NIHR Signal No clear “best” treatment of mild or severe sickness in pregnancy

Published on 3 January 2017

Pregnant women could benefit from simple, cheap, “self-help” remedies for mild nausea and vomiting. Ginger, vitamin B6 and possibly acupressure wrist-bands might relieve symptoms for some women, according to a recent overview of research in this area. The review has identified some promising areas for future research.

For sickness that doesn’t respond to “self-help” remedies, prescribed medication like antihistamines or anti-sickness tablets may help. Hospital treatment, including combinations of drugs and intravenous fluids, may be indicated if this doesn’t work.

The review assessed 73 studies that measured how well 33 types of treatment worked for pregnant women experiencing nausea and vomiting. Severity of symptoms could range from simple “morning sickness” to the more severe condition of hyperemesis gravidarum.

The review gives some evidence on treating pregnant women, but it is limited, especially for more severe symptoms. The authors highlight the need for more robust research to compare treatments with costs and clarify the safety of some drugs.

No clear “best” treatment of mild or severe sickness in pregnancy

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Why was this study needed?

Up to 85% of women experience nausea and vomiting during pregnancy. Usually, symptoms resolve by about 20 weeks of pregnancy and most women can self-manage. However, some women have prolonged, severe vomiting. They may require hospitalisation to treat dehydration, weight loss and electrolyte imbalances that put mother and unborn baby at risk. These severe symptoms, called hyperemesis gravidarum, affect less than one in 100 women.

There are many treatments for sickness in pregnancy. Some women can control symptoms by changing what they eat, others take vitamins and some try alternative therapies such as hypnosis. Doctors can prescribe a number of drugs, though many women would prefer to avoid medication if possible.

This review aimed to assess how well various treatments work for mild to severe nausea and vomiting of pregnancy. They wanted to see how they compare to each other, look at costs, and identify where more research was needed.

What did this study do?

This systematic review identified 64 randomised controlled trials and nine non-randomised comparative studies. Overall, 33 drug and non-drug treatments were included. Most comparisons were to placebo rather than other active treatment.

The main outcome was the severity of symptoms, which was measured using various scales. For example, the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) with a maximum score of 15. Other outcomes included quality of life, maternal and newborn-baby outcomes, and cost-effectiveness.

The studies were very different from each other, varying in treatments given, symptom severity and how this was recorded. Half of the randomised controlled trials and all comparative studies were judged to be lower quality and at risk of bias. The authors could not combine the results in a formal meta- analysis, and the results should be viewed with some caution.

What did it find?

  • Ginger improved nausea and vomiting compared with placebo. This data was limited to treatment of mild symptoms only.
  • Two of eighteen trials found acupressure wristbands improved mild symptoms compared with placebo, but the rest did not find any effect or were poorly reported. on of acupuncture was mixed and unclear.
  • Vitamin B6 helped women with mild to moderate symptoms and it worked best at higher doses. There was some evidence that vitamin B6 combined with an antihistamine works better than but no better than an anti-sickness tablet (ondansetron). In women with more severe symptoms, pre-emptive treatment before symptoms started was best.
  • There was some evidence that antihistamines were more effective than placebo or no treatment in women with mild symptoms.
  • The anti-sickness drugs ondansetron and metoclopramide both drugs tended to improve symptoms.
  • Two studies found that managing some women with moderate to severe symptoms in the outpatient setting worked as well as admitting them to hospital.
  • There was no evidence that any treatments were harmful to women or their babies.

What does current guidance say on this issue?

The Royal College of Gynaecologists and Obstetricians 2016 guidelines advise that women with mild nausea and vomiting are treated in the community.

Anti-sickness medications, such as antihistamines, are advised as the first-choice medication, used in combination if a woman does not respond to one drug. Ondansetron and metoclopramide are thought safe and effective but only advised as second-line medications.

The guidelines say that ginger and acupressure may be used for mild to moderate symptoms. They do not recommend vitamin B6 or hypnotherapy.

For women with more severe symptoms, including those where community treatment has failed, they advise outpatient care if possible, and list specific indications for hospital admission.

What are the implications?

These findings tend to support guideline recommendations to try cheap and simple remedies, such as a ginger or acupressure, as an initial step for mild nausea and vomiting in pregnancy.

However, the evidence is very limited and generally of poor quality. It isn’t clear which drugs work best for severe symptoms that won’t respond to simple measures, as few studies have compared treatments against each other.

