Discussion Questions

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  What were the authors’ aims?

  
  
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  What link might exist between carbon monoxide exposure and preeclampsia?

  
  
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  What was the study design?

  
  
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  What information is contained in the tables?

  
  
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  What is misclassification bias?

  
  
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  What direction should future research take?

Introduction

When surveyed, nearly 22% of pregnant white women aged 15-44 years said they had smoked cigarettes in the previous month; 14.2% of black women and 6.5% of Hispanic women said the same. While cigarette smoking is always discouraged—and particularly during pregnancy—the practice has been shown to reduce the risk of preeclampsia in several populations. Carbon monoxide (CO) released by the burning cigarette appears to increase trophoblast invasion and uteroplacental blood flow, reduce hypoxia-induced apoptosis, and upregulate placental antioxidant systems. This month, Journal Club members discussed a new study by Zhai et al, which looked for a relationship between environmental CO levels and preeclampsia.

Lorie M. Harper, MD, MSCI and George A. Macones, MD, MSCE, Associate Editor

Introduction

When surveyed, nearly 22% of pregnant white women aged 15-44 years said they had smoked cigarettes in the previous month; 14.2% of black women and 6.5% of Hispanic women said the same. While cigarette smoking is always discouraged—and particularly during pregnancy—the practice has been shown to reduce the risk of preeclampsia in several populations. Carbon monoxide (CO) released by the burning cigarette appears to increase trophoblast invasion and uteroplacental blood flow, reduce hypoxia-induced apoptosis, and upregulate placental antioxidant systems. This month, Journal Club members discussed a new study by Zhai et al, which looked for a relationship between environmental CO levels and preeclampsia.

Lorie M. Harper, MD, MSCI and George A. Macones, MD, MSCE, Associate Editor

Background

Harper: What were the authors’ aims in this study?

Keegan: The authors’ primary objective was to evaluate whether maternal exposure to a moderately elevated amount of CO results in a lower risk of preeclampsia. They also examined whether maternal exposure to the same CO concentration is protective against intrauterine growth restriction (IUGR) in the fetuses of mothers who develop preeclampsia.

Harper: Is there a biologically plausible link between CO exposure and preeclampsia?

Trudell: Yes. Preeclampsia is associated with abnormal angiogenesis, and CO plays an important role in angiogenesis through its vasodilatory, anti-apoptotic, and antiinflammatory effects. Several mediators of angiogenesis are involved in human placentation, and these include vascular endothelial growth factor (VEGF), a proangiogenic mediator, and 2 antiangiogenic mediators, soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin (sEng). CO is produced endogenously, mainly during degradation of heme by heme oxygenase. Heme oxygenase-1 (HO-1) is contained in high levels in the human placenta. HO-1 and CO have both been shown to be proangiogenic, upregulating and enhancing the activity of VEGF and inhibiting the antiangiogenic mediators, sFlt-1 and sEng. HO-1-dependent production of CO is also associated with upregulation of soluble guanylyl cyclase, which plays an important role in endothelial cell proliferation. Further, HO-1 levels in the human placenta and exhaled CO levels have been found to be lower in women with preeclampsia compared to women without the disorder.