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BMJ Clinical Evidence logoLink to BMJ Clinical Evidence
. 2009 Jun 3;2009:1405.

Nausea and vomiting in early pregnancy

Mario Festin 1
PMCID: PMC2907767  PMID: 21726485

Abstract

Introduction

More than half of pregnant women suffer from nausea and vomiting, which typically begins by the 4th week and disappears by the 16th week of pregnancy. The cause of nausea and vomiting in pregnancy is unknown, but may be due to the rise in human chorionic gonadotrophin concentration. In 1 in 200 women, the condition progresses to hyperemesis gravidarum, which is characterised by prolonged and severe nausea and vomiting, dehydration, and weight loss.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment for nausea and vomiting in early pregnancy? What are the effects of treatments for hyperemesis gravidarum? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 30 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupressure; acupuncture; antihistamines; corticosteroids; corticotrophins; diazepam; dietary interventions other than ginger; domperidone; ginger; metoclopramide; ondansetron; phenothiazines; and pyridoxine (vitamin B6).

Key Points

More than half of pregnant women suffer from nausea and vomiting, which typically begins by the 4th week and disappears by the 16th week of pregnancy.

  • The cause of nausea and vomiting in pregnancy is unknown, but may be due to the rise in human chorionic gonadotrophin concentration.

  • In 1 in 200 women, the condition progresses to hyperemesis gravidarum, which is characterised by prolonged and severe nausea and vomiting, dehydration, and weight loss.

Ginger may reduce nausea and vomiting in pregnancy compared with placebo, although studies have given inconclusive results.

  • Pyridoxine may be as effective as ginger in reducing nausea, although studies have given inconsistent results about reduction of vomiting.

  • We don't know whether dietary interventions other than ginger are beneficial.

P6 acupressure may reduce nausea and vomiting compared with sham acupressure, but wristbands can be difficult to use.

  • We don't know whether acupressure is more effective than pyridoxine at reducing nausea or vomiting.

We don't know whether acupuncture is more effective than sham acupuncture at reducing nausea and vomiting.

Antihistamines may reduce nausea and vomiting compared with placebo. The antihistamine dimenhydrinate may be as effective as ginger at improving nausea at 7 days, although it seems more effective at reducing vomiting episodes in the first 2 days.

We don't know whether phenothiazines, metoclopramide, or domperidone reduce nausea or vomiting.

Acupressure may be more effective at reducing vomiting episodes in women with hyperemesis gravidarum compared with placebo or control (intravenous fluid therapy).

We don't know whether acupuncture, intramuscular corticotrophin, corticosteroids, diazepam, ginger, metoclopramide, ondansetron, or other dietary interventions are effective in treating hyperemesis gravidarum.

Corticosteroids may be more effective than metoclopramide at reducing vomiting episodes and reducing readmission to the intensive care unit in women with hyperemesis gravidarum.

About this condition

Definition

Nausea and vomiting are common problems in early pregnancy. Although often called “morning sickness”, nausea and vomiting can occur at any time of day and may persist throughout the day. Symptoms usually begin between 4 weeks' and 7 weeks' gestation (1 study found this to be the case in 70% of affected women) and disappear by 16 weeks' gestation in about 90% of women. One study found that less than 10% of affected women suffer nausea, vomiting, or both before the first missed period. Most women do not require treatment, and complete the pregnancy without any special intervention. However, if nausea and vomiting are severe and persistent, the condition can progress to hyperemesis, especially if the woman is unable to maintain adequate hydration, fluid and electrolyte balance, and nutrition. Hyperemesis gravidarum is a diagnosis of exclusion, characterised by prolonged and severe nausea and vomiting, dehydration, and weight loss. Laboratory investigation may show ketosis, hyponatraemia, hypokalaemia, hypouricaemia, metabolic hypochloraemic alkalosis, and ketonuria.

Incidence/ Prevalence

Nausea affects about 70% and vomiting about 60% of pregnant women. The true incidence of hyperemesis gravidarum is not known. It has been documented to range from 3 in 1000 to 20 in 1000 pregnancies. However, most authors report an incidence of 1 in 200.

Aetiology/ Risk factors

The causes of nausea and vomiting in pregnancy are unknown. One theory, that they are caused by the rise in human chorionic gonadotrophin concentration, is compatible with the natural history of the condition, its severity in pregnancies affected by hydatidiform mole, and its good prognosis (see prognosis below). The cause of hyperemesis gravidarum is also uncertain. Again, endocrine and psychological factors are suspected, but evidence is inconclusive. Female fetal sex has been found to be a clinical indicator of hyperemesis. One prospective study found that Helicobacter pylori infection was more common in pregnant women with hyperemesis gravidarum than in pregnant women without hyperemesis gravidarum (number of women with positive serum Helicobacter pylori immunoglobulin G concentrations: 95/105 [91%] with hyperemesis gravidarum v 60/129 [47%] without hyperemesis gravidarum). However, it was not clear whether this link was causal.

Prognosis

One systematic review (search date 1988) found that nausea and vomiting were associated with a reduced risk of miscarriage (6 studies, 14,564 women; OR 0.36, 95% CI 0.32 to 0.42) but found no association with perinatal mortality. Hyperemesis gravidarum is thought by some to induce nutrient partitioning in favour of the fetus, which could explain the association with improved outcome in the fetus. Nausea and vomiting and hyperemesis usually improve over the course of pregnancy, but in one cross-sectional observational study 13% of women reported that nausea and vomiting persisted beyond 20 weeks' gestation. Although death from nausea and vomiting during pregnancy is rare, morbidities, including Wernicke's encephalopathy, splenic avulsion, oesophageal rupture, pneumothorax, and acute tubular necrosis, have been reported.

Aims of intervention

To reduce the incidence and severity of nausea and vomiting in early pregnancy; to reduce the incidence and severity of hyperemesis gravidarum; to minimise adverse effects of treatment and possible teratogenic effects on the fetus.

Outcomes

All women: severity of nausea and vomiting episodes (as measured on validated scales); maternal mortality; in women with hyperemesis gravidarum, we also report: rates of admission or readmission to hospital (includes duration of hospital stay); all women: incidence and severity of adverse effects of treatment; and incidence of teratogenic effects of treatments on the fetus.

Methods

Clinical Evidence search and appraisal May 2008. The following databases were used to identify studies for this systematic review: Medline 1966 to May 2008, Embase 1980 to May 2008, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2008, Issue 2. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), and NICE. We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single blinded, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as “open”, “open label”, or not blinded unless blinding was impossible (e.g., acupressure trials). In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Nausea and vomiting in early pregnancy.

Important outcomes Hospital admission/readmission rates, Maternal mortality, Severity of nausea and vomiting
Studies (Participants) Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment
What are the effects of treatment for nausea and vomiting in early pregnancy?
at least 14 (at least 1853 women) Severity of nausea and vomiting Acupressure versus placebo or control 4 –2 –1 –1 0 Very low Quality points deducted for randomisation flaws and other methodological flaws. Consistency point deducted for conflicting results. Directness point deducted for inclusion of different interventions
1 (66) Severity of nausea and vomiting Acupressure versus pyridoxine (vitamin B6) 4 –2 0 –1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for inclusion of other interventions
at least 7 (at least 1190 women) Severity of nausea and vomiting Antihistamines versus placebo 4 –1 –1 0 0 Low Quality point deducted for randomisation flaws. Consistency point deducted for heterogeneity among studies
3 (216) Severity of nausea and vomiting Ginger versus placebo 4 0 –1 –1 0 Low Consistency point deducted for conflicting results. Directness point deducted for uncertainty about intervention
3 (552) Severity of nausea and vomiting Ginger versus pyridoxine (vitamin B6) 4 0 0 –2 0 Low Directness points deducted for uncertainty about intervention and uncertainty about effects of taking additional ginger products
1 (170) Severity of nausea and vomiting Ginger versus antihistamines 4 –2 –1 0 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for different results at different endpoints
5 (787) Severity of nausea and vomiting Pyridoxine (vitamin B6) versus placebo 4 –2 0 0 0 Low Quality points deducted for randomisation issues and uncertain diagnosis or outcome
2 (648) Severity of nausea and vomiting Acupuncture compared with sham acupuncture or no treatment 4 –1 0 –1 0 Low Quality point deducted for incomplete reporting of results. Directness point deducted for uncertainty about benefit
2 (300) Severity of nausea and vomiting Phenothiazines versus placebo 4 –2 –1 0 0 Very low Quality points deducted for uncertainty about randomisation and allocation. Consistency point deducted for heterogeneity among studies
1 (174) Severity of nausea and vomiting Phenothiazines versus antihistamines 4 –2 0 0 0 Low Quality points deducted for sparse data and incomplete reporting of results
What are the effects of treatments for hyperemesis gravidarum?
1 (66) Severity of nausea and vomiting Acupressure versus placebo or control 4 –2 0 –1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for no direct comparison between interventions
1 (50) Severity of nausea and vomiting Acupuncture versus sham acupuncture 4 –2 0 0 0 Low Quality points deducted for sparse data and incomplete reporting of results
1 (24) Severity of nausea and vomiting Corticosteroids versus placebo 4 –1 0 0 0 Moderate Quality point deducted for sparse data
2 (150) Hospital admission/readmission rates Corticosteroids versus placebo 4 –1 0 –1 0 Low Quality point deducted for sparse data. Directness point deducted for inclusion of other interventions
2 (120) Severity of nausea and vomiting Corticosteroids versus antihistamines 4 –1 –1 0 0 Low Quality point deducted for sparse data. Consistency point deducted for conflicting results at different endpoints
1 (40) Hospital admission/readmission rates Corticosteroids versus antihistamines 4 –1 0 0 0 Moderate Quality point deducted for sparse data
1 (40) Severity of nausea and vomiting Corticosteroids versus metoclopramide 4 –1 0 0 0 Moderate Quality point deducted for sparse data
1 (40) Hospital admission/readmission rates Corticosteroids versus metoclopramide 4 –1 0 0 0 Moderate Quality point deducted for sparse data
1 (32) Severity of nausea and vomiting Corticotrophins versus placebo 4 –2 0 0 0 Low Quality points deducted for sparse data and incomplete reporting
1 (32) Hospital admission/readmission rates Corticotrophins versus placebo 4 –2 0 0 0 Low Quality points deducted for sparse data and incomplete reporting
1 (50) Severity of nausea and vomiting Diazepam versus placebo 4 –2 0 –1 0 Very low Quality points deducted for sparse data and incomplete reporting. Directness point deducted for uncertainty about effect of other interventions
1 (50) Hospital admission/readmission rates Diazepam versus placebo 4 –2 0 –1 0 Very low Quality points deducted for sparse data and incomplete reporting. Directness point deducted for uncertainty about effect of other interventions
1 (43) Severity of nausea and vomiting Carob seed powder plus calcium lactate versus placebo 4 –1 0 –1 0 Low Quality point deducted for sparse data. Directness point deducted for uncertainty about composition of intervention
1 (30) Severity of nausea and vomiting Ginger versus placebo 4 –1 –1 –1 0 Very low Quality point deducted for sparse data. Consistency point deducted for conflicting results on analysis. Directness point deducted for composite outcome
1 (30) Severity of nausea and vomiting Ondansetron versus antihistamines 4 –1 0 0 0 Moderate Quality point deducted for sparse data
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We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Acupressure

