Introduction
Ginger was used as an intervention to treat HG, NVP or various forms of pregnancy sickness in a total of 16 RCTs.13,42,60,63,67,70,74,77,82,89,92,96,102,103,110,113 Heterogeneity was observed in relation to the clinical setting and patient populations in which the studies were conducted, as well as the interventions, comparators and outcomes reported in each trial. As previously described (see Chapter 3, Meta-analysis of included randomised controlled trials) given the differences between trials in patient populations, settings, interventions and, in particular, the heterogeneous nature of the reported outcomes across trials, we did not attempt to perform meta-analyses and have thus reported a narrative summary only for each intervention and comparator set, with additional outcome data presented in .
Results for ginger-based interventions for NVP
Of the included trials, half (n = 8) described the women participants as experiencing symptoms categorised at the mild end of the NVP severity scale.60,63,67,70,82,89,110,113 Six were classed as including participants with mild–moderate symptom severity.13,74,92,96,102,103 The information provided by the remainder was insufficient to categorise objectively severity, although the authors describe the women as experiencing pregnancy-related nausea and vomiting.42,77 Of the 16 studies, 4 were judged to carry a high risk of bias,77,89,92,113 10 low risk,13,60,63,67,70,74,82,102,103,110 and the remainder, unclear due to lack of information.42,96
Ginger capsules versus placebo capsules
Five trials74,89,96,110,113 compared ginger and placebo capsules for the treatment of NVP. The trial by Mohammadbeigi and colleagues89 was a three-arm RCT which compared ginger, metoclopramide and placebo.89 Only one trial74 explicitly reported the effects of ginger in the treatment of HG (which they define as vomiting occurring during pregnancy, presenting prior to the 20th week and of sufficient severity to require hospital admission). However, it is important to note that this deviates from the standard definition of HG (see Chapter 1, Background). Three of these trials were judged to carry a low risk of bias, two high risk due to issues regarding blinding of personnel administering the treatment89 or selective outcome reporting113 and the risk of bias in the remaining trial was unclear.96
Rhodes Index of Nausea, Vomiting and Retching
In the Mohammadbeigi and colleagues89 trial, the observed differences in the RINVR score on the second day (ginger: 26.41 ± 4.12; metoclopramide: 25.56 ± 5.51; placebo: 27.35 ± 3.36) and the fifth day (ginger: 18.71 ± 2.81; metoclopramide: 18.53 ± 5.18; placebo: 23.15 ± 4.03) compared with the first day of treatment (ginger: 31.68 ± 5.32; metoclopramide: 30.00 ± 8.29; placebo: 30.53 ± 4.64) were statistically significant in all groups (p < 0.001).89 Although there was a reduction in scores in all three groups, the authors stated that the intensity of changes was different in ginger (p < 0.01) and metoclopramide (p = 0.03) groups compared with placebo, but did not differ between the ginger and metoclopramide groups (p = 0.51). However, it was not clear from the paper how differences in the intensity of changes were established.
Author-defined symptom severity/relief scales
Fischer-Rasmussen and colleagues74 devised a study-specific severity/relief score based on the degree of nausea, duration and number of episodes of vomiting and change in body weight, and a subjective assessment of the extent to which these symptoms had improved, worsened or stayed the same. In this randomised crossover trial, the authors compared relief scores at day 5 and day 11, following 4 days of treatment with either ginger or placebo capsules. Fischer-Rasmussen and colleagues74 reported that the mean severity scores decreased equally in the two groups. However, given the differences in gestational age at baseline, the scores at points 1 and 11 were not considered directly comparable, and therefore no statistical analysis was carried out. Mean relief scores showed greater relief of symptoms after ginger treatment than after placebo (p = 0.035), with analyses of single-item components demonstrating a particular reduction in vomiting episodes and nausea in the ginger group.
Vutyavanich and colleagues110 used 5-item Likert scales to assess patients’ subjective response to treatment in terms of whether general nausea and vomiting symptoms had worsened, improved or stayed the same. Of the 67 women surveyed, 28 out of 32 (88%) treated with ginger reported that their symptoms improved, compared with only 10 out of 35 (29%) in the placebo group (p < 0.001).
