Therapeutics
In pregnant smokers, the nicotine patch did not increase abstinence or birthweight more than placebo
Berlin I, Grange G, Jacob N, Tanguy ML. Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy. BMJ. 2014;348:g1622.
Clinical impact rating: F ★★★★★★✩ Question
Main results
In pregnant women who smoke, does the 16-hour nicotine patch increase smoking abstinence or infant birthweight?
Study recruitment was stopped early because of time constraints. Nicotine and placebo groups did not differ for complete smoking abstinence (5.5% vs 5.1%, P = 0.87) or weight, length, or head circumference at birth (Table). Fetal loss occurred in 3.9% (nicotine) and 3.5% (placebo) of infants.
Methods Design: Randomized placebo-controlled trial. ClinicalTrials.gov NCT00507975.
Conclusion
Allocation: Concealed.* Blinding: Blinded* (patients, clinicians, monitoring committee, laboratory staff, and statisticians).
In pregnant women who smoked, the 16-hour nicotine patch did not increase smoking abstinence or infant birthweight more than placebo.
Follow-up period: Until end of pregnancy. *See Glossary.
Setting: 23 maternity wards in France. Patients: 403 pregnant women ≥ 18 years of age (median age 29 y, median gestational age 17 wk) at 9 to 20 weeks of gestational age, who smoked ≥ 5 cigarettes/d (median 10 to 11 cigarettes/d), scored ≥ 5 on a motivational scale of quitting smoking (possible range 0 to 10), and were affiliated with a health insurance system. Exclusion criteria included refusal to use, or contraindication to, transdermal patches; use of neuroleptics, antidepressants, or anxiolytics for a chronic psychiatric disorder; use of tobacco products other than cigarettes; use of nicotine replacement therapy (NRT) within the past month; or use of bupropion or varenicline. Eligible women were included if, after a grace period of ≥ 2 weeks, they were unable to quit smoking or reduce the number of cigarettes smoked to < 5/d. Intervention: 16-hour delivery nicotine patches, 10-mg or 15-mg patches yielding 10 to 30 mg/d (n = 203), or placebo patches (n = 199). Initial patch doses were based on saliva cotinine levels before the 2-week grace period; subsequent doses were based on later cotinine levels. Outcomes: Complete continuous abstinence from quit date to delivery (carbon monoxide level in expired air ≤ 8 ppm) and infant birthweight. Secondary outcomes included birth length, birth head circumference, and fetal loss (stillbirth, late miscarriage, newborn death at birth, or medical abortion). The study needed 438 women to have 80% power to detect a difference of 100 g in birthweight between groups (α = 0.05). Patient follow-up: 43% for maternal outcomes and 95% for birth outcomes (intention-to-treat analysis). Nicotine vs placebo patches in pregnant women who smoked† Birth outcomes
Weight (g)
Least squares means Difference of least squares means (95% CI) Nicotine Placebo 3065
3015
Length (cm)
48.3
48.0
Head circumference (cm)
33.7
33.9
50 (−71 to 172) 0.34 (−0.31 to 0.98) −0.2 (−0.63 to 0.24)
†CI defined in Glossary.
17 June 2014 | ACP Journal Club | Volume 160 • Number 12
Sources of funding: Ministry of Health, France and Assistance Publique-Hôpitaux de Paris. For correspondence: Dr. I. Berlin, Hôpital Pitié-Salpêtrière, Paris, France. E-mail [email protected]. ■
Commentary Most women who become pregnant know that smoking during pregnancy may damage the health of the unborn baby. Those who continue to smoke during pregnancy do so not because they are unaware of the risks or do not want to stop: They find quitting very difficult. Providing them with effective assistance is particularly challenging for health care providers. The trial by Berlin and colleagues highlights the continued difficulties in identifying useful smoking cessation interventions. Despite intensive behavioral therapy during the trial, for which there is evidence of efficacy in pregnancy, quit rates were low in both intervention and control groups, and adding NRT had no effect on either maternal abstinence or fetal birthweight. Does the trial definitively exclude a benefit of NRT in pregnancy? Probably not. The trial was rather optimistically designed to detect a 10% absolute difference in abstinence rates, so a smaller effect on quit rates is still possible. Only 43% of patients continued treatment throughout pregnancy, and rates were low in both groups. This lack of adherence may have reduced the chances of finding an effect on fetal birthweight. Nevertheless, together with results of previous trials, the findings do not encourage a policy of routinely offering NRT to pregnant women who smoke. What should clinicians do for patients who are pregnant and smoke? We should continue to provide advice, support, and referral for more intensive behavioral interventions for patients who want them. Given the evidence that pharmacologic therapy can work in other populations, selective use may be appropriate for some patients. Tim Lancaster, MD Nuffield Department of Primary Care Health Sciences Oxford University Oxford, England, UK
© 2014 American College of Physicians
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/930364/ by a Universite Laval Biblioteque User on 07/30/2017
JC11
In pregnant smokers, the nicotine patch did not increase abstinence or birthweight more than placebo
Berlin I, Grange G, Jacob N, Tanguy ML. Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy. BMJ. 2014;348:g1622.
