Hyperemesis Gravidarum
Hyperemesis gravidarum (HG) is the severe end of the spectrum of nausea and vomiting of pregnancy (NVP), characterized by persistent vomiting leading to:
- Weight loss >5% of prepregnancy weight
- Dehydration
- Ketosis/ketonuria
- Electrolyte abnormalities
- Nutritional deficiency
- Functional impairment
It is the most common cause of hospital admission during the first half of pregnancy.
Pathophysiology
The exact mechanism remains unclear and is likely multifactorial.
1. Hormonal Factors
Human Chorionic Gonadotropin (hCG)
Strongest association.
- Symptoms peak when hCG peaks (9–12 weeks)
- Multiple pregnancy → higher hCG
- Molar pregnancy → very high hCG
- Female fetus associated with increased risk
Estrogen
- Delay gastric emptying
- Increase nausea sensitivity
Progesterone
- Reduced GI motility
- Lower esophageal sphincter relaxation
- Gastric dysrhythmias
2. GDF-15 (Growth Differentiation Factor-15)
Current leading hypothesis.
Placenta produces GDF-15.
Higher levels found in women with HG.
Acts on:
- Area postrema
- Brainstem vomiting center
Explains:
- Familial tendency
- Genetic susceptibility
3. Gastrointestinal Factors
- Delayed gastric emptying
- Gastric dysrhythmias
- Helicobacter pylori infection (possible association)
4. Genetic Factors
Risk increased if:
- Mother had HG
- Sister had HG
- Previous pregnancy affected
Genes implicated:
- GDF15
- IGFBP7
Risk Factors
|
Maternal Factors |
Pregnancy Factors |
|
Previous HG |
Multiple gestation |
|
First pregnancy |
Molar pregnancy |
|
Female fetus |
High hCG levels |
|
Obesity |
Trophoblastic disease |
|
Motion sickness |
Twin pregnancy |
|
Migraine |
Female fetus |
|
Family history |
Placental disorders |
Clinical Features
Gastrointestinal
- Severe nausea
- Persistent vomiting
- Inability to tolerate food
- Inability to tolerate fluids
- Excessive salivation (ptyalism)
Consequences
- Weight loss
- Fatigue
- Dizziness
- Weakness
- Orthostatic symptoms
Severe Disease
- Confusion
- Visual disturbances
- Muscle weakness
- Reduced urine output
Physical Examination
Mild
- Dry mucous membranes
- Tachycardia
Moderate
- Orthostatic hypotension
- Weight loss
- Reduced skin turgor
Severe
- Marked dehydration
- Oliguria
- Neurological signs
- Muscle wasting
Diagnostic Criteria
No universal criteria exist.
Commonly accepted diagnosis:
|
Criterion |
Requirement |
|
Persistent vomiting |
Present |
|
Weight loss |
>5% prepregnancy weight |
|
Ketonuria |
Often present |
|
Electrolyte abnormalities |
May occur |
|
Alternative diagnosis excluded |
Required |
Differential Diagnosis
Obstetric Causes
|
Condition |
Distinguishing Features |
|
Hyperemesis gravidarum |
Typical presentation |
|
Multiple gestation |
Large uterus, high hCG |
|
Molar pregnancy |
Vaginal bleeding, very high hCG |
|
Preeclampsia (later) |
Hypertension, proteinuria |
|
Acute fatty liver pregnancy |
Third trimester |
|
HELLP syndrome |
Hemolysis, thrombocytopenia |
Gastrointestinal Causes
|
Condition |
Clues |
|
Gastroenteritis |
Diarrhea, fever |
|
Peptic ulcer disease |
Epigastric pain |
|
Cholecystitis |
RUQ pain |
|
Pancreatitis |
Elevated lipase |
|
Hepatitis |
Marked LFT elevation |
|
Bowel obstruction |
Distension, constipation |
|
Appendicitis |
Localized pain |
Endocrine/Metabolic Causes
|
Condition |
Clues |
|
Hyperthyroidism |
Tremor, goiter |
|
Diabetic ketoacidosis |
Hyperglycemia |
|
Addison disease |
Hypotension |
|
Hypercalcemia |
Elevated calcium |
Neurological Causes
|
Condition |
Clues |
|
Migraine |
Headache |
|
Brain tumor |
Neurological deficits |
|
Raised ICP |
Papilledema |
Investigations
|
Investigation |
Purpose |
|
CBC |
Hemoconcentration |
|
Urea, creatinine |
Renal function |
|
Sodium |
Hyponatremia |
|
Potassium |
Hypokalemia |
|
Chloride |
Hypochloremia |
|
Magnesium |
Deficiency |
|
Calcium |
Metabolic causes |
|
LFT |
Hepatic involvement |
|
Blood glucose |
Exclude DKA |
|
Urinalysis |
Ketones, infection |
Additional Tests
|
Test |
Why |
|
TSH, Free T4 |
Gestational thyrotoxicosis |
|
Amylase/lipase |
Pancreatitis |
|
ECG |
Electrolyte effects |
|
ABG/VBG |
Severe disease |
Ultrasound
Mandatory in most cases.
