Gideon Koren

www.motherisk.org

Ginger in many forms is taken by pregnant women, with the hopes of alleviating the nausea and vomiting of pregnancy. These forms range from ginger tea, cookies, crystals, and sugars to inhaled powder and capsules containing ginger, as well as fresh ginger.

In a recently published metaanalysis of studies on ginger's use as an antiemetic during pregnancy published last month, the authors concluded that the cumulative experience suggests that the herbal supplement may be safe and effective for managing the nausea and vomiting of pregnancy (NVP).

They noted, however, that more observational studies and larger randomized trials were needed before any definitive statement on safety could be made (Obstet. Gynecol. 2005; 105:849–56).

The metaanalysis included six double-blind randomized controlled clinical trials of almost 700 women and an observational study that my colleagues and I conducted on 187 women taking ginger (Am. J. Obstet. Gynecol. 2003;189:1374–7).

This is the first metaanalysis of studies on the use of ginger as an antiemetic during pregnancy.

In the six randomized controlled trials, 500–1,500 mg daily of ginger were used for 3 days to 3 weeks in women who were at less than 20 weeks' gestation.

In four trials, ginger was more effective than placebo in controlling symptoms of NVP, and in the two remaining trials, ginger was as effective as vitamin B₆ although I would add that vitamin B₆—when used alone—is effective mostly for mild cases of NVP, as the authors also note.

No serious adverse effects or pregnancy-related problems were detected in the five studies that looked at safety.

The outcomes evaluated in the randomized trials included prepartum hemorrhage, preeclampsia, preterm birth, congential abnormalities, major malformations, perinatal and neonatal death, birth weights, and gestational age.

In the prospective observational study, we looked primarily at fetal safety, comparing outcomes in 187 pregnant women who took ginger in the first trimester with another 187 women who during the first trimester took drugs known to be nonteratogenic. With one exception, we found no significant differences in adverse pregnancy outcomes between the two groups.

The exception was that there were significantly more infants with birth weights of less than 2,500 g in the comparison group (6.4% compared with 1.6% in the ginger group), even though there were eight pairs of twins in the ginger group.

There were two major malformations in the comparison group, and three in the ginger group (a ventricular septal defect, right lung abnormality, and a kidney abnormality). At age 2, the daughter of a mother who took 1,000 mg of ginger a day from weeks 11 to 20 of gestation, as well as doxylamine/vitamin B₆ in the first trimester, was diagnosed with idiopathic central precocious puberty. This may be a random finding.

In a subgroup of 66 women, we evaluated the effectiveness of ginger by asking them to rank from 0 to 10 how well ginger controlled NVP, with 0 as no effect and 10 as a maximal effect.

The mean score was 3.3, not a very strong effect. Moreover, when we considered response by the form of ginger used (teas, lozenges, and other preparations), only the capsules containing ginger were associated with an effect significantly greater than zero.

Thus, our observational study put effectiveness against placebo into context: While it is helpful to show in randomized controlled trials that ginger has a better antiemetic effect than placebo, the effect is very mild.

There are other options for managing NVP. In Canada, those include Diclectin (the combination of the antihistamine/anticholinergic doxylamine and vitamin B₆, equivalent to Bendectin), which results in higher scores of about 5–6 on this scale. Clinicians should understand that ginger is a very mild antiemetic, and that only certain formulations seem to be better than placebo, and that the teas, lozenges, and other sources of ginger are likely no better than placebo.

Needless to say, many pregnant women are much more comfortable taking a natural product than a medication because of the perception that natural products are safer. But they should be aware that these products are not necessarily as effective as medicinal products, which in the United States and Canada, include ondansetron and metoclopramide.

At Motherisk, we advise women who call about ginger that it is probably safe and may help ease mild NVP, but it is unlikely to help with moderate to severe NVP.

