Cholestasis of Pregnancy Based on RCOG Greentop Guideline 43 January 2006 Max Brinsmead MB BS PhD May 2015

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”

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

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

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

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

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

Fetal Consequences of Cholestasis Increased risk of pre term delivery Controversial Some of this is iatrogenic Increased risk of stillbirth 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

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

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

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

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

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