Pressure applied to a specific point of the body. It does not require needles and can be given by patients themselves. Commercial products available include an elastic band to fit around the wrist with a plastic disc to apply pressure at the P6 point.

Hydatidiform mole

A condition in which there is abnormal cystic development of the placenta. The uterus is often large for the duration of pregnancy and there may be vaginal bleeding, lack of fetal movement and fetal heart sounds, and severe nausea and vomiting. Rarer, but important, complications include haemorrhage, intrauterine infection, hypertension, and persistent gestational trophoblastic disease, which may infiltrate local tissues or metastasise to distant sites.

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Metabolic hypochloraemic alkalosis

Excess base alkali in the body fluids caused by chloride loss.

Moderate-quality evidence

Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

P6 acupressure

Pressure is applied at the P6 (Neiguan) point on the volar aspect of the wrist.

PC6 acupuncture

The needle is applied at the PC6 point located near to the wrist crease.

Very low-quality evidence

Any estimate of effect is very uncertain.

Wernicke's encephalopathy

A severe syndrome caused by a deficiency of thiamine (vitamin B1). It is usually associated with excessive alcohol abuse and is characterised by abnormal eye movements, confusion, and loss of short term memory and muscular coordination.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

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BMJ Clin Evid. 2009 Jun 3;2009:1405.

Acupressure for treating nausea and vomiting in early pregnancy

Summary

P6 acupressure may reduce nausea and vomiting compared with sham acupressure, but wristbands can be difficult to use.

More than half of women having P6 acupressure experience problems with using the wristband.

We don't know whether acupressure is more effective than pyridoxine at reducing nausea or vomiting.

Benefits and harms

Acupressure versus placebo or control:

We found two systematic reviews (search date 2002, and search date from 1989 to 2005), one additional RCT, and one subsequent RCT. The first systematic review examined the effects of acupressure and acupuncture in treating nausea or vomiting in early pregnancy, and pooled results for acupressure and acupuncture together; only those results pertaining to acupressure alone have been included in this section. The review identified three RCTs comparing acupressure (all 3 RCTs assessed P6 acupressure; 500 women) versus sham acupressure. The second systematic review examined the effects of acupressure, acupuncture, and electrical stimulation, and identified nine RCTs comparing acupressure (3 RCTs assessing finger-applied acupressure, and 6 RCTs using wristbands) versus control (no treatment). The three RCTs identified by the first review were identified by the second review. The reviews reported on different comparisons and outcomes and so we report data from both reviews here.

Severity of nausea and vomiting

P6 acupressure compared with sham acupressure or no treatment P6 acupressure may be more effective at reducing the proportion of women who report nausea and vomiting in early pregnancy (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

RCT
3-armed trial 		60 women, mean gestational ages 9.6 to 10.8 weeks
In review 		Mean nausea score 1 day
with P6 acupressure
with no treatment
WMD –2.40 for P6 acupressure v no treatment
95% CI –3.78 to –1.02
P = 0.0006 for P6 acupressure v no treatment
WMD calculated by Clinical Evidence contributor 		Effect size not calculated P6 acupressure

RCT
3-armed trial 		60 women, mean gestational ages 9.6 to 10.8 weeks
In review 		Mean nausea score 6 days
with P6 acupressure
with no treatment
WMD –2.00 for P6 acupressure v no treatment
95% CI –3.37 to –0.63
P = 0.004 for P6 acupressure v no treatment
WMD calculated by Clinical Evidence contributor 		Effect size not calculated P6 acupressure

RCT
3-armed trial 		60 women, mean gestational ages 9.6 to 10.8 weeks
In review 		Mean nausea score 14 days
with P6 acupressure
with no treatment
WMD –2.30 for P6 acupressure v no treatment
95% CI –3.79 to –0.81
P = 0.003 for P6 acupressure v no treatment
WMD calculated by Clinical Evidence contributor 		Effect size not calculated P6 acupressure

RCT
3-armed trial 		60 women, mean gestational ages 9.6 to 10.8 weeks
In review 		Mean nausea score 1 day
with P6 acupressure
with sham acupressure
WMD –0.40 for P6 acupressure v sham acupressure
95% CI –2.01 to +1.21
P = 0.63 for P6 acupressure v sham acupressure
WMD calculated by Clinical Evidence contributor 		Not significant

RCT
3-armed trial 		60 women, mean gestational ages 9.6 to 10.8 weeks
In review 		Mean nausea score 6 days
with P6 acupressure
with sham acupressure
WMD –1.4 for P6 acupressure v sham acupressure
95% CI –2.89 to –0.09
P = 0.07 for P6 acupressure v sham acupressure
WMD calculated by Clinical Evidence contributor 		Not significant

RCT
3-armed trial 		60 women, mean gestational ages 9.6 to 10.8 weeks
In review 		Mean nausea score 14 days
with P6 acupressure
with sham acupressure
WMD –1.7 for P6 acupressure v sham acupressure
95% CI –3.25 to –0.15
P = 0.03 for P6 acupressure v sham acupressure
WMD calculated by Clinical Evidence contributor 		Effect size not calculated P6 acupressure

Systematic review		 350 women, mean gestational ages 7.2 to 10.0 weeks
Data from 1 RCT		 Proportion of women reporting nausea
23/119 (19%) with finger acupressure
108/231 (47%) with control
RR 0.41
95% CI 0.28 to 0.60
P = 0.005
See further information on studies for details of placebo effect 		Moderate effect size finger acupressure

Systematic review		 273 women, mean gestational ages 8 to 11 weeks
5 RCTs in this analysis		 Proportion of women reporting nausea
32/102 (31%) with wristband acupressure
60/106 (57%) with control
RR 0.55
95% CI 0.38 to 0.77
P = 0.007
See further information on studies for details of placebo effect 		Small effect size acupressure

RCT		 138 women randomised at 13 weeks' gestation Frequency and severity of nausea
with acupressure given by a wristband to the P6 acupoint
with sham acupressure wristband
Data were not reported in a way that allowed further statistical calculation

RCT
3-armed trial 		75 pregnant women suffering from nausea with or without vomiting, and who were unable to receive conventional treatment, gestational age range 5 to 12 weeks Nausea (measured using a visual analogue score: 10 cm long vertical and horizontal lines with a scale ranging from 0 = no symptoms to 10 = worst possible symptom) 4 to 6 days
with acupressure (an acupressure band applied to acupoint P6 on days 4 to 6 and removed before going to bed)
with placebo (a band applied to a sham acupressure point on the upper side of the wrists on days 4 to 6 and removed before going to bed)
Absolute results not reported
P >0.05 for acupressure v placebo
See further information on studies for methodological limitations 		Not significant
Vomiting

