Hyperemesis Gravidarum
Severe nausea and vomiting of pregnancy with weight loss, dehydration, and electrolyte derangement.
Also known as: hyperemesis gravidarum, HG, severe morning sickness, NVP
Overview
Severe persistent nausea and vomiting in pregnancy producing >5% pre-pregnancy weight loss, dehydration, ketonuria, and electrolyte abnormalities. Distinguished from typical nausea and vomiting of pregnancy (NVP) by severity and functional impairment.
Epidemiology
Affects 0.3-3% of pregnancies; most common cause of antepartum hospitalization in the first half of pregnancy. Onset usually 4-9 weeks; peaks at 9-13 weeks; resolves by 20 weeks in most.
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Risk factors
- Prior HG (recurrence rate ~15-80%)
- Multiple gestation, molar pregnancy (very high beta-hCG)
- Female fetus, family history
- History of motion sickness, migraine, hyperthyroidism
- GDF15 genetic variation (emerging evidence)
Pathophysiology
Likely multifactorial. Elevated beta-hCG and estrogen levels are strongly implicated; H. pylori infection, altered GI motility, hepatic dysfunction, and recent evidence implicating placental hormone GDF15 acting on hindbrain receptors all contribute.
Clinical presentation
Symptoms
- Persistent vomiting, often unable to tolerate liquids or solids
- Weight loss, fatigue, lightheadedness
- Hypersalivation (ptyalism), heightened sense of smell
Signs / physical exam
- Dry mucous membranes, orthostatic hypotension, tachycardia
- Weight loss documented; possible muscle wasting
- Mild jaundice or epigastric tenderness in severe cases
Differential diagnosis
- Gestational trophoblastic disease (molar pregnancy) — Very high beta-hCG, no fetal heart tones, 'snowstorm' on US, hyperthyroid features
- Acute fatty liver of pregnancy — Third trimester, hypoglycemia, coagulopathy, RUQ pain
- Gastroenteritis — Diarrhea prominent, fever, sick contacts
- Cholecystitis / pancreatitis — Localized RUQ or epigastric pain, elevated LFTs/lipase, gallstones on US
- Hyperthyroidism / thyroid storm — Tachycardia, weight loss, heat intolerance; TSH suppressed; gestational transient hyperthyroidism can co-exist with HG
- DKA — Type 1 DM, anion gap acidosis, hyperglycemia, ketonemia
- UTI / pyelonephritis — Dysuria, CVA tenderness, UA positive
- Increased intracranial process — Headache, focal neuro signs, papilledema
Diagnostic workup
Diagnostic criteria
Clinical: persistent vomiting + >5% pre-pregnancy weight loss + ketonuria/electrolyte derangement, after exclusion of other causes.
Labs
- Urinalysis with ketones and specific gravity
- BMP: hypokalemia, hyponatremia, hypochloremic metabolic alkalosis (from vomiting); BUN/Cr ratio elevated with dehydration
- TSH and free T4: transient gestational hyperthyroidism (suppressed TSH with normal or mildly elevated free T4) common — typically no antithyroid therapy needed
- LFTs (mild AST/ALT elevation up to 200 may occur), amylase/lipase if epigastric pain
- Beta-hCG (rule out molar pregnancy if very high)
Imaging
- Pelvic ultrasound: confirm intrauterine pregnancy, viability, multiple gestation, exclude molar pregnancy
Diagnostic algorithm
| Step | Therapy |
|---|---|
| 1 (Lifestyle) | Small frequent meals, avoid triggers, ginger, acupressure |
| 2 (First-line) | Pyridoxine (B6) +/- doxylamine (Diclegis) |
| 3 (Add) | Antihistamine (dimenhydrinate, meclizine) OR dopamine antagonist (promethazine, metoclopramide) |
| 4 (Refractory) | Ondansetron; methylprednisolone (after 10 wk only) |
| 5 (Severe) | IV hydration (thiamine FIRST), enteral feeding, rare TPN |
Treatment
First-line
- Step 1 (mild): dietary modification — small frequent bland meals, avoid triggers, ginger 250 mg QID, acupressure wristbands
- Step 2: pyridoxine (vitamin B6) 10-25 mg PO every 6-8 h, with or without doxylamine 12.5 mg PO every 6-8 h (combination product Diclegis/Bonjesta is first-line FDA-approved therapy)
- Step 3 (refractory): add antihistamine (dimenhydrinate, diphenhydramine, meclizine) or dopamine antagonist (promethazine, prochlorperazine, metoclopramide)
- Step 4 (severe/refractory): ondansetron (after first-trimester counseling — small association with cleft palate at high doses), or methylprednisolone (use AFTER 10 wk to minimize oral cleft risk)
Hospitalization indication
- Inability to tolerate oral intake despite outpatient therapy, dehydration, electrolyte derangement, or >5% weight loss
- IV crystalloid (LR or NS), thiamine 100 mg before any dextrose to prevent Wernicke encephalopathy
- Repletion of potassium, magnesium
- Antiemetics IV/IM until tolerating PO
Second-line / adjunct
- Enteral feeding (NG, NJ) if persistent inability to tolerate PO and weight loss continues
- Parenteral nutrition reserved for refractory cases — high risk of line sepsis, hepatic dysfunction, thrombosis
Complications
- Wernicke encephalopathy (from thiamine deficiency) — confusion, ataxia, ophthalmoplegia; classically precipitated by IV dextrose without prior thiamine
- Mallory-Weiss tear, esophageal rupture (Boerhaave), pneumomediastinum
- Central pontine myelinolysis from rapid sodium correction
- Acute kidney injury from dehydration
- Maternal depression and anxiety; reduced fetal growth in severe sustained disease
PANCE pearls
- Always give thiamine BEFORE dextrose-containing fluids in any patient with prolonged vomiting — failure to do so can precipitate Wernicke encephalopathy.
- Molar pregnancy should be excluded by ultrasound in any patient with severe HG; the very high beta-hCG and hyperthyroidism it causes can mimic primary HG.
- Doxylamine + pyridoxine is the first-line, pregnancy-safe (Category A) pharmacotherapy and should be started before ondansetron.
- Transient gestational hyperthyroidism in HG resolves spontaneously by 18-20 weeks; antithyroid drugs are generally not indicated.
- Methylprednisolone should be avoided before 10 weeks gestation due to a small increase in oral clefts.
References
- ACOG PB 189 — ACOG Practice Bulletin 189: Nausea and Vomiting of Pregnancy (Obstet Gynecol 2018)
- ACOG CO 814 — ACOG Committee Opinion: Care for Patients with HG
- PUQE Score — Koren et al., Pregnancy-Unique Quantification of Emesis (PUQE) score
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