Obstetric cholestasis


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Obstetric cholestasis

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Obstetric cholestasis

  1. 1. Obstetric cholestasis Aboubakr Elnashar Prof Obs Gyn, Benha university, Egypt elnashar53@hotmail.com Aboubakr Elnashar
  2. 2. Incidence unique to pregnancy. Incidence: not known Scandinavia: 1.5% Chile: 12% Europe: 0.5-1 % Aboubakr Elnashar
  3. 3. Clinical features 1. Pruritus: Severe Limbs& trunk, particularly the palms &soles 2nd halh of pregnancy (usually during the 3rd T) . 2. Insomnia and malaise: common. 3. ±Excoriations No rash. Aboubakr Elnashar
  4. 4. 4. LFT: abnormal. 5. ± dark urine, anorexia 6. Malabsorption of fat: steatorrhoea. Aboubakr Elnashar
  5. 5. Pathogenesis Genetic factors Positive family history: 35% Autosomal dominant sex-limited inheritance. Cholestatic effect of oestrogens& progestogens COCs may precipitate a similar syndrome. 1. Elevated oestrogens: impairment in sulphation of bile acids which is important in attenuating their cholestatic potential. 2. Decrease in hepatocyte membrane fluidity {defect in the methylation of membrane phospholipids& modification in the cholesterol:phospholipid ratio}. Aboubakr Elnashar
  6. 6. Diagnosis By exclusion. 3 steps: 1. History of pruritus without rash 2. Abnormal liver function tests a. Transaminases: Moderate (<3fold) elevation (ALT is the most sensitive) b. Alkaline phosphatase: Raised beyond normal pregnancy values c. Gamma-glutamyl transpeptidase (ƔGT): Raised in 20% d. Bilirubin: Mild elevation: less common e. Serum total bile acid: Increased Primary bile acids (cholic acid& chenodeoxycholic acid): may increase 10 to100-fold Aboubakr Elnashar
  7. 7. Sequence: Increased bile acids ±the only biochemical abnormality ±precede other liver function abnormality Pruritus ±precede the derangement of liver function tests: serial measurements in women with persistent typical itching. Aboubakr Elnashar
  8. 8. 3. Exclusion of other causes of itching& abnormal liver function. a. Liver ultrasound: Gallstones without evidence of extra-hepatic obstruction does not exclude a diagnosis of OC Gallstones are common in women with OC b. Viral serology: for hepatitis A, B, C & E, EBV, CMV c. Liver autoantibodies: for pre-existing liver disease: anti-smooth muscle anti­body: chronic active hepatitis anti-mitochondrial antibodies: primary biliary cirrhosis. Aboubakr Elnashar
  9. 9. Pregnancy Maternal risks 1. Vit K deficiency {malabsorption of fat-soluble vitamins} 2. Increased risk of postpartum hge. Aboubakr Elnashar
  10. 10. Fetal considerations 1. Intrapartum fetal distress: a. Abnormal FHR. e.g. fetal bradycardia, tachycardia or decelerations: 12-22% b. Amniotic fluid meconium: 25-45% 2. PTL: 12-44% 3. IUFD 4. Fetal intracranial hge. Aboubakr Elnashar
  11. 11. Incidence: Difficult to determine {Management include early delivery before the perceived maximum time of risk for the fetus}. Risk of stillbirth increases towards term Perinatal mortality rates: 11 % in earlier studies 2-3.5% in recent studies Mechanisms not known. Aboubakr Elnashar
  12. 12. Factors affecting: 1. Maternal symptoms or transaminase levels: No relation. 2. Serum maternal bile acids: <40 micromol/I: No increase in fetal risk Risk of fetal complications (PTL, asphyxia, meconium) increased by 1-2% per additional micromol/l of serum bile acids. {1. High bile acids have been found in A F& f circulation. 2. Bile acids, especially cholic acid: dose-dependent VC on human placental chorionic veins: reduction of oxygenated blood flow: fetal asphyxia: fetal distress& demise. 3. Bile acids are toxic to rat cardiac myocytes}. Aboubakr Elnashar
  13. 13. Prediction of fetal compromise Difficult 1. Doppler blood-flow analysis in the uterine, umbilical or fetal cerebral arteries: high levels of bile acids have no effect 2. Previous complication: increase risk 3. Repeated amniocentesis to detect meconium: best predictor of fetal compromise. Aboubakr Elnashar
  14. 14. Management 1. Counseling: Risks to the fetus Close surveillance. 2. Liver function tests: including prothrombin time& bile acids: weekly. 3. Fetal well-being monitored at frequent intervals. CTG US: fetal growth liquor volume umbilical artery Doppler blood-flow Aboubakr Elnashar
  15. 15. 4. Delivery at 37-38 w, or when fetal lung maturity is evident {decrease perinatal mortality}. Close monitoring during induction& labour {high risk of fetal distress} The neonate should receive i.m. vit K Aboubakr Elnashar
  16. 16. 5. Drugs: a. Topical emollients Safe but their efficacy is unknown. Diprobase® (Schering-Plough,Welwyn Garden City, UK), Balneum® Plus(Crookes Healthcare, Nottingham,UK), Calamine lotion and aqueous cream with menthol. Aboubakr Elnashar
  17. 17. b. Vit K 10 mg orally/d {reduce maternal&fetal bleeding}. Mandatory if prothrombin time is prolonged. Water-soluble formulation (menadiol sodium phosphate) {co-existent fat malabsorption}. Start at 32 W {increased incidences PTL} women receiving AEDs (start at 36 w) Aboubakr Elnashar
  18. 18. c. Antihistamines Chlorpheniramine (Piriton): 4 mg t.d.s. or promethazine (Phenergan): 25 mg at night: relieve pruritus. Aboubakr Elnashar
  19. 19. d. Ursodeoxycholic acid (UDCA) Ursofalk 250 mg Ursogal Mech of action 1. Reduce hydrophobic bile acids 2. Choleretic agent: reduces serum bile acids. 3. Stimulates the expression of transporters for canalicular& basolateral bile acid export as well as the canalicular phospholipid flippase. Aboubakr Elnashar
  20. 20. Doses: 1000-1500 mg/d in 2 to 3 divided doses Effects: 1. Relief or improvement of pruritus 2. Reduction of total bile acid& liver enzyme in 90%. 3. No reports of adverse fetal or maternal effects. 4. No evidence to support or refute a beneficial effect of on the risk of f compromise& death. Aboubakr Elnashar
  21. 21. e. Rifampicin improves symptoms& biochemical markers of liver injury in cholestaric liver disease {enhances bile acid detoxification as well as bilirubin coniugation}. Combination of rifampicin& UDCA in TT of OC Aboubakr Elnashar
  22. 22. Postpartum 1. Rapid complete recovery: usually 2. Slow recovery: Sometimes, abnormal liver function tests may return to normal only slowly, taking 4-6 w to reach normal values. 3. Worsening: Rarely Aboubakr Elnashar
  23. 23. Recurrence risk/pre-pregnancy counselling 1. Recurence in future pregnancies: 90%. 2. Estrogen-containing oral contraceptives: Avoid If they are used: monitor LFT 3. Progesterone-only pill: {risk of cholestasis is less} monitor the LFT 4. HRT: need not be avoided {this provides only physiological levels of oestrogen} Aboubakr Elnashar
  24. 24. References 1. Piercy C: Handbook of obstetric medicine. 2006: 224-9. 2. RCOG Green Top Guidelines:2011; No43:2-14 3. Evidence Based Obstetrics Gynecology: 2010 Thank You Aboubakr Elnashar