Obstetrics and Gynaecology chapters
Jaundice and liver disease in pregnancy
The causes and mechanisms of jaundice in pregnancy, sorted by trimester: obstetric cholestasis, acute fatty liver, HELLP syndrome and hyperemesis, plus viral hepatitis, gallstones and chronic liver disease.
- Jaundice in pregnancy is either pregnancy-specific (hyperemesis, obstetric cholestasis, HELLP, acute fatty liver) or coincidental (viral hepatitis, gallstones, drugs), and the trimester is the best clue.
- Viral hepatitis is the commonest cause worldwide; hepatitis E can cause fulminant liver failure in the third trimester.
- Obstetric cholestasis gives itching without rash and raised bile acids, treated with UDCA and delivery after 37 weeks; AFLP and HELLP are emergencies needing delivery.
On this page
Overview
Jaundice is uncommon in pregnancy, but it can signal a life-threatening condition for mother and baby. The key to MCQs is to place each cause in its trimester and its mechanism.
Causes fall into three groups:
- Pregnancy-specific: hyperemesis gravidarum, obstetric cholestasis, pre-eclampsia/HELLP, acute fatty liver of pregnancy (AFLP).
- Coincidental (intercurrent): viral hepatitis, gallstones, drugs, sepsis, malaria.
- Pre-existing liver disease: chronic hepatitis B or C, autoimmune hepatitis, primary biliary cholangitis, cirrhosis.
Worldwide, viral hepatitis is the leading cause of jaundice in pregnant women.
Normal liver changes in pregnancy
| Test or sign | Change in normal pregnancy | Why |
|---|---|---|
| Alkaline phosphatase (ALP) | Rises, may be two to three times normal by term | Made by the placenta |
| Albumin | Falls | Dilution by the larger plasma volume |
| Transaminases (ALT, AST), bilirubin, GGT | Stay normal (or slightly lower) | Liver function itself is unchanged |
| Spider naevi, palmar erythema | May appear, especially in the third trimester | High oestrogen |
A raised ALP alone in late pregnancy is usually placental, not liver disease. A raised ALT, AST or bilirubin is never normal in pregnancy and must be explained.
Mechanisms of jaundice
| Mechanism | Bilirubin type | Pregnancy examples |
|---|---|---|
| Pre-hepatic (haemolytic) | Unconjugated | HELLP (haemolysis), malaria, sickle cell crisis, G6PD deficiency, incompatible transfusion |
| Hepatocellular | Mixed | Viral hepatitis, AFLP, hyperemesis, drugs, sepsis |
| Cholestatic (intrahepatic) | Conjugated | Obstetric cholestasis, drugs, primary biliary cholangitis |
| Post-hepatic (obstructive) | Conjugated | Gallstones in the common bile duct, pancreatitis |
Causes by trimester
| Trimester | Pregnancy-specific causes | Always consider |
|---|---|---|
| First | Hyperemesis gravidarum | Viral hepatitis, drugs, gallstones |
| Second | Obstetric cholestasis (usually second half) | Viral hepatitis, gallstones |
| Third | Obstetric cholestasis, pre-eclampsia/HELLP, AFLP | Hepatitis E, malaria, sepsis |
"Sick early, itchy middle, sick-and-bleeding late": hyperemesis in the first trimester; cholestasis from mid-pregnancy; HELLP and AFLP in the third trimester.
Pregnancy-specific causes
Hyperemesis gravidarum
- Severe, persistent vomiting with dehydration, electrolyte upset and weight loss; affects 0.3-2% of pregnancies.
- Linked with high hCG (more common in twins and molar pregnancy).
- Liver enzymes may rise mildly and jaundice is rare; both settle once vomiting is controlled.
- Complications: Wernicke encephalopathy (thiamine lack), Mallory-Weiss tears, malnutrition.
- Treat with IV fluids, thiamine and antiemetics (phenothiazines are safe).
Obstetric cholestasis (intrahepatic cholestasis of pregnancy)
Definition: itching and abnormal liver tests in pregnancy, with no other cause, that both resolve after birth.
