Herbs and Pregnancy
August 2001; Volume 3; 57-61
By Anthony R. Scialli, MD, and Adriane Fugh-Berman, MD
There is no evidence that the use of culinary herbs such as garlic or ginger is harmful during pregnancy, but the growing popularity of medicinal herbs may increase the deliberate or inadvertent use of medicinal herbs during pregnancy, raising the possibility of adverse fetal or neonatal effects.
Prevalence
It is unknown how often medicinal herbs are used during pregnancy. A small study in South Africa of 229 patients in labor found that 55% had taken herbs during pregnancy.1 Herbal use during pregnancy was associated with a higher rate of meconium staining (55.6% compared to 15% in the control group) and cesarean section (38.5% compared to 22% in the control group).
A survey of 172 certified nurse-midwives (CNMs) found that 90 CNMs prescribed or encouraged use of labor-stimulating herbs.2
Echinacea (E. purpurea, E. angustifolia, E. pallida)
The effect of echinacea use during pregnancy was investigated by Motherisk, a Toronto information center that handles telephone calls from women with concerns about pregnancy exposures. Pregnancy outcome was obtained for 206 women who took this herb, 112 of whom used it during the first trimester.3 A control group consisted of 206 women who called Motherisk with questions about echinacea but who did not take it, or who took an antibiotic for upper respiratory infection. The antibiotics were judged by the Motherisk team to have posed no increased risk of birth defects.
Pregnancy outcome information was collected using a questionnaire that was completed by the women. There were 195 live births among women with echinacea exposure, with elective and spontaneous abortion accounting for the remainder of the subjects. There were six children with major congenital malformations in the echinacea-exposed group, including one case each of inguinal hernia, bilateral hydronephrosis, syndactyly, duplication of the renal pelvis, laryngotracheomalacia, and trisomy 18. There were seven children with major congenital malformations in the control group. The rates of major malformations were not different between the groups and were not different from the 3-5% rate that would be expected in the general population.
The major strength of this study is the prospective enrollment of women based on exposure, prior to the women’s awareness of pregnancy outcome. This prospective enrollment avoids the inclusion of more exposed women with abnormal outcomes than of women with normal outcomes. Weaknesses include the possibility that this population was self-selected by having been aware of the availability of Motherisk counseling, and by their interest in seeking counseling. (An unpublished survey of the Organization of Teratology Information Services suggests that women calling these services are predominantly white, middle-class, college-educated, and English-speaking.) Another weakness is the ascertainment of outcome by maternal report. Although maternal report of major birth defects can be expected to be reliable, misreporting of abnormalities that are subtle, difficult to understand, or still under clinical investigation is possible.
The study suggested that "gestational use of echinacea during organogenesis is not associated with a detectable increased risk for major malformations." This conclusion is limited by the ability of a sample of this size to identify an important risk of malformations. The authors’ analysis indicated 80% power to detect a 3.5-fold increase in the rate of major malformations. In other words, if the background risk of major malformations in the population is 3-5%, echinacea exposure would have to give rise to a 10-18% incidence of major malformations to have been detected in a sample of this size. There are medications (including thalidomide and isotretinoin) that produce malformation rates at this level or higher, but most medication exposures that increase the risk of birth defects do so at a considerably lower level (1% or 2%). It would be reasonable to conclude, then, that echinacea is not another thalidomide, but it would be premature to recommend use of this herb during pregnancy based on this study.
St. John’s Wort (Hypericum perforatum)
St. John’s wort is commonly used to treat depression. A report of two women who took St. John’s wort during pregnancy noted no untoward events.4
A recent study tested the effects of prenatal exposure to St. John’s wort on long-term growth in physical maturation of mouse offspring.5 Forty-eight CD-1 mice were randomized to 180 mg/kg/d hypericum or placebo for two weeks before conception and throughout gestation. There were no differences between groups in physical milestones, reproductive capability, perinatal outcomes, or growth and development of first- or second-generation offspring.