Systematic review		 250 women, mean gestational ages 8 to 11 weeks
5 RCTs in this analysis		 Proportion of women reporting vomiting
29/107 (27%) with wristband acupressure
58/131 (44%) with control
RR 0.45
95% CI 0.32 to 0.63
P <0.001
See further information on studies for details of placebo effect 		Moderate effect size wristband acupressure

RCT
3-armed trial 		75 pregnant women suffering from nausea with or without vomiting, and who were unable to receive conventional treatment, gestational age range 5 to 12 weeks Vomiting (measured using a visual analogue score: 10 cm long vertical and horizontal lines with a scale ranging from 0 = no symptoms to 10 = worst possible symptom) 4 to 6 days
with acupressure (an acupressure band applied to acupoint P6 on days 4 to 6 and removed before going to bed)
with placebo (a band applied to a sham acupressure point on the upper side of the wrists on days 4 to 6 and removed before going to bed)
Absolute results not reported
P >0.05 for acupressure v placebo
See further information on studies for methodological limitations 		Not significant
Nausea and vomiting (composite)

Systematic review		 285 women
2 RCTs in this analysis		 Proportion of women reporting morning sickness (not further defined)
37/145 (25%) with acupressure
61/140 (43%) with sham acupressure
RR 0.57
95% CI 0.38 to 0.86 		Small effect size acupressure

RCT		 97 women, 8 to 12 weeks' gestation
In review 		Duration of nausea and vomiting
with active wristband acupressure
with sham wristband acupressure
WMD –1.89 hours/12-hour cycle
95% CI –3.45 hours/12-hour cycle to –0.33 hours/12-hour cycle 		Effect size not calculated active wristband acupressure

RCT		 97 women, 8 to 12 weeks' gestation
In review 		Intensity of nausea and vomiting
with active wristband acupressure
with sham wristband acupressure
WMD –0.25
95% CI –0.62 to +0.12 		Not significant
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 Number of women in this analysis not reported
Data from 1 RCT		 Adverse effects
with acupressure
with control
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No data from the following reference on this outcome.

Acupressure versus pyridoxine (vitamin B6):

We found one RCT comparing wristband acupressure versus pyridoxine over 7 days in women with mild to moderate nausea and vomiting in early pregnancy.

Severity of nausea and vomiting

Acupressure compared with pyridoxine We don't know how acupressure and pyridoxine compare at reducing nausea or vomiting at 7 days (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea and vomiting

RCT		 66 women with mild to moderate nausea and vomiting in early pregnancy, gestational age range 6 to 12 weeks Rhodes index scores evening of the 5th day
with wristband acupressure on the P6 acupoint (instruction to wear the wristband continuously from day 1 to the evening of day 5)
with pyridoxine (50 mg of vitamin B6 twice daily for 5 days)
Absolute results not reported
P >0.05 		Not significant

RCT		 66 women with mild to moderate nausea and vomiting in early pregnancy, gestational age range 6 to 12 weeks Rhodes index scores evening of the 7th day after discontinuation of treatments
with wristband acupressure on the P6 acupoint (instruction to wear the wristband continuously from day 1 to the evening of day 5)
with pyridoxine (50 mg of vitamin B6 twice daily for 5 days)
Absolute results not reported
P >0.05 		Not significant
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 66 women with mild to moderate nausea and vomiting in early pregnancy, gestational age range 6–12 weeks Adverse effects
with wristband acupressure on the P6 acupoint (instruction to wear the wristband continuously from day 1 to the evening of day 5)
with pyridoxine (50 mg of vitamin B6 twice daily for 5 days)
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Further information on studies

The first RCT included in the first systematic review compared P6 acupressure (a band applying pressure to the P6 point) versus sham treatment (a similar band with the point blunted, not exerting pressure on the P6 point). Each type of band was put on each wrist in sequence. Data for the meta-analysis were taken from the third phase, when one group received active treatment to both wrists and the other placebo treatment to both wrists for 72 hours. This RCT had the largest sample size of the two RCTs included in the meta-analysis. The reliability of the randomisation in this first RCT was questioned by another paper. The second RCT in the meta-analysis compared P6 acupoint acupressure versus sham acupressure (pressure applied to a point close to the right elbow), both for 5 minutes every 4 hours on four successive mornings. A control group without treatment was asked only to complete a record form.

Of the six RCTs assessing acupressure applied by a wristband, five RCTs used bilateral wristbands and one RCT used a unilateral wristband for 3 to 14 days. However, it is not clear whether wristbands were applied continuously or whether the results of the crossover RCTs were before or after crossover. In one RCT comparing finger-applied acupressure versus control and versus placebo, unilateral acupressure was applied by finger application on P6 acupoint for 5 to 30 minutes, four times daily or as needed for 4 to 7 days. Placebo effect The review also examined the placebo effects of acupressure (finger and wrist acupressure), and found that the proportion of women reporting nausea was smaller with placebo compared with control, which was of borderline significance (41/112 [37%] with placebo v 77/133 [58%] with control; RR 0.63, 95% CI 0.39 to 1.02; P = 0.0479). This makes the interpretation of results of the effects of acupressure difficult.

The RCT found a significant reduction in the number of women reporting nausea in the treatment (P <0.001) and placebo groups (P <0.05) in days 4 to 6 compared with days 1 to 3. This makes the interpretation of results of the effects of acupressure difficult.

Rhodes index scores, 8-item form: 3 items measure nausea (scores ranging from 3–15) and 5 items measure vomiting and retching (scores ranging from 5–25).

Comment

Conducting high-quality trials is difficult because nausea and vomiting tend to resolve spontaneously, and interventions are difficult to mask and control with credible placebos. In the first systematic review, results were sensitive to the method of calculation used (RR or OR), and the authors commented that the significant relative risk calculation may be an overestimate, as two RCTs that did not meet Clinical Evidence criteria found no evidence of effect. In the second systematic review, there was improvement in the proportion of women who reported nausea or vomiting with all three groups. The significant improvement in the placebo group makes it difficult to interpret results and establish whether they were influenced by a placebo effect. It is possible that the wristbands (placebo) could produce an effect by applying pressure on the P6 acupoint or in its meridian pathway because of their uniform size and elasticity.

The subsequent RCT found acupressure had a therapeutic and placebo effect in reducing symptoms of nausea. However, this study is limited by the small number of participants in each arm. In the RCT comparing acupressure and pyridoxine, women were also advised to take dimenhydrinate in the event of nausea and vomiting. Women were asked to record whether they took dimenhydrinate and, if so, how often. However, it is not clear how many women actually took dimenhydrinate or how often it was taken. It is possible that the reduction in symptoms was largely due to the effects of the rescue drug.

Substantive changes

Acupressure for treating nausea and vomiting in early pregnancy: One systematic review and two RCTs added. The systematic review found that acupressure applied as a wristband reduced the proportion of women reporting nausea and vomiting compared with control. One RCT found no significant difference between acupressure and placebo in the number of women who reported nausea and vomiting. The RCT comparing acupressure and pyridoxine found no significant difference between the two treatments in Rhodes index scores. Categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Antihistamines (H1 antagonists) for treating nausea and vomiting in early pregnancy

Summary

Antihistamines may reduce nausea and vomiting compared with placebo.

The antihistamine dimenhydrinate may be as effective as ginger at improving nausea at 7 days, although it seems more effective at reducing vomiting episodes in the first 2 days.

Benefits and harms

Antihistamines versus placebo:

We found two systematic reviews (search date 1998, 7 RCTs, 1190 women; search date 2002, 6 RCTs, 571 women). The two systematic reviews had five RCTs in common. Antihistamines assessed in the RCTs identified by the reviews were buclizine, dimenhydrinate, hydroxyzine, meclozine, and doxylamine.

Severity of nausea and vomiting

Antihistamines compared with placebo Antihistamines (buclizine, dimenhydrinate, doxylamine, hydroxyzine, and meclozine) may be more effective at reducing nausea and vomiting (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

Systematic review		 571 women
6 RCTs in this analysis		 Nausea
51/355 (14%) with antihistamines
96/216 (44%) with placebo
OR 0.20
95% CI 0.06 to 0.63
The RCTs were old and did not provide details on randomisation or concealment strategies 		Moderate effect size antihistamines
Vomiting

Systematic review		 1190 women
7 RCTs in this analysis		 Treatment failure (defined as treatments that provided little or no benefit in reducing vomiting)
84/775 (11%) with antihistamines
148/415 (36%) with untreated controls
RR 0.34
95% CI 0.27 to 0.43
Significant heterogeneity among RCTs (potentially attributed to variation in drugs in meta-analysis)
The RCTs were old and did not provide details on randomisation or concealment strategies 		Moderate effect size antihistamines
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 200,000 women treated between 1960 and 1991 Teratogenicity
with antihistamines
with placebo
OR 0.76
95% CI 0.60 to 0.94
Result is of borderline significance 		Small effect size placebo

Systematic review		 179 women
3 RCTs in this analysis		 Drowsiness
23/94 (24%) with antihistamines
9/85 (11%) with placebo
RR 2.3
95% CI 1.1 to 4.7
NNH 7
95% CI 3 to 32 		Moderate effect size placebo
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Antihistamines versus ginger:

See option on ginger.

