Key Facts

Hyperemesis gravidarum (HG) represents the severe end of the spectrum of nausea and vomiting in pregnancy. It can cause significant morbidity, including dehydration, electrolyte imbalance, nutritional deficiency, and psychological distress. Early aggressive management improves outcomes.

Epidemiology

NVP affects approximately 70-80% of pregnant women. Hyperemesis gravidarum (severe, requiring treatment) affects approximately 1-3%. Peak onset is 6-8 weeks, peak severity at 8-12 weeks, with resolution by 16-20 weeks in most. Approximately 10% have symptoms beyond 20 weeks, and rarely symptoms persist throughout pregnancy. HG is the most common cause of hospital admission in early pregnancy.

Aetiology

The exact cause is unclear; likely multifactorial:

• hCG: Highest correlation — hCG peaks at 10-12 weeks, mirroring symptom peak; explains increased risk with molar pregnancy and multiple pregnancy
• Oestrogen/progesterone: Hormonal effects on GI motility and chemoreceptor trigger zone
• Helicobacter pylori: Association in some studies
• Genetic: Strong familial tendency; genome-wide association studies identify GDF15 and IGFBP7 as key mediators
• Psychological: Stress and anxiety exacerbate symptoms (but are not causative)

Pathophysiology

Persistent vomiting leads to:

• Dehydration: Volume depletion → pre-renal AKI
• Metabolic alkalosis: Loss of gastric HCl (similar to pyloric stenosis)
• Hypokalaemia: Renal potassium wasting to compensate for alkalosis
• Hyponatraemia: Volume depletion + excessive ADH secretion
• Ketonuria/ketosis: Starvation metabolism — fat mobilisation
• Thiamine deficiency: Can develop rapidly (within 2-3 weeks of vomiting); leads to Wernicke's encephalopathy (confusion, ataxia, ophthalmoplegia) — a medical emergency

Symptoms

• Persistent, severe nausea and vomiting (multiple times per day)
• Inability to tolerate oral food or fluids
• Weight loss >5% of pre-pregnancy weight
• Ptyalism (excessive salivation)
• Sensitivity to smells and food aversions

Signs

• Dehydration: Dry mucous membranes, reduced skin turgor, tachycardia, postural hypotension
• Ketonuria on dipstick (2+ or more)
• Weight loss documented from pre-pregnancy or early pregnancy weight

Psychological Impact

• Significant depression, anxiety, and social isolation
• May consider termination of a wanted pregnancy due to symptom severity
• Post-traumatic stress symptoms in severe cases

Red Flags

• Confusion, ataxia, nystagmus/ophthalmoplegia — Wernicke's encephalopathy (give thiamine immediately)
• Severe hypokalaemia (K⁺ <2.5 mmol/L) — risk of cardiac arrhythmia
• Haematemesis — consider Mallory-Weiss tear from forceful vomiting
• Thyrotoxicosis symptoms — gestational thyrotoxicosis (hCG-mediated) occurs in ~60% of HG
• Abdominal pain or fever — exclude other diagnoses (UTI, appendicitis, pancreatitis)

Bedside

• Weight: Compare to pre-pregnancy or early pregnancy weight — >5% loss supports diagnosis
• Urine dipstick: Ketonuria (grade severity); exclude UTI
• Vital signs: Tachycardia, postural hypotension indicating dehydration
• PUQE score (Pregnancy-Unique Quantification of Emesis): Validated severity assessment tool

Bloods

• U&Es: Hypokalaemia, hyponatraemia, raised urea/creatinine (dehydration)
• FBC: Haemoconcentration
• LFTs: Mildly elevated transaminases in ~50% of HG
• TFTs: Gestational thyrotoxicosis (suppressed TSH, mildly raised fT4) — occurs in ~60% due to hCG cross-reactivity with TSH receptor; usually does not require treatment
• Calcium: Hypercalcaemia can cause vomiting (exclude)
• Amylase/lipase: If pancreatitis suspected

Imaging

• USS: Confirm viability, exclude molar pregnancy, multiple pregnancy

Special Tests

• MSU MC&S: Exclude UTI (can co-exist or mimic HG)
• Serum β-hCG: If molar pregnancy suspected (very high levels)

Non-pharmacological

• Avoid triggers: Identify and avoid food/smell triggers
• Dietary advice: Small, frequent, bland meals; ginger products; dry crackers before rising
• Acupressure: P6 (Nei-Kuan) wrist point — some evidence of benefit
• Psychological support: Acknowledge severity; screen for depression; consider counselling
• Hospital admission criteria: Unable to tolerate oral intake, >5% weight loss, ketonuria ≥3+, electrolyte abnormality, comorbidities

Pharmacological

• First-line antiemetics (RCOG GTG 69):
  • Cyclizine 50mg PO/IV/IM TDS
  • Prochlorperazine 5-10mg PO TDS or 12.5mg IM
  • Promethazine 25mg PO BD-TDS (sedating)
• Second-line: Ondansetron 4-8mg PO/IV BD-TDS (RCOG notes small increased risk of cleft palate in first trimester — discuss with patient)
• Third-line: Metoclopramide 10mg PO/IV TDS (max 5 days — risk of extrapyramidal side effects)
• Corticosteroids: Hydrocortisone 100mg IV BD then convert to prednisolone 40-50mg OD, tapering over 2-3 weeks — reserved for refractory cases not responding to antiemetics; avoid before 11 weeks if possible
• IV fluids: 0.9% NaCl with 20-40 mmol/L KCl; avoid dextrose-containing fluids initially
• Thiamine: 100mg TDS oral or IV — give BEFORE any dextrose-containing fluids to prevent Wernicke's
• Thromboprophylaxis: LMWH during admission if dehydrated/immobilised (RCOG guidance)

Surgical/Interventional

• Not applicable; rarely, total parenteral nutrition (TPN) or NG/NJ feeding may be needed for extreme refractory cases

Referral Criteria

• Unable to tolerate oral fluids — hospital admission
• Weight loss >5% or ketonuria ≥3+ — hospital assessment
• Neurological symptoms (confusion, ataxia) — emergency assessment for Wernicke's
• Significant psychological distress — perinatal mental health support
• Persistent symptoms beyond 20 weeks — specialist obstetric review

• Resolution: Symptoms resolve by 16-20 weeks in ~90% of cases
• Persistent symptoms: ~10% continue beyond 20 weeks; ~1-3% have symptoms throughout pregnancy
• Recurrence: ~50-80% recurrence risk in subsequent pregnancies
• Fetal outcomes: Generally good; slight increased risk of SGA and preterm birth with severe HG
• Maternal outcomes: Excellent with appropriate management; Wernicke's encephalopathy is preventable with thiamine
• Psychological: Significant long-term psychological impact in some women — PTSD-like symptoms, reluctance to have further pregnancies
• Rare complications: Mallory-Weiss tear, oesophageal rupture, central pontine myelinolysis (rapid sodium correction), splenic avulsion

PUQE Score (Pregnancy-Unique Quantification of Emesis)

Antiemetic Stepwise Approach