Hyperemesis Gravidarum (HG)

Definition

• Persistent, severe vomiting requiring medical intervention
• Weight loss >5% of pre-pregnancy body weight
• Ketonuria (starvation metabolism)
• Fluid, electrolyte, and acid-base imbalances
• Associated features: hypersalivation (ptyalism), hyperolfaction, altered taste

Epidemiology

• Occurs in ~0.5-1% of live births (second most common cause of pregnancy-related hospitalization)
• Symptoms begin weeks 4-6, peak weeks 8-12, and typically resolve by week 14-16
• Up to 20% of affected patients have vomiting that persists until delivery
• Leads to elective pregnancy termination in ~2% of cases
• Higher risk groups: young, nulliparous, non-Caucasian women; those with hyperthyroidism, psychiatric disorders, diabetes, GI disorders, or asthma
• Recurrence: 15-19% in subsequent pregnancies if first pregnancy was affected (vs. 0.7% if first pregnancy was unaffected)
• Creasy & Resnik's Maternal-Fetal Medicine

Risk Factors / Associated Conditions

Pathophysiology

• HCG - symptoms worsen during peak HCG; HCG alpha-subunit has TSH-like activity, explaining transient gestational thyrotoxicosis (abnormal TFTs in ~two-thirds of HG patients - does not usually require treatment)
• Estrogen/progesterone - slow GI transit and alter gastric motility
• Gut hormones (ghrelin, leptin) also implicated

• Two meta-analyses confirm increased H. pylori prevalence in HG; eradication may reduce vomiting episodes

• Sleisenger and Fordtran's GI and Liver Disease

Clinical Features

• Severe, persistent nausea and vomiting
• Dry mouth, hypersalivation (ptyalism), hyperolfaction
• Triggers: olfactory, auditory, and visual stimuli
• Pyrosis, hematemesis in some

• Dry mucous membranes, poor skin turgor, hypotension
• Tachycardia, muscle wasting in severe cases

Laboratory Findings

Differential Diagnosis

• Molar pregnancy, hydatidiform mole
• Hyperthyroidism
• Viral hepatitis, liver disease
• Gastroenteritis, peptic ulcer disease
• Appendicitis (especially if lateralized pain)
• Urinary tract infection
• Vestibular disorders (if vertigo predominates)

Management

Step 1 - Dietary and Non-Pharmacologic Measures

• Multiple small meals; avoid empty stomach
• High-carbohydrate diet
• Avoid offensive odors; separate solid and liquid intake
• Ginger has documented benefit

Step 2 - IV Fluid Resuscitation (for hospitalization criteria: hypotension, tachycardia, ketosis, weight loss)

• 2 L of Lactated Ringer's infused over 3-5 hours; subsequent rate to maintain urine output >100 mL/h
• Thiamine 100 mg IV BEFORE any dextrose infusion (to prevent Wernicke encephalopathy)
• After initial LR bolus, switch to D5/0.45NS until ketonuria clears
• Replete potassium (for hypokalemia) and magnesium/calcium (monitor regularly)
• Correct hyponatremia slowly (risk of central pontine myelinolysis if corrected too rapidly)

Step 3 - Pharmacologic Antiemetics (stepwise)

Step 4 - Refractory/Recalcitrant Cases

• Methylprednisolone 16 mg PO/IV q8h x 3 days then 2-week taper
• IV hydrocortisone 300 mg/day x 3 days then taper over 1 week
• Results are conflicting across trials, but some show reduced readmission
• Caution in first trimester - possible weak association with facial clefting (1-2 per 1000 treated)
• Avoid during organogenesis if possible

• Transdermal clonidine (limited data)
• Oral mirtazapine (limited data, fetal effects unknown)
• H. pylori testing and eradication (benefit not fully established)

Step 5 - Nutritional Support

• Enteral nutrition via NG tube - preferred over parenteral, for patients who cannot maintain weight despite medical therapy
• Total Parenteral Nutrition (TPN) - reserved as last resort due to significant complications:
  • Catheter sepsis (~25%)
  • Venous thrombosis (~3%)
  • PICC lines: overall complication rate 50%, severe complications 22%

Complications

• Wernicke encephalopathy (thiamine deficiency) - apathy, drowsiness, ophthalmoplegia, nystagmus, ataxia, memory loss, catatonia - typically presents weeks 14-20
• Mallory-Weiss tears / hematemesis
• Boerhaave syndrome (esophageal rupture)
• Central pontine myelinolysis
• Retinal hemorrhage
• Spontaneous pneumomediastinum
• Gestational polyneuropathy
• Depression, PTSD during pregnancy and postpartum
• Hypokalemia-induced cardiac or respiratory arrest (rare)

• Low birth weight
• Small for gestational age
• Prematurity
• Low 5-minute Apgar scores
• Vitamin K deficiency and bleeding diatheses (if maternal nutrition severely depleted)

Transient Gestational Thyrotoxicosis

Fetal Outcomes

• Low birth weight
• Prematurity
• Small for gestational age
• Apgar scores <7

Recent Evidence (2024-2026)