A precautionary note: Women should also be aware that since there are many formulations of ginger, the amount of ginger in a given form is almost never certain. This is because natural products are not regulated with the same scrutiny as drugs. At this point, more studies comparing ginger with placebo probably are not needed. What would make sense now is to compare the safety and effectiveness of ginger and drugs, such as ondansetron and doxylamine and vitamin B₆, medicinal products that have been proved to be safe and effective for nausea and vomiting in pregnant women.

www.motherisk.org

Ginger in many forms is taken by pregnant women, with the hopes of alleviating the nausea and vomiting of pregnancy. These forms range from ginger tea, cookies, crystals, and sugars to inhaled powder and capsules containing ginger, as well as fresh ginger.

In a recently published metaanalysis of studies on ginger's use as an antiemetic during pregnancy published last month, the authors concluded that the cumulative experience suggests that the herbal supplement may be safe and effective for managing the nausea and vomiting of pregnancy (NVP).

They noted, however, that more observational studies and larger randomized trials were needed before any definitive statement on safety could be made (Obstet. Gynecol. 2005; 105:849–56).

The metaanalysis included six double-blind randomized controlled clinical trials of almost 700 women and an observational study that my colleagues and I conducted on 187 women taking ginger (Am. J. Obstet. Gynecol. 2003;189:1374–7).

This is the first metaanalysis of studies on the use of ginger as an antiemetic during pregnancy.

In the six randomized controlled trials, 500–1,500 mg daily of ginger were used for 3 days to 3 weeks in women who were at less than 20 weeks' gestation.

In four trials, ginger was more effective than placebo in controlling symptoms of NVP, and in the two remaining trials, ginger was as effective as vitamin B₆ although I would add that vitamin B₆—when used alone—is effective mostly for mild cases of NVP, as the authors also note.

No serious adverse effects or pregnancy-related problems were detected in the five studies that looked at safety.

The outcomes evaluated in the randomized trials included prepartum hemorrhage, preeclampsia, preterm birth, congential abnormalities, major malformations, perinatal and neonatal death, birth weights, and gestational age.

In the prospective observational study, we looked primarily at fetal safety, comparing outcomes in 187 pregnant women who took ginger in the first trimester with another 187 women who during the first trimester took drugs known to be nonteratogenic. With one exception, we found no significant differences in adverse pregnancy outcomes between the two groups.

The exception was that there were significantly more infants with birth weights of less than 2,500 g in the comparison group (6.4% compared with 1.6% in the ginger group), even though there were eight pairs of twins in the ginger group.

There were two major malformations in the comparison group, and three in the ginger group (a ventricular septal defect, right lung abnormality, and a kidney abnormality). At age 2, the daughter of a mother who took 1,000 mg of ginger a day from weeks 11 to 20 of gestation, as well as doxylamine/vitamin B₆ in the first trimester, was diagnosed with idiopathic central precocious puberty. This may be a random finding.

In a subgroup of 66 women, we evaluated the effectiveness of ginger by asking them to rank from 0 to 10 how well ginger controlled NVP, with 0 as no effect and 10 as a maximal effect.

The mean score was 3.3, not a very strong effect. Moreover, when we considered response by the form of ginger used (teas, lozenges, and other preparations), only the capsules containing ginger were associated with an effect significantly greater than zero.

Thus, our observational study put effectiveness against placebo into context: While it is helpful to show in randomized controlled trials that ginger has a better antiemetic effect than placebo, the effect is very mild.

There are other options for managing NVP. In Canada, those include Diclectin (the combination of the antihistamine/anticholinergic doxylamine and vitamin B₆, equivalent to Bendectin), which results in higher scores of about 5–6 on this scale. Clinicians should understand that ginger is a very mild antiemetic, and that only certain formulations seem to be better than placebo, and that the teas, lozenges, and other sources of ginger are likely no better than placebo.

Needless to say, many pregnant women are much more comfortable taking a natural product than a medication because of the perception that natural products are safer. But they should be aware that these products are not necessarily as effective as medicinal products, which in the United States and Canada, include ondansetron and metoclopramide.

At Motherisk, we advise women who call about ginger that it is probably safe and may help ease mild NVP, but it is unlikely to help with moderate to severe NVP.

