Herbal medicine use in pregnancy: a new frontier in clinical teratology.

Health care therapies that are not part of conventional medical practices are referred to as complementary and alternative medicine (CAM). In a national survey conducted in the United States, CAM use has increased substantially between 1990 and 1997 with an estimated worth of $27 billion (Eisenberg et al., 1998). Within this time period herbal medicine or phytomedicine use increased by 380% with US sales in 1997 reaching $3.24 billion (Petrie and Peck, 2000). Given the popularity of herbal medicine in the general population, the Motherisk Program, a teratogen information service, has been experiencing an increased number of inquiries from women and health care providers regarding the gestational use of these products. This has led us to establish a special initiative to critically review available knowledge and, as importantly, to conduct prospective research on these compounds. Although increased use of herbal medicine in pregnancy can be attributed to a general trend, women are nevertheless frequent users of CAM (MacLennan et al., 1996; Beal, 1998). In different cultures throughout the world, herbal medicine has a long tradition in women’s reproductive health care (Chez and Jonas, 1997). Due to public perception, manufacturer contraindications, and recommendations by health care providers, pregnant women often avoid prescription and non-prescription drugs in pregnancy even when controlled trials cite safety. Many women use herbal products in pregnancy under the potentially false assumption that ‘‘natural’’ is synonymous with ‘‘safe. ’’ Inadvertent use may also occur because at least half of all pregnancies are not planned (Skrabanek, 1992). In a recent Motherisk study, 98% of surveyed physicians reported that their patients routinely discussed CAM with them. Seventy-four percent of these physicians were unsure about the safety of herbal products in pregnancy (Einarson et al., 2000). Although Medline citations using the heading ‘‘alternative medicine’’ are growing at twice the annual rate of the overall medical literature (Petrie and Peck, 2000), few of these articles are controlled studies and even fewer address the gestational use of these medicinals. The lack of evidence-base information makes assessing the safety/risk of herbal medicine in pregnancy challenging. To address the fetal safety of the commonly used herb echinacea, the Motherisk Program has completed the first prospective controlled study on a medicinal herb in pregnancy (Gallo et al., 2000). The study group consisted of 206 women (112 women used the herb in the first trimester) prospectively followed up after gestational use of echinacea. This cohort was disease-matched (upper respiratory tract ailments) to women exposed to nonteratogenic agents by maternal age, alcohol, and cigarette use. Even though no previous studies had addressed the safety of echinacea in pregnancy, many women in the study group felt echinacea posed a low risk and intentionally used the product in pregnancy. With echinacea exposure during organogenesis the rate of major malformations between the groups was not statistically significant. Other than being aware of the reproductive effects of herbs, pregnant women and health care providers must also consider the potential for adverse effects. Commonly reported adverse reactions resulting from the use of a specific herb include allergic reactions, nausea, vomiting, and sedation (Atherton, 1994; Perharic et al., 1994; Ernst and De Smet, 1996; Shaw et al., 1997). With some level of nausea and vomiting occurring in at least half of all pregnancies (de la Ronde, 1994), the potentiating effect of a herb on these symptoms could be problematic. Documented adverse effects have also resulted from adulteration of herbal products (Perharic et al., 1994; Raman and Jamal, 1997; Shaw et al., 1997). A case of neonatal androgenization attributed to maternal use of a natural product labeled Siberian ginseng (Koren et al., 1990) was subsequently identified as Periploca sepium (Chinese silk vine) (Koren et al., 1994). This example not only stresses the need for improved quality control measures by manufacturers and tighter regulations by government agencies, it also shows the potential risk herbs may cause when used in pregnancy. Herbal medicine may at times be used in conjunction with prescription medication (Beal, 1998; Eisenberg et al., 1998). Herb-drug interactions can occur on a pharmacokinetic and pharmacodynamic level (Blumenthal, 2000), leading to bioavailability, efficacy, and adverse effect profile changes. Even though much of the literature is based on theoretical interactions or cautions it would be prudent for pregnant women and health care providers Birth Defects Research (Part B) 68:499–500 (2003) & 2003 Wiley-Liss, Inc.