Cholestasis of Pregnancy

1. Cholestasis of Pregnancy A talk based on RCOG Greentop Guideline 43 January 2006 Max Brinsmead PhD FRANZCOG January 2011

2. Definition • A multifactorial obstetric condition characterised by... • Pruritis without a skin rash and • Abnormal liver function without other cause • That remits completely after delivery • Also known as “Benign obstetric cholestasis”

3. Incidence • 1:150 pregnancies in a multi ethnic society • 1:20 in Chilean Indians • It has a strong familial and ethnic component

4. Liver Function Tests in Pregnancy • Alkaline phosphatase is increased • There is a placental contribution to the circulating pool • Normal range <260 • GGT, Transaminases and Bilirubin are reduced • By a mean of 20% • GGT <35 • ALT < 30 • AST < 45 • Bile salts • Should be fasting • Normal range is <6 in pregnancy

5. Differential Diagnosis • 40% of pregnant women develop a skin eruption of some sort during pregnancy • Many of which involve pruritis • Pregnancy Urticarial Plaques and Papules (PUPP) • Typically begins in stretch marks on the abdomen • In the final weeks of pregnancy • Can pose a dilemma of management • Eczema and Psoriasis • Typically has a past history • Typical sites involved • Allergic skin reactions • Scabies • Preeclampsia, HELLP and acute yellow atrophy liver

6. Abnormal Liver Function Tests? • Raised AST and ALT • This is Hepatitis • Viral or chronic active • Raised alkaline phosphatase and GGT • This is cholestasis • Typically due to gallstones • Raised GLT and ALT • This is fatty liver • Raised GGT alone • Typically a drug-induced liver effect • Raised ALT alone • This arises from muscle damage • Raised Bilirubin but normal enzymes • This is due to haemolysis or familial hyperbilirubinaemia e.g. Gilberts

7. Maternal Consequences of Cholestasis • Pruritis and scratching • Insomnia • Skin damage • Some reports of increased risk of preeclampsia and urinary tract infection • Vitamin K dependent blood clotting factors may be reduced • Risk of APH and PPH • Controversial

8. Fetal Consequences of Cholestasis • Increased risk of pre term delivery • Controversial • Some of this is iatrogenic • Increased risk of stillbirth • Controversial • Earlier studies suggested 2-3 fold increased risk • Not substantiated by contemporary studies • Is this a consequence of clinical awareness & intervention? • RCOG recommends “women with this condition should be told that current rates of stillbirth are no higher than in the general obstetric population” • Increased risk of meconium liquor and CS

9. Pathogenesis of Fetal Risk • Still unknown • There is evidence that risk of fetal death, premature labour and meconium is related to the concentration of bile salts • Bile salts are oxytocic in vitro • Fetal hypoxia (if it occurs) appears to be acute and not chronic • This makes monitoring difficult

10. Recommended Management • Weekly liver function tests • Oral Vitamin K for mothers • Although prothrombin time is rarely checked • Fetal monitoring • Umbilical Dopplers of no apparent value • Waiting for CTG changes might be too late • Timing of Delivery should be decided on an individual basis • May depend on previous obstetric outcome • Elective delivery after 37 weeks is common • Any marked deterioration in LFT’s is regarded with concern

11. Possible Interventions • Any simple skin emollient for pruritis • Ursodeoxycholic acid • 1.5 – 2.0 G/day • Successfully lowers serum bile salts • May assist with pruritis • But fetal benefit lacking from RCT’s • Maternal Dexamethasone • May have a role • Acts by suppressing the fetal adrenals • Which are the source of fetoplacental “liver toxic” steroids • May assist in fetal lung maturation

12. Recommended Followup • Follow liver function tests back to normal • Oestrogen-containing oral contraceptives are best avoided • Advice to relatives may be required • Counselling and debriefing is required when there has been an adverse obstetric outcome • There is a UK Support Group