Hyperemesis Gravidarum
Summary
Hyperemesis Gravidarum (HG) is a severe form of nausea and vomiting in pregnancy (NVP) characterised by intractable vomiting, weight loss (>5% of pre-pregnancy weight), dehydration, and ketonuria. It affects approximately 0.3-2% of pregnancies and is the most common reason for hospitalisation in the first trimester. Unlike typical "morning sickness" (which affects 70-80% of pregnancies and is self-limiting), HG is debilitating and may persist throughout pregnancy. The exact cause is unknown but is linked to rising hCG levels (Peak at 9-12 weeks), which is why it is more severe in multiple pregnancy and molar pregnancy. Untreated, severe HG can lead to Wernicke Encephalopathy (Thiamine deficiency), electrolyte disturbances, and rarely maternal death. Management involves IV fluid resuscitation, thiamine supplementation, and antiemetics (Cyclizine, Ondansetron, Prochlorperazine). The PUQE Score is used to assess severity. Women with HG require compassionate care and may need multiple admissions. [1,2,3]
Clinical Pearls
"More Than Morning Sickness": HG is NOT just bad morning sickness. It is a distinct, severe condition causing >5% weight loss, Ketonuria, Dehydration.
Give Thiamine BEFORE Glucose: In severe HG, Thiamine (Pabrinex) must be given BEFORE IV glucose/dextrose. Glucose without Thiamine can precipitate Wernicke Encephalopathy.
"Think Molar/Twins": Very severe or early-onset HG should prompt USS to exclude molar pregnancy and multiple pregnancy (High hCG drives worse symptoms).
Ondansetron is Safe: Ondansetron 4-8mg is widely used in HG. Large studies (1.8 million pregnancies) show no increased risk of congenital malformation.
Demographics
| Factor | Notes |
|---|---|
| Prevalence | HG: 0.3-2% of pregnancies. Milder NVP: 70-80%. |
| Onset | Typically starts 4-7 weeks gestation. Peaks 9-12 weeks (hCG peak). |
| Duration | Usually improves by 16-20 weeks. 10% persist entire pregnancy. |
Risk Factors
| Risk Factor | Notes |
|---|---|
| Previous HG | Strongest predictor. ~15-20% recurrence risk. |
| Family History | Genetic component. |
| Multiple Pregnancy | Higher hCG. |
| Molar Pregnancy | Very high hCG. Severe early HG → Exclude molar. |
| Female Fetus | Slightly higher incidence. |
| Thyroid Disorders | Transient gestational thyrotoxicosis (hCG cross-reacts with TSH receptor). |
| Obesity | Some studies show increased risk. |
Proposed Mechanisms
| Mechanism | Notes |
|---|---|
| hCG | Strong correlation. hCG peaks at 9-12 weeks = Peak symptom severity. Multiple pregnancy/Molar = Higher hCG = Worse symptoms. |
| Oestrogen | Contributes to nausea. |
| Progesterone | Slows gastric motility. |
| Helicobacter Pylori | Association with more severe NVP (Controversial). |
| Altered Gastrointestinal Motility | Delayed gastric emptying. |
| Psychological Factors | Stress may exacerbate (But NOT the cause). |
Consequences of Prolonged Vomiting
| Consequence | Notes |
|---|---|
| Dehydration | Reduced oral intake + Vomiting. |
| Electrolyte Disturbance | Hypokalaemia (Vomiting loses K+), Hyponatraemia, Hypochloraemic Metabolic Alkalosis. |
| Ketonuria | Starvation ketosis. Fat breakdown for energy. |
| Thiamine Deficiency | If untreated → Wernicke Encephalopathy (Confusion, Ataxia, Ophthalmoplegia). Preventable with Thiamine. |
| Weight Loss | >5% of pre-pregnancy weight = Diagnostic criterion. |
| Condition | Key Features |
|---|---|
| Hyperemesis Gravidarum | Onset 4-12 weeks, Ketonuria, Weight loss, Severe vomiting, Dehydration. |
| Molar Pregnancy | Very early severe HG, Vaginal bleeding, Large-for-dates uterus, Snowstorm USS. |
| Multiple Pregnancy | Larger uterus, High hCG. |
| Urinary Tract Infection | Dysuria, Frequency, Suprapubic pain, Positive urine culture. |
| Gastroenteritis | Diarrhoea, Fever, Sick contacts, Acute onset. |
| Appendicitis | Right iliac fossa pain, Fever, Raised WCC/CRP. Can occur in pregnancy. |
| Bowel Obstruction | Colicky abdominal pain, Distension, Constipation, X-ray findings. |
| Diabetic Ketoacidosis (DKA) | Known diabetic, High glucose, Metabolic acidosis (Not alkalosis). |
| Thyrotoxicosis | Palpitations, Tremor, Weight loss, Suppressed TSH, Raised T4. |
Symptoms
| Symptom | Notes |
|---|---|
