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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Question 1ReproductiveEasy
A 28-year-old female at 10 weeks gestation has nausea and vomiting that has failed lifestyle modifications and vitamin B6. She has lost 4 lbs. She is now vomiting 8-10 times per day and is dehydrated with ketones in urine. Which of the following is the most likely diagnosis?
  • AViral gastroenteritis
  • BGastroparesis
  • CHyperemesis gravidarum
  • DNormal pregnancy nausea
Reveal answer & full explanation
Correct answer: C — Hyperemesis gravidarum
  • AViral gastroenteritis
  • BGastroparesis
  • CHyperemesis gravidarum
  • DNormal pregnancy nausea

Why Hyperemesis gravidarum is correct

  • Hyperemesis gravidarum is defined by intractable vomiting causing weight loss over 5%, dehydration, and ketonuria in pregnancy — all present here (4 lb loss, 8–10 vomiting episodes/day, dehydration, ketonuria)
  • Failure of lifestyle modifications and vitamin B6 further supports this diagnosis over normal pregnancy nausea

Why the others are wrong

  • A) Viral gastroenteritis — an acute, self-limited illness usually accompanied by diarrhea and often fever; it does not explain vomiting that has persisted long enough for lifestyle measures and vitamin B6 to be tried and to fail in the first trimester
  • B) Gastroparesis — chronic delayed gastric emptying, not specific to pregnancy; typically has no ketonuria in the acute setting and does not follow the pattern of pregnancy-related emesis
  • D) Normal pregnancy nausea — does not cause >5% weight loss, significant dehydration, or ketonuria; responds to lifestyle changes and vitamin B6

Additional high-yield points

  • IV fluids: normal saline (NS) or lactated Ringer's (LR) — avoid dextrose until thiamine is given to prevent Wernicke encephalopathy
  • Thiamine 100 mg IV must be given before dextrose
  • Antiemetics: ondansetron (pregnancy category B/C, avoid in first trimester if possible), promethazine, metoclopramide, prochlorperazine
  • Vitamin B6 (pyridoxine) plus doxylamine (Diclegis) is FDA-approved for nausea and vomiting of pregnancy (NVP)
  • Refractory cases: short course methylprednisolone
  • Severe cases unresponsive to treatment: total parenteral nutrition
Question 2ReproductiveMedium
A 26-year-old woman at 10 weeks gestation presents with 2 weeks of intractable vomiting and inability to keep down liquids. She reports a 6-kg weight loss from her pre-pregnancy weight. On exam she has dry mucous membranes, a heart rate of 112/min, and orthostatic hypotension. Pelvic ultrasound confirms a single intrauterine pregnancy with normal cardiac activity and no molar features. Urinalysis shows large ketones. Which of the following serum laboratory findings best supports the diagnosis of hyperemesis gravidarum?
  • ANon-anion-gap metabolic acidosis, hyperkalemia
  • BHigh-anion-gap metabolic acidosis, hyperglycemia
  • CHyperchloremic metabolic alkalosis, hypernatremia
  • DHypochloremic, hypokalemic metabolic alkalosis
Reveal answer & full explanation
Correct answer: D — Hypochloremic, hypokalemic metabolic alkalosis
  • ANon-anion-gap metabolic acidosis, hyperkalemia
  • BHigh-anion-gap metabolic acidosis, hyperglycemia
  • CHyperchloremic metabolic alkalosis, hypernatremia
  • DHypochloremic, hypokalemic metabolic alkalosis

Why Hypochloremic, hypokalemic metabolic alkalosis is correct

  • Protracted vomiting strips the stomach of hydrogen and chloride ions, generating a metabolic alkalosis; the kidney's effort to retain Na+ and excrete the bicarbonate load drives K+ loss, producing the classic hypochloremic, hypokalemic metabolic alkalosis seen in hyperemesis gravidarum.
  • This pattern, together with ketonuria, an elevated BUN/Cr ratio, and a high urine specific gravity from dehydration, is the expected metabolic picture and supports the clinical diagnosis once molar pregnancy and other causes are excluded by ultrasound and labs.

Why the others are wrong

  • High-anion-gap metabolic acidosis, hyperglycemia: this is the pattern of diabetic ketoacidosis; HG produces starvation ketosis with alkalosis from vomiting, not a hyperglycemic high-gap acidosis.
  • Non-anion-gap metabolic acidosis, hyperkalemia: suggests bicarbonate loss from diarrhea or type 4 RTA; vomiting causes the opposite acid-base and potassium derangement.
  • Hyperchloremic metabolic alkalosis, hypernatremia: vomiting loses chloride, so HG is hypochloremic, not hyperchloremic; serum sodium tends to fall with dehydration and renal compensation rather than rise. The diagnosis of HG remains clinical (persistent vomiting, >5% weight loss, ketonuria or electrolyte derangement) after other causes are excluded.
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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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