Navigating nausea and vomiting during pregnancy

Case scenario

Brooke is 6 weeks pregnant with her second child. In her previous pregnancy she experienced nausea and vomiting but, afraid of causing harm to her baby, did not use any medicines. Now caring for her toddler, Brooke is struggling to cope with her current symptoms. She feels nauseated for 4 hours each day, has vomited once in the past 24

hours and dry heaves at least twice a day. She has no other medical conditions or regular medicines except a daily prenatal multivitamin.

Introduction 

Nausea and vomiting in pregnancy (NVP) is a prevalent pregnancy-induced condition, affecting an estimated 70% of all pregnancies.¹ Approximately 1.1% of pregnant women experience the severe and persistent form, hyperemesis gravidarum (HG).¹ Pharmacists are uniquely placed to offer assessment, education and evidence-based guidance about safe treatments during pregnancy, as well as referring those at risk of HG for comprehensive care.

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Clinical features

NVP is defined as nausea, vomiting and/or dry retching, commencing in the first trimester of pregnancy, without an alternate diagnosis.^1-2 The term ‘morning sickness’ is often used for this condition but neglects the reality that symptoms can occur throughout the day and night.^2-3

The exact cause remains unclear but is likely multifactorial. Heritability estimates suggest a strong genetic influence. Symptoms of NVP and HG typically commence between 4 and 10 weeks of pregnancy, ranging in severity from mild to severe. While most cases will resolve by 16–20 weeks, a small percentage of women will experience symptoms throughout the entire pregnancy.^2-3

HG is an extreme manifestation of NVP which often leads to hospitalisation. It is characterised by early onset of symptoms, significant impairment of oral intake and daily activities, and severe nausea and vomiting, with or without dehydration and/or electrolyte abnormalities.^1,2

Clinical impacts

NVP is often dismissed as a normal consequence of pregnancy without acknowledging the immense impact it can have on individuals and their families.³ While the expectant mother can be reassured that mild to moderate nausea and vomiting are not expected to harm their developing baby, any severity of symptoms can significantly impair quality of life, mental health, and overall wellbeing.^1-3

Severe and persistent symptoms, such as that seen with HG, may lead to weight loss, dehydration, electrolyte imbalances, nutritional deficiencies, and hospitalisation. Uncontrolled HG is associated with adverse pregnancy outcomes for mother and baby such as malnutrition, placental dysfunction (with an increased risk of low-birthweight babies and pre-term delivery), dental erosion, and abnormal thyroid, renal, and liver function.^1-3

Motherisk pregnancy unique quantification of emesis (PUQE-24)

The PUQE-24 scoring system is a validated tool specifically designed to quantify the severity of NVP^1,2. It comprises three questions regarding the incidence of nausea, vomiting, and dry retching experienced within a 24-hour period, with symptoms classified as mild, moderate, or severe (see Table 1). Pharmacists can integrate the PUQE-24 into their practice, along with assessments of food and oral intake and impacts on quality of life, to assess the severity of NVP symptoms and guide interventions within community and ambulatory settings.¹

NVP symptoms should be assessed at each patient encounter as repeated PUQE-24 scores can be used to monitor a patient’s condition and response to medicines over time, with adjustments to medicine regimens made where necessary. PUQE-24 can also help pharmacists identify severe cases that warrant onward referral.

Non-pharmacological management 

Pharmacists can suggest lifestyle modifications (e.g. eating small amounts of well-tolerated foods often and avoiding dietary triggers or strong odours)^1,2,4 and non-pharmacological interventions, such as acupressure wrist bands,¹ that may help alleviate symptoms for some women.

Iron supplementation can aggravate nausea and vomiting. Prenatal multivitamins should be suspended if they are contributing to a woman’s NVP symptoms. If multivitamins are discontinued, supplementation with the critical micronutrients, iodine (150 microgram per day) and folate (at least 400 microgram per day), should be maintained.^1-3 Multivitamins can be resumed once symptoms have abated or as requirements change into the second trimester.

