Nicotine Replacement Therapy Promotes Smoking Cessation During Pregnancy

DURHAM, N.C., Sept. 26 -- Adding nicotine replacement to cognitive behavioral therapy helped pregnant women stop smoking, but didn't prevent relapse after the baby was born, investigators here found.

Combination therapy tripled the smoking cessation rate during pregnancy compared with behavioral therapy alone, Kathryn Pollak, Ph.D., of Duke University, and colleagues, reported online and in the October issue of the American Journal of Preventive Medicine.

By three months postpartum, however, the difference between groups was no longer significant.

"These results are promising for future trials," the authors concluded. "However, more data are needed to determine the safety and benefit of [nicotine replacement therapy] use during pregnancy."

Cognitive behavioral therapy approaches have proven efficacy for inducing smoking cessation during pregnancy. However, the effectiveness is reduced among women who have partners that smoke, who are less educated, or who are heavy smokers.

Nicotine replacement therapy has proven highly effective in nonpregnant smokers and is widely available in nonprescription formulations. Because evidence suggests that nicotine replacement during pregnancy is not more harmful to the fetus compared with smoking, the potential for using these quitting aids to improve smoking cessation during pregnancy has attracted considerable interest, the authors noted.

Dr. Pollak and colleagues prospectively examined the impact of adding nicotine replacement therapy to cognitive behavioral therapy in 181 female smokers who were in weeks 13 to 25 of pregnancy. All of the women had six individual counseling sessions but were randomly assigned in a 1:2 ratio to behavioral therapy alone or to behavioral therapy plus nicotine replacement.

Patients assigned to nicotine replacement could opt for transdermal patches, lozenges, or gum. The patches delivered a nicotine dose that was adjusted according to the patient's smoking history (fewer than 10 cigarettes/day to 15 or more). Patients who chose gum or lozenges were instructed to use one piece as a substitute each time they wanted to smoke a cigarette.

The primary endpoint was the smoking cessation rate, assessed at seven weeks post-randomization, 38 weeks gestation, and three months postpartum. At the seven-week evaluation, 24% of patients randomized to combination therapy had quit smoking compared with only 8% of patients on cognitive behavioral therapy alone (P=0.02).

By 38 weeks gestation the smoking cessation rate had slipped to 18% in the combination arm, but that was still significantly better than the 7% rate in patients assigned to behavioral therapy alone (P=0.04).

At the three-month postpartum assessment, 20% of patients in the combination arm continued to abstain from smoking, but the quit rate had increased to 14% in the behavioral therapy group (P=0.55).

Comparison of adverse events in the two groups revealed no significant differences in preterm birth, NICU admissions, size for gestational age, placenta abruption, or fetal demise. Serum cotinine levels did not differ between women with and without adverse events, and women who smoked had higher cotinine levels than did women assigned to nicotine replacement.

Recruitment was suspended early by an Independent Data and Safety Monitoring Board when an interim analysis found a higher rate of negative birth outcomes in the combined therapy arm than in the behavioral therapy-only arm. In the final analysis, the difference between the arms in rate of negative birth outcomes was 0.09 (P<0.26), when adjusted for previous history of preterm birth.

Among women assigned to combination therapy, 76% reported using the nicotine replacement method as instructed. For every seven days of on replacement therapy, patients were 1.25 times more likely to abstain from smoking.

"Many women who smoke recognize the risks of continuing to smoke during pregnancy, as evidenced by relatively high quit rates during the first trimester," the authors noted. "For those unable to quit on their own, adding [nicotine replacement therapy] to [cognitive behavioral therapy] may improve smoking cessation rates during pregnancy."

The authors noted several limitations. "Even at the originally planned sample size, power to detect differences in specific pregnancy outcomes was lacking. In hindsight, randomization should have been stratified on history of negative pregnancy outcomes. The fact that the women lost to follow-up had more previous negative birth outcomes, smoked more, and had tried to quit during a previous pregnancy may affect generalizability."