Ginseng (Panax ginseng, other Panax species)
Ginseng is an adaptogenic, tonic herb commonly used in Chinese medicine; it also has become popular in the West. A letter to the editor presented 88 women who reported using ginseng during pregnancy.6 There was no apparent increase in adverse pregnancy outcome compared to unexposed women. In another study, ginseng was tested in rats over two generations and caused no adverse effects on reproductive performance including fetal development.7
Blue Cohosh (Caulophyllum thalictroides) and Black Cohosh (Cimicifuga racemosa)
Blue cohosh is used for labor facilitation. The McFarlin survey of CNMs found that 64% of those who prescribed herbs for labor facilitation used blue cohosh and 45% used black cohosh.2 Twenty-one percent of the CNMs reported complications when herbs were used, including nausea, meconium-stained fluid, and transient fetal tachycardia with use of blue and black cohosh.
Maternal use of blue cohosh in high doses for one month prior to birth was associated with acute anterolateral myocardial infarction and congestive heart failure in an infant.8 Severe hypoxic-ischemic symptoms were seen in the baby of a woman who took a mixture of blue cohosh and black cohosh (Cimicifuga racemosa) to induce labor.9 Blue cohosh rhizomes contain caulosaponin and caulophyllosaponin, both saponins with vasoconstrictor activity and cardiotoxic effects.10 Blue cohosh also contains anagyrine in concentrations of up to 290 ppm.11 Anagyrine in lupine (Lupinus species) causes crooked calf disease in the offspring of cows who graze on it.12 Anagyrine is thought to require metabolism by rumen microflora to exhibit teratogenic effects, so it may not have the same effects in humans. One case, however, suggests a link between maternal consumption of anagyrine-containing goat milk and vascular anomaly, skeletal dysplasia, and malformed red blood cells in an infant.13
Tripterygium wilfordii
Also called thunder god vine, Tripterygium wilfordii is a Chinese herb used to treat rheumatoid arthritis and dermatological conditions. Occipital meningoenceph-alocele and cerebellar agenesis were associated with the use of Tripterygium wilfordii early in pregnancy; the herb was being used for the treatment of arthritis.14 Tripterygium wilfordii caused open neural tube defects and other embryotoxic effects in an in vitro whole mouse embryo culture system.15
Eleuthero or Siberian Ginseng (Eleutherococcus senticosis)
Eleuthero is an adaptogenic or tonic herb. Neonatal hirsutism in a baby noted to have hair on the forehead, pubic hair, swollen nipples, and enlarged testes was attributed to the use of Siberian ginseng (Eleutherococcus senticosis) throughout pregnancy and during lactation. However, the wrong herb was blamed; subsequent analysis showed that the herb consumed was actually Chinese silk vine (Periploca sepium).16 E. senticosis also was tested in castrated rats for androgenic effects; daily oral administration of 1.5 g/kg (equivalent to 105 g given to a 70 kg human) of E. senticosis for a week caused no androgenic effects and no overt toxic effects.17
Licorice (Glycyrrhiza glabra)
Besides flavoring candy, licorice commonly is used in both Western and Chinese herbal medicine. A study of 1,049 Finnish women, however, found that heavy intake of licorice candy during pregnancy significantly increased the odds ratio (OR) for birth prior to 38 weeks gestation (OR 2.5, 95% confidence interval 1.1, 5.5, P = 0.03).18 There was no effect on gestational age.
In a rat teratology study, an herbal combination of nine agents, one of which was licorice root, did not increase congenital anomalies and appeared to protect against valproic acid-induced defects.19
Ginger (Zingiber officinale)
Although useful for morning sickness, ginger traditionally has been used for "suppressed menses," a term that is sometimes a euphemism for early pregnancy. An abortifacient effect, however, has not been shown in humans. In a clinical trial of nausea and vomiting of pregnancy, one patient experienced a spontaneous abortion; another underwent induced abortion for non-medical reasons.20 Twenty-five patients went to term and all infants born were normal in terms of appearance, birthweight, and Apgar scores.
Raspberry Leaf (Rubus idaeus)
Raspberry leaf preparations commonly are used as pregnancy tonics. No adverse effects of raspberry leaf preparations have been reported. An Australian retrospective record review of 57 women who had consumed raspberry leaf products during their pregnancy and 51 controls (randomly selected from hospital records of women who stated they had not consumed raspberry leaf products) found no safety problems for women or their babies when raspberry leaf products were consumed during pregnancy.21 (See Alternative Therapies in Women’s Health, April 2001, pp. 25-26.)
