Nicotine Replacement During Pregnancy: Does It Increase Stillbirth Rates?

AbstraCt & Commentary

By John C. Hobbins, MD, Professor and Chief of Obstetrics, University of Colorado Health Sciences Center, Denver, is Associate Editor for OB/GYN Clinical Alert.

Dr. Hobbins reports no financial relationship to this field of study.

Synopsis: Nicotine replacement therapy does not increase the risk of stillbirth in smokers.

Source: Strandberg-Larsen K, et al. Use of nicotine replacement therapy during pregnancy and stillbirth: A cohort study. BJOG 2008 Aug 20; Epub ahead of print.

Cigarettes and pregnancy are a risky combination, and there is an abundance of data to indicate that perinatal outcome is improved if patients can abstain from smoking. However, cigarettes represent a powerful addiction, and many patients cannot quit completely without help, some of whom will choose a form of nicotine replacement therapy (NRT). Nevertheless, one must be sure that the cure is not worse than the problem.

In an attempt to answer this question, a group of investigators interviewed 87,032 patients between 12 and 16 weeks of gestation as part of a data collection program, the Danish National Birth Cohort. They were questioned regarding their smoking habits and whether they used NRT (nicotine gum, nicotine patches, or inhaled products). All pregnancies were tracked through birth.

The investigators were primarily interested in stillbirth (SB) occurring after 20 weeks of gestation. In the overall population of smokers and non-smokers, the SB rate was 5.7 per 1000 (similar to that in the United States). When comparing the SB rate in smokers vs non-smokers, the former had a hazard risk (HR), which, in essence, is a likelihood ratio, of 1.45 (confidence interval = 1.1-1.8). The users of NRT who did not smoke during pregnancy had a HR of 0.67 and, if they did smoke during pregnancy, the HR was 0.83, neither of which was statistically significant.

Commentary

One study has suggested a higher rate of fetal anomalies in NRT users, causing many to wonder if this type of therapy might be worse than the alternative — smoking. The Danish investigators chose to evaluate only the incidence of SB and found that NRT diminished the rate of SB compared with smokers, in general, and had essentially the same rate of SB as non-smokers. This study had indigenous importance since (and this was a surprise to me) 1 of 5 pregnant Danish women smoke, and 2% of the overall pregnant population is on some form of NRT.

It certainly makes public health sense to find ways to discourage smoking since this habit is associated with virtually every adverse pregnancy outcome except, for some reason, preeclampsia. It is also clear that nicotine is not the only noxious component of cigarette smoke. Animal studies and a randomized trial pitting nicotine patches against placebo patches in smoking women suggested larger offspring with nicotine exposure alone, presumably because the nicotine patch worked to diminish the amount of cigarettes smoked.1,2 The study from England following children who were significantly growth restricted in utero showed that those children whose mothers were smokers performed more poorly on developmental function evaluations (Griffith DQ tests) than the other children whose mothers were non-smokers.3

Numerous other studies have shown that smoking mothers have a higher risk of low birthweight and fetal growth restriction, and higher rates of neonatal morbidity. It is granted that there were confounding variables affecting all of these studies, but it would be silly to suggest that cigarette smoking is innocuous to the developing fetus — and anything to cut down the amount of cigarettes smoked could have a beneficial effect.

This study indicates that NRT may cut down the rate of intrauterine demise in smokers. Putting this type of therapy into play after 11 weeks circumvents the possibility of teratogenic effect, and in this study seems not to increase the rate of SB above non-smokers.

References

  1. Morales-Suarez-Varela M, et al. Smoking habits, nicotine use, and congenital malformations. Obstet Gynecol 2006;107:51-57.
  2. Wisborg K, et al. Nicotine patches for pregnant smokers: A randomized controlled trial. Obstet Gynecol 2000;96:967-971.
  3. Soothill PW, et al. Fetal oxygenation at cordocentesis, maternal smoking and child neurodevelopment. Eur J Obstet Gynecol Reprod Biol 1995;59:21-24.