title: Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: McParlin
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Amy
authors.initials: A
authors.lastname: O'Donnell
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Robson
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Beyer
authors.affiliation: Health Economics Group, Institute of Health and Society, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Eoin
authors.initials: E
authors.lastname: Moloney
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bryant
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bradley
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Muirhead
authors.affiliation: Women's Health Academic Centre, King's Health Partners, London, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Nelson-Piercy
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle, Tyne and Wear, United Kingdom6Health and Social Care Institute, Teesside University, Middlesbrough, Cleveland, United Kingdom.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Newbury-Birch
authors.affiliation: North Tyneside Clinical Commissioning Group, North Shields, Tyne and Wear, United Kingdom.
authors.forename: Justine
authors.initials: J
authors.lastname: Norman
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Shaw
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Simpson
authors.affiliation: Former Trustee of Pregnancy Sickness Support, Hull, East Yorkshire, United Kingdom.
authors.forename: Brian
authors.initials: B
authors.lastname: Swallow
authors.affiliation: UK Teratology Information Service (UKTIS) and Institute of Genetic Medicine, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Yates
authors.affiliation: Health Economics Group, Institute of Health and Society, Newcastle, Tyne and Wear, United Kingdom.
authors.forename: Luke
authors.initials: L
authors.lastname: Vale
mesh_terms: D026881:Acupuncture; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000932:Antiemetics / Q000627:therapeutic use*; D004319:Doxylamine / Q000627:therapeutic use; D005260:Female; D020939:Zingiber officinale; D006633:Histamine Antagonists / Q000627:therapeutic use; D006801:Humans; D006939:Hyperemesis Gravidarum / Q000628:therapy*; D009325:Nausea / Q000628:therapy*; D017294:Ondansetron / Q000627:therapeutic use; D008517:Phytotherapy / Q000379:methods; D011247:Pregnancy; D011248:Pregnancy Complications / Q000628:therapy*; D011613:Psychotherapy; D011736:Pyridoxine / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D014803:Vitamin B Complex / Q000627:therapeutic use; D014839:Vomiting / Q000628:therapy
chemical_list: D000305:Adrenal Cortex Hormones; D000932:Antiemetics; D006633:Histamine Antagonists; D014803:Vitamin B Complex; D017294:Ondansetron; D004319:Doxylamine; D011736:Pyridoxine