Prof. Mahmoud Midan
Definition
Obstetric cholestasis is a multifactorial condition of
pregnancy characterised by pruritus in the absence
of a skin rash with abnormal liver function tests
(LFTs), and both of which resolve after birth.
 Usually occurring in the last trimester of pregnancy.
It can, however, occur earlier in gestations.

Investigations to exclude other causes of pruritus
and of abnormal LFTs should be performed.
Background




Prevalence is influenced by genetic and
environmental factors and varies between
populations worldwide .
In England, obstetric cholestasis affects 0.7% of
pregnancies in multiethnic populations and 1.2–
1.5% of women of Indian–Asian or Pakistani–
Asian origin.
In Chile, 2.4% of all pregnancies are affected .
In Indian:- 5% of all pregnancies are affected .
History
In 1987, Wilson reported the
first case of intrahepatic
cholestasis of pregnancy in an
African-American patient.

Histology




The periportal areas show no change, and the
hepatocellular architecture remains undisturbed.
The centrilobular areas, however, reveal dilated bile
canaliculi, many containing bile plugs.
Ultrastructurally, there appears to be some destruction and
atrophy of microvilli in the bile canaliculi.
These changes tend to
regress after pregnancy.
Risk Factors
1. Personal or family history of obstetric
cholestasis.
2. Multiple pregnancy.
3. Carriage of hepatitis C.
4. Presence of gallstones.
Diagnosis
1.
Unexplained pruritus
and Abnormal (LFTs)
And/
Or
2. Raised bile acids.
These acids are deposited in the
skin and probably cause the
1.
2.
Other causes of itching
and
of
liver
dysfunction should be
excluded.
Postnatal resolution of
pruritus and abnormal
LFTs
should
be
confirmed.
extreme pruritus.
Grade C
Pruritus in pregnancy
It
is
common,
affecting 23% of
pregnancies,
of
which
a
small
proportion
will
have
obstetric
cholestasis.
Pruritus of Cholestasis
1- worse at night
2- often widespread
and may involve the
palms of the hands
and/or the soles of
the feet.
1. Other evidence of
cholestasis should be
sought, including pale
stool, dark urine and
jaundice.
2. Other causes of pruritus
must be excluded such as
eczema
or
atopic
eruption of pregnancy.
Pruritus in pregnancy (cont.)
If a rash is present,
polymorphic eruption
of
pregnancy
or
pemphigoid gestations
(blisters) should be
considered.
Jaundice




Approximately, 2 weeks later, clinical jaundice will
develop in 50 % of cases.
The jaundice is usually mild, soon plateaus, and remains
constant until delivery.
The pruritus worsens with the onset of jaundice,
and the patient's skin can become excoriated.
The symptoms usually abate within 2 days after
delivery.
Laboratory abnormalities
Unexplained abnormalities in
1- Transaminases,
1.
2-Gamma-Glutamyl Transferase
And/
Or
3. Bile salts
are considered sufficient to support the
diagnosis of obstetric cholestasis.
2.
Alkaline phosphatase
(non specific as it is
placental in origin so,
it is not reflect liver
disease).
Bilirubin is raised
only infrequently.
Pregnancy-specific reference
ranges for LFTs should be used
(20% of non pregnant value)
Differential Diagnosis
Other causes of pruritus and abnormal LFTs should be sought:1. viral screen for hepatitis A, B, and C, EBV, CMV.
2. primary biliary cirrhosis (for example, anti-smooth muscle and
(liver ultrasound)
3. Pre-eclampsia and acute fatty liver of pregnancy are
antimitochondrial antibodies).
pregnancy-specific causes of abnormal LFTs that might form
part of the differential diagnosis in atypical or early cases.
Maternal morbidity
1.
2.
3.
4.
i.
ii.
Intense pruritus and Consequent sleep
deprivation.
Increase Rate Of CS.
Increase Risk Of PPH.
If cholestasis lasts for several wks, liver
dysfunction may result in:
Decreased vitamin K re-absorption or
Decreased prothrombin production, leading to
a prolongation of the prothrombin time.
Fetal risks
Preterm birth
Obstetricians should be aware (and should advise women)
that the incidence of premature birth, especially iatrogenic,
is increased
.
Spontaneous
preterm birth
(range 4-12%)
Iatrogenic
preterm birth
(range 7–25%)
Grade B
Meconium Passage
Women should be advised of the increased likelihood of
meconium passage in pregnancies affected by obstetric
cholestasis.


More common in preterm obstetric cholestasis pregnancies than in
term obstetric cholestasis pregnancies (25% compared with 12%)
More common in cases with severe cholestasis (defined as bile acids
over 40 micromoles/litre) compared with mild cholestasis (bile acids
under 20 micromoles/litre) (10% compared with 0 %)
Grade B
Still Birth
The current additional risk of stillbirth in
obstetric cholestasis above that of the
general population has not been determined
but is likely to be
Small
For England and Wales in 1980, the perinatal mortality rate
was 13.4, 8.3 in 2002 and 5.4 in 2008
Grade B
Caesarean Section


Caesarean section rates are high, ranging from
10% to 36%.
It is difficult to establish the relative roles played of
obstetric cholestasis itself, of induction of
labour/other obstetric indications and of
obstetrician/patient anxiety.
Postpartum haemorrhage

Despite physiological reasons and a high caesarean
section rate, which might suggest an increased risk
of postpartum haemorrhage, evidence from current
practice does not show this.
Monitoring





Measure LFTs weekly until delivery
If LFTs return to normal, obstetric cholestasis is not
likely to be the correct diagnosis.
If LFTs escalate very rapidly, additional diagnoses
need to be considered and the frequency of
monitoring increased.
A coagulation screen should be performed.
blood pressure measurement and urine check, allow
monitoring of the condition and exclusion of other
diagnoses.
Can fetal death be predicted and prevented?


