Correspondence

Thomas Percival (17401804), emphasised that professional medical ethics should be autonomous from the law and state power.4 An autonomous professional obstetric ethics, unlike Dr Paintins rights-based reductionism, does not give unquestioning acquiescence to the law. &

References
1 Paintin D. Fatally awed?. BJOG 2013;120:371. 2 Chervenak FA, McCullough LB, Brent RL. The professional responsibility model of obstetric ethics: avoiding the perils of clashing rights. Am J Obstet Gynecol 2011;205:315.e15. 3 McCullough LB, Chervenak FA. Ethics in Obstetrics and Gynecology. New York: Oxford University Press, 1994. 4 Percival T. Medical Ethics, or a Code of Institutes and Precepts, Adapted to the Professional Conduct of Physicians and Surgeons. London: Russell and Johnson, 1803. In: Pellegrino ED, editor. The Classics of Medicine Library. Birmingham, AL: Gryphon Editions; 1985.

FA Chervenaka & LB McCulloughb

a b

Weill Medical College of Cornell University, New York, NY, USA; Baylor College of Medicine, Houston, TX, USA

Accepted 14 October 2012.

DOI: 10.1111/1471-0528.12094

Efcacy of nicotine replacement therapy in pregnancy

Sir, Smoking in pregnancy remains an international public health problem and interventions to combat this are required. Myung et al.s1 meta-analysis intends to investigate the efcacy and safety of pharmacotherapies for smoking cessation in pregnancy and includes most of the recent, relevant studies. However, we previously published a similar review2 with more cautious ndings and wish to clarify the reasons for any discrepancies. Myung et al. include two studies that are not in our metaanalysis; one investigated bupropion and the other involved nicotine replacement therapy (NRT). Their review combines ndings from both bupropion and NRT studies, providing a pooled estimate for the efcacy of both interventions. Consequently, the review is unlikely to help to guide treatment decisions about whether or not either drug actually works for smoking cessation in pregnancy. The NRT study which Myung et al. include was quasirandomised and women in one group were offered, but not required to use, NRT. However, all women offered NRT received behavioural support of substantially greater intensity than those who were not.3 As behavioural support helps pregnant women to stop smoking,4 this study does not inform us about the efcacy of NRT but instead tells us about the effectiveness of a behavioural support package to which NRT was sometimes added and by including it,

Myung et al., have probably overestimated the efcacy of pharmacotherapy. The authors do, though, report a subgroup analysis without these two problematic studies, which nds a more conservative effect for NRT only, similar to that which we found.2 From a different subgroup analysis, Myung et al. show, as we did, that placebo-controlled NRT trials provide no conclusive evidence for the efcacy of this therapy and, what evidence there is, comes principally from studies without placebos. We believe that the biases inherent in designs that do not include a placebo help to explain positive ndings from some individual studies. As the evidence for efcacy of NRT in Myung et al.s review derives mainly from studies without placebos, ndings should be considered with caution. Our review, published in early 2011, excluded both randomised controlled trials with unequal levels of behavioural support in active and control arms and nonrandomised controlled trials; this explains why the pooled estimate derived from our analysis is more conservative, indicating that there is insufcient evidence to believe that NRT is efcacious; (pooled risk ratio RR and 95% condence interval for smoking cessation in later pregnancy after using NRT, 1.63, 0.853.14). Recently we have updated our earlier work as a Cochrane Systematic Review; this now includes ndings from a placebo-controlled trial of NRT that recruited 1050 pregnant women.5 This review has similar ndings to our earlier work and will appear in the Cochrane Library in September. Importantly, like Myung et al.,1 after including all randomised controlled trials published by March 2012, we also concluded that there was no evidence that fetal harm has been caused by previously tested doses of NRT. We agree with Myung et al. that further randomised controlled trials investigating the efcacy of NRT are now required, but these should use higher doses of NRT than have previously been trialled. &

References
1 Myung SK, Ju W, Jung HS, Park CH, Oh SW, Seo H, et al. Efcacy and safety of pharmacotherapy for smoking cessation among pregnant smokers: a meta-analysis. BJOG 2012;119:102939. 2 Coleman T, Chamberlain C, Cooper S, Leonardi-Bee J. Efcacy and safety of nicotine replacement therapy for smoking cessation in pregnancy: systematic review and meta-analysis 10. Addiction 2011;106:5261. 3 Hegaard HK, Kjaergaard H, Moller LF, Wachmann H, Ottesen B. Multimodal intervention raises smoking cessation rate during pregnancy. Acta Obstet Gynecol Scand 2003;82:8139. 4 Lumley J, Chamberlain C, Dowswell T, Oliver S, Oakley L, Watson L. Interventions for promoting smoking cessation during pregnancy Cochrane Database of Systematic Reviews 1998, Issue 3. Art. No.: CD001055. DOI: 10.1002/14651858.CD001055.pub2. 5 Coleman T, Cooper S, Thornton JG, Grainge MJ, Watts K, Britton J, et al. A randomized trial of nicotine-replacement therapy patches in pregnancy. N Engl J Med 2012;366:80818.