For mild NVP symptoms, ginger (up to 1,800 mg/day in divided doses, preferably in standardised pharmaceutical form) has been shown to be safe and may be effective in improving nausea.^1,2

Pharmacological management 

During pregnancy, the potential benefits of treating the maternal condition should outweigh any potential risks of treatment to both the pregnant woman and developing baby. Pregnant women (and their healthcare professionals) tend to overestimate the teratogenic risks of medicines, and as a result, many will endure NVP symptoms despite adverse impacts on their own health and wellbeing.³

Evidence-based clinical guidelines are available to support decision-making for NVP and HG management.^1,2,4 The choice of antiemetics should be individualised, based on symptoms, previous response, and tolerance of treatments.^2,4

Many first-line medicines for NVP are available over the counter (OTC) and can be initiated by pharmacists. The following recommended medicines have well-established safety profiles in pregnancy, and none have been shown to be teratogenic.³

Note: For recommended doses and further information about medicines used in NVP, please refer to reputable resources such as the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ), NSW Health, and Therapeutic Guidelines.

OTC teatments

• Pyridoxine/vitamin B6 (up to 200 mg daily) has demonstrated efficacy in reducing mild to moderate nausea.^1,2 It is well tolerated at the recommended doses for NVP. 
• Doxylamine is generally the first antiemetic of choice given its extensive evidence of safety and efficacy for NVP.^1-3 Tablets can be quartered or halved to adjust dose as required and tolerated, particularly during the day when sedation may be an issue. Pharmacists can feel confident in supplying this Category A medicine to pregnant women. The historic warning on doxylamine products which previously stated, ‘do not use in pregnancy’ has been removed (effective 1 July 2023).^3,5 The combination of doxylamine-pyridoxine appears to be more effective than either therapy alone.^1,2 
• Other sedating antihistamines (such as diphenhydramine, promethazine, cyclizine) can be used for their antiemetic properties. Only one antihistamine should be used at a time.¹

Gastric dysmotility often exacerbates the symptoms of NVP. Associated constipation and reflux should be managed accordingly. Pharmacists can recommend lifestyle modifications, antacids, and proton pump inhibitors to manage reflux, and laxatives (such as docusate, macrogol, or lactulose) to treat constipation.^1-3

Prescription treatments

The only first-line agents that require a prescription for NVP are the dopamine antagonists.

• Metoclopramide is a Category A antiemetic, safe for short-term use, but its potential to rarely cause dystonic maternal adverse reactions limits use beyond 5 days.^1,4
• Prochlorperazine is a Category C antiemetic due to its potential to cause neonatal adverse effects if used at high doses close to delivery but is otherwise safe to use during pregnancy.^1,2
• Ondansetron is a second-line agent for NVP where first-line treatments have failed to resolve symptoms.¹ Although the Category B grading implies limited human data, ondansetron is commonly prescribed in pregnancy for NVP and HG, and is supported by extensive clinical experience.^1,2,4 It commonly causes constipation so adjunct laxatives are recommended.
• Corticosteroids are third-line NVP agents, reserved for women with severe/refractory symptoms and usually initiated in a hospital setting.^1,2

Off-label use 

Almost all pharmacological treatments for NVP and HG are ‘off-label’, which involves the use of a medicine outside the scope of its approved product license. While off-label use is extremely common and often unavoidable in obstetric practice, pharmacists must be mindful of regulatory and legal considerations.⁶

Off-label medicine use should be supported by good quality evidence and/or formal guidelines and documented appropriately. Pharmacists must engage in comprehensive discussions with pregnant women, ensuring informed consent and active participation in the decision-making process.^6-8

The ‘off-label’ supply of a Schedule 3, Pharmacist Only medicine, can sometimes cause confusion because pharmacists need to additionally consider scheduling restrictions that may apply to individual agents within the Poisons Standard.⁹ Some medicines in Schedule 3 are restricted to a specified indication and cannot legally be supplied for an alternate use as a Pharmacist Only medicine. For example, prochlorperazine and metoclopramide/paracetamol are Pharmacist Only medicines for the treatment of ‘nausea associated with migraine’, however, they are able to be accessed if required for NVP or HG via a prescription after discussion with a medical practitioner.⁹ All other first-line OTC treatments for NVP, including doxylamine, can be legally supplied by pharmacists for NVP.