| Persistent Vomiting | Multiple times per day. Unable to keep down food/fluids. |
| Nausea | Constant, debilitating. |
| Weight Loss | >5% of pre-pregnancy weight is diagnostic criterion. |
| Fatigue | Profound. |
| Ptyalism (Excessive Salivation) | Unable to swallow saliva. |
| Aversion to Food/Smells | Strong triggers. |
Signs
| Sign | Notes |
|---|---|
| Dehydration | Dry mucous membranes, Reduced skin turgor, Tachycardia, Hypotension, Concentrated urine. |
| Ketonuria | Positive ketones on urine dipstick (++/+++). |
| Weight | Document at each visit. Compare to pre-pregnancy weight. |
| Epigastric Tenderness | May have from retching. |
PUQE Score (Pregnancy-Unique Quantification of Emesis)
Used to assess severity (Score out of 15):
| Score | Severity |
|---|---|
| less than 6 | Mild |
| 7-12 | Moderate |
| ≥13 | Severe |
Bedside
| Test | Findings / Rationale |
|---|---|
| Urine Dipstick | Ketones (Starvation), Specific gravity (Dehydration), Exclude UTI. |
| Weight | Compare to pre-pregnancy. >5% loss = HG. |
| Blood Pressure/Pulse | Tachycardia, Postural hypotension (Dehydration). |
| PUQE Score | Quantify severity. |
Blood Tests
| Test | Findings / Rationale |
|---|---|
| U&Es | Hypokalaemia, Hyponatraemia, Raised Urea (Dehydration). Metabolic alkalosis (From vomiting HCl). |
| FBC | Raised Hct (Haemoconcentration). |
| LFTs | Elevated transaminases in ~50% (Transient). |
| TFTs | Suppressed TSH, Raised T4 in hyperthyroid HG (Due to hCG cross-reactivity with TSH receptor). Usually transient. |
| Blood Glucose | Exclude DKA. |
Imaging
| Imaging | Indication |
|---|---|
| Pelvic USS | Confirm viable intrauterine pregnancy. Exclude molar pregnancy, Multiple pregnancy. |
Management Algorithm
HYPEREMESIS GRAVIDARUM
(Severe NVP + Weight loss >5% + Ketonuria)
↓
INITIAL ASSESSMENT
- PUQE Score
- Weight (Compare to pre-pregnancy)
- Urine ketones, Dipstick
- U&Es, LFTs, TFTs
- USS to confirm viable pregnancy / Exclude molar/twins
↓
ADMISSION CRITERIA
- Unable to tolerate oral fluids/medications
- Ketonuria ≥2+
- Weight loss >5%
- Abnormal electrolytes
- Unable to manage at home
↓
INPATIENT MANAGEMENT
┌──────────────────────────────────────────────────────────┐
│ IV FLUIDS: │
│ - Normal Saline (0.9% NaCl) with KCl as required │
│ - Avoid Dextrose initially (Risk of Wernicke if │
│ Thiamine deficient) │
│ │
│ THIAMINE (Pabrinex): │
│ - Give Pabrinex IV (1 pair vials) BEFORE any dextrose │
│ - Continue oral Thiamine 50mg TDS during admission │
│ - Prevents Wernicke Encephalopathy │
│ │
│ ANTIEMETICS (Stepwise): │
│ First-Line: Cyclizine 50mg IV/IM/PO TDS │
│ OR Prochlorperazine 12.5mg IM / 5mg PO TDS │
│ Second-Line: Ondansetron 4-8mg IV/PO BD-TDS │
│ Third-Line: Metoclopramide 10mg IV/PO TDS (Max 5 days) │
│ Refractory: Steroids (Hydrocortisone → Prednisolone) │
│ - Reserved for severe cases unresponsive │
│ to standard antiemetics │
│ │
│ THROMBOPROPHYLAXIS: │
│ - TED stockings │
│ - Consider LMWH if prolonged admission/severe │
│ dehydration (HG increases VTE risk) │
└──────────────────────────────────────────────────────────┘
↓
OUTPATIENT/DISCHARGE
- Oral antiemetics to take home
- Oral Thiamine
- Safety net: Return if unable to keep down fluids
- Day Unit option for IV fluids if recurrence
Antiemetic Options
| Drug | Dose | Notes |
|---|---|---|
| Cyclizine | 50mg TDS PO/IV/IM | First-line. Antihistamine. May cause drowsiness. |
| Prochlorperazine (Stemetil) | 5-10mg TDS PO or 12.5mg IM | Dopamine antagonist. Can cause dystonia. |
| Ondansetron | 4-8mg BD-TDS PO/IV | 5-HT3 antagonist. Very effective. Safe in pregnancy (Large studies). May cause constipation. |
| Metoclopramide | 10mg TDS PO/IV | Limit to 5 days (MHRA – Dystonia risk). |
| Promethazine | 25mg PO/IM | Useful at night (Sedating). |
| Steroids (Hydrocortisone/Prednisolone) | Specialist use | For refractory HG. Avoid if possible less than 10 weeks (Cleft lip risk). |
Non-Pharmacological
| Intervention | Notes |
|---|---|
| Ginger | May help mild NVP. Limited evidence. |
| Acupressure (P6 Point) | Bands (Sea-Bands). Some evidence. |
| Dietary Advice | Small frequent meals, Avoid triggers, Dry crackers before rising. |
Maternal
| Complication | Notes |
|---|---|
