The nicotine replacement patch was no more effective than a placebo patch was in promoting sustained abstinence from smoking in a study of 1,050 pregnant women published in the March 1 issue of the New England Journal of Medicine.
In addition, "there was no evidence that nicotine replacement therapy had either a beneficial or harmful effect on birth outcomes." However, adherence rates in this study were so low that the researchers’ ability to assess safety was severely limited, said Dr. Tim Coleman of the U.K. Centre for Tobacco Control Studies and the National Institute for Health Research School for Primary Care Research, Nottingham, and his associates.
"[Our] findings suggest that guidelines for smoking cessation in pregnancy should be revised to encourage the use of only those interventions that have a secure evidence base – specifically, behavioral support," they noted.
Use of the nicotine replacement patch is recommended in several such sets of guidelines, owing to the general consensus that it is probably less harmful than smoking is during pregnancy. But there is no good evidence to support such recommendations because individual clinical trials have been too small to definitively establish whether the patch is either effective or safe, and since a meta-analysis of these studies yielded inconclusive results, Dr. Coleman and his colleagues said.
They performed a multicenter, double-blind, randomized clinical trial involving women at 12-24 weeks’ gestation who were heavy smokers and who agreed, at a regular prenatal clinic visit, to set a quit date. On that day, the study subjects were randomly assigned to receive a 1-month supply of transdermal nicotine-replacement patches (521 women) or placebo patches (529 women).
In addition, midwives who were trained in smoking-cessation techniques provided behavioral support at enrollment, on the quit date, 3 days later, and at the 1-month visit. At that visit, study subjects who had quit smoking were given another 1-month supply of patches.
The women "were offered additional support from local National Health Service smoking-cessation services and were encouraged to ask for support from the midwives or smoking-cessation staff."
The midwives later ascertained the study subjects’ smoking status when they were admitted to the hospital for delivery. They also noted how much behavioral support the women had used and their use of study patches, as well as any nonstudy nicotine replacement therapy.
The primary outcome was self-reported abstinence from smoking between the quit date and delivery, which was validated by analysis of exhaled carbon monoxide and salivary cotinine levels. This rate was 9.4% with active patches and 7.6% with placebo patches, a nonsignificant difference, the investigators said (N. Engl. J. Med. 2012;366:808-18).
After the first month of patch use, the rate of smoking abstinence had been significantly higher with active treatment (21.3%) than with placebo (11.7%), but this difference had not persisted beyond that point, largely because of poor compliance. Only 7.2% of the women in the nicotine-replacement group and only 2.8% of those in the placebo group reported using their patches for more than 1 month.
Most of the women had no further contact with their smoking-cessation counselors after the 1-month visit, and very few sought nonstudy smoking-cessation therapy.
Mean birth weights, rates of preterm birth, rates of low birth weight, and rates of congenital abnormalities were similar between the two study groups. There were significantly more cesarean deliveries in the nicotine-replacement group (20.7%) than in the placebo group (15.3%) – an unexpected finding that "seems likely to be a chance occurrence."
"A much larger sample would be required to comprehensively assess the effect of this therapy on infrequent adverse birth outcomes," Dr. Coleman and his associates noted.
"It is possible that for nicotine-replacement therapy to consistently ameliorate nicotine withdrawal symptoms and be effective throughout pregnancy, a higher dose is required. However, this trial did not include assessment of nicotine metabolism and did not assess withdrawal symptoms," they added.
This study was supported by the U.K. National Institute for Health Research’s Health Technology Assessment Programme. Dr. Sue Cooper reported ties to Action on Smoking and Health Scotland. No financial conflicts of interest were reported by the other researchers.