Hyperemesis Gravidarum
Summary
Hyperemesis Gravidarum (HG) is a severe, intractable form of nausea and vomiting in pregnancy (NVP). Unlike common "morning sickness" (which affects 80% of pregnancies), HG is characterized by the Triad of: >5% Weight Loss (from pre-pregnancy weight), Dehydration, and Electrolyte Imbalance (ketonuria). It typically starts at 4-7 weeks, peaks at 9-13 weeks, and resolves by 20 weeks, though 10-20% persist until delivery. [1,2]
Key Facts
- Cause: Exact mechanism unknown, but strongly linked to peak levels of varying isoforms of hCG, Estrogen, and GDF15.
- Severity: Assessed using the PUQE Score (Pregnancy-Unique Quantification of Emesis).
- Mild: less than 6.
- Moderate: 7-12.
- Severe: >13.
Clinical Pearls
Wernicke's Warning: Thiamine (B1) deficiency can develop in as little as 3-4 weeks of vomiting/starvation. If you give a dextrose load to a thiamine-depleted patient, you can precipitate Wernicke's Encephalopathy (Confusion, Ataxia, Ophthalmoplegia). Always give IV Thiamine (Pabrinex) BEFORE or WITH any glucose-containing fluid.
Exclude Molar Pregnancy: Excessive vomiting is a hallmark of Hydatidiform Mole (due to sky-high hCG). An early ultrasound is mandatory to check viability and exclude multiple/molar pregnancies.
Transient Thyrotoxicosis: 60% of HG patients have suppressed TSH and elevated T4 ("Gestational Thyrotoxicosis") because hCG cross-reacts with the TSH receptor. This is transient and rarely needs treatment.
Incidence
- Affects 1-3% of all pregnancies.
- Recurrence rate in future pregnancies is high (up to 80%).
Risk Factors
- Multiple Pregnancy (Twins/Triplets).
- Molar Pregnancy.
- Previous Hyperemesis.
- Female Fetus.
- Nulliparity.
- History of motion sickness or migraine.
Mechanisms
- Hormonal: hCG levels peak at 10-12 weeks, correlating with peak symptoms.
- GDF15: A placental hormone acting on the brainstem vomiting centre. Genetic sensitivity to GDF15 is now considered the primary driver.
- Mechanical: Gastric dysrhythmia.
- Helicobacter pylori: Associated with severe cases.
Symptoms
Signs
- Abdomen: Soft. (Peritonism suggests surgical cause).
- Neuro: Check for nystagmus (Wernicke's).
- Vitals: Tachycardia is an early sign of hypovolaemia.
Urine
- Ketones: 1+ to 4+. A marker of starvation (lipolysis).
- MSU: Rule out UTI (common trigger).
Bloods
- U&E: Hypokalaemia, Hyponatraemia, Raised Urea (Dehydration), AKI.
- LFTs: Mild transaminitis is common (starvation/dehydration).
- TFTs: Suppressed TSH / High T4 (hCG effect).
- Amylase: Exclude pancreatitis.
Imaging
- Ultrasound: Mandatory. Confirm viable intrauterine pregnancy. Check for Twins/Trohpoblastic disease.
Management Algorithm
PREGNANT + VOMITING
(Rule out UTI, Gastro, Ectopic, Appx)
↓
ASSESS SEVERITY (PUQE)
(Weight loss? Ketones? Dehydration?)
↓
┌─────────────┼─────────────┐
MILD MODERATE SEVERE
(Community) (Ambulatory) (Admission)
↓ ↓ ↓
DIETARY + IV FLUIDS IV FLUIDS
ORAL MEDS (Saline) (Correct K+)
IV ANTIEMETICS THIAMINE (IV)
DVT PROPHYLAXIS
STEROIDS (Refractory)
1. Rehydration
- Fluid of Choice: Normal Saline (0.9% NaCl) or Hartmann's.
- Potassium: Replacement essential.
- Dextrose: Avoid initially unless hypoglycaemic (risk of Wernicke's).