A precautionary note: Women should also be aware that since there are many formulations of ginger, the amount of ginger in a given form is almost never certain. This is because natural products are not regulated with the same scrutiny as drugs. At this point, more studies comparing ginger with placebo probably are not needed. What would make sense now is to compare the safety and effectiveness of ginger and drugs, such as ondansetron and doxylamine and vitamin B₆, medicinal products that have been proved to be safe and effective for nausea and vomiting in pregnant women.

www.motherisk.org

Ginger in many forms is taken by pregnant women, with the hopes of alleviating the nausea and vomiting of pregnancy. These forms range from ginger tea, cookies, crystals, and sugars to inhaled powder and capsules containing ginger, as well as fresh ginger.

In a recently published metaanalysis of studies on ginger's use as an antiemetic during pregnancy published last month, the authors concluded that the cumulative experience suggests that the herbal supplement may be safe and effective for managing the nausea and vomiting of pregnancy (NVP).

They noted, however, that more observational studies and larger randomized trials were needed before any definitive statement on safety could be made (Obstet. Gynecol. 2005; 105:849–56).

The metaanalysis included six double-blind randomized controlled clinical trials of almost 700 women and an observational study that my colleagues and I conducted on 187 women taking ginger (Am. J. Obstet. Gynecol. 2003;189:1374–7).

This is the first metaanalysis of studies on the use of ginger as an antiemetic during pregnancy.

In the six randomized controlled trials, 500–1,500 mg daily of ginger were used for 3 days to 3 weeks in women who were at less than 20 weeks' gestation.

In four trials, ginger was more effective than placebo in controlling symptoms of NVP, and in the two remaining trials, ginger was as effective as vitamin B₆ although I would add that vitamin B₆—when used alone—is effective mostly for mild cases of NVP, as the authors also note.

No serious adverse effects or pregnancy-related problems were detected in the five studies that looked at safety.

The outcomes evaluated in the randomized trials included prepartum hemorrhage, preeclampsia, preterm birth, congential abnormalities, major malformations, perinatal and neonatal death, birth weights, and gestational age.

In the prospective observational study, we looked primarily at fetal safety, comparing outcomes in 187 pregnant women who took ginger in the first trimester with another 187 women who during the first trimester took drugs known to be nonteratogenic. With one exception, we found no significant differences in adverse pregnancy outcomes between the two groups.

The exception was that there were significantly more infants with birth weights of less than 2,500 g in the comparison group (6.4% compared with 1.6% in the ginger group), even though there were eight pairs of twins in the ginger group.

There were two major malformations in the comparison group, and three in the ginger group (a ventricular septal defect, right lung abnormality, and a kidney abnormality). At age 2, the daughter of a mother who took 1,000 mg of ginger a day from weeks 11 to 20 of gestation, as well as doxylamine/vitamin B₆ in the first trimester, was diagnosed with idiopathic central precocious puberty. This may be a random finding.

In a subgroup of 66 women, we evaluated the effectiveness of ginger by asking them to rank from 0 to 10 how well ginger controlled NVP, with 0 as no effect and 10 as a maximal effect.

The mean score was 3.3, not a very strong effect. Moreover, when we considered response by the form of ginger used (teas, lozenges, and other preparations), only the capsules containing ginger were associated with an effect significantly greater than zero.

Thus, our observational study put effectiveness against placebo into context: While it is helpful to show in randomized controlled trials that ginger has a better antiemetic effect than placebo, the effect is very mild.

There are other options for managing NVP. In Canada, those include Diclectin (the combination of the antihistamine/anticholinergic doxylamine and vitamin B₆, equivalent to Bendectin), which results in higher scores of about 5–6 on this scale. Clinicians should understand that ginger is a very mild antiemetic, and that only certain formulations seem to be better than placebo, and that the teas, lozenges, and other sources of ginger are likely no better than placebo.

