ginger in nausea and vomiting in pregnancy a meta analysis

8/21/2019 Ginger in Nausea and Vomiting in Pregnancy a Meta Analysis

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Ginger in Nausea and Vomiting of Pregnancy: A Meta-Analysis

Abstract

Nausea and vomiting of pregnancy (NVP) or “morning sickness” is one of the

most common complaints of pregnant women. Persistent and severe nausea and

vomiting can lead to feelings of anxiety and worry about the negative impact it can bring

to the fetus. Ginger ( Zingiber officinale), being a common food condiment and

beverage, is widely available in our country. It has several effects on the gastrointestinal

tract, including antiemetic properties. Despite the many studies using ginger for

treatment of NVP, there is no agreed upon treatment for NVP here in the Philippines.

This meta-analysis showed that ginger was better than placebo in reducing the severity

of nausea and frequency of vomiting episodes. The risk of no relief from nausea and

vomiting using ginger was only 0.29 (95% CI 0.17, 0.50, p < 0.001). Furthermore, this

paper has shown that the risk of cumulative side effects was only 0.32 (95% CI, 0.21,

0.47, p < 0.001), clearly favoring the ginger treatment arm. One study has reported that

fetal outcomes are within the normal range in the ginger group. Therefore, this meta-

analysis has shown that ginger may be used as an alternative choice of treatment for the

management of the aforementioned symptoms.

KEYWORDS: nausea, vomiting, pregnancy, hyperemesis gravidarum, ginger, Zingiberofficinale, meta-analysis


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Introduction

Nausea and vomiting of pregnancy (NVP), more commonly known as “morning

sickness”, is one of the most common complaints of pregnant women. Symptoms

usually begin between the fourth and sixth week of pregnancy and improve by the 15th to

20th week of gestation. The nausea of pregnancy ranges from mild and disturbing to

severe and unremitting, with associated severe vomiting, dehydration, and weight loss.1

Hyperemesis gravidarum is defined as severe nausea and vomiting that cause weight

loss greater than 5% of pre-pregnancy weight with associated electrolyte imbalance and

ketonuria.2 These noxious symptoms may lead to depression, poor nutrition,

absenteeism, and hospitalization.1 Failure to treat these derangements promptly may

lead to renal and hepatic damage.

The etiology of NVP is poorly understood. Several hormones were suggested to be

the cause of NVP and hyperemesis gravidarum. Among these are human chorionic

gonadotropin (hCG), and elevated estrogen. However, the roles of hCG and estrogen

remain controversial. Many pregnant women with hyperemesis have suppressed

thyrotropin-stimulating hormone (TSH) levels. Interaction of hCG and TSH in

pregnant women is still under investigation.3 Gastrointestinal tract dysfunction was

also thought to be a cause of NVP. Delayed gastric motility due to progesterone has

been shown to be a potential cause, including abnormalities of gastric electrical rhythm

(gastric dysrhythmias). A recent study suggested that chronic infection with

Helicobacter pylori may play a role in hyperemesis gravidarum. In this study, 61.8% of


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pregnant women with hyperemesis were found to be positive for the H. pylori genome,

compared with 27.6% of pregnant women without hyperemesis.3

The physical and emotional impact of NVP often results in anxiety and concern

about possible fetal effects. NVP negatively impacts family relationships and has major

consequences on the pregnant woman’s working capabilities.4 Early recognition and

management of NVP prevents progression to hyperemesis gravidarum and improve the

quality of life during pregnancy. Women often try numerous strategies to alleviate

symptoms such as eating small, frequent meals consisting of bland and non-fatty foods.

An alternative to treatment is ginger supplementation. The latter was found to be

beneficial (level IA evidence) and is recommended in the 2002 Clinical Practice

Guidelines of the Society of Obstetricians and Gynecologists in Canada.4

Women with uncomplicated NVP had good pregnancy outcomes: fewer

miscarriages, preterm deliveries, stillbirths, intrauterine growth restriction, and

mortality.3. Hyperemesis gravidarum, on the other hand, has been associated with

increased maternal morbidity such as splenic avulsion, esophageal rupture, Mallory-

Weiss tears, pneumothorax, peripheral neuropathy, preeclampsia, and risks of fetal

growth restriction and mortality.3

Ginger ( Zingiber officinale) is widely available in the Philippines and is a

common food condiment and beverage. Dating back 2500 years in China and India, it

has a long history of medicinal use for ailments such as headaches, nausea, rheumatism

and colds. It has several effects on the gastrointestinal tract, including spasmolytic,


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carminative and absorbent properties.5 Several trials have shown that ginger may be

effective for the treatment of nausea and vomiting in the general population. Despite

the many studies using ginger for treatment of NVP, here in the Philippines, there is no

agreed upon treatment for NVP.