Antihistamines versus phenothiazines:

See option on phenothiazines.

Further information on studies

None.

Comment

A preparation combining doxylamine plus dicycloverine plus pyridoxine assessed in the second review was found to reduce nausea and vomiting. However, this preparation was withdrawn from the market in several countries after publication of papers suggesting teratogenicity, although such claims have subsequently been found to be unreliable.

Substantive changes

Antihistamines (H1 antagonists) for treating nausea and vomiting in early pregnancy: One RCT added. The RCT found that the antihistamine dimenhydrinate improved vomiting for the first 2 days compared with ginger, but there was no significant difference at days 3 to 7. It also found no significant difference in nausea scores between the two groups. Categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Ginger for treating nausea and vomiting in early pregnancy

Summary

Ginger may reduce nausea and vomiting in pregnancy compared with placebo, although studies have given inconclusive results.

Ginger and pyridoxine may be equally effective in reducing nausea, although studies have given inconsistent results about reduction of vomiting.

Ginger may cause heartburn and may be a gastric irritant (in quantities >6 g). In addition, inhalation of ginger dust may lead to immunoglobulin E-mediated allergy.

Benefits and harms

Ginger versus placebo:

We found one systematic review (search date 2004, 3 RCTs). The review did not conduct a meta-analysis.

Severity of nausea and vomiting

Ginger compared with placebo Ginger may be more effective at reducing nausea and vomiting in early pregnancy (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

RCT		 120 women, 5.5 to 18.0 weeks' gestation
In review 		Nausea severity scores each of the four treatment days
with ginger 125 mg in oral capsules taken four times daily for 4 days
with placebo
Absolute results reported graphically
Reported as significant
P value not reported 		Effect size not calculated ginger
Vomiting

RCT		 70 women, over 17 weeks' gestation
In review 		Proportion of women with vomiting 4 days
12/32 (38%) with ginger 250 mg in oral capsules taken four times daily
23/35 (66%) with placebo
RR 0.57
95% CI 0.34 to 0.95
NNT 4
95% CI 2 to 12 		Small effect size ginger

RCT		 26 women, <13 weeks' gestation
In review 		Proportion of women who stopped vomiting 6 days
8/12 (67%) with ginger syrup (15 mL containing ginger 250 mg taken four times daily)
2/10 (20%) with placebo
RR 0.42
95% CI 0.18 to 0.98 		Moderate effect size ginger

RCT		 120 women, 5.5 to 18.0 weeks' gestation
In review 		Dry retching first 2 days of treatment
with ginger 125 mg in oral capsules taken four times daily for 4 days
with placebo
Absolute results not reported
Reported as significant
P value not reported 		Effect size not calculated ginger

RCT		 120 women, 5.5 to 18.0 weeks' gestation
In review 		Episodes of vomiting
with ginger 125 mg in oral capsules taken four times daily for 4 days
with placebo
Absolute results not reported
Reported as not significant
P value not reported 		Not significant
Symptom improvement

RCT		 70 women, over 17 weeks' gestation
In review 		Proportion of women with improved symptoms (non-specifically described) 7 days
28/32 (88%) with ginger 250 mg in oral capsules taken four times daily
10/35 (29%) with placebo
RR 0.18
95% CI 0.07 to 0.45 		Large effect size ginger
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 70 women, over 17 weeks' gestation
In review 		Spontaneous abortions
1/32 (3%) with ginger 250 mg in oral capsules taken four times daily
3/38 (8%) with placebo
P = 0.4
RCT may have been too small to detect a clinically important difference. 		Not significant

RCT		 26 women, <13 weeks' gestation
In review 		Adverse effects
with ginger syrup (15 mL containing ginger 250 mg taken four times daily)
with placebo

RCT		 120 women, 5.5 to 18.0 weeks' gestation
In review 		Adverse effects
with ginger 250 mg in oral capsules taken four times daily
with placebo
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Ginger versus pyridoxine (vitamin B6):

We found one systematic review (search date 2004, 2 RCTs), and one subsequent RCT comparing the effectiveness of ginger versus pyridoxine in the treatment of nausea and vomiting in pregnancy. The review did not conduct a meta-analysis.

Severity of nausea and vomiting

Ginger and pyridoxine compared with pyridoxine Ginger and pyridoxine may be equally effective at improving nausea and vomiting (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

RCT		 138 women, over 16 weeks' gestation
In review 		Mean nausea score (severity graded using a visual analogue scale)
1.4 with oral ginger 500 mg (provided in a capsule) for 3 days
2.0 with pyridoxine 10 mg three times daily for 3 days
P = 0.136 		Not significant

RCT		 291 women, <16 weeks' gestation
In review 		Nausea score change from baseline to days 7, 14, and 21 (estimated and averaged over the three time points)
–3.6 with ginger 1.05 g daily for 3 weeks
–3.9 with pyridoxine 75 mg daily for 3 weeks
Mean difference +0.2
90% CI –0.3 to +0.8 		Not significant
Vomiting

RCT		 138 women, over 16 weeks' gestation
In review 		Mean vomiting score
0.7 with oral ginger 500 mg (provided in a capsule) for 3 days
0.5 with pyridoxine 10 mg three times daily for 3 days
P = 0.498 		Not significant

RCT		 291 women, >16 weeks' gestation
In review 		Vomiting score change from baseline to days 7, 14, and 21 (estimated and averaged over the three time points)
–0.9 with ginger 1.05 g daily for 3 weeks
–0.2 with pyridoxine 75 mg daily for 3 weeks
Mean difference 0.5
90% CI 0 to 0.9 		Not significant

RCT		 291 women, <16 weeks' gestation
In review 		Retching score change from baseline to days 7, 14, and 21 (estimated and averaged over the three time points)
–0.5 with ginger 1.05 g daily for 3 weeks
–0.7 with pyridoxine 75 mg daily for 3 weeks
Mean difference 0.3
90% CI 0 to 0.6 		Not significant
Symptoms (includes composite of nausea and vomiting)

RCT		 291 women, <16 weeks' gestation
In review 		Proportion of women symptom-free any time during the trial
with ginger 1.05 g daily for 3 weeks
with pyridoxine 75 mg daily for 3 weeks
Absolute results not reported
Reported as not significant
P value not reported 		Not significant

RCT		 291 women, <16 weeks' gestation
In review 		Women's perception of an overall reduction in their symptoms
53% with ginger 1.05 g daily for 3 weeks
55% with pyridoxine 75 mg daily for 3 weeks
Absolute numbers not reported
RR 0.97
95% CI 0.77 to 1.21 		Not significant

RCT		 126 women with nausea and vomiting in early pregnancy who needed antiemetics, gestational age at least 16 weeks Mean nausea and vomiting scores (assessed using a modified form of the full Rhodes score) 4 days
3.3 with ginger (650 mg daily) for 4 days
2.6 with pyridoxine (25 mg three times daily) for 4 days
P <0.05 		Effect size not calculated ginger
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 138 women, over 16 weeks' gestation
In review 		Drowsiness
17/64 (27%) with oral ginger 500 mg (provided in a capsule)
21/64 (33%) with pyridoxine 10 mg three times daily for 3 days
P = 0.439 		Not significant

RCT		 138 women, over 16 weeks' gestation
In review 		Dyspepsia
6/64 (9%) with oral ginger 500 mg (provided in a capsule) for 3 days
4/64 (6%) with pyridoxine 10 mg three times daily for 3 days
P = 0.510 		Not significant

RCT		 291 women, <16 weeks' gestation
In review 		Dry retching after swallowing
52% with ginger 1.05 g daily for 3 weeks
56% with pyridoxine 75 mg daily for 3 weeks
Absolute numbers not reported
Significance not assessed

RCT		 291 women, <16 weeks' gestation
In review 		Vomiting after ingestion
2% with ginger 1.05 g daily for 3 weeks
1% with pyridoxine 75 mg daily for 3 weeks
Absolute numbers not reported
Significance not assessed

RCT		 291 women, <16 weeks' gestation
In review 		Burning sensation
2% with ginger 1.05 g daily for 3 weeks
2% with pyridoxine 75 mg daily for 3 weeks
Absolute numbers not reported
Significance not assessed

RCT		 291 women, <16 weeks' gestation
In review 		Belching
9% with ginger 1.05 g daily for 3 weeks
0% with pyridoxine 75 mg daily for 3 weeks
Absolute numbers not reported
P <0.05 		Effect size not calculated pyridoxine

RCT		 291 women, <16 weeks' gestation
In review 		Pregnancy outcome
with ginger 1.05 g daily for 3 weeks
with pyridoxine 75 mg daily for 3 weeks
Reported as not significant
P value not reported 		Not significant

RCT		 126 women with nausea and vomiting in early pregnancy who needed antiemetics, gestational age at least 16 weeks Adverse effects (not further specified)
16/61 (25%) with ginger (650 mg daily) for 4 days
15/62 (24%) with pyridoxine (25 mg three times daily) for 4 days
P = 0.795 		Not significant
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Ginger versus antihistamines:

We found one RCT comparing ginger versus dimenhydrinate for 7 days.

