Blue Cohosh and Perinatal Stroke
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《新英格兰医药杂志》
To the Editor: With the recent decision of the Food and Drug Administration to ban the sale of ephedra in the United States, a broad discussion of the uses, risks, and regulation of herbal preparations has been kindled in the news media. We report a case that raises similar issues with potentially broad implications for the use of other herbal preparations that have a vasoconstrictive effect.
A female infant weighing 3860 g was born at just over 40 weeks' gestation to a healthy 24-year-old woman (gravida 2, para 0). The obstetrician reportedly had advised the woman to drink a tea made from blue cohosh (Caulophyllum thalictroides). Induction of labor is a recognized effect of this herbal supplement,1 and the tea was effective. A cesarean section was performed after a failed attempt at vaginal delivery. The infant had focal motor seizures of the right arm, which began at 26 hours of age, and which were controlled with phenobarbital and phenytoin. A computed tomographic (CT) scan obtained when the infant was two days of age showed an evolving infarct in the distribution of the left middle cerebral artery (Figure 1). The results of thrombophilia studies to assess an innate tendency for excessive blood clotting in the infant were either negative or normal and the family history was negative for embolic or thrombotic disease. Urine and meconium were positive for the cocaine metabolite benzoylecgonine on screening by immunoassay, and these results were confirmed by gas chromatography–mass spectrometry. Testing of the contents of the mother's bottle of blue cohosh and the contents of a sealed bottle of a different preparation of the herb gave the same results.
Figure 1. Axial Section of a Non–Contrast-Enhanced Cranial CT Scan Obtained on the Infant's Second Day of Life.
The low-density region in the distribution of the left middle cerebral artery indicates an ischemic infarct.
These toxicologic studies suggest that either benzoylecgonine is a metabolite of both cocaine and blue cohosh or the blue cohosh was contaminated with cocaine. The preparation called "Inca tea" contains coca leaves and can also cause a positive test for cocaine on toxicologic screening.2 Maternal cocaine use is a well-known cause of perinatal stroke.3 In addition, blue cohosh contains the glycosides caulosaponin and caulophyllosaponin, which can cause uterine contraction and coronary-artery constriction in the rat and dose-dependent contraction of a bovine and porcine carotid-artery preparation.4 Also present is the alkaloid methylcytisine, a nicotinic agonist. The case of a neonate who had an acute myocardial infarction after maternal ingestion of an excessive dose of blue cohosh has been reported.5 Although the earlier report does not prove that blue cohosh was the cause of this infant's stroke, it does lend support to the presence of a pathophysiologic mechanism. The relationship between the herbal preparation and the infant's condition is striking and worthy of further study.
Richard S. Finkel, M.D.
Children's Hospital of Philadelphia
Philadelphia, PA 19104-4399
finkel@email.chop.edu
Karen M. Zarlengo, M.D.
Littleton Adventist Hospital
Littleton, CO 80122
References
Castleman M. The new healing herbs: the classic guide to nature's best medicines featuring the top 100 time-tested herbs. Emmaus, Pa.: Rodale Press, 2001.
Jackson GF, Saady JJ, Poklis A. Urinary excretion of benzoylecgonine following ingestion of Health Inca Tea. Forensic Sci Int 1991;49:57-64.
Volpe JJ. Effect of cocaine use on the fetus. N Engl J Med 1992;327:399-407.
Ferguson HC, Edwards LD. A pharmacological study of a crystalline glycoside of Caulophyllum thalictroides. J Am Pharmaceutical Assn 1954;43:16-21.
Jones TK, Lawson BM. Profound neonatal congestive heart failure caused by maternal consumption of blue cohosh herbal medication. J Pediatr 1998;132:550-552.
Related Letters:
More on Blue Cohosh and Perinatal Stroke
Potterton D., Chan G. M., Nelson L. S., Finkel R. S., Zarlengo K. M.
A female infant weighing 3860 g was born at just over 40 weeks' gestation to a healthy 24-year-old woman (gravida 2, para 0). The obstetrician reportedly had advised the woman to drink a tea made from blue cohosh (Caulophyllum thalictroides). Induction of labor is a recognized effect of this herbal supplement,1 and the tea was effective. A cesarean section was performed after a failed attempt at vaginal delivery. The infant had focal motor seizures of the right arm, which began at 26 hours of age, and which were controlled with phenobarbital and phenytoin. A computed tomographic (CT) scan obtained when the infant was two days of age showed an evolving infarct in the distribution of the left middle cerebral artery (Figure 1). The results of thrombophilia studies to assess an innate tendency for excessive blood clotting in the infant were either negative or normal and the family history was negative for embolic or thrombotic disease. Urine and meconium were positive for the cocaine metabolite benzoylecgonine on screening by immunoassay, and these results were confirmed by gas chromatography–mass spectrometry. Testing of the contents of the mother's bottle of blue cohosh and the contents of a sealed bottle of a different preparation of the herb gave the same results.
Figure 1. Axial Section of a Non–Contrast-Enhanced Cranial CT Scan Obtained on the Infant's Second Day of Life.
The low-density region in the distribution of the left middle cerebral artery indicates an ischemic infarct.
These toxicologic studies suggest that either benzoylecgonine is a metabolite of both cocaine and blue cohosh or the blue cohosh was contaminated with cocaine. The preparation called "Inca tea" contains coca leaves and can also cause a positive test for cocaine on toxicologic screening.2 Maternal cocaine use is a well-known cause of perinatal stroke.3 In addition, blue cohosh contains the glycosides caulosaponin and caulophyllosaponin, which can cause uterine contraction and coronary-artery constriction in the rat and dose-dependent contraction of a bovine and porcine carotid-artery preparation.4 Also present is the alkaloid methylcytisine, a nicotinic agonist. The case of a neonate who had an acute myocardial infarction after maternal ingestion of an excessive dose of blue cohosh has been reported.5 Although the earlier report does not prove that blue cohosh was the cause of this infant's stroke, it does lend support to the presence of a pathophysiologic mechanism. The relationship between the herbal preparation and the infant's condition is striking and worthy of further study.
Richard S. Finkel, M.D.
Children's Hospital of Philadelphia
Philadelphia, PA 19104-4399
finkel@email.chop.edu
Karen M. Zarlengo, M.D.
Littleton Adventist Hospital
Littleton, CO 80122
References
Castleman M. The new healing herbs: the classic guide to nature's best medicines featuring the top 100 time-tested herbs. Emmaus, Pa.: Rodale Press, 2001.
Jackson GF, Saady JJ, Poklis A. Urinary excretion of benzoylecgonine following ingestion of Health Inca Tea. Forensic Sci Int 1991;49:57-64.
Volpe JJ. Effect of cocaine use on the fetus. N Engl J Med 1992;327:399-407.
Ferguson HC, Edwards LD. A pharmacological study of a crystalline glycoside of Caulophyllum thalictroides. J Am Pharmaceutical Assn 1954;43:16-21.
Jones TK, Lawson BM. Profound neonatal congestive heart failure caused by maternal consumption of blue cohosh herbal medication. J Pediatr 1998;132:550-552.
Related Letters:
More on Blue Cohosh and Perinatal Stroke
Potterton D., Chan G. M., Nelson L. S., Finkel R. S., Zarlengo K. M.