WHO recommendation on interventions for the relief of nausea during pregnancy

WHO recommendation on interventions for the relief of nausea during pregnancy

 

Recommendation

Ginger, chamomile, vitamin B6 and/or acupuncture are recommended for the relief of nausea in early pregnancy, based on a woman’s preferences and available options.

(Recommended)

 

Publication history

First published: November 2016

Updated: No update planned

Assessed as up-to-date: November 2016

 

Remarks

  • In the absence of stronger evidence, the GDG agreed that these non-pharmacological options are unlikely to have harmful effects on mother and baby.
  • Women should be informed that symptoms of nausea and vomiting usually resolve in the second half of pregnancy.
  • Pharmacological treatments for nausea and vomiting, such as doxylamine and metoclopramide, should be reserved for those pregnant women experiencing distressing symptoms that are not relieved by nonpharmacological options, under the supervision of a medical doctor.

 

Background

Women’s bodies undergo substantial changes during pregnancy, which are brought about by both hormonal and mechanical effects. These changes lead to a variety of common symptoms – including nausea and vomiting, low back and pelvic pain, heartburn, varicose veins, constipation and leg cramps – that in some women cause severe discomfort and negatively affects their pregnancy experience. In general, symptoms associated with mechanical effects, e.g. pelvic pain, heartburn and varicose veins, often worsen as pregnancy progresses. Symptoms of nausea and vomiting are experienced by approximately 70% of pregnant women and usually occur in the first trimester of pregnancy (1); however, approximately 20% of women may experience nausea and vomiting beyond 20 weeks of gestation (2).

 

Methods

The ANC recommendations are intended to inform the development of relevant health-care policies and clinical protocols. These recommendations were developed in accordance with the methods described in the WHO handbook for guideline development (3). In summary, the process included: identification of priority questions and outcomes, retrieval of evidence, assessment and synthesis of the evidence, formulation of recommendations, and planning for the implementation, dissemination, impact evaluation and updating of the guideline.

The quality of the scientific evidence underpinning the recommendations was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) (4) and Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) (5) approaches, for quantitative and qualitative evidence, respectively. Up-to-date systematic reviews were used to prepare evidence profiles for priority questions. The DECIDE (Developing and Evaluating Communication Strategies to support Informed Decisions and Practice based on Evidence) (6) framework, an evidence-to-decision tool that includes intervention effects, values, resources, equity, acceptability and feasibility criteria, was used to guide the formulation and approval of recommendations by the Guideline Development Group (GDG) – an international group of experts assembled for the purpose of developing this guideline – at three Technical Consultations between October 2015 and March 2016.

To ensure that each recommendation is correctly understood and applied in practice, the context of all context-specific recommendations is clearly stated within each recommendation, and the contributing experts provided additional remarks where needed.

In accordance with WHO guideline development standards, these recommendations will be reviewed and updated following the identification of new evidence, with major reviews and updates at least every five years.

Further information on procedures for developing this recommendation are available here.

 

Recommendation question

For this recommendation, we aimed to answer the following question:

  • For pregnant women (P), what interventions (pharmacological or non-pharmacological) for nausea and vomiting (I) compared with no interventions (C) reduce morbidity and improve outcomes (O)?

 

Evidence summary

The evidence on the effects of various interventions for nausea and vomiting in pregnancy was derived from a Cochrane systematic review (2). The review included 41 trials involving 5449 women in whom a wide variety of pharmacological and nonpharmacological interventions were evaluated. Trials were conducted in a variety of HICs and LMICs, and most included pregnant women at less than 16 weeks of gestation with mild to moderate nausea and vomiting. Alternative therapies and non-pharmacological agents evaluated included acupuncture, acupressure, vitamin B6, ginger, chamomile, mint oil and lemon oil. Pharmacological agents included antihistamines, phenothiazines, dopamine-receptor antagonists and serotonin 5-HT3 receptor antagonists. Due to heterogeneity among the types of interventions and reporting of outcomes, reviewers were seldom able to pool data. The primary outcome of all interventions was maternal relief from symptoms (usually measured using the Rhodes Index), and perinatal outcomes relevant to this guideline were rarely reported.