Severity of nausea and vomiting

Ginger compared with antihistamines We don't know how ginger and dimenhydrinate compare at reducing nausea (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

RCT		 170 women, gestational age <16 weeks Daily mean nausea scores (measured on a visual analogue scale: 10 cm vertical line with a scale ranging from 0 = no nausea to 10 =  severe nausea) days 1 to 7 of treatment
with ginger (0.5 g twice daily) for 7 days
with dimenhydrinate (50 mg twice daily) for 7 days
Absolute results reported graphically
P <0.05 		Not significant
Vomiting

RCT		 170 women, gestational age <16 weeks Daily mean vomiting episodes days 1 to 2 of treatment
with ginger (0.5 g twice daily) for 7 days
with dimenhydrinate (50 mg twice daily) for 7 days
Absolute results reported graphically
P <0.05 		Effect size not calculated dimenhydrinate

RCT		 170 women, gestational age <16 weeks Daily mean vomiting episodes days 3 to 7 of treatment
with ginger (0.5 g twice daily) for 7 days
with dimenhydrinate (50 mg twice daily) for 7 days
Absolute results reported graphically
P >0.05 		Not significant
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 170 women, gestational age >16 weeks Episodes of drowsiness
5/85 (6%) with ginger (0.5 g twice daily) for 7 days
66/85 (78%) with dimenhydrinate (50 mg twice daily) for 7 days
P >0.01 		Effect size not calculated ginger

RCT		 170 women, gestational age <16 weeks Occurrence of heartburn
13/85 (15%) with ginger (0.5 g twice daily) for 7 days
9/85 (11%) with dimenhydrinate (50 mg twice daily) for 7 days
P = 0.403 		Not significant
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Further information on studies

The ginger used in the RCT was derived from fresh ginger roots and given in capsules. The authors of the RCT warn that different preparations of ginger may have different potencies and therefore different magnitudes of effects. The active ingredient that improves nausea and vomiting has not been isolated.

The 3 physical symptoms measured with the Rhodes index score are defined as: episodes of nausea, duration of nausea, and number of vomits, measured on a scale ranging from 3 (lowest = slight nausea) to 15 (highest = severe nausea and vomiting). In this study, 3/61 (5%) women in the ginger group and 4/62 (7%) in the vitamin B6 group took other ginger products, which may confound the results.

The RCT identified by the systematic review found that both ginger and pyridoxine significantly reduced nausea scores (from 5.0 to 3.6 with ginger v from 5.3 to 3.3 with pyridoxine; P <0.001 for either intervention v baseline) and number of vomiting episodes (from 1.9 to 1.2 with ginger v from 1.7 to 1.2 with pyridoxine; P <0.001 for either intervention v baseline) from baseline.

Comment

A review of the literature on the effects of ginger reported that ginger may cause heartburn and may be a gastric irritant (in quantities >6 g). In addition, inhalation of ginger dust may lead to immunoglobulin E-mediated allergy.

Substantive changes

Ginger for treating nausea and vomiting in early pregnancy: Two RCTs added. One RCT found that ginger was more effective at reducing nausea and vomiting scores compared with pyridoxine. One RCT comparing ginger and antihistamines found that dimenhydrinate improved vomiting for the first 2 days compared with ginger, but there was no significant difference at days 3 to 7. It also found no significant difference in nausea scores between the two groups. Categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Pyridoxine (vitamin B6) for treating nausea and vomiting in early pregnancy

Summary

Pyridoxine may be as effective as ginger in reducing nausea, although studies have given inconsistent results about reduction of vomiting.

We don't know how pyridoxine and acupressure compare at reducing nausea or vomiting.

Benefits and harms

Pyridoxine (vitamin B6) versus placebo:

We found two systematic reviews (search dates 1998 and 2002). Two RCTs were common to both reviews.

Severity of nausea and vomiting

Pyridoxine compared with placebo Pyridoxine may be more effective at reducing nausea but not vomiting (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

Systematic review		 395 women
2 RCTs in this analysis		 Nausea scores
with pyridoxine
with placebo
WMD –0.99
95% CI –1.47 to –0.51
The method of randomisation was unclear in one RCT 		Effect size not calculated pyridoxine

Systematic review		 392 women
2 RCTs in this analysis		 Nausea (change in a 10-cm visual analogue scale)
with pyridoxine
with placebo or no treatment
WMD 0.99 cm
95% CI 0.51 cm to 1.47 cm 		Effect size not calculated pyridoxine
Vomiting

Systematic review		 392 women
2 RCTs in this analysis		 Vomiting
with pyridoxine
with placebo or no treatment
RR 0.76
95% CI 0.36 to 1.66 		Not significant
Failure rate

Systematic review		 949 women
3 RCTs in this analysis		 “Failure rates”
with pyridoxine
with placebo
RR 0.97
95% CI 0.78 to 1.20
The method of randomisation was unclear in one RCT 		Not significant
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 1369 women Major fetal malformations
with pyridoxine
with placebo
RR 1.05
95% CI 0.60 to 1.84 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Pyridoxine (vitamin B6) versus acupressure:

See option on acupressure.

Pyridoxine (vitamin B6) versus ginger:

See option on ginger.

Comment

None.

Substantive changes

Pyridoxine (vitamin B6) for treating nausea and vomiting in early pregnancy: Two RCTs added. The RCT comparing acupressure and pyridoxine found no significant difference between the two treatments in Rhodes index scores. The other RCT found that pyridoxine was less effective compared with ginger at reducing nausea and vomiting scores. Categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Acupuncture for treating nausea and vomiting in early pregnancy

Summary

We don't know whether acupuncture is more effective than sham acupuncture at reducing nausea and vomiting.

Benefits and harms

Acupuncture compared with sham acupuncture or no treatment:

We found two systematic reviews (search date 2002, and search date from 1989 to 2005). The first systematic review examined the effects of acupressure and acupuncture in treating nausea or vomiting in early pregnancy, and identified two RCTs comparing acupuncture versus sham acupuncture or no treatment. The second systematic review examined the effects of acupressure, acupuncture, and electrical stimulation, and identified two RCTs comparing acupuncture versus control (no treatment) in treating nausea or vomiting in early pregnancy. Two RCTs were identified by both reviews. We report the results of these RCTs separately, as the first review pooled results for acupressure and acupuncture together in its analyses, and the second review included studies in women with hyperemesis (which we cover as a separate question). However, both reviews reported similar results of the effects of acupuncture in women with nausea and vomiting in early pregnancy.

Severity of nausea and vomiting

Acupuncture compared with sham acupuncture or no treatment We don't know whether acupuncture is more effective at reducing nausea and retching in early pregnancy (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

RCT
4-armed trial 		593 women with nausea and vomiting in early pregnancy
In review 		Improvement in nausea 1 week
13/135 (10%) with weekly traditional acupuncture for 4 weeks
4/127 (3%) with no acupuncture for 4 weeks
RR 0.93 for traditional acupuncture v no acupuncture
95% CI 0.88 to 0.99
See further information on studies for details on possible placebo effect 		Small effect size traditional acupuncture

RCT
4-armed trial 		593 women with nausea and vomiting in early pregnancy
In review 		Improvement in nausea 2 weeks
with weekly PC6 acupuncture for 4 weeks
with no acupuncture for 4 weeks
Absolute results not reported
P <0.05 for PC6 acupuncture v no acupuncture
See further information on studies for details on possible placebo effect 		Effect size not calculated PC6 acupuncture

RCT		 55 women, 6 to 10 weeks' gestation
In review 		Proportion of women who reported nausea
with multisite acupuncture
with sham acupuncture
P = 0.9 		Not significant
Vomiting

RCT
4-armed trial 		593 women with nausea and vomiting in early pregnancy
In review 		Dry retching
with weekly PC6 acupuncture for 4 weeks
with no acupuncture for 4 weeks
P <0.001 for PC6 acupuncture v no acupuncture
See further information on studies for details on possible placebo effect 		Effect size not calculated PC6 acupuncture
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT
4-armed trial 		593 women with nausea and vomiting in early pregnancy
Further report of reference 		Perinatal outcome, congenital abnormalities, pregnancy complications, or other infant outcomes
with weekly traditional acupuncture for 4 weeks
with weekly PC6 acupuncture for 4 weeks
with weekly 8 sham acupuncture for 4 weeks
with no acupuncture for 4 weeks
Open in a new tab

No data from the following reference on this outcome.

Further information on studies

The RCT noted a significant improvement in nausea in all groups receiving an intervention (traditional acupuncture, PC6 acupuncture, or sham acupuncture), which makes it difficult to establish whether the results for this RCT were influenced by a placebo effect. The RCT reported that 8 sham acupuncture significantly improved nausea and dry retching compared with no acupuncture after three weeks (P <0.01). Results between the two groups were significant after 3 weeks of treatment.

