A reproductive screening test of feverfew: is a full reproductive study warranted?

Feverfew is currently used in the treatment of migraine and arthritis. It is traditionally contraindicated in pregnancy but there are no studies confirming this warning. An in vivo and in vitro preliminary screen was performed using a rat model: five female rats were orally dosed with 839 mg/kg feverfew daily on either gestation days (GD) 1-8 or 8-15. On GD20, rats were sacrificed and fetuses, placentae and ovaries were collected. The fetuses were weighed and examined for malformations. While maternal weight gain appeared to be reduced, ANCOVA analysis suggested that the difference was due to litter size, rather than treatment. Pre-implantation loss appeared increased but this was not statistically significant in the feverfew GD1-8 group. Fetuses exposed to feverfew from GD8-15 were smaller than ethanol controls perhaps as a result of the increased frequency of runts in treated litters. Feverfew induced toxicity when GD10.5 embryos were cultured for 26 h in rat serum to which extract was added. The results of the present preliminary study suggest that a comprehensive reproductive study of feverfew is warranted.