Hyperemesis Gravidarum

Hyperemesis gravidarum (HG) is the severe, intractable end of the spectrum of nausea and vomiting of pregnancy (NVP) — distinguished from ordinary "morning sickness" by persistent vomiting causing weight loss, dehydration, ketonuria and electrolyte/acid-base derangement. It is a clinical diagnosis of exclusion, and its single biggest NEET PG trap is the thiamine-before-dextrose rule to prevent Wernicke's encephalopathy.

Definition & classification

NVP affects up to 70–80% of pregnancies and is physiological. HG is the pathological extreme, occurring in roughly 0.3–3% of pregnancies, and is the commonest indication for hospital admission in the first half of pregnancy.

Classically HG is defined by a triad:

1. Persistent, intractable vomiting (not relieved by routine measures)
2. Weight loss > 5% of pre-pregnancy body weight
3. Dehydration with ketonuria and electrolyte imbalance (hypokalaemia, hyponatraemia, hypochloraemic metabolic alkalosis)

High-yield: The defining laboratory hallmark separating HG from simple morning sickness is ketonuria + electrolyte disturbance + >5% weight loss. Mere frequent vomiting without these is not HG.

A useful clinical severity tool is the PUQE score (Pregnancy-Unique Quantification of Emesis), which grades NVP from the number of vomiting/retching episodes and hours of nausea per day.

PUQE-24 score	Severity
≤ 6	Mild
7–12	Moderate
≥ 13	Severe

Etiology & pathophysiology

The cause is multifactorial, but the dominant association is with human chorionic gonadotropin (β-hCG). hCG shares a common α-subunit with TSH and stimulates the thyroid (thyrotropic effect), so HG is frequently accompanied by biochemical/gestational transient hyperthyroidism.

Conditions with high hCG levels therefore strongly predispose to HG:

• Molar pregnancy (hydatidiform mole) — extremely high hCG
• Multiple gestation (twins, triplets)
• Female fetus (slightly higher risk)
• Previous HG (recurrence risk is significant)

Other contributors:

• Oestrogen and progesterone — relax lower oesophageal sphincter and slow gastric emptying.
• Helicobacter pylori — associated in some studies.
• Psychological / genetic factors — recently the gene GDF15 (growth differentiation factor 15) has been strongly implicated; high fetal GDF15 with low maternal pre-pregnancy sensitivity precipitates severe vomiting.
• Thyroid dysfunction — transient gestational thyrotoxicosis.

High-yield: Always rule out a molar pregnancy and multiple gestation in severe HG — an early ultrasound is mandatory. Disproportionately severe HG = think mole/twins.

Pathophysiologic cascade (flow):

Persistent vomiting → loss of gastric HCl + dehydration → hypochloraemic, hypokalaemic metabolic alkalosis → starvation → ketosis/ketonuria → if prolonged and untreated → thiamine (B1) depletion → Wernicke's encephalopathy + Mallory-Weiss tears + acute kidney injury.

A subtle point: although vomiting classically causes alkalosis, severe starvation ketosis and dehydration can later add a metabolic acidosis, so a mixed picture may appear.

Clinical features

• Onset typically before 9 weeks of gestation (almost always < 16 weeks); peaks around 9–13 weeks.
• Intractable nausea and vomiting, inability to retain food/fluids.
• Weight loss, dry mucous membranes, sunken eyes, poor skin turgor, postural hypotension, tachycardia, oliguria (signs of dehydration).
• Ptyalism (excessive salivation) and dysgeusia.
• Features of transient hyperthyroidism: palpitations, tremor, heat intolerance — but usually no goitre and no ophthalmopathy (distinguishing from Graves').

High-yield: Onset of vomiting after 9–10 weeks, or new vomiting in the second/third trimester, should make you doubt HG and search for another cause (gastroenteritis, hepatitis, pancreatitis, raised ICP, UTI/pyelonephritis).

Diagnosis & investigations

HG is a clinical diagnosis of exclusion. Investigations confirm severity and screen for complications/differentials.