Comment

The second systematic review compared three different types of acustimulation (acupressure, acupuncture, and electrical stimulation). The acupuncture intervention did not reduce nausea. It may not be acceptable for studies to compare interventions as varied as these. The number of acupuncture trials is limited for pregnant women, perhaps because it is impossible to self-administer acupuncture, and acupuncture may also be inconvenient for women experiencing chronic symptoms of nausea and vomiting. The review reported inconsistencies in frequencies of acupuncture, which varied from three times daily for 2 days to once weekly for 4 weeks.

Substantive changes

Acupuncture for treating nausea and vomiting in early pregnancy: One systematic review added. The review identified the same RCTs already reported and came to similar conclusions. Categorisation unchanged (Unknown effectiveness).

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Dietary interventions (other than ginger) for treating nausea and vomiting in early pregnancy

Summary

We found no clinically important results from RCTs about the effects of dietary interventions (other than ginger) in treating women with nausea and vomiting in early pregnancy.

Benefits and harms

Dietary interventions (other than ginger):

We found no systematic review or RCTs.

Further information on studies

None.

Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Domperidone for treating nausea and vomiting in early pregnancy

Summary

We found no clinically important results from RCTs about the effects of domperidone in treating women with nausea and vomiting in early pregnancy.

Benefits and harms

Domperidone:

We found no systematic review or RCTs.

Further information on studies

None.

Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Metoclopramide for treating nausea and vomiting in early pregnancy

Summary

We found no clinically important results from RCTs about the effects of metoclopramide in treating women with nausea and vomiting in early pregnancy.

Benefits and harms

Metoclopramide:

We found no systematic review or RCTs.

Further information on studies

None.

Comment

Studies of the teratogenic potential of metoclopramide are limited. One review of the safety of drugs for the treatment of nausea and vomiting reported no malformations among four first-trimester exposures to metoclopramide. The risk of tardive dyskinesia associated with long-term or high-dose use of metoclopramide has been highlighted by the FDA (http://www.fda.gov).

Clinical guide:

Metoclopramide is commonly used in clinical practice in some countries, but clinical trials are needed to evaluate its effect on nausea and vomiting in pregnancy fully.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Phenothiazines for treating nausea and vomiting in early pregnancy

Summary

We don't know whether phenothiazines reduce nausea or vomiting.

Benefits and harms

Phenothiazines versus placebo:

We found one systematic review (search date 2002; 2 RCTs, 300 women). We also found one review (search date 1998) focusing on adverse effects.

Severity of nausea and vomiting

Phenothiazines compared with placebo Phenothiazines may be no more effective at reducing nausea (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

Systematic review		 300 women
2 RCTs in this analysis		 Nausea
34/153 (22%) with phenothiazines
97/147 (66%) with placebo
RR 0.28
95% CI 0.06 to 1.29 (random effects model)
Random effects model used because of significant heterogeneity between RCTs
The RCTs identified by the review were old and lacked sufficient information to appraise the quality of randomisation or allocation concealment 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 78,440 women Teratogenicity
with phenothiazines
with placebo
RR 1.00
95% CI 0.84 to 1.18 		Not significant

Systematic review		 161 women
Data from 1 RCT		 Teratogenicity
with phenothiazines
with placebo
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Phenothiazines versus antihistamines:

We found one RCT.

Severity of nausea and vomiting

Phenothiazinesompared with antihistamines We don't know how prochlorperazine (a phenothiazine) and promethazine (an antihistamine) compare at reducing nausea and vomiting (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Vomiting

RCT
3-armed trial 		174 outpatient women in the first trimester of a singleton pregnancy Mean number of emesis episodes day 3
1.1 with prochlorperazine (25 mg rectal suppositories every 12 hours as needed)
0.8 with promethazine (25 mg orally every 6 hours as needed)
Significance not assessed
Symptoms (global)

RCT
3-armed trial 		174 outpatient women in the first trimester of a singleton pregnancy Proportion of women reporting no improvement or worsening of symptoms (5-point scale ranging from “much worse” to “much better”) day 3
About 60% with prochlorperazine (25 mg rectal suppositories every 12 hours as needed)
About 60% with promethazine (25 mg orally every 6 hours as needed)
Absolute results reported graphically
Significance not assessed
Open in a new tab

Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT
3-armed trial 		174 outpatient women in the first trimester of a singleton pregnancy Neonatal anomaly
1/50 (2%) with prochlorperazine (25 mg rectal suppositories every 12 hours as needed)
0/52 (0%) with promethazine (25 mg orally every 6 hours as needed)
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Further information on studies

None.

Comment

The trials identified by the review were old and lacked sufficient information to appraise the quality of randomisation or allocation concealment. A more conservative (random effects) analysis was used in the review because of significant heterogeneity between studies. Fixed-effect analysis found a reduction in nausea with phenothiazines, but this analysis had significant heterogeneity and should be interpreted with caution.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Acupressure for treating hyperemesis gravidarum

Summary

Acupressure may be more effective at reducing vomiting episodes in women with hyperemesis gravidarum compared with placebo or control (intravenous fluid therapy).

Benefits and harms

Acupressure versus placebo or control:

We found one systematic review (search date from 1989 to 2005) examining the effects of acupressure, acupuncture, and electrical stimulation in women with nausea and vomiting during pregnancy. The review identified one RCT for acupressure in women with hyperemesis, but pooled data for a mixed population of women with nausea and vomiting and women with hyperemesis; hence it is not discussed further. We found one RCT.

Severity of nausea and vomiting

Acupressure compared with placebo or control P6 acupressure may be more effective at reducing nausea and vomiting in women with hyperemesis gravidarum (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea and vomiting

RCT
3-armed trial 		66 women diagnosed with hyperemesis gravidarum; gestational age range 5 to 30 weeks Mean nausea and vomiting scores (assessed using modified form of full Rhodes index score) third day after admission
17.57 with acupressure at the Neiguan point (P6) applied using the thumb for 10 minutes three times daily for 5 to 7 days
22.05 with placebo (acupressure applied around the radial pulse at the wrist) for 5 to 7 days
21.59 with control (conventional intravenous fluid therapy) for 5 to 7 days
P = 0.014 for among-group difference
See further information on studies for data on placebo versus control

RCT
3-armed trial 		66 women diagnosed with hyperemesis gravidarum; gestational age range 5 to 30 weeks Mean nausea and vomiting scores fouth day after admission
12.48 with acupressure at the Neiguan point (P6) applied using the thumb for 10 minutes three times daily for 5 to 7 days
19.38 with placebo (acupressure applied around the radial pulse at the wrist) for 5 to 7 days
17.91 with control (conventional intravenous fluid therapy) for 5 to 7 days
P <0.001 for among-group difference
See further information on studies for data on placebo versus control

RCT
3-armed trial 		66 women diagnosed with hyperemesis gravidarum; gestational age range 5 to 30 weeks Mean nausea and vomiting scores day of discharge
9.22 with acupressure at the Neiguan point (P6) applied using the thumb for 10 minutes three times daily for 5 to 7 days
14.67 with placebo (acupressure applied around the radial pulse at the wrist) for 5 to 7 days
13.05 with control (conventional intravenous fluid therapy) for 5 to 7 days
P <0.001 for among-group difference
See further information on studies for data on placebo versus control
Open in a new tab

Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

Nausea and vomiting were assessed using a modified form of the full Rhodes Index score (6 physical symptoms of Rhodes score: frequency of nausea and vomiting, amount of vomitus, duration of nausea, and degree of discomfort caused by nausea and vomiting measured on a scale ranging from 6 [lowest = slight nausea] to 30 [highest = severe nausea and vomiting]). The RCT reported no significant difference in mean nausea and vomiting scores among the three groups on the day of admission (mean nausea and vomiting scores: 26.26 with acupressure v 26.24 with placebo v 25.86 with control; P = 0.901 for all groups). The RCT did not assess between-group comparisons for acupressure versus either placebo or control. However, the RCT found no significant difference in nausea and vomiting scores between the placebo and control groups (P = 0.802). The study also reported no significant difference in the levels of ketonuria among the three groups on discharge (P = 0.063, absolute numbers not reported); however, levels of ketonuria were controlled more quickly in the P6 acupressure group compared with placebo or control groups during hospital stay.

Comment

Conducting high-quality trials in this area is complicated, as interventions are difficult to mask and control with credible or appropriate placebos.

Substantive changes

Acupressure for treating hyperemesis gravidarum: One RCT added, which found that acupressure was more effective at reducing nausea and vomiting episodes compared with placebo and control (conventional intravenous fluid). Categorised as Likely to be beneficial.

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Acupuncture for treating hyperemesis gravidarum

Summary

We don't know whether acupuncture is effective in treating hyperemesis gravidarum.

Benefits and harms

Acupuncture versus sham acupuncture:

We found one crossover RCT comparing PC6 acupuncture versus sham acupuncture.