 

Non-pharmacological agents versus placebo or no treatment

Ten trials evaluated non-pharmacological interventions including ginger (prepared as syrup, capsules or powder within biscuits) (7 trials from the Islamic Republic of Iran, Pakistan, Thailand and the USA involving 578 participants), lemon oil (one Iranian study, 100 participants), mint oil (one Iranian study, 60 participants), chamomile (one Iranian study, 105 participants), and vitamin B6 interventions (two studies in Thailand and the USA; 416 participants) compared with no treatment or placebo.

Ginger: Low-certainty evidence from several small individual studies suggests that ginger may relieve symptoms of nausea and vomiting. A study from Pakistan found that ginger reduced nausea symptom scores (68 women; MD: 1.38 lower on day 3, 95% CI: 0.03–2.73 lower), and vomiting symptom scores (64 women; MD: 1.14 lower, 95% CI: 0.37–1.91 lower), and an Iranian study showed improvements in nausea and vomiting symptom scores on day 7 in women taking ginger supplements compared with placebo (95 women; MD: 4.19 lower, 95% CI: 1.73–6.65 lower). Data from the studies in Thailand and the USA showed a similar direction of effect on nausea symptoms in favour of ginger.

Lemon oil: Low-certainty evidence from one small Iranian study suggests that lemon oil may make little or no difference to nausea and vomiting symptom scores (100 women; MD: 0.46 lower on day 3, 95% CI: 1.27 lower to 0.35 higher), or to maternal satisfaction (the number of women satisfied with treatment) (1 trial, 100 women; RR: 1.47, 95% CI: 0.91–2.37).

Mint oil: The evidence on mint oil’s ability to relieve symptoms of nausea and vomiting is of very low certainty.

Chamomile: Low-certainty evidence from one small study suggests that chamomile may reduce nausea and vomiting symptoms scores (70 women; MD: 5.74 lower, 95% CI: 3.17–8.31 lower).

Vitamin B6 (pyridoxine): Moderate-certainty evidence from two trials (one used 25 mg oral vitamin B6 8-hourly for 3 days, the other used 10 mg oral vitamin B6 8-hourly for 5 days) shows that vitamin B6 probably reduces nausea symptoms scores (388 women, trials measured the change in nausea scores from baseline to day 3; MD: 0.92 higher score change, 95% 0.4–1.44 higher), but low-certainty evidence suggests that it may have little or no effect on vomiting (2 trials, 392 women; RR: 0.76, 95% CI: 0.35–1.66).

 

Acupuncture and acupressure versus placebo or no treatment

Five studies (601 participants) evaluated P6 (inner forearm) acupressure versus placebo, one Thai study (91 participants) evaluated auricular acupressure (round magnetic balls used as ear pellets) versus no treatment, one study in the USA (230 participants) evaluated P6 acustimulation therapy (nerve stimulation at the P6 acupuncture point) versus placebo, and a four-arm Australian study (593 women) evaluated traditional Chinese acupuncture or P6 acupuncture versus P6 placebo acupuncture or no intervention.

Low-certainty evidence suggests that P6 acupressure may reduce nausea symptom scores (100 women; MD: 1.7 lower, 95% CI: 0.99–2.41 lower) and reduce the number of vomiting episodes (MD: 0.9 lower, 95% CI: 0.74–1.06 lower). Low-certainty evidence WHO recommendations on antenatal care for a positive pregnancy experience 76 suggests that auricular acupressure may also reduce nausea symptom scores (91 women; MD: 3.6 lower, 95% CI: 0.58–6.62 lower), as may traditional Chinese acupuncture (296 women; MD: 0.7 lower, 95% CI: 0.04–1.36 lower). Low-certainty evidence suggests that P6 acupuncture may make little or no difference to mean nausea scores compared with P6 placebo acupuncture (296 women; MD: 0.3 lower, 95% CI: 1.0 lower to 0.4 higher).