There is a need for stronger research into treatments for severe nausea and vomiting in pregnancy to guide NHS treatment. High quality evidence comparing the cost, effectiveness and safety of different drugs would help providers provide better advice on the treatments that do or don’t work.

Citation and Funding

O'Donnell A, McParlin C, Robson SC, et al. Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment. Health Technol Assess. 2016;20(74):1-268.

This project was funded by the Health Technology Assessment programme of the National Institute for Health Research.

Bibliography

NHS Choices. Drugs, ginger and acupuncture best for morning sickness. London: Department of Health; 2016.

NHS Choices. Vomiting and sickness in pregnancy. London: Department of Health; 2015.

RCOG. The management of nausea and vomiting of pregnancy and hyperemesis gravidarum (Green-top guideline no. 69). London. Royal College of Obstetricians and Gynaecologists; 2016.

Why was this study needed?

Up to 85% of women experience nausea and vomiting during pregnancy. Usually, symptoms resolve by about 20 weeks of pregnancy and most women can self-manage. However, some women have prolonged, severe vomiting. They may require hospitalisation to treat dehydration, weight loss and electrolyte imbalances that put mother and unborn baby at risk. These severe symptoms, called hyperemesis gravidarum, affect less than one in 100 women.

There are many treatments for sickness in pregnancy. Some women can control symptoms by changing what they eat, others take vitamins and some try alternative therapies such as hypnosis. Doctors can prescribe a number of drugs, though many women would prefer to avoid medication if possible.

This review aimed to assess how well various treatments work for mild to severe nausea and vomiting of pregnancy. They wanted to see how they compare to each other, look at costs, and identify where more research was needed.

What did this study do?

This systematic review identified 64 randomised controlled trials and nine non-randomised comparative studies. Overall, 33 drug and non-drug treatments were included. Most comparisons were to placebo rather than other active treatment.

The main outcome was the severity of symptoms, which was measured using various scales. For example, the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) with a maximum score of 15. Other outcomes included quality of life, maternal and newborn-baby outcomes, and cost-effectiveness.

The studies were very different from each other, varying in treatments given, symptom severity and how this was recorded. Half of the randomised controlled trials and all comparative studies were judged to be lower quality and at risk of bias. The authors could not combine the results in a formal meta- analysis, and the results should be viewed with some caution.

What did it find?

  • Ginger improved nausea and vomiting compared with placebo. This data was limited to treatment of mild symptoms only.
  • Two of eighteen trials found acupressure wristbands improved mild symptoms compared with placebo, but the rest did not find any effect or were poorly reported. on of acupuncture was mixed and unclear.
  • Vitamin B6 helped women with mild to moderate symptoms and it worked best at higher doses. There was some evidence that vitamin B6 combined with an antihistamine works better than but no better than an anti-sickness tablet (ondansetron). In women with more severe symptoms, pre-emptive treatment before symptoms started was best.
  • There was some evidence that antihistamines were more effective than placebo or no treatment in women with mild symptoms.
  • The anti-sickness drugs ondansetron and metoclopramide both drugs tended to improve symptoms.
  • Two studies found that managing some women with moderate to severe symptoms in the outpatient setting worked as well as admitting them to hospital.
  • There was no evidence that any treatments were harmful to women or their babies.

What does current guidance say on this issue?

The Royal College of Gynaecologists and Obstetricians 2016 guidelines advise that women with mild nausea and vomiting are treated in the community.

Anti-sickness medications, such as antihistamines, are advised as the first-choice medication, used in combination if a woman does not respond to one drug. Ondansetron and metoclopramide are thought safe and effective but only advised as second-line medications.

The guidelines say that ginger and acupressure may be used for mild to moderate symptoms. They do not recommend vitamin B6 or hypnotherapy.

For women with more severe symptoms, including those where community treatment has failed, they advise outpatient care if possible, and list specific indications for hospital admission.

What are the implications?

These findings tend to support guideline recommendations to try cheap and simple remedies, such as a ginger or acupressure, as an initial step for mild nausea and vomiting in pregnancy.

However, the evidence is very limited and generally of poor quality. It isn’t clear which drugs work best for severe symptoms that won’t respond to simple measures, as few studies have compared treatments against each other.

There is a need for stronger research into treatments for severe nausea and vomiting in pregnancy to guide NHS treatment. High quality evidence comparing the cost, effectiveness and safety of different drugs would help providers provide better advice on the treatments that do or don’t work.