Nausea outcomes
Willetts and colleagues113 examined the effect of a ginger extract on pregnancy-induced nausea.113 The RINVR was used to assess nausea experience in terms of frequency, duration and distress (in addition to vomiting and retching) 1 hour after treatment was administered. For both the ginger extract and placebo groups, there was a reduction in the overall nausea experience score from baseline to day 1 of treatment, which then remained at this reduced level until day 4 of treatment. The effect of ginger extract relative to placebo on nausea experience was calculated as a difference parameter for 4 consecutive days of treatment post baseline. On days 1, 2 and 4, the authors state that the difference parameter was significantly less than zero, and that results showed a significant effect for ginger on nausea experience by/on day 4. However, the authors did not report p-values and added a note of caution as results were considered likely to be confounded by a regression-to-the-mean effect.
Mohammadbeigi and colleagues89 also measured nausea severity with the RINVR. The observed difference in nausea severity between the second to the fifth days of the intervention and the first day was significant in all three groups (p < 0.001). However, there were differences observed in the intensity of changes in the ginger (p < 0.01) and metoclopramide (p = 0.01) groups compared with the placebo group. The difference in intensity was not different between the ginger and metoclopramide groups (p = 0.68).
Ozgoli and colleagues96 investigated the effect of ginger capsules on NVP.96 They measured nausea intensity twice a day for 4 days using a 10-point VAS, which was converted into author-defined categories of severe, moderate, mild and no nausea (where 10 = most severe and 0 = absence of nausea). Based on these categories, nausea improved in the ginger group compared with the placebo group: after treatment, 28% of women who had taken ginger capsules had no nausea compared with 10% in the placebo group (p < 0.05). There were also more women who reported severe nausea in the placebo group (15%) than in the ginger group (9%) (p < 0.05).
Vutyavanich and colleagues110 also used a VAS to assess severity of nausea. The mean change in nausea scores (baseline minus average post-therapy nausea scores for all women) was greater in the ginger group than in the placebo group (p = 0.014). To account for three missing patients in the placebo group, the authors assumed that their nausea scores changed as much as subjects with the best improvement for the purposes of intent-to-treat analysis. These results were sensitive to plausible extreme value sensitivity analysis and differences in nausea scores were no longer significant (p = 0.08). When the mean change in nausea scores were compared at baseline and at the end of the trial at day 4, there was a greater reduction in nausea scores in the ginger group than in the placebo group (p = 0.035 and p = 0.005 in analyses that did and did not impute for three missing placebo values respectively).
Vomiting outcomes
In the Willetts and colleagues113 trial there was no difference between ginger extract and placebo groups for vomiting symptoms assessed using the RINVR.
Mohammadbeigi and colleagues89 also measured vomiting severity with the RINVR.89 Vomiting severity decreased in the ginger, metoclopramide and placebo arms between the second to fifth days of intervention compared with the first day (p < 0.01). There was an observed difference between the ginger (p < 0.05) and metoclopramide (p = 0.02) groups compared with the placebo group. However, there was no difference between the ginger and metoclopramide groups (p = 0.72).
In the trial of Ozgoli and colleagues,96 there was a 50% decrease in the number of vomiting episodes in the ginger group post-treatment period (p < 0.05). In the control group, a 9% reduction was reported, which was not statistically significant. The between-group rate of reduction in number of vomiting episodes was also significant (p < 0.05).
After 4 days of treatment, the proportion of women in the Vutyavanich and colleagues trial110 who had vomiting was lower in the ginger compared with the placebo group (37.5% vs. 68.0%; p = 0.021). Similarly, a greater reduction in vomiting episodes was found in the ginger group compared with placebo (based on baseline number of episodes minus average number of vomiting episodes over the 4 days of treatment) (p < 0.001).
Retching outcomes
In the Willetts and colleagues113 trial, using the RINVR to assess symptoms, ginger extract was shown to lower retching symptom scores compared with the placebo group for the first 2 of 4 consecutive days of treatment.
