Smoking, Pregnancy, and Infertility

Smoking during pregnancy is the most important modifiable risk factor associated with adverse pregnancy outcomes. It is associated with 5 percent of infant deaths, 10 of preterm births, and 30 percent of small for gestational age infants.

In addition, smoking and secondhand smoke exposure increases the risk of infertility, placental abruption, preterm premature rupture of membranes (PPROM), and placenta previa.

Despite the known harmful effects of smoking on the health of mothers and their children, it is estimated that 22 percent of American women of reproductive age smoke cigarettes. Overall estimates of smoking rates during pregnancy vary based on the method of data collection; the Pregnancy Risk Assessment Monitoring System (PRAMS) survey reported a prevalence of 14 percent in 2005 in the United States. When analyzed by state, the prevalence of smoking anytime during pregnancy ranged from 6 percent in Utah to 36 percent in West Virginia. The exact prevalence of smoking during pregnancy is difficult to discern, not only because of incomplete records, but also because most studies rely on self-reported smoking behavior and are therefore subject to underreporting.

Impaired fetal oxygen delivery is the best-studied cause of adverse outcome in pregnant women who smoke. Pathologic evaluations of the placentas of smokers have shown structural changes, including a reduction in the fraction of capillary volume and increased thickness of the villous membrane when compared to nonsmokers. Both of these factors may contribute to abnormal gas exchange within the placenta. Exposure to cigarette smoke also acutely decreases intervillous perfusion, possibly via nicotine-induced vasospasm. Another problem is that carbon monoxide exposure from smoking causes the formation of carboxyhemoglobin, which has multiple effects on systemic and fetal oxygen delivery.

Smoking may also result in direct damage to fetal genetic material. One study compared the chromosomal instability of amniocytes from smokers and non-smokers, and noted an increased incidence of structural chromosomal abnormalities among women who smoked regularly. Most of these abnormalities were the result of deletions or translocations, and many were localized to the 11q23 region, which is also associated with several hematologic malignancies.

Other possible mechanisms responsible for adverse fetal outcomes in mothers who smoke include direct toxicity of the more than 2500 substances found in cigarettes, such as ammonia, polycyclic aromatic hydrocarbons, hydrogen cyanide, vinyl chloride, nitrogen oxide, and carbon monoxide. In addition, there are over 4000 chemicals in mainstream tobacco smoke, which is drawn through the tobacco column and exits through the mouthpiece during puffing. The number of compounds emitted in tobacco smoke may actually exceed 100,000.

Animal models suggest that nicotine can directly impair lung development due to interaction with nicotinic acetylcholine receptors (nAChR). Prenatal nicotine exposure also can blunt the cardiorespiratory response to postnatal hypoxemia in sheep. Similarly, term human infants with significant cotinine levels at delivery are limited in their ability to maximize and vary their heart rate during the first four hours of life.

Finally, exposure to nicotine results in sympathetic activation leading to acceleration of fetal heart rate and a reduction in fetal breathing movement. While the consequences of these changes are not well understood, both of these parameters are used as indicators of fetal well-being.

The negative impact of cigarette smoking on fetal health is well established. Cigarette smoking has been associated with numerous adverse outcomes, including spontaneous pregnancy loss, placental abruption, PPROM, placenta previa, preterm labor and delivery, low birth weight (LBW), and ectopic pregnancy. While the pathophysiology is not completely understood, as discussed above, several possible mechanisms related to impaired gas exchange, direct toxicity, and sympathetic activation have been proposed.

Although smoking cessation during pregnancy is of maximal benefit if it occurs early in the first trimester, quitting at any time during pregnancy can have some beneficial effects. For women unable to quit smoking, reducing the number of cigarettes smoked still has maternal and fetal benefits.