Needless to say, many pregnant women are much more comfortable taking a natural product than a medication because of the perception that natural products are safer. But they should be aware that these products are not necessarily as effective as medicinal products, which in the United States and Canada, include ondansetron and metoclopramide.

At Motherisk, we advise women who call about ginger that it is probably safe and may help ease mild NVP, but it is unlikely to help with moderate to severe NVP.

A precautionary note: Women should also be aware that since there are many formulations of ginger, the amount of ginger in a given form is almost never certain. This is because natural products are not regulated with the same scrutiny as drugs. At this point, more studies comparing ginger with placebo probably are not needed. What would make sense now is to compare the safety and effectiveness of ginger and drugs, such as ondansetron and doxylamine and vitamin B₆, medicinal products that have been proved to be safe and effective for nausea and vomiting in pregnant women.

The 2004 asthma treatment guidelines for pregnant women, issued by the National Asthma Education and Prevention Program in January, meet a great need for guidance in this area. The guidelines, which also include a table on the stepwise approach to managing asthma in pregnancy, are the first to be issued on treating asthma in pregnant women in more than 10 years.

A better understanding of the inflammatory nature of the disease has promoted a major shift in therapy. Anti-inflammatory medications, most notably corticosteroids, and mast cell stabilizers (leukotriene inhibitors) are now the first-line treatments. Theophylline is rarely used today to treat asthma, but the guidelines say that at recommended doses it has proved safe in pregnancy.

The authors of the document, a multidisciplinary expert panel, systematically reviewed available evidence on asthma treatment in pregnancy. Some of the key findings are:

▸ Inhaled corticosteroids can reduce the risk of asthma exacerbations and improve lung function. There is no evidence linking them to increases in congenital malformations or other adverse outcomes. When taken through the inhaled route, systemic exposure is much less than with oral corticosteroids. Budesonide has the most data backing its safety in pregnancy, making it the “preferred inhaled corticosteroid,” the guidelines state. But the document notes that there are no data indicating the other agents are unsafe in pregnancy.

▸ Oral corticosteroids may be necessary for treating women with severe asthma. There are conflicting data on their safety in pregnancy, but they may be warranted in women with severe disease, according to the guidelines. In the general population, there is an association between use of oral corticosteroids in the first trimester and an increased risk for cleft lip and/or palate, compared with nonuse (0.3% vs. 0.1%), but not many asthmatic pregnant women have been included in these studies.

This risk for oral cleft has been shown in animals and in humans. Our Motherisk Program systematically reviewed studies and found a two- to threefold increase in oral cleft (with first-trimester exposure), which probably is not the case for inhaled steroids because the systemic dose is much smaller. Clearly, patients who are prescribed oral corticosteroids in the first trimester should be informed of this risk.

During the second and third trimester, oral steroids cannot cause malformations. But there are studies, which do not include patients with asthma, indicating that systemic exposure to corticosteroids may be associated with some CNS damage in babies. Most of these data were from studies of premature infants whose mothers received corticosteroids to enhance lung maturation.

There is evidence that repeating the dose of corticosteroids more than once may increase the risk of adverse brain outcome in premature babies. Although this evidence is not yet conclusive, it is fair to say that if a woman needs high-dose corticosteroids late in pregnancy, such a possibility should be discussed with her before prescribing these agents.

▸ The short-acting β2-agonist albuterol is the preferred drug in this class for treating acute symptoms, and the available data on the safety of β2-agonists are reassuring, the guidelines say. Albuterol has been studied in many millions of patients worldwide and in thousands of pregnant women, and there is no indication whatsoever that it has any teratogenic effects. Since it is inhaled, systemic exposure is not great.

▸ For women with persistent asthma who are not well controlled on low-dose inhaled corticosteroids, increasing the dose or adding a long-acting β-agonist is recommended, but there are not enough data indicating which approach is preferable, according to the guidelines. It is fair to say that β-agonists have not been shown to be teratogenic, and I agree with the panel that there is no reason to prefer one treatment option over the other.

▸ Cromolyn, used as a preventive treatment, appears to be safe, based on available evidence, the guidelines state.

