Herb
PREGNANCY RECOMMENDATION: Contraindicated
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of feverfew in human pregnancy have been located. The only animal reproduction study used a dose, based on weight, that was much higher than a typical human dose. This dose comparison cannot be assessed because doses should be compared based on BSA or AUC. Although embryolethality was suggested by the study, this outcome did not reach statistical significance. Moreover, no structural anomalies were observed in the study. The herb has been used in traditional and folk medicine for approximately 2500 years, so it is doubtful if consumption of the herb is associated with major birth defects. Feverfew does have emmenagogue activity and might cause abortion but, apparently, the doses used for this purpose have not been quantified. Its reported use for morning sickness, again without specifying a dose, suggests that a dose–effect relationship exists. Because the toxic dose is unknown, feverfew should not be used in pregnancy.
FETAL RISK SUMMARY
Feverfew is a plant that grows wild throughout the world, including North America. It is a short, bushy plant with a height up to 1 m (about 3.3 feet) and yellow flowers that bloom from July to October. The herb has been used in traditional and folk medicine for approximately 2500 years. The name feverfew comes from its antipyretic properties. It has been known as “medieval aspirin.” Feverfew has been used for a long list of medical conditions, including migraine. It also has been used to treat labor, menstrual disorders, potential miscarriage, morning sickness, and as an abortifacient. Because of the risk of abortion, it is considered contraindicated in pregnancy (1–3).
A large number of chemicals have been identified in feverfew. The major biologically active constituents are thought to be the sesquiterpene lactones, 85% of which are parthenolide. Other chemicals found in the plant are flavonoids, volatile oils, and miscellaneous other substances (1).
Because of the absence of animal reproduction studies, a 2006 study was conducted to screen pregnant rats to determine if a full reproductive study was warranted (3). The daily feverfew dose used was 839 mg/kg, which was 58.7 times the recommended human dose of 1 g/day (assumed to be in a 70-kg adult). Rats were treated daily on either gestational days (GDs) 1–8 to establish if the herb affects implantation and early development, or GDs 8–15 to detect if feverfew affects major organ development. In the GD1–8 group, an increase in preimplantation loss was observed, but the increase was not statistically significant. However, the number of liveborn pups was significantly fewer in the GD1–8 group compared with the GD8–15 group. There was also some indication that fetuses had lower weights than controls in the GD8–15 group, but this may have been due to the increased number of runts (defined as two standard deviations less than the mean litter weight of the controls) in the feverfew-exposed group. None of the treated fetuses had gross internal or external structural anomalies. Based on the overall results, the investigators concluded that a full reproductive study was warranted (3).
It is not known if feverfew crosses the human placenta. The dried leaf powder is standardized to contain at least 0.2% of parthenolide that has a molecular weight of about 248 (4). The molecular weight alone suggests that it will cross to the embryo and/or fetus.
BREASTFEEDING SUMMARY
No reports describing the use of feverfew during lactation have been located. The dried leaf powder is standardized to contain at least 0.2% of parthenolide that has a molecular weight of about 248 (4). The molecular weight alone suggests that it will be excreted into breast milk. Because of the potential risk of toxicity for a nursing infant, women consuming feverfew should not breastfeed (1,2).
References
1.Feverfew. The Review of Natural Products. St. Louis, MO: Facts and Comparisons, 2006.
2.Feverfew. Natural Medicines Comprehensive Database. 10th ed. Stockton, CA: Therapeutic Research Faculty, 2008:584–5.
3.Yao M, Ritchie HE, Brown-Woodman PD. A reproductive screening test of feverfew: is a full reproductive study warranted? Reprod Toxicol 2006;22:688–93.
4.Feverfew. In: Sweetman SC, ed. Martindate: The Complete Drug Reference. 34th ed. London, UK: Pharmaceutical Press, 2005:469.