Safety outcomes
Fetal outcomes and maternal adverse events were reported in four out of five included trials.74,89,96,110 Fischer-Rasmussen and colleagues74 reported one miscarriage and one termination in trial participants. These data are summarised in the text following but it should be noted that given the anticipated rarity of these events, small trials are likely to provide unreliable estimates. No congenital anomalies were reported and the mean birthweight/gestation at delivery were within normal ranges. No adverse effects were reported in the trial of Ozgoli and colleagues96 Vutyavanich and colleagues110 reported one miscarriage in the intervention ginger and three in placebo group, delivery at term in the majority of pregnancies in both groups (placebo = 91.4%, ginger = 96.9%; no p-value reported) and no congenital anomalies. See Appendix 8, Secondary outcome data for full details, with additional UKTIS ginger data provided in Appendix 7.
Ginger syrup versus placebo syrup
The trial of Keating and Chez82 reported on the effect of ginger syrup versus non-ginger-containing placebo syrup on nausea and vomiting in early pregnancy. This trial was judged as carrying a low risk of bias.
Combined severity score
No combined score reported.
Nausea outcomes
Nausea severity was measured using the 10-point VAS: 10 out of 13 (77%) women who received ginger had at least a 4-point improvement on the 10-point nausea scale by day 9; whereas only 2 out of 10 (20%) of the women in the placebo group had the same improvement. Conversely, no woman in the ginger group, but seven (70%) in the placebo group, had a ≤ 2-point improvement on the nausea scale at both 9 and 14 days. It was not reported whether or not these differences were statistically significant.
Vomiting outcomes
Eight out of 12 women in the ginger group who were vomiting daily at the beginning of treatment stopped vomiting by day 6 compared with 2 out of 10 (20%) women in the placebo. Again, it was not reported whether or not this difference was statistically significant.
Retching outcomes
No independent retching outcomes reported.
Safety outcomes
No safety-related outcome data were reported by Keating and Chez.82 See Appendix 7 for additional UKTIS ginger data.
Ginger biscuit versus placebo biscuit
We identified one trial,60 judged at low risk of bias, which reported on the effect of ginger biscuits on nausea and vomiting in early pregnancy.
Author-defined symptom severity/relief scales
Basirat and colleagues60 used a 5-item Likert scale to assess patients’ subjective response to treatment in terms of whether symptoms had worsened, improved or remained the same. They found that a higher proportion of women consuming ginger compared with placebo biscuits reported improved symptoms: 28 out of 32 (88%) compared with 21 out of 30 (70%) (p = 0.043).
Nausea outcomes
Nausea severity was assessed via a 10-point VAS. The average improvement in nausea scores (baseline minus average post-therapy nausea scores of day 1–4 for all subjects) in the ginger group was significantly greater than that in the placebo group. The nausea score [standard deviation (SD)] on day 4 in the placebo and ginger groups decreased to 3.03 (SD 2.47) from 4.67 (SD 1.97) and 3.03 (SD 2.19) from baseline score of 5.88 (SD 1.83), respectively (p = 0.01).
Vomiting outcomes
The average reduction in the number of vomiting episodes (baseline minus average post-therapy nausea scores of day 1–4 for all subjects) was greater in the ginger biscuit group (0.96 ± 0.21) than in the placebo biscuit group (0.62 ± 0.19). However, this difference was not significant (p = 0.243). After 4 days of treatment, the proportion of women who had no vomiting in the ginger group (11/32, 34%) was greater than that in the placebo group (6/30, 20%). It was not reported whether or not this difference was statistically significant.
Retching outcomes
No independent retching outcomes reported.
Safety outcomes
No safety-related outcome data were reported by Basirat and colleagues.60 See Appendix 7 for additional UKTIS ginger data.
Ginger versus vitamin B6
Six trials compared ginger with vitamin B6 capsules for the treatment of NVP in pregnancy.67,70,77,92,102,103 Most of these trials were judged as being at a low risk of bias.67,70,102,103 However, risk of bias in the trial of Haji Seid Javari and colleagues77 was judged as unclear, and Nanreji and colleagues92 was judged as being at a high risk of bias due to concerns with regard to the blinding process and allocation concealment.
Rhodes Index of Nausea, Vomiting and Retching
Chittumma and colleagues67 used a modified version of the RINVR to assess change in nausea and vomiting severity (comprised episodes of nausea, duration of nausea and numbers of vomits). The trial found a reduction in symptoms in both groups [ginger from 8.7 (SD 2.2) to 5.4 (SD 2.0); vitamin B6 from 8.3 (SD 2.5) to 5.7 (SD 2.3); p < 0.05]. However, the mean score reduction (i.e. improvement in symptoms) with ginger was greater than with vitamin B6 (3.3 ± 1.5 vs. 2.6 ± 1.3) (p < 0.05).