- Affects about 0.7% of pregnancies, with ethnic and family variation; it recurs in later pregnancies and may recur with the combined oral contraceptive pill.
- Mechanism: an inherited sensitivity of liver cells to oestrogen reduces bile flow, so bile acids build up in the blood.
- Clinical: itching without a rash, worst on the palms and soles and at night; usually in the second half of pregnancy. Jaundice, if present, is mild.
- Tests: raised serum bile acids and raised transaminases. Exclude viral hepatitis, gallstones and autoimmune disease (viral serology, liver ultrasound, autoantibodies).
- Risks: to the mother, sleeplessness from itching; to the fetus, spontaneous preterm birth, meconium, and intrauterine fetal death.
- Treatment: ursodeoxycholic acid (UDCA) improves itching and liver tests, but has not been shown to improve fetal outcome. Emollients help the skin.
- Delivery: usually offered after 37 weeks.
- Liver tests should return to normal after birth; check them postnatally.
In obstetric cholestasis the danger is to the baby, not the mother. UDCA treats symptoms; timing of delivery is the protective step.
Pre-eclampsia and HELLP syndrome
- HELLP = Haemolysis, Elevated Liver enzymes, Low Platelets, a severe form of pre-eclampsia in 2-4% of affected women.
- Mechanism: fibrin is laid down under the liver endothelium, injuring liver cells; platelets are used up and red cells are fragmented.
- Presentation: epigastric or right upper quadrant pain, nausea and vomiting; blood pressure may be only mildly raised or even normal.
- Complications: acute kidney injury, placental abruption, DIC, liver haematoma or rupture, eclampsia, stillbirth (fetal loss up to 60%).
- Management: stabilise the mother (blood pressure, magnesium sulfate to prevent fits), correct clotting problems, then deliver.
A woman with epigastric pain in the third trimester and normal blood pressure can still have HELLP. Always check platelets and liver enzymes.
Acute fatty liver of pregnancy (AFLP)
- Rare but dangerous: acute liver failure in the third trimester, from microvesicular fat in the liver cells.
- Associated with a defect of fatty acid oxidation (LCHAD deficiency) in the fetus; more common in first pregnancies, twins and male fetuses in standard teaching.
- Features: malaise, nausea, vomiting, abdominal pain, then jaundice; may progress to encephalopathy.
- Key tests: hypoglycaemia, coagulopathy (prolonged PT, low fibrinogen), raised uric acid, renal impairment, raised white cell count, raised transaminases.
- Management: correct glucose and clotting, supportive care in a high dependency or intensive care setting, and prompt delivery.
- Historically a high death rate; milder forms are now recognised earlier.
Hypoglycaemia in a jaundiced woman in the third trimester points to AFLP (liver failure) rather than HELLP.
HELLP vs AFLP vs obstetric cholestasis
| Feature | Obstetric cholestasis | HELLP | AFLP |
|---|---|---|---|
| Timing | Second half | Third trimester (or just after birth) | Third trimester |
| Main symptom | Itching | Epigastric pain | Vomiting, malaise, jaundice |
| Hypertension | No | Usually (may be mild) | Sometimes |
| Platelets | Normal | Low | Normal or low |
| Glucose | Normal | Normal | Low |
| Clotting | Normal | Abnormal if DIC | Markedly abnormal |
| Treatment | UDCA, deliver after 37 weeks | Stabilise and deliver | Stabilise and deliver urgently |
Coincidental causes
Viral hepatitis
- Same features as outside pregnancy: anorexia, nausea, malaise, dark urine, jaundice, tender liver, very high transaminases.
- Acute hepatitis in the first trimester is linked with miscarriage.
- Hepatitis E (faeco-oral, waterborne after floods): more likely to cause fulminant hepatic failure, especially in first pregnancies and the third trimester; roughly one in five women who catch it in the third trimester die where care is limited. It is also linked with preterm birth, FGR and stillbirth.
- Hepatitis A (about 1 in 1,000 pregnancies): spread to the fetus is extremely rare.
- Herpes simplex hepatitis: rare but serious; responds to aciclovir.
- Transmission of hepatitis B and C to the baby is covered in the viral infections chapter.
"E for Expectant mothers in danger."