Clinical impact rating: F ★★★★★★✩ Question
Main results
In pregnant women who smoke, does the 16-hour nicotine patch increase smoking abstinence or infant birthweight?
Study recruitment was stopped early because of time constraints. Nicotine and placebo groups did not differ for complete smoking abstinence (5.5% vs 5.1%, P = 0.87) or weight, length, or head circumference at birth (Table). Fetal loss occurred in 3.9% (nicotine) and 3.5% (placebo) of infants.
Methods Design: Randomized placebo-controlled trial. ClinicalTrials.gov NCT00507975.
Conclusion
Allocation: Concealed.* Blinding: Blinded* (patients, clinicians, monitoring committee, laboratory staff, and statisticians).
In pregnant women who smoked, the 16-hour nicotine patch did not increase smoking abstinence or infant birthweight more than placebo.
Follow-up period: Until end of pregnancy. *See Glossary.
Setting: 23 maternity wards in France. Patients: 403 pregnant women ≥ 18 years of age (median age 29 y, median gestational age 17 wk) at 9 to 20 weeks of gestational age, who smoked ≥ 5 cigarettes/d (median 10 to 11 cigarettes/d), scored ≥ 5 on a motivational scale of quitting smoking (possible range 0 to 10), and were affiliated with a health insurance system. Exclusion criteria included refusal to use, or contraindication to, transdermal patches; use of neuroleptics, antidepressants, or anxiolytics for a chronic psychiatric disorder; use of tobacco products other than cigarettes; use of nicotine replacement therapy (NRT) within the past month; or use of bupropion or varenicline. Eligible women were included if, after a grace period of ≥ 2 weeks, they were unable to quit smoking or reduce the number of cigarettes smoked to < 5/d. Intervention: 16-hour delivery nicotine patches, 10-mg or 15-mg patches yielding 10 to 30 mg/d (n = 203), or placebo patches (n = 199). Initial patch doses were based on saliva cotinine levels before the 2-week grace period; subsequent doses were based on later cotinine levels. Outcomes: Complete continuous abstinence from quit date to delivery (carbon monoxide level in expired air ≤ 8 ppm) and infant birthweight. Secondary outcomes included birth length, birth head circumference, and fetal loss (stillbirth, late miscarriage, newborn death at birth, or medical abortion). The study needed 438 women to have 80% power to detect a difference of 100 g in birthweight between groups (α = 0.05). Patient follow-up: 43% for maternal outcomes and 95% for birth outcomes (intention-to-treat analysis). Nicotine vs placebo patches in pregnant women who smoked† Birth outcomes
Weight (g)
Least squares means Difference of least squares means (95% CI) Nicotine Placebo 3065
3015
Length (cm)
48.3
48.0
Head circumference (cm)
33.7
33.9
50 (−71 to 172) 0.34 (−0.31 to 0.98) −0.2 (−0.63 to 0.24)
†CI defined in Glossary.
17 June 2014 | ACP Journal Club | Volume 160 • Number 12
Sources of funding: Ministry of Health, France and Assistance Publique-Hôpitaux de Paris. For correspondence: Dr. I. Berlin, Hôpital Pitié-Salpêtrière, Paris, France. E-mail [email protected]. ■
Commentary Most women who become pregnant know that smoking during pregnancy may damage the health of the unborn baby. Those who continue to smoke during pregnancy do so not because they are unaware of the risks or do not want to stop: They find quitting very difficult. Providing them with effective assistance is particularly challenging for health care providers. The trial by Berlin and colleagues highlights the continued difficulties in identifying useful smoking cessation interventions. Despite intensive behavioral therapy during the trial, for which there is evidence of efficacy in pregnancy, quit rates were low in both intervention and control groups, and adding NRT had no effect on either maternal abstinence or fetal birthweight. Does the trial definitively exclude a benefit of NRT in pregnancy? Probably not. The trial was rather optimistically designed to detect a 10% absolute difference in abstinence rates, so a smaller effect on quit rates is still possible. Only 43% of patients continued treatment throughout pregnancy, and rates were low in both groups. This lack of adherence may have reduced the chances of finding an effect on fetal birthweight. Nevertheless, together with results of previous trials, the findings do not encourage a policy of routinely offering NRT to pregnant women who smoke. What should clinicians do for patients who are pregnant and smoke? We should continue to provide advice, support, and referral for more intensive behavioral interventions for patients who want them. Given the evidence that pharmacologic therapy can work in other populations, selective use may be appropriate for some patients. Tim Lancaster, MD Nuffield Department of Primary Care Health Sciences Oxford University Oxford, England, UK
© 2014 American College of Physicians
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/930364/ by a Universite Laval Biblioteque User on 07/30/2017
JC11
