What is the issue and why is it important?
Although severe nausea and vomiting in pregnancy (hyperemesis gravidarum) rarely causes death, it is an important cause of ill health with emotional, physical, and economic consequences. Women may need hospital treatment and may not be able to work and it occasionally causes pregnancy complications and adverse outcomes for babies such as low birthweight. Many pharmaceutical, complementary, and alternative therapies are available and the objective of this review was to examine the effectiveness and safety of interventions for hyperemesis gravidarum.
What evidence did we find?
Twenty-five trials (involving 2052 women) were included examining 18 different comparisons covering a range of interventions including acupressure/acupuncture, outpatient care, intravenous fluids, and various commonly used anti-sickness drugs. The quality of included studies was mixed and for most outcomes findings were from single studies with low numbers of women taking part and the evidence was assessed as being of low or very low quality. We have described findings for selected important comparisons below, the remaining comparisons are described in detail in the main text.
There was no clear evidence of differences between acupuncture and placebo for symptoms of anxiety or depression, spontaneous abortion, preterm birth or perinatal death.
There was insufficient evidence to identify clear differences between acupuncture and metoclopramide (an anti-nausea medication) for reduction or cessation in nausea or vomiting.
Women taking vitamin B6 had a slightly longer hospital stay compared with placebo but there was no clear evidence of differences in other outcomes including the average number of episodes of vomiting, hospital readmission rate, or side effects.
A comparison between two anti-nausea medications, metoclopramide and ondansetron, identified no clear difference in the severity of nausea or vomiting, but more women taking metoclopramide complained of drowsiness and dry mouth. In a study comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness and dizziness but there were no clear differences between groups for other important outcomes including quality of life and other side effects. In a study looking at ondansetron versus promethazine women spent similar lengths of time in hospital but there was increased sedation with promethazine.
Regarding corticosteroids, there was no difference in days of hospital admission compared to placebo, but there was a decreased readmission rate. For other important outcomes including pregnancy complications, spontaneous abortion, stillbirth and congenital abnormalities, preterm birth and side effects, there was insufficient evidence to identify differences between groups.
In a study comparing hydrocortisone (a corticosteroid) with metoclopramide, no data were available for primary outcomes, but there was no difference in hospital readmission rate.
In a study comparing promethazine and prednisolone (a corticosteroid) those receiving prednisolone had increased nausea at 48 hours but not at 17 days. There was no clear difference in the number of episodes of vomiting. There was insufficient evidence to identify differences between groups for stillbirth and neonatal death and preterm birth
What does this mean?
Given that there was little evidence to support the superiority of one intervention over another in the treatment of hyperemesis, larger controlled trials are needed on these therapies. More research should be done comparing the side effects and safety, as well as the economic costs and benefits of these interventions to aid in the selection of the optimal treatment.
Reporting on adverse maternal and infant outcomes was limited and we did not find any studies on dietary or other lifestyle interventions.
On the basis of this review, there is little high-quality and consistent evidence supporting any one intervention, which should be taken into account when making management decisions. There was also very limited reporting on the economic impact of hyperemesis gravidarum and the impact that interventions may have.
The limitations in interpreting the results of the included studies highlights the importance of consistency in the definition of hyperemesis gravidarum, the use of validated outcome measures, and the need for larger placebo-controlled trials.
Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for hospitalization during pregnancy. While a previous Cochrane review examined interventions for nausea and vomiting in pregnancy, there has not yet been a review examining the interventions for the more severe condition of hyperemesis gravidarum.
To assess the effectiveness and safety, of all interventions for hyperemesis gravidarum in pregnancy up to 20 weeks' gestation.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (20 December 2015) and reference lists of retrieved studies.
Randomized controlled trials of any intervention for hyperemesis gravidarum. Quasi-randomized trials and trials using a cross-over design were not eligible for inclusion.
We excluded trials on nausea and vomiting of pregnancy that were not specifically studying the more severe condition of hyperemesis gravidarum.
Two review authors independently reviewed the eligibility of trials, extracted data and evaluated the risk of bias. Data were checked for accuracy.
Twenty-five trials (involving 2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. The comparisons covered a range of interventions including acupressure/acupuncture, outpatient care, intravenous fluids, and various pharmaceutical interventions. The methodological quality of included studies was mixed. For selected important comparisons and outcomes, we graded the quality of the evidence and created 'Summary of findings' tables. For most outcomes the evidence was graded as low or very low quality mainly due to the imprecision of effect estimates. Comparisons included in the 'Summary of findings' tables are described below, the remaining comparisons are described in detail in the main text.
No primary outcome data were available when acupuncture was compared with placebo, There was no clear evidence of differences between groups for anxiodepressive symptoms (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.40; one study, 36 women, very low-quality evidence), spontaneous abortion (RR 0.48, 95% CI 0.05 to 5.03; one study, 57 women, low-quality evidence), preterm birth (RR 0.12, 95% CI 0.01 to 2.26; one study, 36 women, low-quality evidence), or perinatal death (RR 0.57, 95% CI 0.04 to 8.30; one study, 36 women, low-quality evidence).
There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (RR 1.40, 95% CI 0.79 to 2.49 and RR 1.51, 95% CI 0.92 to 2.48, respectively; very low-quality evidence).
In a study with 92 participants, women taking vitamin B6 had a slightly longer hospital stay compared with placebo (mean difference (MD) 0.80 days, 95% CI 0.08 to 1.52, moderate-quality evidence). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40 to 1.40, low-quality evidence) or side effects.
A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15 to 3.55, and MD -0.10, 95% CI -1.63 to 1.43; one study, 83 women, respectively, very low-quality evidence). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23 to 4.69, and RR 2.38, 95% CI 1.10 to 5.11, respectively; moderate-quality evidence). There were no clear differences between groups for other side effects.
In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (RR 0.70, 95% CI 0.56 to 0.87, RR 0.48, 95% CI 0.34 to 0.69, and RR 0.31, 95% CI 0.11 to 0.90, respectively, moderate-quality evidence). There were no clear differences between groups for other important outcomes including quality of life and other side effects.
In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (MD 0.00, 95% CI -1.39 to 1.39, very low-quality evidence), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00 to 0.94, low-quality evidence) .
Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70 to 0.10; very low-quality evidence), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50 to 0.94; four studies, 269 women). For other important outcomes including pregnancy complications, spontaneous abortion, stillbirth and congenital abnormalities, there was insufficient evidence to identify differences between groups (very low-quality evidence for all outcomes). In other single studies there were no clear differences between groups for preterm birth or side effects (very low-quality evidence).
For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00 to 1.28;one study, 40 women).
In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 hours (RR 2.00, 95% CI 1.08 to 3.72; low-quality evidence), but not at 17 days (RR 0.81, 95% CI 0.58 to 1.15, very low-quality evidence). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. There was insufficient evidence to identify differences between groups for stillbirth and neonatal death and preterm birth.