Hepatitis E is waterborne and acute only; it does not become chronic. In Pakistan, think of it after floods or water contamination.
Gallstones and cholecystitis
- Pregnancy promotes sludge and stones: oestrogen raises cholesterol in bile; progesterone relaxes smooth muscle and slows emptying.
- Gallstones are common in pregnancy, but acute cholecystitis is uncommon (about 0.1%).
- Treatment: start conservatively (IV fluids, electrolytes, gut rest, analgesia, broad-spectrum antibiotics), especially in the first and third trimesters.
- Relapse is common; if surgery is needed, cholecystectomy (open or laparoscopic) is best in the second trimester.
- Gallstones are also the commonest cause of pancreatitis in pregnancy.
Drugs and sepsis
Drug-induced hepatitis (for example anti-tuberculosis drugs, methyldopa in standard teaching), severe sepsis and malaria (haemolysis plus liver involvement) can all cause jaundice.
Pre-existing liver disease
| Condition | Pregnancy points |
|---|---|
| Autoimmune hepatitis | Anti-smooth muscle and antinuclear antibodies; flares in pregnancy or postpartum; continue immunosuppression; fetal loss around 20% if active |
| Primary biliary cholangitis | Destruction of small bile ducts; reduced fertility; usually stable on UDCA; may flare after birth |
| Cirrhosis | Rare in pregnancy (anovulation); varices bleed in about 25%, so screen with endoscopy from the second trimester; risks of liver failure and encephalopathy |
Approach to a jaundiced pregnant woman
- History: gestation, itching, vomiting, abdominal pain, headache, travel, water source, drugs, previous episodes.
- Examination: blood pressure, urine protein, liver size and tenderness, signs of liver failure, fetal wellbeing.
- Bloods: LFTs with bile acids, FBC and blood film (haemolysis), platelets, clotting, glucose, renal function, uric acid, viral serology (A, B, C, E), malaria test in endemic areas.
- Imaging: liver and biliary ultrasound (stones, duct dilatation, haematoma).
- Fetal assessment: CTG and growth scan.
Expect: viral hepatitis as the leading cause of jaundice in pregnant women worldwide; hepatitis E causing fulminant failure in the third trimester; ALP rising normally from the placenta while transaminases should not; obstetric cholestasis with itching of palms and soles, raised bile acids, UDCA and delivery after 37 weeks, and its fetal risk; HELLP with epigastric pain, low platelets and sometimes normal blood pressure; AFLP with hypoglycaemia, coagulopathy and microvesicular fat, treated by delivery; trimester sorting; gallstones and surgery timing in the second trimester.
Quick revision
- Trimester 1: hyperemesis; trimester 2-3: cholestasis; trimester 3: HELLP, AFLP, hepatitis E.
- Normal pregnancy: ALP up (placenta), albumin down, ALT/AST/bilirubin normal.
- Obstetric cholestasis: itch, no rash, bile acids up; UDCA; deliver after 37 weeks; risk of stillbirth.
- HELLP: haemolysis, high enzymes, low platelets; may have little hypertension; deliver.
- AFLP: hypoglycaemia, coagulopathy, renal failure; microvesicular fat; deliver.
- Hepatitis E: faeco-oral; fulminant in late pregnancy; no chronic state.
- Gallstones: conservative first; surgery in the second trimester.
Written by The House Job from standard references (Obstetrics by Ten Teachers; Davidson's Principles and Practice of Medicine).
FAQ
Why is the alkaline phosphatase raised in normal pregnancy?
The placenta makes its own alkaline phosphatase, so levels climb in later pregnancy without any liver disease.
Does UDCA prevent stillbirth in obstetric cholestasis?
It eases itching and improves liver tests but has not been proven to improve outcome for the baby, which is why delivery is usually offered after 37 weeks.
What single blood test helps separate AFLP from HELLP?
Blood glucose: a low glucose reflects failing liver function and points to AFLP, whereas a low platelet count with haemolysis is the hallmark of HELLP.
Why is hepatitis E feared in pregnancy?
It can progress to fulminant liver failure, especially in the third trimester, and carries a high death rate for women in low-resource settings.