Purpose:
- Confirm viable pregnancy
- Rule out molar pregnancy
- Detect multiple gestation
Laboratory Abnormalities
|
Abnormality |
Mechanism |
|
Ketonuria |
Starvation |
|
Hypokalemia |
Vomiting |
|
Hyponatremia |
Fluid loss |
|
Hypochloremia |
Gastric acid loss |
|
Metabolic alkalosis |
Vomiting |
|
Metabolic acidosis |
Starvation ketosis |
|
Elevated AST/ALT |
Common |
|
Elevated bilirubin |
Dehydration |
|
Elevated hematocrit |
Hemoconcentration |
Complications
Maternal
Fluid/Electrolyte
- Severe dehydration
- AKI
- Hypokalemia
- Hyponatremia
Nutritional
- Malnutrition
- Vitamin deficiencies
- Hypoproteinemia
Neurological
- Wernicke encephalopathy
- Peripheral neuropathy
- Central pontine myelinolysis (rare)
Hematologic
- Venous thromboembolism
Gastrointestinal
- Mallory-Weiss tear
- Esophageal rupture (rare)
Fetal
|
Complication |
Risk |
|
Low birth weight |
Increased |
|
Small for gestational age |
Increased |
|
Preterm birth |
Slight increase |
|
Congenital anomalies |
Not increased |
|
Fetal loss |
Usually not increased if treated |
Wernicke Encephalopathy
The most feared complication.
Cause-Thiamine deficiency due to prolonged vomiting.
Classical Triad
|
Feature |
Description |
|
Ophthalmoplegia |
Nystagmus, gaze palsy |
|
Ataxia |
Gait disturbance |
|
Confusion |
Altered mental status |
Only one-third have complete triad.
Prevention
Always administer thiamine before glucose-containing fluids.
Recommended Dose
- Thiamine 100–500 mg IV daily
- Before dextrose administration
Management
Goals
- Correct dehydration
- Correct electrolytes
- Stop vomiting
- Restore nutrition
- Prevent complications
Outpatient Management
Suitable if:
- Mild symptoms
- Tolerating some oral intake
- No major electrolyte abnormalities
Dietary Measures
General Advice
- Small frequent meals
- Dry foods
- High-protein snacks
- Avoid fatty foods
- Avoid strong odors
Useful Foods
- Crackers
- Toast
- Rice
- Potatoes
- Bananas
Pharmacologic Treatment
First-Line Therapy
Pyridoxine (Vitamin B6)
- 10–25 mg PO every 6–8 hr
Doxylamine
- 12.5 mg every 6–8 hr
Combination is guideline-preferred first-line treatment.
Antiemetics
|
Drug |
Dose |
|
Metoclopramide |
10 mg q8h |
|
Promethazine |
12.5–25 mg |
|
Prochlorperazine |
5–10 mg |
|
Dimenhydrinate |
50 mg |
|
Cyclizine |
50 mg |
Serotonin Antagonist
Ondansetron-4–8 mg PO/IV
Useful second-line therapy.
Corticosteroids
Reserved for refractory disease.
Regimen-Hydrocortisone 100 mg IV q12h
ThenPrednisolone 40–50 mg/day
Gradual taper.
Avoid before 10 weeks if possible.
Inpatient Management
Indications for Admission
|
Indication |
|
Inability to tolerate oral intake |
|
Weight loss >5% |
|
Significant dehydration |
|
Electrolyte abnormalities |
|
Ketonuria |
|
Failed outpatient therapy |
|
AKI |
|
Severe symptoms |
Intravenous Fluids
Preferred
Normal saline + potassium replacement.
Avoid excessive dextrose initially.
Thiamine
Before glucose administration.
Example
- Thiamine 100 mg IV
- Then dextrose-containing fluids if needed
Nutritional Support
Enteral Nutrition
Preferred whenever possible.
Methods:
- Nasogastric tube
- Nasojejunal tube
Total Parenteral Nutrition (TPN)
Only when:
- Enteral feeding fails
- Severe malnutrition develops
Risks:
- Sepsis
- Thrombosis
- Liver dysfunction