Management of pregnancy associated emesis

Nausea during the first trimester of pregnancy does NOT require pharmacological intervention. Severe vomiting is associated with multiple pregnancy and hydatidiform moles and these need to be excluded.

Usually nausea and vomiting improve after 14-16 weeks of pregnancy although many women will experience more nausea, and occasionally vomiting, whilst pregnant than during non-pregnancy.

Symptoms can usually be controlled by dietary measures e.g. avoidance of greasy foods and having frequent small meals.

NICE suggest that (1):

• if a woman requests or would like to consider treatment, the following interventions appear to be effective in reducing symptoms:
  • non-pharmacological
    • ginger
    • P6 acupressure
  • pharmacological
    • antihistamines.

UK guidance notes that (2):

• ketonuria is not an indicator of dehydration and should not be used to assess severity
  • ketonuria is not an indicator of dehydration and is not associated with severity of nausea and vomiting of pregnancy (NVP) or hyperemesis gravidarum (HG)
  • suggests clinical assessment and findings suggestive of dehydration
    • heart rate (tachycardia in dehydration)
    • blood pressure (hypotension in dehydration)
    • respiratory rate (tachypnoea in dehydration)
    • signs of dehydration such as sunken eyes, dry lips and mouth, oliguria or anuria, tachycardia and hypotension
• Recommended antiemetic therapies and dosages
  • First line
    • Doxylamine and Pyridoxine (vitamin B6) 20/20mg PO at night, increase to additional 10/10 mg in morning and 10/10mg at lunchtime if required. or
    • Cyclizine 50 mg PO, IM or IV 8 hourly, or
    • Prochlorperazine 5–10 mg 6–8 hourly PO (or 3 mg buccal); 12.5 mg 8 hourly IM/IV; 25 mg PR daily, or
    • Promethazine 12.5–25 mg 4–8 hourly PO, IM or IV, or
    • Chlorpromazine 10–25 mg 4–6 hourly PO, IM or IV
    • notes:
      • there are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine and they should be prescribed initially when required for nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum (HG)
  • Second line
    • Metoclopramide 5–10 mg 8 hourly PO, IV/IM/SC, or
    • Domperidone 10 mg 8 hourly PO; 30 mg 12 hourly PR , or
    • Ondansetron 4 mg 8 hourly or 8 mg 12 hourly PO; 8 mg over 15 minutes 12 hourly IV; 16 mg daily PR
    • notes
      • with respect to metoclopramide
        • metoclopramide is safe and effective and can be used alone or in combination with other antiemetics
        • because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these
      • with respect to ondansetron
        • women taking ondansetron may require laxatives if constipation develops)
        • is evidence that ondansetron is safe and effective
        • Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective
        • women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG
  • Third line
    • Hydrocortisone 100 mg twice daily IV and once clinical improvement occurs, convert to prednisolone 40–50 mg daily PO, with the dose gradually tapered (by 5-10 mg per week) until the lowest maintenance dose that controls the symptoms is reached
    • notes
      • corticosteroids should be reserved for cases where standard therapies have failed; when initiated they should be prescribed in addition to previously started effective antiemetics. Women taking corticosteroids should have their blood pressure monitored and a screen for diabetes mellitus
  • IM intramuscular; IV intravenous; PO by mouth; PR by rectum

Whilst managing hyperemesis in pregnancy one should always consider pregnancy related causes of hyperemesis (e.g. multiple pregnancy) and causes of hyperemesis predisposed to by pregnancy (e.g. urinary tract infection).

Notes:

• thyroid function should be assessed in all women with hyperemesis gravidarum. This is because hyperthyroidism may result from higher serum concentrations of BHCG, which has TSH-like activity. Generally, hyperthyroidism associated with increased levels of BHCG resolves spontaneously after the first trimester (3). If hyperthyroidism is detected then initially supportive treatment is recommended. If the condition is persistent or severe then treatment with thionamides e.g. propylthiouracil, may be recommended
• use of prednisolone in the treatment of hyperemesis gravidarum
  • there is evidence that promethazine reduces the symptoms of hyperemesis gravidarum faster than prednisolone, but during prolonged treatment, prednisolone has at least the same effects on the symptoms and less drug side-effects (4)
• there is evidence concerning the efficacy of both pyridoxine hydrochloride (vitamin B6) and ginger in the management of nausea and vomiting in pregnancy
  • one study has shown that ginger reduced symptoms to the same extent as vitamin B6 (5)
• doxylamine succinate-pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy (6)
• women should be asked about previous adverse reactions to antiemetic therapies (2)
  • if adverse reactions occur, there should be prompt cessation of the medications
• combinations of different drugs should be used in women who do not respond to a single antiemetic (2)
• thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition (2)

Reference:

1. NICE (2008). Antenatal care.
2. RCOG Green Top Guidelines (February 2024).The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69)
3. Prescriber (2002), 13 (10), 50-68.
4. Ziaei S et al. The efficacy low dose of prednisolone in the treatment of hyperemesis gravidarum. Acta Obstet Gynecol Scand 2004;83:272-5.
5. Smith C et al. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obset Gynecol 2004;103:639-45.
6. Korean G et al. Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial. BMC Pregnancy Childbirth. 2015; 15: 59.