Pregnancy-Unique Quantification of Emesis and Nausea scale
Haji Seid Javadi and colleagues77 measured changes in symptoms using the PUQE scoring system (capturing numbers of nausea, vomiting and retching episodes, along with severity). The study found an improvement in PUQE scores between baseline and the subsequent 4 days of treatment [ginger 8.32 (SD 2.19), vitamin B6 7.77 (SD 1.80); p < 0.001]. However, this difference between groups was not significant (p = 0.172).
Author-defined symptom severity/relief scales
At the 1-week follow-up point, Ensiyeh and Sakineh70 used a 5-point Likert scale (much worse, worse, same, better, much better) to assess overall treatment response. On day 7, 29 out of 35 (82.9%) women in the ginger group reported an improvement in general symptoms, compared with 23 out of 34 (67.6%) in the vitamin B6 group. However, this difference was not significant (p = 0.52).
Nausea outcomes
Sripramote and Lekhyananda103 used a 10-point VAS to measure nausea severity at baseline (pre treatment) and days 1–3 (post treatment).103 Comparing baseline and post treatment, there was a reduction in mean score change in both ginger (1.4, SD 2.22) and vitamin B6 groups (2.0, SD 2.19) (p < 0.001 for both groups). However, the difference between groups was not statistically significant (p = 0.136).
Ensiyeh and Sakineh70 also used a 10-point VAS to assess nausea severity between baseline and the first 4 days of treatment. They found a greater mean change in nausea score over the 4 days in the ginger group (2.2 ± 1.9) compared with the vitamin B6 group (2.2 ± 1.9) (p = 0.024).
Smith and colleagues102 used the RINVR to assess differences in nausea severity between baseline and at days 7, 14 and 21. Equivalent reductions in mean differences over time were reported for both treatment groups (mean difference 0.2, 90% CI –0.3 to 0.8).
Narenji and colleagues92 used a 10-point VAS to assess nausea severity. However, although both groups reduced their mean nausea scores [vitamin B6 mean change 0.7 (SD 1.99), ginger mean change 1.0 (SD 1.32)], there was no difference between groups (p = 0.8).
Vomiting outcomes
Sripramote and Lekhyananda103 assessed vomiting severity by the change in number of vomiting episodes. Both groups showed a reduction in the mean number of vomiting episodes [ginger group 0.7 (SD 2.18), p = 0.003; vitamin B6 group 0.5 (SD 1.44), p = 0.008]. However, the mean change difference between groups was not significant.
Ensiyeh and Sakineh70 also assessed the change in number of vomiting episodes between baseline and the first 4 days of treatment. Although number of vomiting episodes decreased in both groups (ginger 0.6 ± 0.7, vitamin B6 0.5 ± 1.1), this difference was not statistically significant (p-value reported as p = 1.101 in the paper, which we assume is a reporting error).
Narenji and colleagues92 also found a reduction in the number of episodes of vomiting in both groups. However, they reported no difference between groups (although did not provide a p-value).
Smith and colleagues102 used the RINVR to assess differences in vomiting severity between baseline and at days 7, 14 and 21. Equivalent reductions in mean differences over time were reported for both treatment groups (mean difference 0.5, 90% CI 0.0 to 0.9).
Retching outcomes
Smith and colleagues102 used the RINVR to assess differences in retching severity between baseline and at days 7, 14 and 21. Equivalent reductions in mean differences over time were reported for both treatment groups (mean difference 0.3, 90% CI –0.0 to 0.6).
In the trial of Haji Seid Javadi and colleagues,77 changes in retching severity were assessed by PUQE scores. There was no difference in the reduction of retching between the vitamin B6 group and ginger groups (p = 0.333).
Safety outcomes
Fetal outcomes and maternal adverse events were reported in four out of the six included trials.67,70,102,103 These data are summarised in the text following but as noted previously, given the anticipated rarity of these events, small trials are likely to provide unreliable estimates.
