Obstetric cholestasis

1. Obstetric cholestasis
Aboubakr Elnashar
Prof Obs Gyn, Benha university, Egypt
elnashar53@hotmail.com
Aboubakr Elnashar

2. Incidence
unique to pregnancy.
Incidence: not known
Scandinavia: 1.5%
Chile: 12%
Europe: 0.5-1 %
Aboubakr Elnashar

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. LFT:
abnormal.
5. ± dark urine, anorexia
6. Malabsorption of fat:
steatorrhoea.
Aboubakr Elnashar

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. 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. 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. 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. Pregnancy Maternal risks
1. Vit K deficiency
{malabsorption of fat-soluble vitamins}
2. Increased risk of postpartum hge.
Aboubakr Elnashar

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. 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. 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. 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. 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. 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. 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. 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. c. Antihistamines
Chlorpheniramine (Piriton): 4 mg t.d.s. or
promethazine (Phenergan): 25 mg at night: relieve
pruritus.
Aboubakr Elnashar

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. 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. 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. 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. 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. 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