Ginger is a perennial plant typically growing two to four feet in height and

preferring warm, humid climates. It has narrow, glossy, bright green leaves, and its

summer flowers are yellowish green.9 Ginger has been used in several forms, e.g. tea,

preserves, syrup, and capsules. A number of pungent constituents and active

ingredients constitute ginger. Steam distillation of powdered ginger produces ginger oil,

containing a high proportion of sesquiterpene hydrocarbons, predominantly

zingiberene. The major pungent compounds in ginger yielded potentially active

gingerols, which can be converted to shogaols, zingerone, and paradol. The compound

6-gingerol may be responsible for the characteristic taste of ginger. Zingerone and

shogaols are found in small amounts in fresh ginger and in larger amounts in dried or

extracted products.5 Ginger acts within the gastrointestinal tract by increasing tone

and peristalsis due to anticholinergic and antiserotonin action.10 The exact mechanism,

however, is not clearly understood.

The compounds 6-gingerol and 6-shogaol have been shown to have a number of

pharmacological activities, including antipyretic, analgesic, antitussive, and hypotensive

effects. Ginger has also been studied for motion sickness, post-surgical and

chemotherapy-induced nausea and osteoarthritis.


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Review of Related Literature

There are no evidence-based guidelines that exist for the management of NVP.

Traditionally, dietary and lifestyle changes have been the mainstay of treatment, and

there is little reason to question the assumption that dietary recommendations are safe.6

Such dietary advice consists of eating small portions of food at frequent intervals,

ingesting dry toast or crackers upon arising, and eating bland low-fat foods.7

Among the many histamine antagonists (H1 blockers), the following have been

indicated for nausea and vomiting: buclizine, cyclizine, dimenhydrinate,

diphenhydramine, doxylamine, hydroxyzine, and meclizine. H1 receptor antagonists

have no human teratogenic potential. Among the anticholinergics, only dicyclomine and

scopolamine are used for treatment of nausea and vomiting in the nonpregnant

population, however, no effectiveness trials for NVP have been published. Several

dopamine antagonists such as phenothiazines, domperidone, droperidol,

metoclopromide and trimethobenzamide may be used to treat NVP. Anecdotal cases,

however, have associated first trimester phenothiazine use with major malformations.

Most reviews and editorials advise that antiemetic therapy be instituted only when

women are unable to maintain hydration, nutrition, or both. Metoclopramide has not

been extensively studied for the treatment of NVP, even though it was used in clinical

practice in many countries. HT3 antagonists, such as ondansetron, are the most widely

used of this class of drugs, and is considered safe for pregnancy. Corticosteroids (e.g

dexamethasone, prednisolone) may also be effective for NVP, and stemmed from the

hypothesis that severe NVP may result from ACTH deficiency.6


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Evidence from controlled trials has shown that all of the following are safe and

effective for treatment of varying degrees of NVP: bendectin/diclectin (doxylamine,

pyridoxine), antihistamine (H1 blockers), and phenothiazines. If success is not achieved

with one of these agents, then it is reasonable to switch to another. Also, many of these

agents may be used in combination (e.g antihistamines, pyridoxine, metoclopromide,

along with non-pharmacologic approaches).6

Pyridoxine (vitamin B6) has been demonstrated to be effective in trials using

doses of 30-75 mg/day. Up to 100 mg/day can be given in divided doses; however, the

most common regimen is 25 mg three times per day which is well tolerated with least

side effects. The most commonly prescribed drugs is metoclopramide (category A)

usually a dose of 10 mg 3-4 times per day as necessary. A sedating antihistamine such

as promethazine may be of benefit as an additional therapy.8

Several studies have suggested acupressure as treatment for NVP. The most

common location for acupressure is the pericardium 6 (P6) or Neiguan point, located

three fingerbreadths above the wrist on the volar surface.3 The efficacy of P6

accupressure in reducing symptoms of NVP was investigated in a 7-day study. In this

prospective, randomized, placebo-controlled study, 161 pregnant patients with NVP

received P6 acupressure, placebo or no therapy (control). Women in the treatment

group were given acupressure wristbands (Sea-Bands) and instructed to apply the bands

at the wrist. Ninety-two and a half percent of patients who completed the study had a

significant decrease in nausea, vomiting, retching, regardless of which randomized

group they were assigned. This study suggested that the use of P6 acupressure provides


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no significant medical benefit.7 Since acupressure is a nonpharmacologic intervention

with no known adverse side effects, it may also be offered to patients.