No pregnancy outcomes were reported by either Sripramote and Leekhyananda103 or Chittumma and colleagues,67 and both trials found only minor side effects in both groups. Sripramote and Leekhyananda103 found no difference in rates of sedation (ginger 26.6% vs. vitamin B6 32.8%; p = 0.439), or heartburn (ginger 9.4% vs. vitamin B6 6.3%; p = 0.510). In the trial of Chittumma and colleagues,67 minor side effects such as sedation, heartburn and arrhythmia were reported, but the difference between groups was not significant (% experiencing side effects: ginger 25.4%, vitamin B6 23.8%; p = 0.80).
Ensiyeh and Sakineh70 reported slight drowsiness in 7% of the hydroxyzine-treated patients. In terms of miscarriages, the ginger group reported two events and the vitamin B6 group reported one event. However, no congenital abnormalities or neonatal problems were reported in either group. Smith and colleagues102 reported no differences between groups in terms of live births, congenital abnormalities or birthweight (p > 0.05). See Appendix 8, Secondary outcome data for full details, with additional UKTIS ginger data provided in Appendix 7.
Ginger capsules versus acupressure
The trial of Saberi and colleagues13 reported a randomised comparison of the effectiveness of ginger capsules versus acupressure to relieve NVP. A control arm was also included where no intervention was performed during the 7 days of the trial. Analysis was performed on all participants. This study was judged as carrying low risk of bias.
Rhodes Index of Nausea, Vomiting and Retching
The authors calculated the mean difference in the overall RINVR scores between the three groups by subtracting the pre-intervention (3 days before intervention) from the post-intervention (4 days after treatment) scores. It was significantly greater (p < 0.001) in the ginger group (8.61 ± 5.32) than in the acupressure (4.17 ± 5.53) and control groups (–0.84 ± 3.72). The authors reported that the total RINVR scores was reduced by 49% in the ginger group and by 29% in the acupressure group. There was little change in the control group (raised to 0.06%). It was not reported if the difference between these three groups was significant.
Nausea outcomes
The difference in nausea severity (as assessed by the RINVR in the same way as above) was found to be lower in the ginger group (3.94 ± 2.58) compared with the acupressure (2.00 ± 2.37) or control groups (0.18 ± 1.24) (p = 0.001 for differences between groups). A similar trend was observed in the reduction percentage of scores (ginger 48%, acupressure 29%, control 0.03%), although it was not reported if this difference was significant.
Vomiting outcomes
The difference in vomiting severity (as assessed by the RINVR in the same way as above) was found to be lower in the ginger group (2.66 ± 2.64) compared with the acupressure (0.64 ± 2.14) or control groups (–0.17 ± 2.12) (p = 0.001). A similar trend was observed in the reduction percentage of scores (ginger, –52%; acupressure, 19%; control, –0.24%), although it was not reported if this difference was significant.
Retching outcomes
The difference in retching severity (assessed as above) was also found to be lower in the ginger group (2.01 ± 1.56) compared with the acupressure (1.52 ± 1.86) or control groups (0.31 ± 1.36) (p = 0.001 for differences between groups). A similar trend was observed in the percentage reduction of scores (ginger 46%, acupressure 37%, control –0.09%), although it was not reported if this difference was significant.
Safety outcomes
Saberi and colleagues13 did not report pregnancy-related outcomes and found no side effects in trial participants. See Appendix 7 for additional UKTIS ginger data.
Ginger versus doxylamine–pyridoxine
Biswas and colleagues63 reported a randomised, comparison of ginger extract tablets versus doxinate (doxylamine 10 mg plus pyridoxine 10 mg) in the treatment of nausea and vomiting during pregnancy. Patients were blinded to the treatment, whereas investigators were not. However, overall, this study was judged to have a low risk of bias.
Combined severity score
No combined score reported.
Nausea outcomes
Nausea was assessed in terms of severity (using the 10-point VAS) and number of spells. Both groups showed a significant decline in nausea severity median score {ginger from 34.5 [interquartile range (IQR) 0.0–91.0] to 0.00 [IQR 0.0–52.0]; doxylamine–pyridoxine from 30.4 [IQR 0.0–100.0] to 0.0 [IQR 0.0–65.0]} and number of nausea spells {ginger from 3.0 [IQR 1.0–10.0] to 0.43 [IQR 0.00–12.00]; doxylamine-pyridoxine from 4.0 [IQR 0.0–12.00(sic)] to 0.6 [IQR 0.0–7.7]} (p = 0.001). However, between group differences were not significant at any time point.
