In a woman in her first trimester presenting with persistent vomiting, weight loss, and dehydration, how do I differentiate hyperemesis gravidarum from infectious gastroenteritis and what are the appropriate treatments for each condition?

Differentiating Hyperemesis Gravidarum from Gastroenteritis in First Trimester

Hyperemesis gravidarum (HG) is distinguished from gastroenteritis by its onset before 22 weeks gestation, absence of fever or infectious prodrome, weight loss ≥5% of pre-pregnancy weight, ketonuria, and symptom duration extending beyond 24-48 hours—whereas gastroenteritis typically presents with acute onset, fever, diarrhea, and resolution within 1-3 days. 1, 2

Key Clinical Differentiators

Hyperemesis Gravidarum Features

• Timing: Onset before week 22 of gestation, typically starting at 6-8 weeks 1
• Vomiting pattern: Persistent, intractable vomiting without relief, often triggered by specific odors or foods 1
• Associated symptoms: Severe nausea without diarrhea as primary feature, ptyalism (excessive salivation) 1, 2
• Weight trajectory: Progressive weight loss ≥5% of pre-pregnancy weight 1, 2
• Laboratory findings: Ketonuria, electrolyte imbalances (hypokalemia, hyponatremia, hypochloremia), metabolic alkalosis, elevated liver enzymes in 40-50% of cases (rarely >1,000 U/L) 1, 2, 3
• Physical exam: Orthostatic hypotension, decreased skin turgor, dry mucous membranes, muscle wasting in severe cases 1

Gastroenteritis Features

• Timing: Can occur at any gestational age, acute onset over hours
• Vomiting pattern: Acute, self-limited, often accompanied by prominent diarrhea
• Associated symptoms: Fever, abdominal cramping, myalgias, recent sick contacts or food exposure
• Duration: Typically resolves within 24-72 hours
• Laboratory findings: Normal or mildly elevated liver enzymes, possible metabolic acidosis (from diarrhea), absence of ketonuria after initial rehydration

Diagnostic Workup

Essential Laboratory Tests

• Electrolyte panel: Check sodium, potassium, chloride, magnesium—HG causes hypokalemia (can be severe at 2.2 mEq/L), hyponatremia, hypochloremia 2, 3
• Urinalysis: Ketonuria confirms inadequate caloric intake and supports HG diagnosis 2, 4
• Liver function tests: AST/ALT elevated in 40-50% of HG cases; if >1,000 U/L, consider alternative hepatobiliary pathology 1, 2
• Renal function: BUN/creatinine ratio elevated in dehydration; severe HG can cause acute kidney injury with creatinine >6 mg/dl 3
• Venous blood gas: Metabolic alkalosis suggests HG (from vomiting gastric acid), metabolic acidosis suggests gastroenteritis (from diarrhea) 2
• Thyroid function tests: Only if clinical hyperthyroidism signs present; biochemical hyperthyroidism common in HG but rarely requires treatment 2

Imaging

• Abdominal ultrasound: Rule out multiple/molar pregnancy, gallstones, cholecystitis, hepatobiliary pathology 1, 2

Red Flags Suggesting Alternative Diagnosis

• Fever >38°C suggests infection 1
• Abdominal pain out of proportion to vomiting suggests surgical abdomen
• Neurologic symptoms (confusion, ataxia, eye movement abnormalities) suggest Wernicke's encephalopathy from thiamine deficiency 2
• Persistent liver enzyme elevation despite symptom resolution warrants investigation for other liver disease 2

Treatment Algorithm for Hyperemesis Gravidarum

Immediate Stabilization (All Patients)

• IV fluid resuscitation: Correct dehydration targeting urine output ≥1 L/day and resolution of ketonuria 2, 4
• Electrolyte replacement: Aggressive potassium and magnesium repletion—hypokalemia with hypomagnesemia prolongs QT interval and increases arrhythmia risk 2, 4
• Thiamine supplementation: Critical to prevent Wernicke's encephalopathy—start 100 mg daily orally for minimum 7 days, then 50 mg daily maintenance; if vomiting persists or oral intake impossible, switch immediately to IV thiamine 200-300 mg daily 1, 2, 4
• ECG monitoring: Check QT interval if electrolyte abnormalities present 2