Conclusion
Blue cohosh has been associated with several cases of adverse neonatal outcomes. Tripterygium wilfordii has been associated with a single case of occipital meningoencephalocele and cerebellar agenesis; however, an animal study demonstrating open neural tube defects supports causality. There is no evidence to date that use of St. John’s wort, echinacea, ginseng, eleuthero, or raspberry leaf during pregnancy is harmful.
As is true for therapeutics in nonpregnant women, medications, including herbal therapies, should not be used unless there is adequate evidence of safety and efficacy. Midwives and herbalists who care for pregnant women should use an evidence-based approach and should recognize that almost all effective medicines can have problematic side effects.
References
1. Mabina MH, et al. The effect of traditional herbal medicines on pregnancy outcome. The King Edward VIII Hospital experience. S Afr Med J 1997;87:1008-1010.
2. McFarlin BL, et al. A national survey of herbal preparation use by nurse-midwives for labor stimulation. Review of the literature and recommendations for practice. J Nurse Midwifery 1999;44:205-216.
3. Gallo M, et al. Pregnancy outcome following gestational exposure to echinacea. Arch Intern Med 2000;160: 3141-3143.
4. Grush LR, et al. St. John’s wort during pregnancy. JAMA 1998;280:1566.
5. Rayburn WF, et al. Effect of prenatally administered hypericum (St. John’s wort) on growth and physical maturation of mouse offspring. Am J Obstet Gynecol 2001;184:191-195.
6. Chin RK. Ginseng and common pregnancy disorders [letter]. Asia Oceania J Obstet Gynaecol 1991;17: 379-380.
7. Hess FG Jr, et al. Reproduction study in rats of ginseng extract G115. Food Chem Toxicol 1982;20: 189-192.
8. Jones TK, Lawson BM. Profound neonatal congestive heart failure caused by maternal consumption of blue cohosh herbal medication. J Pediatr 1998;132:550-552.
9. Gunn TR, Wright IM. The use of black and blue cohosh in labour. N Z Med J 1996;109:410-411.
10. Irikura B, Kennelly EJ. Blue cohosh: A word of caution. Altern Ther Women’s Health 1999;1:81-83.
11. Betz JM, et al. Gas chromatographic determination of toxic quinolizidine alkaloids in blue cohosh Caulophyllum thalictroides (L.) Michx. Phytochem Anal 1998;9: 232-236.
12. Keeler RF. Livestock models of human birth defects, reviewed in relation to poisonous plants. J Anim Sci 1988;66:2414-2427.
13. Ortega JA, Lazerson J. Anagyrine-induced red cell aplasia, vascular anomaly, and skeletal dysplasia. J Pediatr 1987;111:87-89.
14. Takei A, et al. Meningoencephalocele associated with Tripterygium wilfordii treatment. Pediatr Neurosurg 1997;27:45-48.
15. Chan WY, Ng TB. Adverse effect of Tripterygium wilfordii extract on mouse embryonic development. Contraception 1995;51:65-71.
16. Awang DVC. Maternal use of ginseng and neonatal androgenization [letter]. JAMA 1991;266:363.
17. Waller DP, et al. Lack of androgenicity of Siberian ginseng. JAMA 1992;267:2329.
18. Strandberg TE, et al. Birth outcome in relation to licorice consumption during pregnancy. Am J Epidemiol 2001;153:1085-1088.
19. Minematsu S, et al. Effects of Shosaiko-to-go-keishikashakuyaku-to (TJ-960) on the valproic acid induced anomalies of rat fetuses [English abstract]. Nippon Yakurigaku Zasshi 1990;96:265-273.
20. Fischer-Rasmussen W, et al. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1990;38:19-24.
21. Parsons M, et al. Raspberry leaf and its effect on labour: Safety and efficacy. J Australian Coll Midwives 1999;12:20-25.
August 2001; Volume 3; 57-61
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