Lucan · Conditions

Hyperemesis gravidarum

Australian guidance: RANZCOG Hyperemesis Statement

1. Definition and epidemiology

Hyperemesis gravidarum (HG) is a severe form of nausea and vomiting in pregnancy characterised by persistent vomiting, weight loss exceeding 5% of pre-pregnancy body weight, dehydration, and ketonaemia or ketonuria, typically arising in the first trimester. It is distinct from the milder nausea and vomiting of pregnancy that affects up to 80% of pregnant women; HG affects approximately 0.3 to 3% of pregnancies in Australia and is the leading cause of hospitalisation in the first trimester. Rates are higher in multiple pregnancies and in women with a prior history of HG.

2. Pathophysiology

The pathophysiology of HG is incompletely understood but is closely linked to rising serum human chorionic gonadotrophin (hCG) levels in early pregnancy (Robbins Ch 22). hCG shares structural homology with thyroid-stimulating hormone and can stimulate thyroid hormone production, resulting in transient gestational hyperthyroidism in severe cases. Oestrogen, which rises in parallel with hCG, sensitises the chemoreceptor trigger zone and slows gastric motility, compounding nausea. Helicobacter pylori seropositivity has been associated with HG in multiple studies, suggesting an additive gastric mucosal susceptibility. Genetic predisposition is supported by a familial clustering pattern and concordance in monozygotic twin pairs. Psychosocial factors may amplify severity but are not causative. The resulting protracted vomiting leads to dehydration, hypochloraemic hypokalaemic metabolic alkalosis, thiamine depletion, and in extreme cases Wernicke encephalopathy from vitamin B1 deficiency.

3. Clinical presentation and diagnostic criteria

HG typically presents between 4 and 10 weeks of gestation and usually resolves by 20 weeks, although approximately 20% of women continue to have symptoms beyond this point. Key features include intractable vomiting occurring multiple times daily, inability to tolerate oral fluids or diet, significant weight loss, and signs of dehydration including tachycardia, dry mucous membranes, reduced skin turgor, and reduced urine output. Ptyalism (excessive salivation) is a recognised associated symptom. The PUQE (Pregnancy-Unique Quantification of Emesis) score is used to quantify severity. Importantly, HG is a diagnosis of exclusion; alternative causes of vomiting in pregnancy including urinary tract infection, appendicitis, cholestasis, pancreatitis, gastroenteritis, and molar pregnancy must be considered. According to the RANZCOG Hyperemesis Gravidarum Statement, the diagnosis requires the combination of persistent vomiting, weight loss and at least one objective marker of metabolic disturbance.

4. Investigations and AU-specific cutoffs

Investigation should proceed in a stepwise fashion guided by clinical severity.

Urine: urinalysis for ketones (2+ or greater supports significant ketonaemia warranting admission), specific gravity, and microscopy and culture to exclude urinary tract infection.

Blood tests: full blood count (raised haematocrit reflects haemoconcentration), urea and electrolytes (hypokalaemia, raised urea indicate dehydration), serum creatinine, liver function tests (transaminase elevation up to 200 U/L is seen in severe HG and does not necessitate separate investigation), thyroid function tests (transient hyperthyroidism with suppressed TSH occurs in up to 60% of HG cases and does not require antithyroid treatment unless biochemically and clinically hyperthyroid), and blood glucose. Serum thiamine level should be checked before intravenous dextrose is administered, as dextrose without prior thiamine replacement precipitates Wernicke encephalopathy.

Imaging: pelvic ultrasound at first presentation to confirm intrauterine pregnancy, exclude multiple gestation or gestational trophoblastic disease (both of which produce markedly elevated hCG and are associated with more severe vomiting), and assess foetal viability.

Admission thresholds in AU clinical practice: inability to tolerate oral fluids for more than 24 hours, ketonuria 2+ or greater, weight loss exceeding 5% of pre-pregnancy weight, or any clinical sign of dehydration.

5. Management

Management follows a stepwise approach aligned with the RANZCOG Hyperemesis Gravidarum Statement and is staged by severity.

