What is the initial approach to diagnose and manage a pregnant woman presenting with symptoms suggestive of hyperemesis gravidarum?

Hyperemesis Gravidarum Diagnosis and Initial Management

Diagnostic Criteria

Hyperemesis gravidarum is diagnosed clinically by the presence of persistent vomiting, weight loss ≥5% of pre-pregnancy weight, dehydration, and ketonuria, typically occurring before 22 weeks gestation. 1

The diagnosis requires:

• Persistent vomiting with inability to maintain adequate oral intake 1
• Weight loss ≥5% of pre-pregnancy weight 1
• Clinical dehydration (dry mucous membranes, decreased skin turgor, tachycardia, orthostatic hypotension) 1
• Ketonuria on urinalysis 1

Note that ketonuria alone does not determine severity—it simply confirms inadequate caloric intake 2. The diagnosis is primarily clinical, not laboratory-based.

Initial Clinical Assessment

History and Physical Examination

Obtain specific details about:

• Vomiting frequency and duration (≥5-7 episodes daily suggests severe disease) 1
• Pre-pregnancy weight and current weight to calculate percentage loss 1
• Prior history of hyperemesis gravidarum (strongest risk factor for recurrence) 1
• Risk factors: hyperthyroid disorders, molar pregnancy, multiple gestation, female fetus, diabetes, asthma 1
• Neurologic symptoms: confusion, ataxia, eye movement abnormalities (suggests Wernicke's encephalopathy) 1

Physical examination must focus on:

• Dehydration signs: dry mucous membranes, decreased skin turgor, tachycardia, orthostatic vital signs 1
• Neurologic examination for neuropathy or vitamin deficiency 1
• Nutritional status assessment 1

Severity Scoring

Use the Motherisk Pregnancy-Unique Quantification of Emesis (PUQE) score to objectively assess severity and track response to treatment over time 1, 3. This evaluates nausea duration, vomiting frequency, and retching frequency over 12 hours 3.

Essential Diagnostic Workup

Required Laboratory Tests

• Electrolyte panel (sodium, potassium, chloride, bicarbonate) to detect hyponatremia, hypokalemia, hypochloremia, and alkalemia 1, 4
• Liver function tests (AST, ALT)—approximately 50% of patients have abnormal transaminases, though rarely >1,000 U/L 1
• Urinalysis for ketonuria 1
• Thyroid function tests (TSH, free T4)—hCG has thyroid-stimulating activity and can cause biochemical hyperthyroidism 1, 3
• Renal function (creatinine, BUN) to assess for acute kidney injury 4

Imaging

Abdominal/pelvic ultrasonography is essential to:

• Detect multiple or molar pregnancies (both cause extremely elevated hCG and worsen hyperemesis) 1, 5
• Assess fetal growth 1
• Rule out hepatobiliary causes (gallstones, cholecystitis occur in 40-50% with elevated liver enzymes) 1
• Exclude renal or vascular pathology 1

Immediate Management Algorithm

Step 1: Stabilization and Prevention of Complications

Immediate intravenous fluid resuscitation is the cornerstone of initial management 1, 3. This corrects dehydration and often improves liver chemistry abnormalities 1.

Critical: Thiamine supplementation must be started immediately to prevent Wernicke's encephalopathy 1, 3:

• Thiamine 300 mg orally daily if patient can tolerate oral intake 1
• If vomiting persists or oral intake impossible: thiamine 200-300 mg IV daily for at least 3-5 days 1
• For suspected Wernicke's encephalopathy: thiamine 500 mg IV three times daily (1,500 mg total) 1

Electrolyte replacement with particular attention to:

• Potassium (aim for ≥3.0 mmol/L) 1
• Magnesium 1

Step 2: First-Line Antiemetic Therapy

Doxylamine 10-20 mg combined with pyridoxine (vitamin B6) 10-20 mg every 8 hours is the preferred first-line pharmacologic treatment 1. This combination is safe throughout pregnancy and breastfeeding 1.

Alternative first-line agents with similar safety profiles 1:

• Promethazine (antihistamine) 1
• Cyclizine (antihistamine) 1
• Prochlorperazine (phenothiazine) 1

Withdraw phenothiazines immediately if extrapyramidal symptoms develop 1.

Step 3: Second-Line Therapy for Inadequate Response

Metoclopramide is the preferred second-line agent when first-line antihistamines fail, with less drowsiness and fewer discontinuations compared to promethazine 1.

Ondansetron should be reserved as second-line therapy due to concerns about congenital heart defects when used before 10 weeks gestation, though recent data suggest the risk is low 1. Use on a case-by-case basis before 10 weeks 1.

Step 4: Third-Line Therapy for Severe Refractory Cases

Methylprednisolone is reserved as last resort for severe hyperemesis that fails other therapies 1:

• Dosing: 16 mg IV every 8 hours for up to 3 days 1
• Then taper over 2 weeks to lowest effective dose 1
• Maximum duration: 6 weeks 1
• Caution in first trimester: slight increased risk of cleft palate before 10 weeks gestation 1

Non-Pharmacologic Interventions

• Small, frequent, bland meals (BRAT diet: bananas, rice, applesauce, toast) 1
• High-protein, low-fat meals 1
• Avoidance of specific food triggers and strong odors 1
• Ginger supplementation 250 mg four times daily may be considered 1

Critical Pitfalls to Avoid

Do not rely on ketonuria to determine severity—it only confirms inadequate intake, not disease severity 2.

Do not use PRN or intermittent antiemetic dosing in severe cases—switch to around-the-clock scheduled administration for better symptom control 1.

Do not skip the stepwise approach—jumping directly to corticosteroids or alternative agents like olanzapine violates evidence-based guidelines 1.

Do not delay thiamine supplementation—pregnancy increases thiamine requirements, and hyperemesis rapidly depletes stores within 7-8 weeks, with complete exhaustion possible after only 20 days of inadequate intake 1.

Persistent liver chemistry abnormalities despite symptom resolution should prompt investigation for another etiology (gallstones, cholecystitis, viral hepatitis) 1.

Monitoring and Follow-up

• Serial PUQE scores to track symptom trajectory 1, 3
• Regular assessment of hydration status and electrolyte balance 1, 3
• Weight monitoring—stabilization or gain (not continued loss) is critical for clinical improvement 1
• Fetal growth monitoring, especially with insufficient maternal weight gain—monthly scans from viability in severe cases 1, 3

When to Hospitalize

Hospitalization is required for 1:

• Refractory symptoms despite outpatient management 1
• Organ dysfunction (acute kidney injury, severe transaminasemia) 4
• Inability to maintain oral intake of 1,000 kcal/day for several days 1
• Progressive weight loss ≥5% despite treatment 1
• Electrolyte abnormalities requiring IV correction 4

Prognosis and Patient Education

Symptoms typically resolve by week 16 in >50% of patients and by week 20 in 80%, though 10% may experience symptoms throughout pregnancy 1.

Recurrence risk is high (40-92%) in subsequent pregnancies 1.

Early intervention is crucial to prevent progression from mild nausea and vomiting to hyperemesis gravidarum 1.

Untreated hyperemesis is associated with low birth weight, small for gestational age infants, premature delivery, and decreased maternal quality of life 1.