Poor outcome cannot currently be predicted by
biochemical results and delivery decisions should not be
based on results alone.
Grade B
No specific method of antenatal fetal monitoring for the
prediction of fetal death can be recommended.
Grade D


Ultrasound and CTG are not reliable methods for
preventing fetal death in cholestasis.
Grade C
Continuous fetal monitoring in labour should be offered.
It Is Difficult to predict fetal death??


Until the pathophysiology of obstetric cholestasis
and fetal death is more clearly defined and the
level of risk is clarified, prediction and prevention
of fetal death will remain challenging.
Fetal death is usually sudden. There is no evidence
of placental insufficiency. Fetal growth restriction
and oligohydramnios are not features of the
disease.
Management

Women with obstetric cholestasis should be
booked in under consultant-led, team based care
and give birth in a hospital unit.
Should women with obstetric cholestasis be offered
elective early delivery ??

A discussion should take place with women regarding induction of labour after
37+0 weeks of gestation.

Women should be informed of the increased risk of perinatal morbidity from
early intervention (after 37+0 weeks of gestation).

Women should be informed of the inability to predict stillbirth if the pregnancy
continues.

Women should be informed that the case for intervention (after 37+0 weeks of
gestation) may be stronger in those with more severe biochemical abnormality
(transaminases and bile acids).
Grade B
Treatment


There is no evidence that any specific
treatment improves fetal or neonatal
outcomes.
All such therapies should be discussed with
the individual woman with this in mind.
Topical emollients
(calamine lotion and aqueous
cream with menthol).
Safe
but their efficacy
is unknown
Grade C
Systemic treatments

1.
2.
Aim:- relieve pruritus
Colestyramine.
Antihistamines such as chlorphenamine may provide
some but not significant impact on pruritus.
3.
Activated charcoal and guar gum do not relieve
pruritus.
Cholestyramine (Cholestran Pack 4 gm).
A total of 8 to 16 g/day in three to four divided doses
A.
B.
C.
D.
A poorly tolerated bile acid-chelating agent.
May improve pruritus in some women
May also exacerbate vitamin K deficiency
(fetal ICH), check PT weekly
No randomised trials and is not in clinical use .
S-adenosyl methionine

There is insufficient evidence to demonstrate
whether it is effective for either control of
maternal symptoms or for improving fetal
outcome
It is not recommended
Grade A
Ursodeoxycholic acid (UDCA)


Improves pruritus and liver function.
No robust data concerning protection against
stillbirth and safety to the fetus or neonate.
Mechanism of action:
enhance bile acid clearance across the placenta, This may protect the
hepatocyte membrane from the damaging toxicity of bile salts.
Grade A
Dexamethasone
10 mg orally for 7 days and then stopping over 3 days


should not be first-line therapy for treatment of
obstetric cholestasis, nor should it be used outside of
a randomised controlled trial without a thorough
consultation with the woman.
The results are conflicting, with some improvement in
symptoms and biochemistry in some women.
Grade D
Role of vitamin K

1.
Obstetric cholestasis can result in:Reduced absorption of dietary fats due to failure of excretion of
bile salts into the GIT and reduced micelle formation.
2.
Increased fat excretion (subclinically or clinically apparent as
steatorrhoea) has been reported to affect the absorption of fatsoluble vitamins including vitamin K, which is required for the
manufacture of coagulation factors 11,V11, 1X and X.
vitamin K
5- 10 mg daily oral, aiming to improve both maternal and neonatal
levels, which are assumed to be deficient, and therefore reduce
postpartum haemorrhage and fetal or neonatal bleeding



When the prothrombin time is prolonged, the use of watersoluble vitamin K (menadiol sodium phosphate) is indicated.
When prothrombin time is normal, vitamin K in low doses
should be used only after careful counselling about the likely
benefits but small theoretical risk.
Postnatal vitamin K must be offered to the babies in the usual way
Grade D
POSTNATAL



LFTs should be deferred for at least 10 days
postnatally (6-8 wks)
Grade D
In normal pregnancy, LFTs may increase in the first
10 days of the puerperium.
Postnatal resolution of symptoms and of biochemical
abnormalities is required to secure the diagnosis.
Evidence level III
contraceptive choices
Usually avoiding Estrogencontaining methods.
Recurrence


Intrahepatic cholestasis tends to recur in
subsequent pregnancies, but the severity may
vary from one pregnancy to the next.
In their Chilean study, Gonzalez et al. reported
a recurrence rate of 70 % in singleton
pregnancies.