| Wernicke Encephalopathy | PREVENTABLE. Thiamine deficiency → Confusion, Ataxia, Ophthalmoplegia. Give Thiamine BEFORE glucose. |
| Mallory-Weiss Tear | Oesophageal mucosal tear from retching → Haematemesis. |
| Electrolyte Disturbance | Hypokalaemia → Arrhythmias. Hyponatraemia → Confusion. |
| Acute Kidney Injury | Severe dehydration. |
| Venous Thromboembolism | Dehydration + Pregnancy → Increased VTE risk. |
| Psychological Morbidity | Depression, Anxiety, PTSD. HG significantly impacts mental health. May affect bonding. |
| Termination of Pregnancy | Some women request TOP due to severity. |
Fetal
| Complication | Notes |
|---|---|
| Low Birth Weight | Associated with severe prolonged HG with >5% weight loss. |
| Preterm Birth | Slightly increased risk. |
| SGA | Some studies. |
| Factor | Notes |
|---|---|
| Typical Course | Symptoms usually improve by 16-20 weeks (After hCG falls). 10% persist throughout pregnancy. |
| Recurrence | 15-20% recurrence risk in future pregnancies. |
| Long-Term | No long-term maternal effects. Fetus usually unaffected if adequately treated. |
| Psychological Impact | High rates of depression, Anxiety, PTSD. Support essential. |
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum | RCOG GTG 69 (2016) | Thiamine before dextrose, Antiemetic ladder, VTE prophylaxis. |
| HG Care Pathway | NICE QS | Ambulatory care options, Day units. |
Key Points
- Ondansetron Safety: Large cohort studies (>1.8 million pregnancies) show no significant increase in congenital malformations.
- Steroids: Reserved for refractory cases. Some evidence of benefit. Risk of cleft lip if used less than 10 weeks.
What is Hyperemesis Gravidarum?
It is a severe form of pregnancy sickness – much worse than ordinary "morning sickness." It causes persistent vomiting that leads to dehydration, weight loss, and difficulty keeping down food or fluids.
Is it just bad morning sickness?
No. Morning sickness is usually manageable and settles by 12-14 weeks. Hyperemesis is debilitating – you may be unable to work, care for yourself, or even keep water down. It often requires hospital treatment.
What causes it?
We don't fully understand the cause, but it is linked to pregnancy hormones (hCG), which peak around 9-12 weeks. It is more common in twin pregnancies (Higher hCG).
Is my baby okay?
Yes, in most cases. If you receive treatment (Fluids, Vitamins, Anti-sickness medication), the baby is usually unaffected.
What is the treatment?
- Fluids through a drip (If you cannot keep fluids down).
- Anti-sickness tablets or injections (Safe in pregnancy).
- Vitamin B1 (Thiamine) – Very important to prevent a rare but serious complication.
Will it happen again?
There is about a 15-20% chance of it recurring in a future pregnancy. But knowing this means we can sometimes prevent it with early anti-sickness medication before symptoms start.
Primary Sources
- Royal College of Obstetricians and Gynaecologists. The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum (GTG 69). 2016.
- Huybrechts KF, et al. Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring. JAMA. 2018;320(23):2429-2437. PMID: 30561481.
- London V, et al. Hyperemesis Gravidarum: A Review of Recent Literature. Pharmacology. 2017;100(3-4):161-171. PMID: 28614831.
Common Exam Questions
- Diagnostic Criteria: "What defines HG vs Normal NVP?"
- Answer: Weight loss >5% pre-pregnancy weight + Ketonuria + Dehydration.
- Thiamine: "Why must Thiamine be given before IV glucose?"
- Answer: Glucose metabolism consumes Thiamine. In deficient patients, giving glucose without Thiamine precipitates Wernicke Encephalopathy.
- Investigation to Exclude: "What must be excluded in very severe/early HG?"
- Answer: Molar Pregnancy (Very high hCG) and Multiple Pregnancy.
- First-Line Antiemetic: "What is first-line antiemetic in HG?"
- Answer: Cyclizine 50mg TDS (Or Prochlorperazine).
Viva Points
- Wernicke Triad: Confusion, Ataxia, Ophthalmoplegia. Often incomplete. IRREVERSIBLE if severe.
- PUQE Score: Pregnancy-Unique Quantification of Emesis. Quantifies severity.
- VTE Risk: Dehydration + Pregnancy = High VTE risk. Consider TED stockings and LMWH.
- Ondansetron is Safe: Large studies show no increased teratogenicity.
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