Some women with NVP and hyperemesis may become depressed or exhibit

affective changes. It is important that these women receive appropriate support from

family members and medical and nursing staff. Consultation is indicated if a pregnant

woman is depressed, domestic violence is suspected, or evidence of substance abuse or

psychiatric illness exists. Other non-pharmacologic treatments include intravenous

fluid, enteral or parenteral nutrition.3

The 2002 Clinical Practice Guidelines of the Society of Obstetricians and

Gynecologists in Canada include alternative therapies such as ginger supplementation

as beneficial for NVP (Level IA).4 There were several studies which revealed that ginger

may be used effectively for women with NVP. Thus, there is a growing interest in the

use of ginger as an alternative treatment for NVP since it is readily available and very

inexpensive.

A randomized, cross-over, double blind study by Sontakke et al in 2003

concluded that powdered ginger root was effective in reducing nausea and vomiting

induced by low dose cyclophosphamide in combination with drugs causing mild

emesis.11 Another double-blind randomized controlled trial by Nanthakomon et al

studied the efficacy of ginger in the prevention of nausea and vomiting in 120 patients

undergoing major gynecologic surgery. This study concluded that ginger is effective in

the prevention of nausea and vomiting after major gynecologic surgery.11


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In an article by Borrelli et al12 in 2005, six double-blind randomized controlled

trials using ginger on women with NVP with a total of 675 participants and a

prospective observational cohort study (n=187) were analyzed. Based on this study,

ginger may be an effective therapy for nausea and vomiting in pregnancy; however,

more observational studies with a larger sample size are needed to confirm the

encouraging preliminary data on ginger safety.12

A comparative study on the safety and effectiveness of ginger for treatment of

NVP was published by Portnoi et al in 2003. In this study, pregnant women taking

ginger during the first trimester of pregnancy and pregnant women exposed to non-

teratogenic but not antiemetic medications were followed-up for pregnancy outcome.

Of the 187 pregnancies studied, there were 181 live births, 2 still births, 3 spontaneous

and 1 threatened abortion. There were no statistical difference in the outcomes between

the ginger group and the comparison group. The results of this study suggest that

ginger does not appear to increase the rates of major malformations.13 To date, there

have been no published reports of fetal anomalies associated with the use of ginger.

However, one investigator warned that ginger root contains thromboxane synthetase

inhibitor, which may interfere with testosterone receptor binding in the fetus. Other

investigators noted that although safety data are lacking, people in many cultures use

ginger as a spice; the amounts used are similar to those commonly prescribed for the

treatment of NVP.3

The efficacy of ginger as treatment for nausea and vomiting of pregnancy had

been discussed in detail in several randomized trials. No pooled evidence exists


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regarding its efficacy and safety in the treatment of nausea and vomiting of pregnant

women in their first trimester of pregnancy. So far, no similar on-going meta-analysis

in the local setting is currently being undertaken. Moreover, the use of ginger has not

been widely utilized here in the Philippines despite the fact that ginger is widely

cultivated here in our country.

Rationale of the Study

There is paucity of data to support or detract the claims that ginger is effective in

the treatment of nausea and vomiting of pregnancy. This review will therefore

investigate the cumulative effects of ginger as well as its safety on the treatment of

nausea and vomiting of pregnant women.

General Objective

To determine the efficacy of ginger in the treatment of nausea and vomiting

among pregnant women during the first and second trimesters of pregnancy.