Severity of nausea and vomiting

Acupuncture compared with sham acupuncture Active PC6 acupuncture may be more effective at reducing nausea and vomiting in women with hyperemesis gravidarum (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

RCT
Crossover design 		50 women admitted to hospital with vomiting (all women were vomiting on the day of randomisation); gestational age range 6 to 16 weeks Time to resolution of nausea
with PC6 acupuncture (applied 5 mm beneath the skin on the lateral side of the forearm)
with sham acupuncture (applied 1–2 mm beneath the skin on the lateral side of the forearm)
P = 0.032 		Effect size not calculated PC6 acupuncture
Vomiting

RCT
Crossover design 		50 women admitted to hospital with vomiting (all women were vomiting on the day of randomisation); gestational age range 6 to 16 weeks Proportion of women who vomited day 4
7/17 (41%) with PC6 acupuncture (applied 5 mm beneath the skin on the lateral side of the forearm)
12/16 (75%) with sham acupuncture (applied 1–2 mm beneath the skin on the lateral side of the forearm)
P = 0.049 		Effect size not calculated PC6 acupuncture
Open in a new tab

Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT
Crossover design 		50 women admitted to hospital with vomiting (all women were vomiting on the day of randomisation); gestational age range 6 to 16 weeks Adverse effects
with PC6 acupuncture (applied 5 mm beneath the skin on the lateral side of the forearm)
with sham acupuncture (applied 1–2 mm beneath the skin on the lateral side of the forearm)
Open in a new tab

Further information on studies

The RCT found no significant differences between groups with regard to food intake and the need for intravenous fluids (reported as not significant; significance assessments not performed).

Comment

The placebo treatment (sham acupuncture) used in the RCT was superficial acupuncture on an area away from a “real” acupuncture point. Needles were inserted only 1–2 mm into the skin. The authors of the RCT state that this kind of stimulation minimises the specific effects of acupuncture. However, it may not be an entirely inert placebo, as some sensory stimulation does occur.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Corticosteroids for treating hyperemesis gravidarum

Summary

We don't know whether corticosteroids are effective in treating hyperemesis gravidarum.

Corticosteroids may be more effective than metoclopramide at reducing vomiting episodes and reducing readmission to the intensive care unit in women with hyperemesis gravidarum.

Benefits and harms

Corticosteroids versus placebo:

We found two systematic reviews (search dates 1998 and 2002), which identified one RCT. We found one subsequent RCT.

Severity of nausea and vomiting

Corticosteroids compared with placebo Corticosteroids seem to be no more effective at reducing persistent vomiting in women with hyperemesis gravidarum (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Vomiting

RCT		 25 women with severe hyperemesis, mean gestational age of 10.6 weeks for prednisolone and 8.3 weeks for placebo
In review 		Persistent vomiting
5/12 (42%) with oral prednisolone 20 mg twice daily for 1 week
7/12 (58%) with placebo for 1 week
RR 0.71
95% CI 0.31 to 1.63
The RCT may have been too small to detect a clinically important effect. 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Hospital admission/readmission rates

Corticosteroids compared with placebo Corticosteroids may be no more effective at reducing hospital readmission rates in women with persistent vomiting (low-quality evidence)

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Hospital admission/readmission rates

RCT		 25 women with severe hyperemesis, mean gestational age of 10.6 weeks for prednisolone and 8.3 weeks for placebo
In review 		Readmission to hospital
5/12 (42%) with oral prednisolone 20 mg twice daily for 1 week
8/12 (67%) with placebo for 1 week
RR 0.63
95% CI 0.29 to 1.36
The RCT may have been too small to detect a clinically important effect 		Not significant

RCT		 126 women, <20 weeks' gestation Number of women requiring readmission to hospital for hyperemesis gravidarum
19/56 (34%) with intravenous methylprednisolone 125 mg followed by an oral prednisolone taper (40 mg for 1 day, 20 mg for 3 days, 10 mg for 3 days, 5 mg for 7 days)
19/54 (35%) with placebo (for the same regimen)
P = 0.89 		Not significant
Open in a new tab

Maternal mortality

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 109,602 women Teratogenicity
with corticosteroids
with control
RR 1.24
95% CI 0.97 to 1.60 		Not significant

RCT		 126 women, <20 weeks' gestation Pregnancy complications
with intravenous methylprednisolone 125 mg followed by an oral prednisolone taper (40 mg for 1 day, 20 mg for 3 days, 10 mg for 3 days, 5 mg for 7 days)
with placebo for the same regimen
Reported as not significant
P value not reported 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Corticosteroids versus antihistamines:

We found two systematic reviews (search dates 1998 and 2002), which identified one RCT. We found one subsequent RCT.

Severity of nausea and vomiting

Corticosteroids compared with antihistamines We don't know how corticosteroids and antihistamines compare at reducing nausea and vomiting (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

RCT		 80 pregnant women, 6 to 12 weeks' gestation Proportion of women with severe nausea during the first 48 hours
20/40 (50%) with oral prednisolone 5 mg daily for 10 days
10/40 (25%) with oral promethazine 75 mg daily for 10 days
P = 0.02 		Effect size not calculated promethazine

RCT		 80 pregnant women, 6 to 12 weeks' gestation Proportion of women with severe nausea at 3 to 10 days
14/40 (35%) with oral prednisolone 5 mg daily for 10 days
15/40 (38%) with oral promethazine 75 mg daily for 10 days
P = 0.80 		Not significant

RCT		 80 pregnant women, 6 to 12 weeks' gestation Proportion of women with severe nausea at day 17
22/40 (56%) with oral prednisolone 5 mg daily for 10 days
27/40 (69%) with oral promethazine 75 mg daily for 10 days
P = 0.23 		Not significant
Vomiting

RCT		 40 women admitted to hospital at <16 weeks' gestation
In review 		Persistence of vomiting
with oral methylprednisolone
with promethazine
OR 1.56
95% CI 0.25 to 9.94 		Not significant
Open in a new tab

Hospital admission/readmission rates

Methylprednisolone compared with antihistamines Methylprednisolone seems to be more effective than promethazine at reducing rates of subsequent admission to hospital, but may be associated with adverse effects (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Hospital admission/readmission rates

RCT		 40 women admitted to hospital at <16 weeks' gestation
In review 		Readmission to hospital
0/17 (0%) with oral methylprednisolone
5/18 (28%) with promethazine
OR 0.11
95% CI 0.02 to 0.71 		Large effect size methylprednisolone
Open in a new tab

No data from the following reference on this outcome.

Maternal mortality

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 80 pregnant women, 6 to 12 weeks' gestation Drowsiness at both 48 hours and between days 3 to 10
0/40 (0%) with oral prednisolone 5 mg daily for 10 days
6/40 (15%) with oral promethazine 75 mg daily for 10 days
P = 0.026 (at both 48 hours and between days 3–10) 		Effect size not calculated prednisolone

RCT		 80 pregnant women, 6 to 12 weeks' gestation Incidence of abdominal pain at 48 hours
2/40 (5%) with oral prednisolone 5 mg daily for 10 days
6/40 (15%) with oral promethazine 75 mg daily for 10 days
Reported as not significant
P value not reported 		Not significant

RCT		 80 pregnant women, 6 to 12 weeks' gestation Incidence of abdominal pain between days 3 to 10
0/40 (0%) with oral prednisolone 5 mg daily for 10 days
4/40 (10%) with oral promethazine 75 mg daily for 10 days
Reported as not significant
P value not reported 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Corticosteroids versus metoclopramide:

We found one RCT.

Severity of nausea and vomiting

Corticosteroids compared with metoclopramide Hydrocortisone seems more effective at reducing vomiting episodes in women with hyperemesis gravidarum (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Vomiting

RCT		 40 women with intractable hyperemesis gravidarum admitted to intensive care at <16 weeks' gestation Reduction of mean number of vomiting episodes day 2
41% with intravenous hydrocortisone (300 mg/day) for 1 week
17% with intravenous metoclopramide (10 mg three times daily) for 1 week
P <0.0001 		Effect size not calculated hydrocortisone

RCT		 40 women with intractable hyperemesis gravidarum admitted to intensive care at <16 weeks' gestation Reduction of mean number of vomiting episodes day 3
72% with intravenous hydrocortisone (300 mg/day) for 1 week
51% with intravenous metoclopramide (10 mg three times daily) for 1 week
P <0.0001 		Effect size not calculated hydrocortisone

RCT		 40 women with intractable hyperemesis gravidarum admitted to intensive care at <16 weeks' gestation Reduction of mean number of vomiting episodes day 7
96% with intravenous hydrocortisone (300 mg/day) for 1 week
77% with intravenous metoclopramide (10 mg three times daily) for 1 week
P <0.0001 		Effect size not calculated hydrocortisone
Open in a new tab

Hospital admission/readmission rates

Corticosteroids compared with metoclopramide Corticosteroids seem more effective at reducing rates of readmission to the intensive care unit within 2 weeks of initial therapy in women with recurrent severe persistent vomiting (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Hospital admission/readmission rates

RCT		 40 women with intractable hyperemesis gravidarum admitted to intensive care at <16 weeks' gestation Proportion of women readmitted to the intensive care unit for recurrence of severe persistent vomiting within 2 weeks of initial treatment
0/20 (0%) with intravenous hydrocortisone (300 mg/day) for 1 week
6/20 (30%) with intravenous metoclopramide (10 mg three times daily) for 1 week
P <0.0001 		Effect size not calculated hydrocortisone
Open in a new tab

Maternal mortality

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

None.