Investigation	Typical finding in HG
Urine dipstick	Ketonuria (key), high specific gravity
Serum electrolytes	↓ Na⁺, ↓ K⁺, ↓ Cl⁻
Arterial/venous blood gas	Hypochloraemic metabolic alkalosis (later acidosis possible)
Urea/creatinine	Raised (pre-renal AKI from dehydration)
LFTs	Mild transaminitis (transient, in up to 50%)
TFTs	↑ free T4, suppressed TSH (transient gestational thyrotoxicosis)
Haematocrit	Raised (haemoconcentration)
Pelvic ultrasound	Confirm viable intrauterine pregnancy; exclude mole / multiple gestation

High-yield: The investigation of choice to exclude the most dangerous mimics (molar and multiple pregnancy) is a transvaginal/abdominal ultrasound. Ketonuria on urine dipstick is the simplest bedside marker of severity.

The transient hyperthyroidism of HG (gestational transient thyrotoxicosis) does NOT require antithyroid drugs — it resolves as hCG falls (by ~18–20 weeks). Treating it with carbimazole/PTU is a classic wrong answer.

Management & drug of choice

Management is supportive + antiemetic, in a stepwise escalation. Severe cases need admission, IV rehydration, and electrolyte correction.

Stepwise approach:

1. Admit if unable to tolerate oral fluids, ketonuria, significant weight loss, or failed outpatient therapy.
2. IV fluid resuscitation → normal saline (0.9% NaCl) is preferred. Add potassium chloride as guided by serum K⁺. Avoid dextrose-containing fluids initially.
3. Thiamine (vitamin B1) supplementation BEFORE any dextrose/glucose load.
4. Antiemetics in escalating ladder.
5. Nutritional support — enteral if prolonged; TPN as last resort.

High-yield (THE classic NEET PG trap): Always give thiamine BEFORE glucose/dextrose. Administering carbohydrate to a thiamine-depleted patient consumes the remaining thiamine in glucose metabolism and precipitates Wernicke's encephalopathy. Order: Thiamine → then dextrose.

Antiemetic ladder:

Line	Drugs
First line	Pyridoxine (vitamin B6) ± doxylamine (antihistamine); antihistamines — promethazine, cyclizine
Second line	Dopamine antagonists — metoclopramide, prochlorperazine, domperidone
Third line	Ondansetron (5-HT3 antagonist)
Refractory	Corticosteroids (hydrocortisone IV → oral prednisolone)

• Pyridoxine (B6) + doxylamine is the classic recognised first-line drug of choice in pregnancy (the original "Bendectin"/Diclegis combination), with the best safety data.
• Metoclopramide is widely used and safe; watch for extrapyramidal effects.
• Ondansetron — effective; counsel on a small reported association with cleft palate/oral clefts if used in the first trimester (data debated), and QT prolongation.
• Steroids are reserved for refractory HG.

Adjuncts: thromboprophylaxis (dehydration + admission + pregnancy = high VTE risk → LMWH/TED stockings), antacids/PPIs for reflux, and antiemetic-friendly small frequent bland meals on recovery.

High-yield: Pyridoxine (B6) ± doxylamine = first-line. Steroids = last resort. Thiamine = always before dextrose. LMWH for VTE prophylaxis because dehydration + immobility raise clot risk.

Complications

Maternal:

• Wernicke's encephalopathy — thiamine deficiency; classic triad confusion + ophthalmoplegia + ataxia; may progress to Korsakoff psychosis. Largely preventable with thiamine.
• Mallory-Weiss tear → haematemesis from repeated forceful vomiting.
• Electrolyte disturbances → hypokalaemia (arrhythmia), hyponatraemia. Over-rapid correction of hyponatraemia → central pontine myelinolysis (osmotic demyelination).
• Acute kidney injury (pre-renal), dehydration, oesophageal rupture (Boerhaave) rarely.
• Vitamin K deficiency → maternal coagulopathy and fetal intracranial bleed.
• Venous thromboembolism, depression/anxiety, rhabdomyolysis.

Fetal:

• Low birth weight, IUGR, prematurity in severe untreated disease (poor maternal nutrition).
• Generally good fetal outcome when HG is well managed.

High-yield: Two iatrogenic dangers to remember: (1) dextrose before thiamine → Wernicke's; (2) too-rapid correction of hyponatraemia → central pontine myelinolysis. Both are favourite exam distractors.