2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2013 RCOG

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Correspondence

T Coleman,a C Chamberlain,b M-A Davey,c SE Coopera & J Leonardi-Beed

Division of Primary Care, University of Nottingham, Nottingham, UK; bInternational Public Health Unit, Department of Epidemiology and Preventive Medicine, Monash University, Prahran, Vic., Australia; c Mother and Child Health Research, La Trobe University, Melbourne, Vic., Australia; dDivision of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
Accepted 23 August 2012.
DOI: 10.1111/1471-0528.12064
a

Efcacy of nicotine replacement therapy in pregnancy

Authors Reply Sir, We appreciate the letter of Coleman et al.1 in response to our report in BJOG.2 First, we are very sorry that we did not include in our review Coleman et al.s review,3 which was published in early 2011. We should have searched and reviewed previous literature on this issue more thoroughly. Second, we agree with them that there is insufcient evidence to support the use of pharmacotherapy for smoking cessation in pregnant smokers because no signicant efcacy was found in the three placebo-controlled trials, whereas a signicant efcacy was found only in the four non placebocontrolled trials. We already described this in the limitations section of the Discussion. We concluded that there may be clinical evidence to support the use of pharmacotherapy for smoking cessation among pregnant smokers. Third, when we reviewed their previous meta-analysis and then compared it with ours, we found that Coleman et al. used a random-effects model in all the analyses, whereas we used both xed-effects and random-effects models according to the results of the heterogeneity test (i.e. xed-effects model for data showing less heterogeneity and random-effects model for data showing heterogeneity). Coleman et al. reported the pooled risk ratio (RR) and 95% condence interval (95% CI) for smoking cessation in later pregnancy

after using nicotine replacement therapy (NRT) was 1.63 (0.853.14) using a random-effects model. When we performed a xed-effects meta-analysis using data shown in Figure 2 of Coleman et al.s review (I2 = 45%; in our review, when I2 is <50%, we used a xed-effects model), NRT was efcacious (pooled RR, 1.47; 95% CI 1.052.05; I2 = 44.9%). Hence, the main reason why the ndings and conclusions are not consistent between the two metaanalyses, although similar data were used, is that different models were used, respectively. If Coleman et al. applied a xed-effects model when I2 is <50%, their conclusion would also be that NRT is efcacious, as in our review. Last, the remaining issue would be that we should present more conservative ndings when the pooled effect sizes are different in the meta-analyses by using between xed-effects and random-effects models in case of less heterogeneity. We, basically, think that using a xed-effects model is reasonable although the ndings are different between the two models if the heterogeneity test shows less heterogeneity (i.e. I2 < 50%). However, we want to hear other experts opinions on this issue. &

References
1 Coleman T, Chamberlain C, Davey M-A, Cooper SE, Leonardi-Bee J. Efcacy of nicotine replacement therapy in pregnancy. BJOG 2013;120:3734. 2 Myung SK, Ju W, Jung HS, Park CH, Oh SW, Seo HG, et al. Efcacy and safety of pharmacotherapy for smoking cessation among pregnant smokers: a meta-analysis. BJOG 2012;119:102939. 3 Coleman T, Chamberlain C, Cooper S, Leonardi-Bee J. Efcacy and safety of nicotine therapy for smoking cessation in pregnancy: systematic review and meta-analysis. Addiction 2011;106:5261.

S-K Myunga & HG Seob

a

Family Medicine Clinic, Smoking Cessation Clinic, Centre for Cancer Prevention and Detection, Carcinogenesis Research Branch, National Cancer Centre, Goyang, Republic of Korea bFamily Medicine Clinic, Smoking Cessation Clinic, Centre for Cancer Prevention and Detection, National Cancer Centre, Goyang, Republic of Korea

Accepted 3 October 2012.

DOI: 10.1111/1471-0528.12065

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2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2013 RCOG