 

Pharmacological agents versus placebo

One study evaluated an antihistamine (doxylamine) and another evaluated a dopamine-receptor antagonist (metoclopramide). Certain other drugs evaluated in the review (hydroxyzine, thiethylperazine and fluphenazine) are from old studies and these drugs are no longer used in pregnant women due to safety concerns.

Moderate-certainty evidence suggests that doxylamine plus vitamin B6 probably reduces nausea and vomiting symptom scores compared with placebo (1 study, 256 women; MD: 0.9 lower on day 15, 95% CI: 0.25–1.55 lower). Low-certainty evidence from this study suggests that there may be little or no difference in headache (256 women; RR: 0.81, 95% CI: 0.45–1.48) or drowsiness (256 women; RR: 1.21, 95% CI: 0.64–2.27) between doxylamine plus vitamin B6 and placebo.

Low-certainty evidence on metoclopramide (10 mg) suggests that this agent may reduce nausea symptom scores (1 trial, 68 women; MD: 2.94 lower on day 3, 95% CI: 1.33–4.55 lower). There was no side-effect data on metoclopramide in the review.

No studies compared ondansetron (a 5HT3 receptor antagonist) with placebo. Two small studies compared ondansetron with metoclopramide and doxylamine, respectively, but evidence on relative effects was uncertain.

 

Additional considerations

Low-certainty evidence from single studies comparing different non-pharmacological interventions with each other – namely acupuncture plus vitamin B6 versus P6 acupuncture plus placebo (66 participants), traditional acupuncture and P6 acupuncture (296 participants), ginger versus chamomile (70 participants), P6 acupuncture versus ginger (98 participants), and ginger versus vitamin B6 (123 participants) – suggests there may be little or no difference in effects on relief of nausea symptoms.

Low-certainty evidence suggests that there may be little or no difference between ginger and metoclopramide on nausea symptom scores (1 trial, 68 women; MD: 1.56 higher, 95% 0.22 lower to 3.34 higher) or vomiting symptom scores (68 women; MD: 0.33 higher, 95% CI: 0.69 lower to 1.35 higher) on day 3 after the intervention.

Side-effects and safety of pharmacological agents were poorly reported in the included studies. However, drowsiness is a common side-effect of various antihistamines used to treat nausea and vomiting.

Metoclopramide is generally not recommended in the first trimester of pregnancy, but is widely used (7). A study of over 81 700 singleton births in Israel reported that they found no statistically significant differences in the risk of major congenital malformations, low birth weight, preterm birth or perinatal death between neonates exposed (3458 neonates) and not exposed to metoclopramide in the first trimester of gestation.

Resources

Costs associated with non-pharmacological remedies vary. Acupuncture requires professional training and skills and is probably associated with higher costs. Vitamin B6 (pyridoxine hydrochloride tablets) could cost about US$ 2.50 for 90 × 10 mg tablets (8).

Equity

The impact on equity is not known. Acceptability Qualitative evidence from a range of LMICs suggests that women may be more likely to turn to traditional healers, herbal remedies or traditional birth attendants (TBAs) to treat these symptoms (moderate confidence in the evidence) (9). In addition, evidence from a diverse range of settings indicates that while women generally appreciate the interventions and information provided during antenatal visits, they are less likely to engage with services if their beliefs, traditions and socioeconomic circumstances are ignored or overlooked by healthcare providers and/or policy-makers (high confidence in the evidence). This may be particularly pertinent for acupuncture or acupressure, which may be culturally alien and/or poorly understood in certain contexts.

Feasibility

A lack of suitably trained staff may limit feasibility of certain interventions (high confidence in the evidence) (10).