Citation and Funding

O'Donnell A, McParlin C, Robson SC, et al. Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment. Health Technol Assess. 2016;20(74):1-268.

This project was funded by the Health Technology Assessment programme of the National Institute for Health Research.

Bibliography

NHS Choices. Drugs, ginger and acupuncture best for morning sickness. London: Department of Health; 2016.

NHS Choices. Vomiting and sickness in pregnancy. London: Department of Health; 2015.

RCOG. The management of nausea and vomiting of pregnancy and hyperemesis gravidarum (Green-top guideline no. 69). London. Royal College of Obstetricians and Gynaecologists; 2016.

Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment

Published on 1 October 2016

O'Donnell A, McParlin C, Robson SC, Beyer F, Moloney E, Bryant A, Bradley J, Muirhead C, Nelson-Piercy C, Newbury-Birch D, Norman J, Simpson E, Swallow B, Yates L, Vale L.

Health Technology Assessment Volume 20 Issue 74 , 2016

Background Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are more severe and the most severe form of NVP – hyperemesis gravidarum (HG) – affects 0.3–1.0% of pregnant women. There is no widely accepted point at which NVP becomes HG. Objectives This study aimed to determine the relative clinical effectiveness and cost-effectiveness of treatments for NVP and HG. Data sources MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, PsycINFO, Commonwealth Agricultural Bureaux (CAB) Abstracts, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, British Nursing Index, Science Citation Index, Social Sciences Citation Index, Scopus, Conference Proceedings Index, NHS Economic Evaluation Database, Health Economic Evaluations Database, China National Knowledge Infrastructure, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from inception to September 2014. References from studies and literature reviews identified were also examined. Obstetric Medicine was hand-searched, as were websites of relevant organisations. Costs came from NHS sources. Review methods A systematic review of randomised and non-randomised controlled trials (RCTs) for effectiveness, and population-based case series for adverse events and fetal outcomes. Treatments: vitamins B6 and B12, ginger, acupressure/acupuncture, hypnotherapy, antiemetics, dopamine antagonists, 5-hydroxytryptamine receptor antagonists, intravenous (i.v.) fluids, corticosteroids, enteral and parenteral feeding or other novel treatment. Two reviewers extracted data and quality assessed studies. Results were narratively synthesised; planned meta-analysis was not possible due to heterogeneity and incomplete reporting. A simple economic evaluation considered the implied values of treatments. Results Seventy-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder (n = 20) it was unclear. The non-randomised studies (n = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo (n = 12); steroid versus usual treatment (n = 7); ginger versus placebo (n = 6); ginger versus vitamin B6 (n = 6); and vitamin B6 versus placebo (n = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin® [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices. Limitations The main limitations were the quantity and quality of the data available. Conclusion There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and larger trials of the main therapies considered within the UK NHS are needed. Study registration This study is registered as PROSPERO CRD42013006642. Funding The National Institute for Health Research Health Technology Assessment programme.

There are a number of scales used to measure nausea and vomiting severity in pregnancy. The PUQE (Pregnancy-Unique Quantification of Emesis and Nausea) score has three questions and a maximum score of 15. The RINVR (Rhodes Index of Nausea, Vomiting and Retching) contains eight questions and a maximum score of 40. The McGill Nausea Questionnaire measures nausea by a rating index, using nine sets of words to relate the person’s feelings around nausea. The NVPI (Nausea and Vomiting of Pregnancy Instrument) has three questions and a maximum score of 15. A VAS (Visual Analogue Scale) can be used where patients rate their symptoms on a scale of zero to 10.

Expert commentary

Anti-sickness medications and IV fluids are commonly used for hyperemesis gravidarum but little information exists about their effectiveness. Studies are difficult to compare because different definitions of the condition exist, and many different symptoms and outcomes are measured.

Several medications showed benefit for less severe pregnancy sickness, but information is lacking for severe illness where the need is greatest.

This review has revealed the knowledge gaps which must be addressed if women are to have the good quality information they need to guide their treatment choices in pregnancy. It should stimulate researchers, working with patients, to direct future research to where there is most need.

Dr Margaret O’Hara, Patient Representative (Pregnancy Sickness Support)

Categories

  •   Fertility and childbirth, Gastrointestinal disorders, Acute and general medicine