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CHAPTER 28  Obstetric cholestasis (OC)

Prevalence and background Risks

• Prevalence – 0.7% of pregnancies. More common (1.2–1.5%) in women of Indian or Pakistani
origin.
• It is a multifactorial condition, influenced by genetic and environmental aspects and varies Maternal
among populations.
• OC is characterized by intense pruritus in the absence of a skin rash, with abnormal liver • Meconium-stained liquor (MSL), CS or PPH:
function tests (LFTs), neither of which have an alternative cause and both of which remit * MSL is more common in preterm than term OC pregnancy (25% vs 12%)
following delivery. and preterm controls (18% vs 3%).
• It is a diagnosis of exclusion. * MSL may be more common in those with severe cholestasis (defined as bile
acids > 40 μ mol/l) compared with mild cholestasis.
* CS rates are high, ranging from 10% to 36%.
* PPH is reported to range from 2% to 22%.

Fetus
History and examination
• Pruritus – typically worse at night, often widespread and may involve the palms of the hands or • Prematurity – increased, mainly iatrogenic (range 7–25%), risk of spontaneous
the soles of the feet. premature delivery is only slightly increased compared with general population
• Consequent sleep deprivation (range 4–12%).
• Evidence of cholestasis – pale stool, dark urine. • Stillbirth – risk in ‘untreated’ OC is unclear. Studies between 2001 and 2011
• Family history of OC. reported the PNM rate 5.7/1000. These are comparable to that of general
• Skin inspection – no rash. population – PNM is reported as 8.3 in 2002 and 5.4 in 2008.
• Skin trauma from intense scratching may be seen (excoriations).

Investigations Differential diagnosis

• LFTs – abnormal transaminases, GGT, bilirubin, and/or bile salts. • Other causes of pruritus (see Chapter 44 Pruritus in pregnancy).
* Use pregnancy-specific reference ranges. • Other causes of abnormal LFTs:
* Isolated elevation of bile salts may occur. * Viral infections – hepatitis A, B, C, EBV, and CMV.
* Normal levels of bile salts do not exclude the diagnosis. Substantial number of women * Liver autoimmune conditions – chronic active hepatitis and
will have pruritus for days or weeks before the development of abnormal LFTs. If pruritus primary biliary cirrhosis.
persists, LFTs should be measured every 1–2 weeks. • PET and acute fatty liver of pregnancy in atypical cases.
• Viral screen.
• Liver USS.
• Liver autoimmune screen (anti-smooth muscle, antimitochondrial antibodies) may be indicated.

107 CHAPTER 28  Obstetric cholestasis (OC)

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108 SECTION 3  Antenatal Care

Monitoring

Maternal
• LFTs weekly.
• Do not decide delivery based on the degree of abnormality of biochemical
tests, as current data are not robust enough to demonstrate or exclude a
correlation between levels of liver enzymes or bile salts and IUD.
• Bile salts may play a role in fetal demise. However, it is unclear whether bile
acid concentrations are related to fetal outcome.
Fetus
• No specific fetal monitoring for the prediction of fetal death can be recommended.
• IUD is usually sudden and seems to be due to acute anoxia. There is no evidence of placental
insufficiency. USS including UtAD assessment is not a reliable method for preventing fetal death.
• CTG – lack of predictability of future fetal wellbeing of a normal CTG is a major limitation of the
use of this test.
• Amniocentesis – too invasive.
• Maternal detection of movements is simple, inexpensive, and not time-consuming but its role in
monitoring pregnancy complicated by OC has not been evaluated.

Management
There is no evidence that any specific treatment improves maternal symptoms or neonatal outcomes.

Topical emollients and antihistamines Ursodeoxycholic acid S adenosyl methionine

• Topical emollients are safe but their efficacy is unknown.
Clinical experience suggests that for some women they may
provide slight temporary relief of pruritus.
• Antihistamines such as chlorpheniramine may provide some
welcome sedation at night but do not make a significant
impact on pruritus.
• There is lack of data concerning improvement in pruritus, protection • There is insufficient evidence to show
against SB, and safety to the fetus. whether it is effective for either control
• UDCA can displace more hydrophobic endogenous bile salts from the of maternal symptoms or improving
bile acid pool and thereby protect the hepatocyte membrane from their fetal outcome.
damaging toxicity and enhance bile acid clearance across the placenta
from the fetus.
• As the pathophysiology of OC and the mechanism of fetal demise are
uncertain, the possible role of UDCA is unclear.

Vitamin K Dexamethasone

• OC can result in reduced absorption of dietary fats, due to failure of excretion of bile salts into the
GIT and reduced micelle formation, leading to reduced absorption of fat-soluble vitamins including
vitamin K, which is required for the manufacture of coagulation factors 2, 7, 9, 10.
• Daily supplementation of vitamin K aims to improve both maternal and neonatal levels and
therefore reduce PPH and fetal or neonatal bleeding.
• Do not offer as first-line therapy for OC outside of RCT.
• Observational reports – results are conflicting.
• The general concern about adverse fetal and neonatal neurological effects of
repeated courses of maternally administered dexamethasone limits the potential
use of it.
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Time and mode of delivery

• Stillbirths in OC have been reported across all gestations. As gestation advances, the risk of
delivery (prematurity, respiratory distress, failed induction) versus the uncertain fetal risk of
continuing the pregnancy (stillbirth) may justify IOL after 37 weeks.
• IOL at 37 weeks – while it is certain that delivery at 37 weeks will prevent a SB beyond that
gestation, it is not known how high the risk of such an SB might be. Risks of perinatal (respiratory
morbidity and admission to SCBU) and maternal morbidity are increased.
• Offer continuous fetal monitoring in labour.

Postnatal care
• Repeat LFTs – postnatal resolution of symptoms and of biochemical abnormalities is required
to secure the diagnosis. In normal pregnancy, LFTs may increase in the first 10 days of the
puerperium; in a pregnancy complicated by OC, defer routine measurement of LFTs beyond this
time.
• Offer postnatal vitamin K for the babies.

Follow-up
• To ensure that LFTs have returned to normal, pruritus resolves, and to provide appropriate
counselling.
• Reassure about the lack of long-term sequelae for mother and baby.
• Discuss contraceptive choices (avoid oestrogen-containing methods).
• Risk of recurrence is high.
• Increased incidence of OC in family members.

What not to do
• Any specific fetal monitoring modality for the prediction of fetal death.
• Dexamethasone or S adenosyl methionine for management.
• Decide delivery based on the degree of abnormality of biochemical tests.

Obstetric Cholestasis. RCOG Green-top Guideline No. 43; April 2011.

109 CHAPTER 28  Obstetric cholestasis (OC)