ABSTRACT & COMMENTARY
Passive Smoking Exposure and Preeclampsia
By John C. Hobbins, MD
Professor, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora
Dr. Hobbins reports no financial relationships relevant to this field of study.
SYNOPSIS: A study that has focused on patients who are exposed to second-hand smoke shows a higher rate of preeclampsia than nonsmokers.
SOURCE: Luo ZC, et al. Plasma cotinine indicates an increased risk of preeclampsia in previous and passive smokers. Am J Obstet Gynecol 2014; 210:232.e1-5.
Although smoking during pregnancy is associated with increased rates of fetal growth restriction, preterm birth, and placental abruption, some studies have suggested a lower rate of preeclampsia in smokers.1 Investigators involved in the Canadian/Mexican study to assess the efficacy of vitamins C and E in preventing preeclampsia (the International Trial of Anti-oxidant Supplementation for the Prevention of Preeclampsia—INTRAPP)2 resurrected banked bloods from 733 patients, obtained at 24-26 weeks, for analysis of plasma cotinine content. This metabolite has been used as an objective method to detect smokers when found in levels above a preset threshold. However, the authors were particularly interested in patients who exhibited lower levels of cotinine, suggesting that they were either passively exposed to cigarette smoke or they had recently stopped smoking. Specimens from chronic hypertensives were excluded, leaving a final study cohort of 605 patients/samples. The authors then used stringent criteria from patient records to identify those who either developed gestational hypertension or preeclampsia. They applied a currently used plasma cotinine of > 3.0 ug/mL to single out current smokers, 2.0-3.0 ug/mL to define those who recently stopped or had been passively exposed to smokers, and levels < 2.0 ug/mL to signify nonsmokers.
Thirty patients (5%) developed preeclampsia while 67 patients in the study group developed gestational hypertension. The "passive/recently stopped" group had a significantly increased risk of preeclampsia compared with control nonsmokers (odds ratio [OR], 6.06; 95% confidence interval [CI], 2.32-15.85). However, there was no association in this group with the development of gestational hypertension compared with controls (OR, 1.48; CI, 0.54-4.07). In this study, smokers did not seem to be protected from preeclampsia (OR, 1.04; CI, 0.22-4.95), but only 47 smokers were in the analysis.
COMMENTARY
It is counter-intuitive that a habit that has such undesirable pregnancy consequences should result in a decreased risk of a condition that is at the heart of the maternal/placental connection. Now it is just as puzzling that those who have recently stopped smoking, or have been exposed to cigarette smoke, are now more vulnerable to preeclampsia. Studies that rely on self-reported data are inherently flawed and the concept of using a metabolite does seem to be a more objective way to study this relationship. Yet, unfortunately, it has been difficult at lower levels of cotinine to separate out the passively exposed women from the recently stopped smokers who may have a low residual level of this metabolite. So the investigators lumped them together.
It is clear that there are many more potentially noxious components in cigarette smoke than nicotine — the often blamed culprit — that could affect transport of oxygen and nutrients to the fetus. For example, carbon monoxide concentrations are quite high in smokers and I recall one study that is now more than 30 years old (and I can’t find the citation) that showed carbon monoxide levels in smokers to be as high as workers stationed at that time in the Midtown Tunnel in New York City. However, if looking for a possible protector for preeclampsia, carbon monoxide interferes in vitro with the action of tyrosine kinase, an anti-angiogenic factor whose levels are elevated in preeclampsia. In any case, carbon monoxide has a far shorter half-life than other longer-lasting combustibles in second-hand cigarette smoke that could overmatch carbon monoxide’s fading protective effect on the placental bed (if there really is one).
Latest figures show that 10.7% of Americans continue to smoke during pregnancy. Of those who smoke within 3 months of pregnancy, 54% quit when becoming pregnant, but 44% will pick up the habit again postpartum.3 A stunning fact is that 1 in 5 people still smoke in the United States, exposing 88 million non-smokers to second-hand smoke.4 The earlier studies suggesting a lessened risk of preeclampsia in smokers might have sent the wrong message, especially since they might have been tainted by being dependent on self-reported information. This study, using perhaps a more objective measure of cigarette smoke exposure, enforces the message that pregnant patients should even avoid passive cigarette smoke, a situation most commonly occurring in the household or in bars and restaurants that allow smoking.
References
- Engel SM, et al. Maternal smoking, preeclampsia, and infant health outcomes in New York City 1995-2003. Am J Epidemiol 2009;169:33-40.
- Luo ZC, et al. Plasma cotinine indicates an increased risk of preeclampsia in previous and passive smokers. Am J Obstet Gynecol 2014; 210:232.e1-5.
- Centers for Disease Control and Prevention. 2010 Pregnancy Risk and Monitoring System (PRAMS); 2010. Available at: http://www.cdc.gov/prams/. Accessed April 28, 2014.
- King BA, et al. Current tobacco use in the United States: Findings from the National Adult Tobacco Survey. Am J Pub Health 2012;102:e93-100.
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