Key differentials

Because HG is a diagnosis of exclusion, know what else causes vomiting in pregnancy.

Condition	Discriminating clue
Ordinary morning sickness (NVP)	No weight loss, no ketonuria, no electrolyte derangement
Molar pregnancy	Very high hToCG, "snowstorm"/cluster-of-grapes USG, uterus large for dates
Multiple gestation	Multiple sacs/fetuses on USG, high hCG
Gastroenteritis	Diarrhoea, fever, contacts; vomiting at any gestation
Acute fatty liver of pregnancy / pre-eclampsia (HELLP)	Third trimester, hypertension, deranged LFTs, low platelets
Pyelonephritis / UTI	Fever, loin pain, dysuria, pyuria
Hepatitis / pancreatitis / cholecystitis	Pain, jaundice, raised enzymes
Raised intracranial pressure	Headache, focal signs, papilloedema, projectile vomiting
DKA / Addison's / hyperthyroidism (Graves')	Goitre, ophthalmopathy, persistent disease beyond 20 weeks

A key timing rule: vomiting that begins after 9 weeks or in later pregnancy is rarely HG — look elsewhere.

Recently asked / exam angle

NEET PG, INI-CET and FMGE repeatedly test the concepts, not just recall:

• "Thiamine before dextrose" — the single most asked single-best-answer point. A dehydrated HG patient given IV dextrose develops confusion/ophthalmoplegia → answer is to have given thiamine first.
• Acid-base question: vomiting in HG → hypochloraemic hypokalaemic metabolic alkalosis is the expected ABG.
• First-line antiemetic in pregnancy → pyridoxine (B6) + doxylamine; steroids only when refractory.
• Disproportionately severe HG → investigate with USG to exclude molar/multiple pregnancy.
• TFTs in HG → transient thyrotoxicosis (low TSH, high T4) needing no antithyroid drug — resolves spontaneously.
• Wernicke's triad — confusion, ophthalmoplegia, ataxia — and its prevention.
• Image/clinical vignette: ketonuria on dipstick + >5% weight loss = HG, not morning sickness.
• Newer aspect: GDF15 gene/hormone association — appearing in recent question banks.

Mnemonic for the antiemetic/management ladder — "Please Don't Vomit, Stay Hydrated": Pyridoxine (+doxylamine) → Dopamine antagonists (metoclopramide) → Vomiting blocker ondansetron (5-HT3) → Steroids → Hydration + thiamine throughout.

Mnemonic for HG criteria — "5-K": 5% weight loss, Ketonuria, K+ (electrolyte) imbalance.

Mnemonic for Wernicke's — "COAT" (a thiamine-deficient brain needs a COAT): Confusion, Ophthalmoplegia, Ataxia, Thiamine treatment.

Rapid revision

1. HG = intractable vomiting + >5% weight loss + ketonuria + electrolyte imbalance; incidence ~0.3–3%.
2. Commonest cause of hospital admission in early pregnancy; onset typically before 9 weeks, almost always <16 weeks.
3. β-hCG is the main driver → severe HG suggests molar pregnancy or multiple gestation → do an ultrasound.
4. Classic ABG: hypochloraemic, hypokalaemic metabolic alkalosis.
5. Ketonuria on urine dipstick is the simplest bedside severity marker.
6. First-line antiemetic in pregnancy = pyridoxine (B6) ± doxylamine.
7. Antiemetic ladder: B6/antihistamine → metoclopramide/prochlorperazine → ondansetron → corticosteroids (refractory).
8. ALWAYS give thiamine BEFORE dextrose — dextrose first precipitates Wernicke's encephalopathy.
9. Use normal saline for resuscitation, add KCl as needed; correct hyponatraemia slowly to avoid central pontine myelinolysis.
10. Transient gestational thyrotoxicosis (↓TSH, ↑T4) needs no antithyroid drug — self-resolves by ~18–20 weeks.
11. Give VTE prophylaxis (LMWH) — dehydration + admission raise clot risk; watch for vitamin K deficiency.
12. Vomiting starting after 9 weeks or in late pregnancy is NOT HG — exclude HELLP, AFLP, pyelonephritis, hepatitis, raised ICP.