Specific Objective:

1. To determine the efficacy of ginger using a meta-analysis of randomized

controlled trials

2. To measure the severity of nausea and vomiting and the number of episodes

3. To make symptom assessment using Likert scales


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4. To determine the adverse effects of ginger on the pregnancy and pregnancy

outcomes

Materials and Methodology

L i t er a t u r e Sea r ch an d Sea r ch S t r a t eg y

The Cochrane Pregnancy and Childbirth trial registry was searched for meta-

analysis of studies on nausea and vomiting in pregnancy, hyperemesis gravidarum, and

ginger treatment. No articles were found. The search was expanded to MEDLINE,

EMBASE and LILACS using the keywords nausea, vomiting, pregnancy, hyperemesis

gravidarum, ginger and meta-analysis under publication type and covered the period

1966 to 2008. A search of the following journals: Philippine Journal of Obstetrics and

Gynecology, American Journal of Obstetrics and Gynecology, British Journal of

Obstetrics and Gynecology, Clinical Obstetrics and Gynecology, and Obstetrics and

Gynecology was done and cross referencing from bibliographies of relevant articles.

Ten out of one hundred and twenty potentially relevant studies screened met the

inclusion criteria and contained usable data. The search yield and process of

elimination of studies is summarized in Figure 1. The profile of each trial is tabulated in

Table 1.


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Methodology

A total of 10 studies were assessed. These studies were published between 1991 to

2008. The latest study reviewed was published in 2008 (study 8) while earliest was

published back in 1991 (study 1). Majority of the studies were based in Asia

predominantly Thailand (Study 2, 4,7,9) while two studies were based in Australia

(study 5,6), one study based in the United States (study 3), one in Denmark (study 1)

and one in Iran (study 8).

Duplicate copies of the 10 articles were subjected for independent assessment by

the author and 2 other co-reviewers. Disagreement between reviewers was resolved by

consensus.

A predefined data collection form was used by each reviewer to abstract each

study to assess study characteristics, particularly that of the participants, methodology,

intervention and outcomes. Method of randomization, allocation concealment, dropout

rates and intention to treat analysis was determined and recorded using the data

extraction form of the pregnancy and childbirth review groups. Data was encoded in

RevMan 4.2.10. Peto Odds ratios was computed using the random effects model.

Heterogeneity was determined using the chi-square test and I squared test for

heterogeneity.


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Results

Figure-1 Literature Yield

Profile of Participants and Study Design

All studies investigated the effect of ginger on pregnancy-related nausea and

vomiting although one study included subjects with hyperemesis gravidarum (Study 10).

The inclusion criteria for age of gestation varied. Four trials randomized singleton

pregnancies less than 16 weeks’ gestation (study 4, 6, 7 & 9), two studies were conducted

among less than 17 weeks (study 2, 8), and two more studies had it done among less

than 20 weeks (study 1,5).

Potentially relevant studiesidentified: citations or abstracts

screened for retrieval (n= 120)

Full studies retrieved for moredetailed evaluation (n= 32 )

Potentially appropriate studies tobe included in the analysis(either quantitative meta-analysis

or qualitative) (n=17 )

Studies with usable informationby outcome (n= 10)

Excluded due to study design (non-randomized, non-comparative)(n=88)

Excluded due to inability to extractstatistical estimate , unclear

randomization procedures (n=15)

No desired outcomes completelyreported (n=6)

No Intention to treat analysis (n=2)


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A total sample pool of 1,041 pregnancies was included at the start of the trial.

Sample size ranged from 30 (study 1) to 291 subjects (study 6). After the clinical trial,

the sample size recorded was 966 (range from 23 to 235).

Random assignment to the ginger arm ranged from 13 to 120 while the range for

the control/placebo arm was from 10 to 115. All were randomized double blind

controlled trials involving ginger compared to placebo (study 1,2,3,5) or vitamin B6

(study 4,6,9) or dimenhydrinate (study 7). Only one trial (study 1) was a cross-over

trial. This study was included since a clear cut wash out period for succeeding

interventions was pre-specified in the protocol and the objective assessments for relief

of nausea and vomiting were reported.

All studies mentioned adequacy of randomization by establishing sample

homogeneity at baseline in terms of age, severity of symptoms, gestational age, co-

morbid conditions and requirement for other medications.

Nature of Interventions

The dosage of administration of ginger either in extract, powdered or syrup form

varied and are as follows: 0.5 mg/day (study 7) ; 125 mg four times a day (study 5) ;

250 mg four times a day (study 1,2,3); 350 mg three times a day (study 6) and 500 mg

three times a day (study 4); 650 mg three times a day (study 9) and 1 gram daily (study

8), the highest dose.