Stepwise Pharmacologic Management

First-Line (Mild to Moderate):

• Doxylamine-pyridoxine combination: 10-20 mg doxylamine + 10-20 mg pyridoxine, preferred initial antiemetic, safe throughout pregnancy 1, 2, 4
• Alternative first-line: Promethazine or other H1-antihistamines 1, 4
• Ginger: 250 mg capsule four times daily 1

Second-Line (Moderate to Severe):

• Metoclopramide: 5-10 mg orally/IV every 6-8 hours—preferred over promethazine due to less drowsiness, dizziness, dystonia, and fewer discontinuations despite similar efficacy 1, 2, 4
• Ondansetron: 8 mg orally/IV every 8 hours—reserve as second-line due to concerns about congenital heart defects when used before 10 weeks gestation (though recent data suggest low risk); use case-by-case before 10 weeks 1, 2, 4
• Caution: Withdraw metoclopramide or promethazine immediately if extrapyramidal symptoms develop 2, 4

Third-Line (Severe Refractory Cases):

• Methylprednisolone: 16 mg IV every 8 hours for up to 3 days, then taper over 2 weeks to lowest effective dose, maximum duration 6 weeks—reserve as last resort only after first and second-line therapies fail 1, 2, 4
• Risk: Slight increased risk of cleft palate if given before 10 weeks gestation 2, 4

Nutritional Support

• Dietary modifications: Small, frequent, bland meals (BRAT diet: bananas, rice, applesauce, toast), high-protein/low-fat meals, avoid strong odors and specific triggers 1, 2
• Enteral feeding: Nasojejunal tube (better tolerated than nasogastric) for patients with ≥5-7 vomiting episodes daily despite maximal antiemetics, progressive weight loss ≥5%, or inability to maintain 1,000 kcal/day for several days 2
• Parenteral nutrition: Consider only after enteral feeding fails 2

Monitoring Parameters

• Daily until stable: Weight, urine output, electrolytes, renal function 2
• Serial assessment: PUQE (Pregnancy-Unique Quantification of Emesis) score to track symptom severity 2, 4
• Thiamine status: Check every trimester, especially with inadequate weight gain 2
• Fetal monitoring: Monthly growth scans from viability in severe cases 2, 4

Treatment for Gastroenteritis in Pregnancy

Supportive Care

• Oral rehydration: Glucose-electrolyte solutions preferred over plain water 2
• IV fluids: If unable to tolerate oral intake, use isotonic crystalloid
• Antiemetics: Ondansetron 4-8 mg as needed (safe in pregnancy for short-term use)
• Dietary advancement: Clear liquids → BRAT diet → regular diet as tolerated
• Avoid: NSAIDs, bismuth subsalicylate (teratogenic), fluoroquinolones

When to Suspect Gastroenteritis is Actually HG

• Symptoms persist beyond 72 hours without fever or diarrhea resolution 1
• Development of ketonuria or significant weight loss 2
• Recurrent episodes throughout first trimester 1

Critical Pitfalls to Avoid

• Do not delay thiamine: Start immediately in all HG patients—thiamine stores deplete within 7-8 weeks of persistent vomiting, and reserves can be exhausted after only 20 days of inadequate intake 2
• Do not use PRN antiemetics in severe cases: Switch to scheduled around-the-clock dosing for continuous symptom control 2
• Do not tell patients to "drink more water": Hypotonic fluids worsen losses; use glucose-electrolyte solutions 2
• Do not skip the stepwise approach: Jumping directly to corticosteroids or olanzapine violates evidence-based guidelines 2
• Do not overlook QT prolongation: Monitor ECG with ondansetron use, especially with electrolyte abnormalities 2

Multidisciplinary Involvement

Severe refractory HG requires coordination with maternal-fetal medicine, gastroenterology, nutrition services, and mental health professionals—anxiety and depression are common with severe HG 1, 2, 4

Expected Course

HG symptoms resolve by week 16 in >50% of patients and by week 20 in 80%, though 10% experience symptoms throughout pregnancy; recurrence risk in subsequent pregnancies is 40-92% 1, 2, 4