Botanicals^*

Three published placebo-controlled trials have addressed the safety and efficacy of ginger (Zingiber officinale) for morning sickness. The 1990 trial by Fischer-Rasmussen et al⁶ randomly assigned 30 pregnant women admitted to the hospital with hyperemesis gravidarum before the 20th week of gestation to receive either 250 mg of powdered ginger capsules four times per day or placebo for a 4-day period followed by a 2-day washout and crossover to the other treatment. A scoring system was used to assess the degree of nausea, vomiting, and weight loss before onset of the trial and then as reevaluated on days 5 and 11 after treatment. The relief scores were greater for ginger than placebo with a reduced number of vomiting episodes and degree of nausea. Subjective assessment by the women showed that 70.4% preferred the period when they received ginger; only 14.8% preferred placebo. No adverse effects on pregnancy outcome were noted.

Vutyavanich et al⁷ conducted a randomized, double-blind, placebo-controlled study of 70 women (n = 67) with nausea of pregnancy, with or without vomiting, before the 17th week of gestation. The primary outcome was improvement in nausea symptoms. Women received either 250-mg powdered ginger capsules or placebo four times daily for a 4-day period. A visual analog scale (VAS) and Likert scale were used as measuring instruments. The VAS scores decreased (improved) significantly in the ginger group compared with placebo (P = 0.014). Vomiting episodes were also significantly decreased (P < 0.001). At the 1-week follow up visit, 28 of 32 subjects in the ginger group had improvement of nausea symptoms, whereas only 10 of 35 in the placebo group experienced improvement (P < 0.001). Minor side effects were noted in both groups; more heartburn was noted in the ginger group. No adverse effects were noted on pregnancy outcomes.

In 2003, a double-blind placebo-controlled trial randomly assigned 120 women before the 20th week of gestation, who had experienced morning sickness daily for at least a week and had no relief of symptoms through dietary changes, to receive either 125 mg of ginger extract (EV.EXT 35; equivalent to 1.5 g of dried ginger) or placebo four times per day.⁸ The nausea experience score was significantly less for the ginger extract group relative to the placebo group after the first day of treatment and this difference was present for each treatment day. For retching symptoms, the ginger extract group had significantly lower symptom scores than the placebo group for the first 2 days only. In contrast to the other published studies, no significant difference was noted between ginger extract and placebo groups for any of the vomiting symptoms. Twenty-one women were excluded from the final analysis because of insufficient data (12 for adverse events and 9 for noncompliance). Adverse events included spontaneous abortion (n = 4 women [3 in the ginger group, 1 in the placebo group]), intolerance of the treatment (n = 4 [all in the ginger group]), worsening of treatment requiring further medical assistance (n = 3 [1 in the ginger group, 2 in the placebo group]), and allergic reaction to treatment (n = 1 [ginger group]). Follow-up of the pregnancies revealed normal ranges of birth weight, gestational age, Apgar scores, and frequencies of congenital abnormalities when the study group infants were compared with the general population of infants born at the Royal Hospital for Women for the year 1999-2000.

Interestingly, the German Commission E and American Herbal Products Association contraindicate the use of ginger during pregnancy. This appears to be based on two concerns. The first is that the inhibition of thromboxane synthetase may affect testosterone binding in the fetus,⁹ although inhibition of thromboxane synthetase occurs at doses higher than those used in the studies. The second concern is in vitro evidence that gingerol and shogoal, isolated components of ginger, exhibit mutagenic activity in certain salmonella strains.¹⁰ However, researchers have also found antimutagenic compounds in ginger.¹¹ Even in large doses, a study in rats failed to find malformations in the offspring of animals who were administered 20 g/L or 50 g/L of ginger tea in their drinking water from gestation days 6 to 15 and then sacrificed at day 20. No gross morphologic malformations were seen in the treated fetuses. Fetuses exposed to ginger tea were found to be significantly heavier than controls and had more advanced skeletal development as determined by measurement of sternal and metacarpal ossification centers. No maternal toxicity was observed in this study, although embryonic loss in the treatment group was almost double that of the controls (P < 0.05). Researchers at the Hospital for Sick Children in Toronto, Canada, studied 187 pregnant women who used some form of ginger in the first trimester. They reported that the risk of these mothers having a baby with a congenital malformation was no higher than in a control group.¹² In the published human studies, one spontaneous abortion (among 32 in the ginger group),⁷ one spontaneous abortion (of 27 in the crossover design study),⁶ and three spontaneous abortions (of 60 in the ginger group)⁸ were reported, although one of the three spontaneous abortions in last group occurred in a woman who had not begun taking the treatment. Alhough the total number of women in these clinical trials is small, the rate of spontaneous abortion is not any greater than that seen in the general population. Given the vast numbers of women around the globe who consume ginger during pregnancy, it is unlikely that there is significant risk associated with its use in moderation. It appears reasonable for a woman to use small amounts of ginger, 250 mg four times per day, for the relief of morning sickness.¹³