Need to refer

In cases where NVP symptoms are severe (PUQE-24 score ≥13 or inability to tolerate food or fluids), or where initial interventions have failed, pharmacists should refer women to clinicians with expertise in managing NVP and HG, such as an obstetrician or general practitioner.^1,2 Hospitalisation and the administration of intravenous fluids and/or enteral or parenteral nutrition may be required in severe cases.

Conclusion

Pharmacists can contribute significantly to the wellbeing of pregnant women by assessing NVP symptom severity, offering evidence-based recommendations, and tailoring individual treatments to improve maternal health outcomes.

Key points

• Substituting iron-containing multivitamins with iodine and folic acid supplements may improve NVP symptoms.
• Evidence-based NVP and HG management guidelines can help pharmacists support women in making informed decisions about their medicines use during pregnancy.
• Pharmacists can (and should) recommend safe and effective OTC treatments for NVP, including non-pharmacological strategies, ginger, pyridoxine, doxylamine (or other sedating antihistamine), laxatives, and acid-suppression treatments.including non-pharmacological strategies, ginger, pyridoxine, doxylamine (or other sedating antihistamine), laxatives and acid-suppression treatments.

Further reading

For more detailed information on management of NVP and HG (including recommended doses), pharmacists can refer to:

• SOMANZ Guideline for the Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum 2019. At: www.somanz.org
• NSW Health Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum Guideline 2022. At: www1.health.nsw.gov.au/pds/Pages/doc.aspx?dn=GL2022_009
• Gray SG, McGuire TM. Navigating off-label and unlicensed medicine use in obstetric and paediatric clinical practice. J Pharm Pract Res 2019;49(4):389–95. At: https://doi.org/10.1002/jppr.1605

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References

1. NSW Health. Nausea and vomiting in pregnancy and hyperemesis gravidarum. 2022. At: www1.health.nsw.gov.au/pds/Pages/doc.aspx?dn=GL2022_009
2. Society of Obstetric Medicine of Australia and New Zealand. Guideline for the management of nausea and vomiting in pregnancy and hyperemesis gravidarum. 2019. At: www.somanz.org/approval-of-written-guidelines-by-somanz/
3. Paola S, Batagol R. Nausea and vomiting in pregnancy: Addressing the myths. 2023. At:
   https://ajp.com.au/cpd-activities/nausea-and-vomiting-in-pregnancy-addressing-the-myths
4. Therapeutic Guidelines. 2023. Nausea and vomiting during pregnancy; [updated 2016 Mar]. At: https://tgldcdp.tg.org.au/viewTopic?etgAccess=true&guidelinePage=Gastrointestinal&topicfile=c_GIG_Gastro-oesophageal-reflux-in-adultstopic_1&guidelinename=auto&sectionId=r_GIG_Nausea-and-vomiting-during-pregnancytopic_7#r_GIG_Nausea-and-vomiting-during-pregnancytopic_7
5. Therapeutic Goods Administration (TGA). Medicines Advisory Statements Specification updates. 2022. At: https://pink.citeline.com/-/media/supporting-documents/pink-sheet/2022/02/p0222aus_5.pdf
6. Gray SG, McGuire TM. Navigating off-label and unlicensed medicine use in obstetric and paediatric clinical practice. J Pharm Pract Res 2019;49(4):389–95.
7. Bell JS, Richards GC. Off-label medicine use; Ethics, practice and future directions. Aust J Gen Prac 2021;50(5):329–331.
8. Council of Australian Therapeutic Advisory Groups. Rethinking medicines decision-making in Australian hospitals: Guiding principles for the quality use of off-label medicines. 2013. At: www.catag.org.au/wp-content/uploads/2012/08/OKA9963-CATAG-Rethinking-Medicines-Decision-Making-final1.pdf
9. Therapeutic Goods Administration. Poisons Standard. 2015. At: www.tga.gov.au/how-we-regulate/ingredients-and-scheduling-medicines-and-chemicals/poisons-standard-and-scheduling-medicines-and-chemicals/poisons-standard-susmp