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Trial Endpoints

All trials primarily investigated the effect of ginger on nausea severity using a

visual analogue scale (VAS), nausea frequency, as well as vomiting episodes using Likert

scales ranging from a 4-point system (study 1) to a 10-point system (study 3). We

observed differences in the qualifying criteria across severity grade as established in

each trial, hence a composite assessment of the mean change in scores were not done

and could even lead to difficulty in the interpretation of the scores when statistically

combined. A more specific tool such as the Rhode’s Index form was utilized in three

studies (study 5,6,9). One study investigated the change in health status using the MOS

36-item Short Form Health Survey (Study 6). In all studies, within-group comparison

of symptom scores from baseline to post-treatment date was done as well as between-

group comparisons were made.

In all studies, authors concluded a significant drop in the symptom scores from

baseline. Ginger was better than placebo in reducing the severity of nausea and the

frequency of vomiting episodes in all trials except for trial 5 which claimed otherwise

concerning ginger’s anti-emetic potential.

Only three studies reported the actual proportion of patients improving as

documented by the observed drop in post-treatment scores. (study 2,3,8).

Six studies documented the adverse effects of ginger which were predominantly

minor such as heart burn , abdominal discomfort while sedating effects were reported


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among those who used dimenhydrinate as control. One study (1) documented changes

in maternal body weight, while one study investigated any fetal effects of ginger (study

5). The latter study claimed no adverse fetal effects compared to the general sample of

controls compared in the study.

Included Trials

Table-1 summarizes the included trials in this study, with the study design,

nature of participants, interventions, trial endpoints, results and the quality score (value

assigned to represent the validity of a study either for a specific criterion).

Table-1 General Description of Included Trials, Meta-analysis of Gingerfor Nausea & Vomiting in Pregnancy, 2008

Study(Year)

Design Nature ofParticipants

Interventions TrialEndpoints

Results QualitScore

1Fisher-Rasmussen(1991)

Randomizeddouble blindcross-over trial

30 women with AOG


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(2003) double blindcontrolled trial

women with AOG< 16 weeks

G=64,C=64)

ginger versus10mg vitamin B6TID for 3days

scores Vomiting

frequency Minor side-

effects

change in scorespost-treatment between ginger &placebo but notsignificant

Vomiting episodesreduced

significantly in bothgroups Sedative effects for

ginger = 26.6% vs32.8% ; heart burn=9.4% vs 6.3%

5 Willets(2003)

Randomizeddouble blindplacebo-controlled trial

120 women with AOG< 20 weeks

G=60,C=60

125 mggingerextract(equiv= to1.5 g ) givenQI D for 4days

Rhode’snausea index

Birthweight,gestationalage, APGARscores

Nausea scores andretching episodeslesser in favor forginger

No difference in vomiting

Fetal outcomes within normalrange in the ginger

group

5

6Smith(2004)

Randomizeddouble blindcontrolled trial


G=120,C=115

1.05 mgginger vs 75mg vitaminB6 daily for3 weeks

Nausea & vomitingscores at day7,14,21

Vomiting, retchingscores were similarin both groups

5

7Pongrojpaw(2007)



0.5 mgginger versus 50mgdimenhydrinate for 7

days

VAS scoresfor nausea

Frequency of vomiting

Vomiting episodesstatistically greaterin the ginger group vs control duringday 1-2

No significant

difference seenduring day 3-7 Drowsiness greater

in dimenhydrinate(77.64% vs 5.88%)

5

8Ensiyeh(2008)



G=35,C=35

1gramginger vs40 mg vitamin B6for 7 days

VAS forseverity ofnausea, no.of vomitingepisodes

Drop in VAS scoresdropped from baseline in favor forginger (29/35) vs23/34 in control

Decreased vomitingin both groups(non-significantdifference)

5

9Chittuma

(2007)

Randomized

double blindcontrolled trial

126

women with AOG< 16 weeks

123returnedfor follow-up

650 mg

ginger vs 25mg vitaminB6 givenTID for 4days only

Rhode’s

symptomscoreincludingfrequencies,duration andepisodes ofnausea

% side-effects

Mean change in

scores in favor forginger

Minor side-effectsin ginger-25.4% vs23.8% in thecontrol

5

VAS-visual analogue scale, G-ginger, C-control, AOG –age of gestation


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Effect of Ginger on Nausea and Vomiting

Three studies reported the proportion of patients improving in terms of nausea

and vomiting severity. From three pooled studies, treatment benefit is seen. The risk of

no relief from nausea using ginger was only 0.29 (95% CI 0.17, 0.50, p


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Adverse Events of Ginger Treatment in Nausea and Vomiting in Pregnancy