Mild to moderate HG can be managed in the outpatient setting with dietary advice (small, frequent, low-fat, high-carbohydrate meals; cold foods to reduce olfactory triggering; ginger supplementation 250 mg four times daily has evidence for mild benefit), correction of aggravating factors, and first-line antiemetics.

Severe HG requires hospital admission for intravenous fluid resuscitation. The preferred fluid is normal saline (0.9% sodium chloride) with potassium chloride supplementation guided by serum potassium; dextrose-containing fluids are avoided as initial resuscitation until thiamine has been administered. Thiamine 100 mg intravenously must be given before any glucose-containing fluid to prevent Wernicke encephalopathy. Antiemetics are administered parenterally or via the buccal or rectal route until the patient can tolerate oral therapy. Enteral nasogastric feeding is considered when weight loss is severe and antiemetic therapy fails; total parenteral nutrition is reserved for refractory cases where enteral access is not achievable or tolerated, given its higher complication profile. Cessation of iron-containing supplements (which commonly worsen nausea) and pyridoxine (vitamin B6) 25 mg three times daily are standard adjuncts.

6. Pharmacology and AU PBS notes

First-line antiemetics:

Doxylamine 25 mg with pyridoxine 25 mg orally at night (combination available as Diclegis or compounded preparation; pyridoxine PBS General Schedule). This combination has the longest safety record in pregnancy.

Metoclopramide (Maxolon) 10 mg orally, intramuscularly, or intravenously every 8 hours. PBS General Schedule. Risk of extrapyramidal effects with prolonged use; maximum 5-day continuous course is recommended by the TGA.

Promethazine (Phenergan) 12.5 to 25 mg orally or intramuscularly every 4 to 6 hours. PBS General Schedule. Sedation is a common limiting side effect.

Second-line antiemetics:

Ondansetron (Zofran, Ondansetron AN) 4 to 8 mg orally or intravenously every 8 hours. PBS streamlined authority is not applicable for nausea in pregnancy; ondansetron is used on private prescription or under hospital formulary in this context. RANZCOG guidance and the 2021 Motherisk update note that while earlier studies suggested a small cardiac teratogenic signal (ventricular septal defects), subsequent larger registries have not confirmed this association, and ondansetron is considered acceptable when first-line agents have failed. It should not be used beyond 12 weeks without reassessment of the risk-benefit ratio given the evolving evidence base.

Prochlorperazine (Stemetil) 5 to 10 mg orally or 12.5 mg intramuscularly. PBS General Schedule. Used when promethazine is not tolerated.

Corticosteroids (methylprednisolone) are used in refractory HG as a last resort before parenteral nutrition; evidence is limited and there is a theoretical first-trimester risk of oral clefts, so they are generally avoided before 10 weeks.

7. Complications and monitoring

Maternal complications include Wernicke encephalopathy (prevented by mandatory thiamine supplementation before intravenous dextrose), hypokalaemia with associated cardiac dysrhythmia, oesophageal rupture (Boerhaave syndrome) from forceful vomiting, Mallory-Weiss mucosal tears, and renal injury from protracted dehydration. Central pontine myelinolysis can occur with overly rapid sodium correction if hyponatraemia is present. Liver dysfunction (transaminase elevation, rarely jaundice) is self-limiting and resolves with treatment of HG. Venous thromboembolism risk is elevated by dehydration and immobility in hospitalised patients; thromboprophylaxis with compression stockings and early mobilisation is standard, with low-molecular-weight heparin (enoxaparin) considered for prolonged admission per local venous thromboembolism policy.

Foetal complications include low birth weight (associated with severe weight loss and prolonged ketonaemia), small for gestational age, and preterm birth in the most severe and refractory cases. There is no consistent association between treated HG and major congenital anomalies.

Monitoring during admission: daily weight, urine output and ketone measurement, electrolytes every 24 to 48 hours until stable, repeat thyroid function at 4 to 6 weeks if initially suppressed, and psychological support given the high rates of anxiety and depression associated with HG. Outpatient follow-up should include weight monitoring at each antenatal visit and reassessment if symptoms recur after initial resolution.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.