▸ Leukotriene modifiers, the document notes, have “minimal” data on their use in pregnancy, but there are some reassuring animal data. We at Motherisk are prospectively collecting information on cases of pregnant women exposed to these drugs, and so far, they do not appear to be major teratogens.

I would also add that since asthma is often accompanied by allergy, effective management of allergic symptoms can prevent asthmatic attacks in many cases. H1 blockers are safe in pregnancy.

A copy of the guidelines can be found at www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm

The 2004 asthma treatment guidelines for pregnant women, issued by the National Asthma Education and Prevention Program in January, meet a great need for guidance in this area. The guidelines, which also include a table on the stepwise approach to managing asthma in pregnancy, are the first to be issued on treating asthma in pregnant women in more than 10 years.

A better understanding of the inflammatory nature of the disease has promoted a major shift in therapy. Anti-inflammatory medications, most notably corticosteroids, and mast cell stabilizers (leukotriene inhibitors) are now the first-line treatments. Theophylline is rarely used today to treat asthma, but the guidelines say that at recommended doses it has proved safe in pregnancy.

The authors of the document, a multidisciplinary expert panel, systematically reviewed available evidence on asthma treatment in pregnancy. Some of the key findings are:

▸ Inhaled corticosteroids can reduce the risk of asthma exacerbations and improve lung function. There is no evidence linking them to increases in congenital malformations or other adverse outcomes. When taken through the inhaled route, systemic exposure is much less than with oral corticosteroids. Budesonide has the most data backing its safety in pregnancy, making it the “preferred inhaled corticosteroid,” the guidelines state. But the document notes that there are no data indicating the other agents are unsafe in pregnancy.

▸ Oral corticosteroids may be necessary for treating women with severe asthma. There are conflicting data on their safety in pregnancy, but they may be warranted in women with severe disease, according to the guidelines. In the general population, there is an association between use of oral corticosteroids in the first trimester and an increased risk for cleft lip and/or palate, compared with nonuse (0.3% vs. 0.1%), but not many asthmatic pregnant women have been included in these studies.

This risk for oral cleft has been shown in animals and in humans. Our Motherisk Program systematically reviewed studies and found a two- to threefold increase in oral cleft (with first-trimester exposure), which probably is not the case for inhaled steroids because the systemic dose is much smaller. Clearly, patients who are prescribed oral corticosteroids in the first trimester should be informed of this risk.

During the second and third trimester, oral steroids cannot cause malformations. But there are studies, which do not include patients with asthma, indicating that systemic exposure to corticosteroids may be associated with some CNS damage in babies. Most of these data were from studies of premature infants whose mothers received corticosteroids to enhance lung maturation.

There is evidence that repeating the dose of corticosteroids more than once may increase the risk of adverse brain outcome in premature babies. Although this evidence is not yet conclusive, it is fair to say that if a woman needs high-dose corticosteroids late in pregnancy, such a possibility should be discussed with her before prescribing these agents.

▸ The short-acting β2-agonist albuterol is the preferred drug in this class for treating acute symptoms, and the available data on the safety of β2-agonists are reassuring, the guidelines say. Albuterol has been studied in many millions of patients worldwide and in thousands of pregnant women, and there is no indication whatsoever that it has any teratogenic effects. Since it is inhaled, systemic exposure is not great.

▸ For women with persistent asthma who are not well controlled on low-dose inhaled corticosteroids, increasing the dose or adding a long-acting β-agonist is recommended, but there are not enough data indicating which approach is preferable, according to the guidelines. It is fair to say that β-agonists have not been shown to be teratogenic, and I agree with the panel that there is no reason to prefer one treatment option over the other.

▸ Cromolyn, used as a preventive treatment, appears to be safe, based on available evidence, the guidelines state.

▸ Leukotriene modifiers, the document notes, have “minimal” data on their use in pregnancy, but there are some reassuring animal data. We at Motherisk are prospectively collecting information on cases of pregnant women exposed to these drugs, and so far, they do not appear to be major teratogens.