 

Further information and considerations related to this recommendation can be found in the WHO guidelines, available at:

http://apps.who.int/iris/bitstream/10665/250796/8/9789241549912-websupplement-eng.pdf?ua=1

 

Implementation considerations

  • The successful introduction of evidence-based policies related to antenatal care into national programmes and health care services depends on well-planned and participatory consensus-driven processes of adaptation and implementation. These processes may include the development or revision of national guidelines or protocols based on this recommendation.
  • The recommendation should be adapted into locally-appropriate documents and tools that are able to meet the specific needs of each country and health service. Modifications to the recommendation, where necessary, should be justified in an explicit and transparent manner.
  • An enabling environment should be created for the use of this recommendation, including changes in the behaviour of health care practitioners to enable the use of evidence-based practices.
  • Local professional societies may play important roles in this process and an all-inclusive and participatory process should be encouraged.
  • Antenatal care models with a minimum of eight contacts are recommended to reduce perinatal mortality and improve women’s experience of care. Taking this as a foundation, the GDG reviewed how ANC should be delivered in terms of both the timing and content of each of the ANC contacts, and arrived at a new model – the 2016 WHO ANC model – which replaces the previous four-visit focused ANC (FANC) model. For the purpose of developing this new ANC model, the ANC recommendations were mapped to the eight contacts based on the evidence supporting each recommendation and the optimal timing of delivery of the recommended interventions to achieve maximal impact.

 

Research implications

The GDG identified this priority question related to this recommendation

  • What is the prevalence of common physiological symptoms among pregnant women in low-resource settings, and can the offer of treatment of these symptoms reduce health inequality, improve ANC coverage and improve women’s pregnancy experiences?

 

Related links

WHO recommendations on antenatal care for a positive pregnancy experience

(2016) - full document and evidence tables

Managing Complications in Pregnancy and Childbirth: A guide for midwives and doctors

Pregnancy, Childbirth, Postpartum and Newborn Care: A guide for essential practice

WHO Programmes: Sexual and Reproductive health

Maternal Health

 

 

References

  1. Einarson TR, Piwko C, Koren G. Quantifying the global rates of nausea and vomiting of pregnancy: a meta analysis. J Popul Ther Clin Pharmacol. 2013; 20(2):e171–83.
  2. Matthews A, Haas DM, O’Mathúna DP, Dowswell T. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015; (9):CD007575.
  3. WHO handbook for guideline development, 2nd edition. Geneva: World Health Organization; 2014 (http://www.who.int/kms/handbook_2nd_ ed.pdf, accessed 6 October 2016).
  4. GRADE [website]. The GRADE Working Group; 2016 (http://gradeworkinggroup.org/, accessed 27 October 2016).
  5. GRADE-CERQual [website]. The GRADECERQual Project Group; 2016 (https://cerqual. org/, accessed 27 October 2016).
  6. The DECIDE Project; 2016 (http://www.decide-collaboration.eu/, accessed 27 October 2016).
  7. Matok I, Gorodischer R, Koren G, Sheiner E, Wiznitzer A, Levy A. The safety of metoclopramide use in first trimester of pregnancy. N Engl J Med. 2009;360:2528–35
  8. Joint Formulary Committee. Vitamin deficiency. Chapter 9: Blood and Nutrition. In: British National Formulary (BNF) 72. London: BMJ Publishing Group Ltd and Royal Pharmaceutical Society; 2016.
  9. Downe S, Finlayson K, Tunçalp Ö, Gülmezoglu AM. Factors that influence the use of routine antenatal services by pregnant women: a qualitative evidence synthesis. Cochrane Database Syst Rev. 2016;(10):CD012392
  10. Downe S, Finlayson K, Tunçalp Ö, Gülmezoglu AM. Factors that influence the provision of good quality routine antenatal care services by health staff: a qualitative evidence synthesis. Cochrane Database Syst Rev. 2016

 

Citation: WHO Reproductive Health Library. WHO recommendation on interventions for the relief of nausea during pregnancy. (November 2016). The WHO Reproductive Health Library; Geneva: World Health Organization.