2. Antiemetics (Simultaneous not sequential)
RCOG Green-top Guideline 69 recommends a stepwise approach:
- First Line:
- Cyclizine 50mg PO/IV/IM.
- Prochlorperazine (Stemetil) 12.5mg PO/IV/IM.
- Promethazine (Avomine).
- Second Line:
- Metoclopramide (Maxolon) - EPS risk (limit to 5 days).
- Domperidone.
- Ondansetron (Zofran) - Highly effective. Note: Historic concerns about cleft lip are minor; benefits usually outweigh risks.
- Third Line:
- Corticosteroids (Prednisolone/Hydrocortisone). For refractory cases. Stop if no improvement.
3. Supplements
- Thiamine: Oral or IV (Pabrinex).
- Folic Acid: Continue.
- Pyridoxine (Vit B6): Can help nausea.
- Ginger: Evidence supports benefit for mild NVP.
4. Thromboprophylaxis
- Dehydration + Pregnancy + Immobility = Very High VTE Risk.
- LMWH (Clexane/Fragmin) and TED stockings should be prescribed for all admissions.
- Maternal:
- Wernicke's Encephalopathy: Permanent brain damage.
- Mallory-Weiss Tear: Oesophageal bleeding from retching.
- Acute Kidney Injury.
- VTE: Pulse Embolism.
- Mental Health: Depression / PTSD / Termination of wanted pregnancy.
- Fetal:
- Small for Gestational Age (SGA) if weight loss severe.
- No increased risk of malformations (from the HG itself).
- Most resolve by 20 weeks.
- Excellent fetal outcomes if managed.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| GTG 69 | RCOG (2016) | Management of Nausea and Vomiting in Pregnancy and HG. |
| Antiemetics | Cochrane | Antihistamines and Ondansetron are effective. |
Landmark Evidence
1. Ondansetron Safety
- Large cohort studies have reassured that Ondansetron does not significantly increase the risk of major congenital malformations, though a tiny increase in oral clefts cannot be entirely excluded (approx 3 extra cases per 10,000). RCOG advises it is safe to use.
Is this just Morning Sickness?
No. Morning sickness is uncomfortable but manageable. Hyperemesis is a medical condition where you cannot keep any food or water down, leading to weight loss and harmful chemical changes in your blood.
Will it hurt the baby?
Generally, no. The baby is very good at taking what it needs from you, even if you are eating very little. The main risk to the baby is if you become severely dehydrated, so our priority is fluids for you.
Can I take medicines?
Yes. The medicines we use (Cyclizine, Ondansetron) have been used in millions of pregnancies and are considered safe. Being severely ill and dehydrated is much riskier for the pregnancy than taking these medicines.
Primary Sources
- RCOG Green-top Guideline No. 69. The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum. 2016.
- Fejzo MS, et al. Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum. Nat Commun. 2018.
- Holmgren C, et al. Hyperemesis in pregnancy. Clin Obstet Gynecol. 2018.
Common Exam Questions
- Diagnosis: "Triad of HG?"
- Answer: 5% Weight loss + Dehydration + Electrolytes/Ketones.
- Investigation: "First line imaging?"
- Answer: Early Ultrasound (Exclude Molar/Twin).
- Safety: "Fluid to avoid initially?"
- Answer: Dextrose (Wernicke's risk).
- Treatment: "First line anti-emetic?"
- Answer: Cyclizine or Prochlorperazine. (Ondansetron is 2nd line).
- Complication: "Treatment for Wernicke's prevention?"
- Answer: Thiamine (Pabrinex).
Viva Points
- Transient Gestational Thyrotoxicosis: Explain why TSH is low in HG. (T4 and human Chorionic Gonadotropin (hCG) share structural similarity. High hCG stimulates the thyroid. This is physiological, not Graves' disease).
- VTE Risk: Why anticoagulate? Virchow's triad is fulfilled (Hypercoagulable state of pregnancy + Stasis from bed rest + Vessel injury/Dehydration).
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.