Raspberry leaf and peppermint teas are also recommended for morning sickness. Peppermint has a long history of quieting a queasy stomach and is safe for use during pregnancy; however, it can aggravate gastroesophageal reflux, another common symptom of pregnancy. Raspberry is not observed to be effective for morning sickness in my experience, but the tea is safe.

Vitamin B₆

Two double-blind, placebo-controlled, randomized clinical trials have been conducted to determine the efficacy of vitamin B₆ during pregnancy. The study by Sahakian et al¹⁴ in 1991 found that 25 mg of vitamin B₆ three times per day was superior to placebo for reducing severe nausea by day 3 of treatment but made little difference for milder cases of nausea. At the completion of therapy, significantly fewer subjects (25.8%) in the pyridoxine group compared with the placebo group (53.6%) had vomiting.

A larger study conducted in 1995 found that only nausea was reduced, not vomiting, when women received 10 mg of pyridoxine hydrochloride three times per day for 5 days. The mean change in nausea scores in the pyridoxine group was significantly greater than those in the placebo group. After 5 days of treatment, 36% of women in the active group had vomiting versus 34% of women in placebo group (33.9%); this difference was not statistically significant.¹⁵

Potential confounders in all trials studying morning sickness include the natural fluctuation of the condition over time, the quantification of a subjective symptom such as nausea, and a notable placebo effect. The 1995 study used a dose of 30 mg/day versus the 75 mg/day used in the previous study. Thirty mg/day may be insufficient to alter the number of episodes of emesis. Vitamin B₆, at doses used in the aforementioned clinical trials, appears to be safe during pregnancy. The Food and Drug Administration (FDA) categorized the recommended daily allowance dose of 2.2 mg/day as pregnancy category A; if used in doses greater than the recommendation it is classified as FDA pregnancy category C.¹⁶ Although pyridoxine is a water-soluble vitamin, it is associated with toxicity when taken in large doses over time. The majority of toxicity occurs at doses of 500 mg/day or higher, but a few reports of toxicity occurred with prolonged ingestion of 150 mg/day.¹⁷

Acupuncture

Acupuncture and acupressure have been shown to be useful for alleviating morning sickness. The National Institutes of Health Consensus Development Conference on Acupuncture in 1997 stated “There is clear evidence that needle acupuncture treatment is effective for post-operative and chemotherapy nausea and vomiting, and nausea of pregnancy and post-operative dental pain.” Six of seven clinical trials found that acupressure is effective for relieving morning sickness.¹⁸ Acupressure wristbands are popular and readily available. Many women find these a less expensive alternative to acupuncture, which offers a noninvasive and effective remedy for pregnancy-associated nausea and vomiting.

Botanicals

A number of herbs are used to soothe esophageal irritation, including several that are safe for use in pregnancy. Two herbs that are readily available are chamomile (Matricaria recutita) and marshmallow (Althaea officinalis). No significant clinical research has been conducted to evaluate the effectiveness of chamomile teas or extracts for the treatment of gastrointestinal inflammation; however, the herb is widely accepted for this purpose by many authorities. Animal studies have shown that oral administration of (-)-α-bisabolol reduces gastric toxicity induced by acetylsalicylic acid¹⁹ and inhibits the development of ulcers caused by indomethacin, ethanol, and stress.²⁰ Chamomile, known in Spanish as manzanilla, is one of the most popular herbs used by Mexican Americans and is commonly recommended during pregnancy to ease nausea and heartburn and as a general relaxant.

The leaf and root of marshmallow are rich in mucopolysaccharides that soothe and protect the esophageal lining from irritation. Marshmallow was a food herb for centuries and is considered safe for use during pregnancy. The German health authorities endorse the use of marshmallow root for “mild inflammation of the gastric mucosa.”²¹ There are no known contraindications to marshmallow; however, because of the high mucilage content, marshmallow may delay the absorption of medications.²² Prescription medications should be taken at least 30 minutes before using this herb.