The risk of cumulative side effects of ginger treatment based on three pooled

studies was only 0.32 (95% CI 0.21, 0.47, p


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all studies except 1 (study 5), ginger was better than placebo in reducing the severity of

nausea and frequency of vomiting episodes (Figure -2). The aromatic, spasmolytic,

carminative and absorbent properties of ginger suggest that it has direct effects on the

gastrointestinal tract. Ginger acts within the gastrointestinal tract by increasing tone

and peristalsis due to anticholinergic and antiserotonin action.10 Study 5, however,

concluded that the nausea scores and retching episodes are less in the ginger arm, but

there is no difference in vomiting. This may be attributable to the preparation of

ginger as extract rather than capsule formulation.

Herbal products are generally perceived as “being natural and free of side

effects”.14 However, ginger has few recorded side effects. In large doses, ginger may

increase gastric exfoliation and antiprostaglandin activity in vitro.10 Hence, another

primary endpoint of this meta-analysis is the determination of adverse events associated

with ginger treatment. From Figure 3, the risk of cumulative side effects was only 0.32

(95% CI 0.21, 0.47, p < 0.001), clearly favoring the ginger treatment arm. Pregnant

women who took ginger reported unfavorable effects which include sedation, heart

burn, and mild abdominal discomfort. Only one study (study 5) reported that fetal

outcomes are within normal range in the ginger group. The sedative effect of ginger is

not well understood.

Publication Bias

Publication bias is of concern for all systematic reviews which may lead to a false

positive overall result. This review is not without publication bias. Sources of this bias


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may include failure to search for studies with very small effect sizes despite our

exhaustive search, studies that did not report the outcomes completely and

heterogeneity of the individual studies included.

Conclusions

Nausea and vomiting remain a considerable quandary with regard to its effect in

pregnancy. This meta-analysis presented the efficacy of ginger on the treatment of

nausea and vomiting. The antiemetic efficacy of ginger was found to be equal to that of

the control group. Hence, ginger may be used as an alternative choice of treatment for

the management of the aforementioned symptoms.

The adverse events described with use of ginger showed a very small cumulative

risk relative to the benefit that may occur from its use.

Recommendations

An update of this meta-analysis will be done accounting for the studies in which

only abstracts were included as we await full text responses from the respective authors.


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(understanding and treating nausea and vomiting of pregnancy) Am J Obstet

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2. Cunningham, W et al. Williams Obstetrics 22nd ed. USA: McGraw Hill, 2005.

3. Quinlan JD, Hill DA. Nausea and vomiting of pregnancy. Am Fam Physician

2003; 68:121-8.

4. Arsenault, M; Lane, CA. Clinical Practice Obstetrics Committee. The

Management of Nausea and Vomiting of Pregnancy. J Obstet Gynaecol Can

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5. Zingiber officinale ( Ginger). Alternative Medicine Review 2003;8(3).

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7. Meltzer DI. Complementary therapies for nausea and vomiting in early

pregnancy. Family Practice 2000;17:570-3.

8. Sheehan P. Hyperemesis gravidarum assessment and management. Australian

Family Physician 2007;36(9):698-700.

9. Ginger. Medscape. 1995-2005.

10. Nanthakomon T, Pongrojpaw D. The efficacy of ginger in prevention of

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Thai 2006 supp; 89(4):S130-6.


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11. Sontakke S, Thawani V, Naik MS. Ginger as an antiemetic in nausea and

vomiting induced by chemotherapy: a randomized, cross-over, double blind

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12. Borrelli, F; Capasso, R; Aviello, G; Pittler, M; Izzo, AA. Effectiveness and safety

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comparative study of the safety and effectiveness of ginger for the treatment of

nausea and vomiting in pregnancy. Am J Obstet Gynecol 2003; 189:1375-7.

14. Smith, C; Crowther, C; Willson, K; Hotham, N; McMillian, V. A randomized

controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet

Gynecol 2004; 103(4): 639-44.

15. H.E.R. Foundation. Rhodes Index Assessment Tool. Internal Consensus on

Standards for Studying the Efficacy of Pharmacological Therapies for Nausea

and Vomiting of Pregnancy. April 2004.

16. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the

effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in

early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai

2007; 90(1):15-20.

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ginger in nausea and vomiting in pregnancy a meta analysis

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