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Vomiting in Pregnancy – What Works

December 12, 2016

Short Attention Span Summary

Hyperemesis – evidence-based best treatment
Recent questions have arisen about the safety of ondansetron in pregnancy.  Here is an audio summary of ondansetron safety in pregnancy on UrgentCare:RAP, in case you missed it.  This article is not about safety, rather, what works.  All the agents covered worked better than placebo, including ginger, pyridoxine (+/- doxylamine), metoclopramide, promethazine, and ondansetron.  Ondansetron had better efficacy across the spectrum of low to high severity of illness.  Also corticosteroids were beneficial in severe cases.

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All of these agents work.  Ondansetron worked better than others as severity increased.  Corticosteroids are an option for severe cases.


JAMA. 2016 Oct 4;316(13):1392-1401. doi: 10.1001/jama.2016.14337.

Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review.

McParlin C1, O’Donnell A2, Robson SC3, Beyer F2, Moloney E4, Bryant A2, Bradley J2, Muirhead CR2, Nelson-Piercy C5, Newbury-Birch D6, Norman J7, Shaw C2, Simpson E2, Swallow B8, Yates L9, Vale L4.

Author information:

1Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, Tyne and Wear, United Kingdom.

2Institute of Health and Society, Newcastle University, Newcastle, Tyne and Wear, United Kingdom.

3Institute of Cellular Medicine, Newcastle University, Newcastle, Tyne and Wear, United Kingdom.

4Health Economics Group, Institute of Health and Society, Newcastle, Tyne and Wear, United Kingdom.

5Women’s Health Academic Centre, King’s Health Partners, London, United Kingdom.

6Institute of Health and Society, Newcastle University, Newcastle, Tyne and Wear, United Kingdom6Health and Social Care Institute, Teesside University, Middlesbrough, Cleveland, United Kingdom.

7North Tyneside Clinical Commissioning Group, North Shields, Tyne and Wear, United Kingdom.

8Former Trustee of Pregnancy Sickness Support, Hull, East Yorkshire, United Kingdom.

9UK Teratology Information Service (UKTIS) and Institute of Genetic Medicine, Newcastle, Tyne and Wear, United Kingdom.



Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse physical and psychological sequelae.


To summarize current evidence on effective treatments for nausea and vomiting in pregnancy and hyperemesis gravidarum.

Evidence Review:

Databases were searched to June 8, 2016. Relevant websites and bibliographies were also searched. Titles and abstracts were assessed independently by 2 reviewers. Results were narratively synthesized; planned meta-analysis was not possible because of heterogeneity and incomplete reporting of findings.


Seventy-eight studies (n  = 8930 participants) were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies. Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6, antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and ondansetron (for moderate symptoms) were associated with improved symptoms compared with placebo. One RCT (n = 86) reported greater improvements in moderate symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms} to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]). For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine combination taken preemptively reduced risk of recurrence of moderate-severe symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]). One RCT (n = 83) found that ondansetron was associated with lower nausea scores on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9] for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there was no difference in trend in nausea scores over the 14-day study period, trend in vomiting scores was better in the ondansetron group (P = .042). One RCT (n = 159) found no difference between metoclopramide and promethazine after 24 hours (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1-4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or promethazine or metoclopramide in women with severe symptoms. Improvements were seen in all corticosteroid groups, but only a significant difference between corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5% at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]). For other interventions, evidence was limited.

Conclusions and Relevance:

For mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. Overall the quality of evidence was low.

PMID: 27701665 [PubMed – in process]

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