I would also add that since asthma is often accompanied by allergy, effective management of allergic symptoms can prevent asthmatic attacks in many cases. H1 blockers are safe in pregnancy.

A copy of the guidelines can be found at www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm

The 2004 asthma treatment guidelines for pregnant women, issued by the National Asthma Education and Prevention Program in January, meet a great need for guidance in this area. The guidelines, which also include a table on the stepwise approach to managing asthma in pregnancy, are the first to be issued on treating asthma in pregnant women in more than 10 years.

A better understanding of the inflammatory nature of the disease has promoted a major shift in therapy. Anti-inflammatory medications, most notably corticosteroids, and mast cell stabilizers (leukotriene inhibitors) are now the first-line treatments. Theophylline is rarely used today to treat asthma, but the guidelines say that at recommended doses it has proved safe in pregnancy.

The authors of the document, a multidisciplinary expert panel, systematically reviewed available evidence on asthma treatment in pregnancy. Some of the key findings are:

▸ Inhaled corticosteroids can reduce the risk of asthma exacerbations and improve lung function. There is no evidence linking them to increases in congenital malformations or other adverse outcomes. When taken through the inhaled route, systemic exposure is much less than with oral corticosteroids. Budesonide has the most data backing its safety in pregnancy, making it the “preferred inhaled corticosteroid,” the guidelines state. But the document notes that there are no data indicating the other agents are unsafe in pregnancy.

▸ Oral corticosteroids may be necessary for treating women with severe asthma. There are conflicting data on their safety in pregnancy, but they may be warranted in women with severe disease, according to the guidelines. In the general population, there is an association between use of oral corticosteroids in the first trimester and an increased risk for cleft lip and/or palate, compared with nonuse (0.3% vs. 0.1%), but not many asthmatic pregnant women have been included in these studies.

This risk for oral cleft has been shown in animals and in humans. Our Motherisk Program systematically reviewed studies and found a two- to threefold increase in oral cleft (with first-trimester exposure), which probably is not the case for inhaled steroids because the systemic dose is much smaller. Clearly, patients who are prescribed oral corticosteroids in the first trimester should be informed of this risk.

During the second and third trimester, oral steroids cannot cause malformations. But there are studies, which do not include patients with asthma, indicating that systemic exposure to corticosteroids may be associated with some CNS damage in babies. Most of these data were from studies of premature infants whose mothers received corticosteroids to enhance lung maturation.

There is evidence that repeating the dose of corticosteroids more than once may increase the risk of adverse brain outcome in premature babies. Although this evidence is not yet conclusive, it is fair to say that if a woman needs high-dose corticosteroids late in pregnancy, such a possibility should be discussed with her before prescribing these agents.

▸ The short-acting β2-agonist albuterol is the preferred drug in this class for treating acute symptoms, and the available data on the safety of β2-agonists are reassuring, the guidelines say. Albuterol has been studied in many millions of patients worldwide and in thousands of pregnant women, and there is no indication whatsoever that it has any teratogenic effects. Since it is inhaled, systemic exposure is not great.

▸ For women with persistent asthma who are not well controlled on low-dose inhaled corticosteroids, increasing the dose or adding a long-acting β-agonist is recommended, but there are not enough data indicating which approach is preferable, according to the guidelines. It is fair to say that β-agonists have not been shown to be teratogenic, and I agree with the panel that there is no reason to prefer one treatment option over the other.

▸ Cromolyn, used as a preventive treatment, appears to be safe, based on available evidence, the guidelines state.

▸ Leukotriene modifiers, the document notes, have “minimal” data on their use in pregnancy, but there are some reassuring animal data. We at Motherisk are prospectively collecting information on cases of pregnant women exposed to these drugs, and so far, they do not appear to be major teratogens.

I would also add that since asthma is often accompanied by allergy, effective management of allergic symptoms can prevent asthmatic attacks in many cases. H1 blockers are safe in pregnancy.

A copy of the guidelines can be found at www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm