Reproductive · PANCE / PANRE

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

StepTherapy
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
Stepwise management of nausea/vomiting of pregnancy and hyperemesis gravidarum (ACOG PB 189).

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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