Nicotine Patches in Pregnant Smokers
Nicotine Patches in Pregnant Smokers
Objective To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day).
Design Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013.
Setting 23 maternity wards in France.
Participants 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks’ gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group.
Interventions Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support.
Main outcome measures The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air ≤8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis.
Results Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self reported median compliance rate was 85% (interquartile range 56-99%) in the nicotine patch group and 83% (56-95%) in the placebo patch group, assessed at 1016 visits. The mean birth weight was 3065 g (SE 44 g) in the nicotine patch group and 3015 g (SE 44 g) in the placebo patch group (P=0.41). Diastolic blood pressure was significantly higher in the nicotine patch group than in the placebo patch group. The frequency of serious adverse events was similar between the groups, although more non-serious adverse reactions, mainly of skin, occurred in the nicotine patch group.
Conclusion The nicotine patch did not increase either smoking cessation rates or birth weights despite adjustment of nicotine dose to match levels attained when smoking, and higher than usual doses.
Trial registration ClinicalTrials.gov NCT00507975.
Smoking during pregnancy increases the risk of adverse pregnancy and birth outcomes and may have long lasting effects in offspring. Despite relatively high spontaneous smoking cessation rates among pregnant smokers, smoking during pregnancy remains a major public health issue. A meta-analysis of interventions to help pregnant smokers quit has shown a modest overall efficacy on abstinence (risk ratio 0.94, 95% confidence interval 0.93 to 0.96). The addition of nicotine replacement therapies (NRT) to behavioural smoking cessation interventions in pregnant smokers is based on their excellent safety profile and proved efficacy in other populations of smokers. Several statements have called for the immediate implementation of well conducted clinical trials.
Despite a lack of conclusive evidence on the use of NRT for smoking cessation in pregnant women, such treatment is recommended by French and UK health authorities, but not by US guidelines. Previous trials had insufficient power to draw conclusions about the efficacy and safety of NRT in pregnancy. Two recent meta-analyses and one sufficiently powered recent study concluded that NRT are not effective in helping pregnant women to stop smoking. However, previous studies only assessed doses of up to 15 mg of nicotine a day, had a duration of exposure of not more than eight weeks, reported low compliance rates, and did not adjust the daily nicotine dose on an individual basis. Adjustment of the daily dose is important because the metabolism of nicotine is accelerated during pregnancy, and standard doses can result in under-dosing and consequently less efficacy. Individual dose adjustment could allow a close to 100% substitution rate and also avoid overdosing, which may potentially lead to an increased risk of adverse events.
To tackle the lack of information on the safety and efficacy of NRT in pregnant smokers, the French Ministry of Health initiated a public grant application in 2005. In response to this initiative we performed a multicentre, double blind, randomised, placebo controlled, parallel group, nationwide study to assess the efficacy of 16 hour nicotine patches, with doses individually adjusted and potentially ranging from 10-30 mg/day.
Abstract and Introduction
Abstract
Objective To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day).
Design Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013.
Setting 23 maternity wards in France.
Participants 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks’ gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group.
Interventions Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support.
Main outcome measures The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air ≤8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis.
Results Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self reported median compliance rate was 85% (interquartile range 56-99%) in the nicotine patch group and 83% (56-95%) in the placebo patch group, assessed at 1016 visits. The mean birth weight was 3065 g (SE 44 g) in the nicotine patch group and 3015 g (SE 44 g) in the placebo patch group (P=0.41). Diastolic blood pressure was significantly higher in the nicotine patch group than in the placebo patch group. The frequency of serious adverse events was similar between the groups, although more non-serious adverse reactions, mainly of skin, occurred in the nicotine patch group.
Conclusion The nicotine patch did not increase either smoking cessation rates or birth weights despite adjustment of nicotine dose to match levels attained when smoking, and higher than usual doses.
Trial registration ClinicalTrials.gov NCT00507975.
Introduction
Smoking during pregnancy increases the risk of adverse pregnancy and birth outcomes and may have long lasting effects in offspring. Despite relatively high spontaneous smoking cessation rates among pregnant smokers, smoking during pregnancy remains a major public health issue. A meta-analysis of interventions to help pregnant smokers quit has shown a modest overall efficacy on abstinence (risk ratio 0.94, 95% confidence interval 0.93 to 0.96). The addition of nicotine replacement therapies (NRT) to behavioural smoking cessation interventions in pregnant smokers is based on their excellent safety profile and proved efficacy in other populations of smokers. Several statements have called for the immediate implementation of well conducted clinical trials.
Despite a lack of conclusive evidence on the use of NRT for smoking cessation in pregnant women, such treatment is recommended by French and UK health authorities, but not by US guidelines. Previous trials had insufficient power to draw conclusions about the efficacy and safety of NRT in pregnancy. Two recent meta-analyses and one sufficiently powered recent study concluded that NRT are not effective in helping pregnant women to stop smoking. However, previous studies only assessed doses of up to 15 mg of nicotine a day, had a duration of exposure of not more than eight weeks, reported low compliance rates, and did not adjust the daily nicotine dose on an individual basis. Adjustment of the daily dose is important because the metabolism of nicotine is accelerated during pregnancy, and standard doses can result in under-dosing and consequently less efficacy. Individual dose adjustment could allow a close to 100% substitution rate and also avoid overdosing, which may potentially lead to an increased risk of adverse events.
To tackle the lack of information on the safety and efficacy of NRT in pregnant smokers, the French Ministry of Health initiated a public grant application in 2005. In response to this initiative we performed a multicentre, double blind, randomised, placebo controlled, parallel group, nationwide study to assess the efficacy of 16 hour nicotine patches, with doses individually adjusted and potentially ranging from 10-30 mg/day.
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