The SNAP trial: a randomised placebo-controlled trial of nicotine replacement therapy in pregnancy – clinical effectiveness and safety until 2 years after delivery, with economic evaluation

Abstract

BackgroundSmoking during pregnancy causes many adverse pregnancy and birth outcomes. Nicotine replacement therapy (NRT) is effective for cessation outside pregnancy but efficacy and safety in pregnancy are unknown. We hypothesised that NRT would increase smoking cessation in pregnancy without adversely affecting infants.ObjectivesTo compare (1) at delivery, the clinical effectiveness and cost-effectiveness for achieving biochemically validated smoking cessation of NRT patches with placebo patches in pregnancy and (2) in infants at 2 years of age, the effects of maternal NRT patch use with placebo patch use in pregnancy on behaviour, development and disability.DesignRandomised, placebo-controlled, parallel-group trial and economic evaluation with follow-up at 4 weeks after randomisation, delivery and until infants were 2 years old. Randomisation was stratified by centre and a computer-generated sequence was used to allocate participants using a 1 : 1 ratio. Participants, site pharmacies and all study staff were blind to treatment allocation.SettingSeven antenatal hospitals in the Midlands and north-west England.ParticipantsWomen between 12 and 24 weeks’ gestation who smoked ≥ 10 cigarettes a day before and ≥ 5 during pregnancy, with an exhaled carbon monoxide (CO) reading of ≥ 8 parts per million (p.p.m.).InterventionsNRT patches (15 mg per 16 hours) or matched placebo as an 8-week course issued in two equal batches. A second batch was dispensed at 4 weeks to those abstinent from smoking.Main outcome measuresParticipants: self-reported, prolonged abstinence from smoking between a quit date and childbirth, validated at delivery by CO measurement and/or salivary cotinine (COT) (primary outcome). Infants, at 2 years: absence of impairment, defined as no disability or problems with behaviour and development. Economic: cost per ‘quitter’.ResultsOne thousand and fifty women enrolled (521 NRT, 529 placebo). There were 1010 live singleton births and 12 participants had live twins, while there were 14 fetal deaths and no birth data for 14 participants. Numbers of adverse pregnancy and birth outcomes were similar in trial groups, except for a greater number of caesarean deliveries in the NRT group. Smoking: all participants were included in the intention-to-treat (ITT) analyses; those lost to follow-up (7% for primary outcome) were assumed to be smoking. At 1 month after randomisation, the validated cessation rate was higher in the NRT group {21.3% vs. 11.7%, odds ratio [OR], [95% confidence interval (CI)] for cessation with NRT, 2.05 [1.46 to 2.88]}. At delivery, there was no difference between groups’ smoking cessation rates: 9.4% in the NRT and 7.6% in the placebo group [OR (95% CI), 1.26 (0.82 to 1.96)]. Infants: at 2 years, analyses were based on data from 888 out of 1010 (87.9%) singleton infants (including four postnatal infant deaths) [445/503 (88.5%) NRT, 443/507 (87.4%) placebo] and used multiple imputation. In the NRT group, 72.6% (323/445) had no impairment compared with 65.5% (290/443) in placebo (OR 1.40, 95% CI 1.05 to 1.86). The incremental cost-effectiveness ratio for NRT use was £4156 per quitter (£4926 including twins), but there was substantial uncertainty around these estimates.ConclusionsNicotine replacement therapy patches had no enduring, significant effect on smoking in pregnancy; however, 2-year-olds born to women who used NRT were more likely to have survived without any developmental impairment. Further studies should investigate the clinical effectiveness and safety of higher doses of NRT.Trial registrationCurrent Controlled Trials ISRCTN07249128.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 18, No. 54. See the NIHR Journals Library programme website for further project information.

The Role of Nicotine in the Effects of Maternal Smoking during Pregnancy on Lung Development and Childhood Respiratory Disease. Implications for Dangers of E-Cigarettes

“…The combination of the addictive nature of nicotine with the perception of relative safety suggests that e-cigarette use during pregnancy will likely increase (4). Although nicotine replacement therapy has been used during pregnancy (5,6), on the basis that nicotine alone will be safer than conventional cigarette use, the potential continued use of e-cigarettes by e-cigarette-only users during pregnancy raises heightened safety concerns of e-cigarette use during pregnancy. The fact that about half of conventional cigarette users continue to smoke while pregnant (7,8) suggests that significant numbers of e-cigarette users will also continue e-cigarette use during pregnancy, thus exposing the fetus to nicotine.…”

The London Exercise And Pregnant smokers (LEAP) trial: a randomised controlled trial of physical activity for smoking cessation in pregnancy with an economic evaluation

“…Women were eligible for inclusion in the trial if they were between 10 and 24 weeks' gestation and outcomes were collected at the end of pregnancy (between 36 weeks' gestation and 10 weeks post partum); therefore, the time horizon of the trial was up to 9 months. A clinical trial of NRT for smoking cessation (Smoking, Nicotine, and Pregnancy; SNAP) 95,96 was approved by the NIHR HTA programme shortly before this study began and, as both studies used similar outcome measures, a similar approach has been taken to economic evaluation to permit comparison.…”

“…Assumptions concerning the need to change semi-disposable mouth pieces and batteries were taken from the SNAP trial. 96 It was assumed that a treadmill would last for 10 years and that three midwives would require training in that time; therefore, annual costs were calculated as one-tenth of the cost of a treadmill plus one-tenth of the cost of training three midwives, calculated as 1 day of PA training and 1 day of smoking cessation training received by each midwife. The costs of training were derived from the costs of training in the LEAP trial.…”

“…92 However, these mainly US-based studies are limited by not including data for infant outcomes and therefore cannot easily be compared with this study. One previous study (the SNAP trial 96 ), based in the UK, has considered infant outcomes and conducted a similar analysis as used in the present study. The SNAP trial assessed the cost-effectiveness of NRT for smoking cessation.…”

Celebrating and honouring midwifery in New Zealand

“…Although some studies have demonstrated an increase in cessation rates with the use of specific support services, others have shown little or no effect (Chamberlain et al, 2013). In particular, the use of NRT has been shown to have little effect on cessation rates in pregnant women (Cooper et al, 2014). Recent studies have focused on the use of material or financial incentives (e.g., vouchers exchangeable for retail items) .…”