quit %16.324.835.7 Lost to follow-up %29.431.721.2 a. Provided by specialist practitioners in 75% of cases

10. Predictors of CO-validated 4-week abstinence 2-level multivariable logistic regression, n=3,880 Odds ratio (OR) 95% Confidence interval (CI) p value Medication, reference: None Single NRT1.060.60 to 1.860.84 Combination NRT1.931.13 to 3.290.02 Intervention setting, reference: Specialist clinic Home visit1.160.89 to 1.510.28 Primary care0.570.41 to 0.790.001 Other setting1.000.70 to 1.420.98 Intervention type, reference: One-to-one Group0.620.35 to 1.120.11 Drop-in0.580.42 to 0.820.002 Other0.970.69 to 1.360.85 Months pregnant, per month increase0.950.91 to 0.990.02 Also adjusted for ethnicity, age, occupational grade

11. Further results Dependence Those using combination NRT more dependent. F(2,1124)=14.26, p<0.001 Sensitivity analyses a.Including those without information on stage of pregnancy b.Excluding all lost to follow-up  Results remain: Combination NRT benefit over no medication, single NRT no benefit.

12. Single NRT shows no benefit - in line with RCTs But combination NRT associated with success –Not due to differences in intervention or client characteristics, including dependence Common non-specialist treatment (primary care) and later stage of pregnancy associated with worse outcomes Limitation: Correlational design, but adjusted Suggests need for full-scale RCT Discussion

13. First evidence on combination NRT in pregnancy Exposes foetus to higher levels of nicotine than single NRT or stopping all use of nicotine, but: –Other options associated with resumed smoking –NRT delivers nicotine without carbon monoxide and other reproductive toxins in cigarettes High-quality evidence-based behavioural support 6,7 should be provided regardless of medication 6 Lumley et al, Cochrane, 2009 7 Lorencatto et al, NTR, 2012

14. Conclusions Use of a combination of nicotine transdermal patch and a faster acting form of nicotine replacement therapy appears to confer a benefit in terms of promoting smoking cessation during pregnancy. While this conclusion is based on observational data, it lends support to this treatment option pending confirmation by a randomised controlled trial.

15. Thank you www.ncsct.co.uk leonie.brose@ncsct.co.uk