Vomiting outcomes
Vomiting was assessed in terms of severity (using the 10-point VAS) and number of episodes. Again, both groups showed a decline in severity [ginger from median 14.00 (range 0.00–73.00) to median 0.00 (range 0.00–30.00); doxylamine–pyridoxine from median 22.00 (range 0.00–87.00) to median 0.00 (range 0.00–47.00)] and vomiting episodes [ginger from median 0.14 (range 0.00–5.50) to median 0.15 (range 0.00–5.50); doxylamine–pyridoxine from median 2.00 (range 0.00–6.00) to median 0.00 (range 0.00–2.80)]. However, as above, between group differences were not significant at any time point.
Retching outcomes
No independent retching outcomes reported.
Safety outcomes
No stillbirths, congenital anomalies, neonatal or fetal complications were reported in the trial of Biswas and colleagues63 See Appendix 7 for additional UKTIS ginger data.
Ginger versus antihistamine (dimenhydrinate) capsules
Pongrojpaw and colleagues42 examined the effect of ginger versus antihistamine (dimenhydrinate) capsules in the treatment of NVP. Risk of bias was unclear due to lack of information provided in this abstract.
Combined severity score
No combined score reported.
Nausea outcomes
The mean nausea score during days 1–7 of the treatment decreased in both groups. There was no significant difference in the daily mean nausea scores between both groups (p > 0.05).
Vomiting outcomes
The frequency of vomiting episodes during days 1–7 of the treatment decreased in both groups. There was no significant difference in the daily mean number of vomiting episodes between days 3–7 post treatment (p > 0.05), although the daily mean number of vomiting episodes in the dimenhydrinate group during days 1 and 2 of the treatment was less than in the ginger group (p < 0.05).
Retching outcomes
No independent retching outcomes reported.
Safety outcomes
No pregnancy outcomes were reported; however, Pongrojpaw and colleagues42 found a significant difference in drowsiness after treatment (dimenhydrinate 77.6% compared with ginger 5.9%; p < 0.01). These data are summarised in the text following, but it should be noted that given the anticipated rarity of these events small trials are likely to provide unreliable estimates. See Appendix 8, Secondary outcome data for full details, noting the aforementioned caveat in relation to generalisability of this safety data, with additional UKTIS ginger data provided in Appendix 7.
Ginger versus metoclopramide
The 2011 trial of Mohammadbeigi and colleagues89 randomised women to ginger, metoclopramide or placebo capsules for the treatment of pregnancy sickness. Details are reported in Ginger capsules versus placebo capsules concerning ginger versus placebo. In summary, both were found to be were efficacious but there was no evidence that one treatment was superior to the other. Furthermore, as detailed above, the trial was judged as carrying a high risk of bias due to concerns over lack of blinding of trial personnel.
Summary
The evidence available for ginger was predominantly at low risk of bias or the risk of bias was unclear, with four exceptions.
77,89,92,113Ginger is one of the most widely reported interventions but the evidence is limited and generalisability relates to women with less severe nausea and vomiting symptoms receiving ginger treatment.
The quality of the evidence for ginger versus placebo is low and was downgraded due to clinical heterogeneity and imprecision. Further research is very likely to have an important impact on our confidence in the estimate of effect and may change the estimate. There was a sparseness of data in the other comparisons, so they were further downgraded to very low quality of evidence and we are very uncertain about the estimates.
The identified studies comparing ginger preparations with placebo generally reported evidence of an improvement over a range of symptoms with the use of ginger.
When consideration is restricted to those studies at low risk of bias, the results are less clear cut. Ginger looks promising in reducing symptoms, but the findings are not conclusive.
For the comparison of ginger preparations with acupressure, ginger again looks promising, but the evidence is very limited in both quantity and quality.
For the comparison of ginger versus vitamin B6 there are some higher-quality studies, but in general there was little evidence of a difference in the severity of symptoms between groups. There were few data for the comparisons of ginger against doxylamine–pyridoxine or antihistamine or metoclopramide, and minimal evidence suggesting any difference between groups.
Overall, there is a suggestion that ginger might be better than placebo in reducing the severity of symptoms, but more larger, better-quality studies are required for this and all other comparators.