Comment

Clinical guide:

The rates of spontaneous resolution of symptoms in control groups were high. The possible benefit of methylprednisolone in preventing subsequent admission to hospital must be balanced against possible adverse effects of steroids given in the first trimester of pregnancy. Clinical judgement would be more important in specific situations as there are no reports of adverse effects; however, these may be rare but serious.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Corticotrophins for treating hyperemesis gravidarum

Summary

We don't know whether intramuscular corticotrophin is effective in treating hyperemesis gravidarum.

Benefits and harms

Corticotrophins versus placebo:

We found two systematic reviews (search dates 1998 and 2002) of corticotrophins in hyperemesis gravidarum, which identified the same sole RCT.

Severity of nausea and vomiting

Corticotrophins compared with placebo Intramuscular corticotrophin may be no more effective at improving nausea scores in women with hyperemesis gravidarum, but we don't know whether it is more effective at reducing vomiting (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nausea

RCT		 32 women, gestational ages and severity of hyperemesis not reported
In review 		Nausea relief scores (measured on a scale ranging from 15 = lack of nausea to 20 = worst possible hyperemesis)
with intramuscular corticotrophin (adrenocorticotrophic hormone) 0.5 mg
with placebo
Absolute results not reported
WMD relief score +0.6
95% CI –1.65 to +2.85 		Not significant
Vomiting

RCT		 32 women, gestational ages and severity of hyperemesis not reported
In review 		Time from starting treatment to stopping vomiting
with intramuscular corticotrophin (adrenocorticotrophic hormone) 0.5 mg
with placebo
Absolute results not reported
Significance not assessed
Open in a new tab

Hospital admission/readmission rates

Corticotrophins compared with placebo Intramuscular corticotrophin may be no more effective at reducing hospital readmission rates in women with hyperemesis gravidarum (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Hospital admission/readmission rates

RCT		 32 women, gestational ages and severity of hyperemesis not reported Number of readmissions to hospital
with intramuscular corticotrophin (adrenocorticotrophic hormone) 0.5 mg
with placebo
Significance not assessed
Open in a new tab

Maternal mortality

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 32 women
Data from 1 RCT		 Adverse effects
with corticotrophin
with placebo
Open in a new tab

No data from the following reference on this outcome.

Further information on studies

None.

Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Diazepam for treating hyperemesis gravidarum

Summary

We don't know whether diazepam is effective in treating hyperemesis gravidarum.

Benefits and harms

Diazepam versus placebo:

We found one systematic review (search date 2002, 1 RCT).

Severity of nausea and vomiting

Corticotrophins compared with placebo We don't know whether diazepam is more effective at reducing the severity of nausea and vomiting in women with hyperemesis gravidarum (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Vomiting

Systematic review		 50 women admitted to hospital
Data from 1 RCT		 Persistence of vomiting 2 days
with intravenous diazepam 20 mg daily followed by oral diazepam 5 mg twice daily
with intravenous fluid followed by placebo
OR 0.64
95% CI 0.10 to 4.19
Assessment not clearly reported
The trial was too small to draw reliable conclusions 		Not significant
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Hospital admission/readmission rates

Corticotrophins compared with placebo We don't know whether diazepam is more effective at reducing readmissions to hospital in women with hyperemesis gravidarum (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Hospital admission/readmission rates

Systematic review		 50 women admitted to hospital
Data from 1 RCT		 Readmission to hospital
4% with intravenous diazepam 20 mg daily followed by oral diazepam 5 mg twice daily
27% with intravenous fluid followed by placebo
Absolute numbers not reported
Significance not assessed
The trial was too small to draw reliable conclusions.
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Maternal mortality

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

None.

Comment

The rate of resolution in the control group was high, and the effects of the vitamins used in the RCT are unknown.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Dietary interventions (other than ginger) for treating hyperemesis gravidarum

Summary

We don't know whether dietary interventions are effective in treating hyperemesis gravidarum.

Benefits and harms

Carob seed powder plus calcium lactate versus placebo:

We found no systematic review. We found one crossover RCT comparing 1 g daily of a powder containing 96.5% carob seed flour plus 3.5% calcium lactate versus placebo for 3 weeks.

Severity of nausea and vomiting

Carob seed powder plus calcium lactate compared with placebo We don't know whether dietary supplementation with carob seed flour plus calcium lactate is more effective at relieving vomiting in women with hyperemesis gravidarum (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Vomiting

RCT
Crossover design 		43 women Relief of vomiting (subjective improvement)
20/34 (59%) with 1 g daily of a powder containing 96.5% carob seed flour plus 3.5% calcium lactate for 3 weeks
18/36 (50%) with placebo for 3 weeks
RR 1.18
95% CI 0.82 to 1.70
The RCT was conducted in 1966, so it is unclear whether the composition of carob seed flour now commercially available is the same as was used in this RCT 		Not significant
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT
Crossover design 		43 women Adverse effects
with 1 g daily of a powder containing 96.5% carob seed flour plus 3.5% calcium lactate for 3 weeks
with placebo for 3 weeks
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Further information on studies

None.

Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Ginger for treating hyperemesis gravidarum

Summary

We don't know whether ginger is effective in treating hyperemesis gravidarum.

Benefits and harms

Ginger versus placebo:

We found two systematic reviews (search dates 2002 and 2004). Both reviews identified the same crossover RCT.

Severity of nausea and vomiting

Ginger compared with placebo We don't know whether ginger is more effective at reducing hyperemesis scores at 4 days in women with hyperemesis gravidarum (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Hyperemesis gravidarum

RCT
Crossover design 		30 women admitted to hospital with hyperemesis gravidarum
In review 		Hyperemesis score (evaluates degree of nausea and vomiting, weight gain, and participant-reported symptom relief; higher score indicates fewer symptoms) after 4 days (before crossover)
4.1 with ginger 250 mg in oral capsules taken four times daily
0.9 with placebo
P = 0.035 in RCT
WMD +3.15 (as calculated by review)
95% CI –0.92 to +7.22
The RCT was too small to allow reliable conclusions
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT
Crossover design 		30 women admitted to hospital with hyperemesis gravidarum, 27 women included in the analysis
In review 		Adverse effects
with ginger 250 mg in oral capsules taken four times daily
with placebo
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Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Metoclopramide for treating hyperemesis gravidarum

Summary

We don't know whether metoclopramide is effective in treating hyperemesis gravidarum, as we found no clinically important results from RCTs.

Benefits and harms

Metoclopramide versus placebo:

We found no systematic review or RCTs.

Metoclopramide versus corticosteroids:

See option on corticosteroids.

Further information on studies

None.

Comment

Studies of the teratogenic potential of metoclopramide are limited. One review of the safety of drugs for the treatment of nausea and vomiting reported no malformations among four first-trimester exposures to metoclopramide. The risk of tardive dyskinesia associated with long-term or high-dose use of metoclopramide has been highlighted by the FDA (http://www.fda.gov).

Clinical guide:

Metoclopramide is commonly used in clinical practice in some countries, but clinical trials are needed to fully evaluate its effects on nausea and vomiting in pregnancy.

Substantive changes

Metoclopramide for treating hyperemesis gravidarum: One RCT found that metoclopramide was less effective at reducing vomiting episodes and readmission to the intensive care unit compared with corticosteroids. Other drugs and interventions may be more useful. Categorised as Unlikely to be beneficial.

BMJ Clin Evid. 2009 Jun 3;2009:1405.

Ondansetron for treating hyperemesis gravidarum

Summary

We don't know whether ondansetron is effective in treating hyperemesis gravidarum.

Benefits and harms

Ondansetron versus placebo:

We found no systematic review or RCTs.

Ondansetron versus antihistamines:

We found one systematic review (search date 2002, 1 RCT, 30 women admitted to hospital).

Severity of nausea and vomiting

Ondansetron compared with antihistamines Ondansetron and promethazine seem to be equally effective at 48 hours at reducing the proportion of women with hyperemesis gravidarum (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Vomiting

RCT		 30 women admitted to hospital
In review 		Proportion of women vomiting 48 hours
1/15 (7%) with ondansetron 10 mg in 50 mL intravenous solution over 30 minutes
3/15 (20%) with promethazine 50 mg in 50 mL intravenous solution over 30 minutes
RR 0.33
95% CI 0.04 to 2.85
The RCT was too small to draw reliable conclusions 		Not significant
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Maternal mortality

No data from the following reference on this outcome.

Hospital admission/readmission rates

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 30 women admitted to hospital
In review 		Sedation
0/15 (0%) with ondansetron 10 mg in 50 mL intravenous solution over 30 minutes
8/15 (53%) with promethazine 50 mg in 50 mL intravenous solution over 30 minutes
P = 0.002 		Effect size not calculated ondansetron
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No data from the following reference on this outcome.

Further information on studies

None.

Comment

None.

Substantive changes

No new evidence

Articles from BMJ Clinical Evidence are provided here courtesy of BMJ Publishing Group

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