PRO & CON

OB/GYN News, June 15, 2001

Should nicotine replacement therapy be used during pregnancy?

YES

Women who smoke during pregnancy assume a large risk of serious complications. Some women do quit smoking during pregnancy, but many don't, and those who do not quit tend to be the more addicted women. Behavioral programs do help a bit, but they don't help the more addicted smokers. Experience with nonpregnant women shows that nicotine replacement therapy is useful in helping people quit, especially the more highly addicted smokers. So it makes sense that some kind of medication to help pregnant women stop smoking would be worthwhile.

On the other hand, nicotine itself can potentially harm the fetus. The issue of nicotine replacement therapy during pregnancy clearly requires a careful analysis of the relative risks and benefits. With Dr. Delia A. Dempsey, I have recently published an article reviewing these risks and benefits (Drug Safety, 24[4]:277-322, 2001).

My argument for nicotine replacement therapy has three elements. First, in most cases you're not exposing the woman to any more nicotine than she's getting as a result of smoking, maybe less. Second, you're exposing them in a way that's less hazardous to them. That is, inhaling nicotine in smoke results in higher arterial blood levels and more intense physiologic responses, compared with nicotine taken from pharmaceutical preparations. Third, cigarette smoke contains many toxic substances aside from nicotine, including carbon monoxide, a well-known teratogen that causes abnormalities in brain development. It contains oxidant gasses that can affect blood vessels in the placenta and fetus, and it contains heavy metals that can have adverse effects on fetal brain development.

I acknowledge that nicotine replacement therapy in pregnancy has not been proven to increase cessation rates. The one published study on this did not show a difference in cessation rates, although it did show an improvement in birthweights in the children who received nicotine, which may be a result of their mothers having smoked fewer cigarettes (Obstet. Gynecol. 96[6]:967-71, 2000). The benefits, although theoretical, have not been demonstrated, and this dearly needs to be studied further.

The mode of nicotine replacement therapy may make a difference. If you look at the trials with the gum, the transdermal patch, the inhaler, and the nasal spray, they all increase cessation rates about twofold over placebo. But the average amount of nicotine absorbed is quite different. For the patch, the average absorbed dose is between 15 mg and 21 mg; for the other forms, it's about 10 mg.

For this reason, some have argued that pregnant women are better off using methods other than the patch. The advantage of the patch is that it is easier to use. Women who are nauseated don't like to use the gum, and they often find the nasal spray irritating. Physicians who are concerned about overall exposure to nicotine could choose to measure levels of cotinine, a metabolite of nicotine, before and after the start of therapy to ensure that their patients are not getting more nicotine than they got from smoking. I do recommend the use of the 16-hour patch instead of the 24-hour patch, since it gives the baby's brain some time off nicotine.

Finally, some critics have charged that pharmaceutical companies are behind the effort to market nicotine replacement products to pregnant women. My experience, however, is that pharmaceutical companies see that pregnant women-constitute a minuscule market, and the use of any medication in this population certainly raises problematic liability issues.

Dr. Neal L.

Benowitz is a professor of medicine and a clinical pharmacologist at the University of California, San Francisco.

NO

A recent metaanalysis indicates that maternal smoking is responsible for tens of thousands of perinatal deaths and neonatal ICU admissions, and for 50%-500% increases in the incidence of sudden infant death syndrome, learning disabilities, and disruptive behaviors (J. Fam. Pract. 40[4]:385-94, 1995).

At the outset, it might seem obvious that nicotine replacement therapy with transdermal patches would be a desirable approach to smoking cessation in pregnant women. After all, whereas cigarette smoke contains nicotine, it also contains hydrogen cyanide, carbon monoxide, and numerous injurious substances that are not present with nicotine replacement therapy. The underlying assumption, of course, is that these other substances are the major contributors to adverse perinatal outcomes. Unfortunately, two decades of research with animal models that simulate blood nicotine levels found in smokers or in users of the transdermal nicotine patch indicate otherwise. Nicotine is a potent developmental neurotoxin and by itself reproduces most of the features of maternal smoking: intrauterine growth retardation, fetal brain damage, cognitive and learning problems, and hypoxia intolerance that contributes to perinatal mortality and SIDS (J. Pharmacal. Exp. Ther. 285[3]:931-45, 1998).