GTG 43 - Intrahepatic cholestasis of pregnancy - June 2022

Question 1

What symptoms and tests should indicate a clinician to diagnose intrahepatic cholestasis of pregnancy (ICP)?

Answer 1

Itching in skin of normal appearance
Raised peak random total bile acid of 19 or more.

Question 2

When should additional lab and/or imaging investigations be considered?

Answer 2

Atypical clinical symptoms,
Presence of relevant comorbidities,
Early onset severe ICP
— If any of the above consider discussing with a hepatologist.
Postnatally - if resolution of abnormal LFTs is delayed or does not occur.

Question 3

How is a diagnosis of ICP confirmed?

Answer 3

In the postnatal period (at least 4 weeks after birth) with resolution of itching and LFTs and BA returning to normal.

Question 4

What should women be advised regarding the risk of still birth and isolated ICP?

Answer 4

The risk of stillbirth only increases above the population rate once their serum bile acid concentration is 100 or more.

Question 5

What term should be used describe the condition of itching with peak BA concentrations <19micromol/L

Answer 5

Gestational pruritis

Question 6

What BA levels constitute mild ICP?

Answer 6

19-39micromol/l

Question 7

What BA levels constitute moderate ICP

Answer 7

40-99micromol/L

Question 8

What Ba levels constitute severe ICP?

Answer 8

100micromol/L or more.

Question 9

What should women with isolated mild ICP (BA 19-39) and no other risk factors be advised regarding stillbirth risk and TOB?

Answer 9

With mild ICP the risk of stillbirth is similar to the background risk.
Consider options of planned birth by 40 weeks or ongoing ANC according to national guidance.

Question 10

What should women with isolated moderate ICP (BA 40-99) and no other risk factors be advised regarding stillbirth risk and TOB?

Answer 10

The known risk of stillbirth is similar to the background risk UNTIL 38-39 weeks.
Consider planned birth at 38-39 weeks.

Question 11

What should women with isolated severe ICP (BA 100 or more) and no other risk factors be advised regarding stillbirth risk and TOB?

Answer 11

The risk of stillbirth is higher than the background risk.
Consider planned birth at 35-36 weeks gestation.

Question 12

What should women with ICP and a twin pregnancy be advised regarding stillbirth risk?

Answer 12

The risk of stillbirth is higher compared to a twin pregnancy without ICP

Question 13

Which co-morbidities increase the risk of stillbirth with ICP. These may influence discussions regarding TOB.

Answer 13

GDM
PET
multiple pregnancy

Question 14

What is the prevalence of ICP in multi-ethnic populations and in Indian-Asian or Pakistani-Asian origin

Answer 14

0.7% in multi ethnic
1.2-1.5% in Indian-Asian/Pakistani-Asian

Question 15

What approximate percentage of women develop itching in pregnancy

Answer 15

Around 25%.
Most do not develop ICP

Question 16

Are the levels of AST or ALT associated with pregnancy outcome?

Answer 16

No

Question 17

Should women with itching and raised transaminases but normal BA concentrations be given a diagnosis of ICP?

Answer 17

No.
This is supported by a systematic review - no association between abnormal maternal transaminase concentrations and stillbirth.

Question 18

Is there variation in BA concentration with fasting or prandial readings?

Answer 18

Yes.
Prandial readings are higher than fasting.
Taking random non fasting levels maximises the chance of detecting peak bile acid readings that are of greater clinical importance for preventing adverse pregnancy outcome.

Question 19

Up to how long after itching commences can gestational pruritis develop into ICP?
how often should women with gestational pruritis have monitoring?

Answer 19

up to 15 weeks.
The frequency of review and tests should be on an individual basis but gestational age should be considered as ICP is more likely to develop in the third trimester.

Question 20

Pruritis and biochemical abnormalities usually persist throughout the pregnancy however they commonly fluctuate.
What if they resolve completely?

Answer 20

If they resolve completely for the remainder of pregnancy it is unlikely the original diagnosis was correct. (i.e monitoring should continue?).
In discussion and agreement with the woman ongoing care can usually return to normal.
TOB should be based on usual practice, although be cautious particularly if BA levels were ever >100.

Question 21

Should women with suspected ICP be routinely screened for other causes of the clinical picture of ICP?

Answer 21

The likelihood of identifying a viral, autoimmune or structural cause for the itching and liver derangement that is not suspected on clinical grounds is extremely low.

Question 22

In which women should additional investigations for ICP be considered?

Answer 22

women with an atypical or uncertain picture of ICP:
markedly elevated transaminases,
ICP in 1st or 2nd trimester or
rapidly progressive biochemical picture,
any features of liver failure or
evidence of acute infection or
if resolution does not occur postnatally.

Question 23

When should discussion with a hepatologist occur?

Answer 23

Women who develop pruritis and LFT abnormalities and BA in the first or 2nd trimester are more likely to have a genetic predisposition or alternative/additional diagnosis.
Especially the first trimester.

Question 24

Women with ICP are more likely to develop pre-eclampsia. OR 3.7. What monitoring should occur?

Answer 24

Alongside reviews of ICP women should receive BP and urinalysis screening for PET.

Question 25

Women with ICP are more likely to have GDM. What monitoring should occur?

Answer 25

Additional testing for GDM is not currently recommended.
Risk assessment and testing for GDM should follow national guidelines.

Question 26

ICP is associated with later risks of hepatobiliary disease (usually gallstones), immune mediated diseases (DM, thyroid disease, psoriasis, inflam. polyarthropathies, crohns disease). Should screening be offerred

Answer 26

Gallstones are common and the immune mediated diseases have a low absolute incidence.
There is no proven benefit for screening.

Question 27

Although uncertain, What is thought to be the pathophysiology of stillbirth in ICP?

Answer 27

Bile acids may cause an acute fetal anoxic event possibly due to fetal arrhythmia or acute placental vessel spasm.

Question 28

What is the risk of perinatal morbidity?

Answer 28

Advise women with moderate or severe ICP that they have a higher chance of:
- spontaneous (OR 3.47) or iatrogenic preterm birth (OR 3.65)
- meconium stained amniotic fluid during labour and birth OR 2.6
- their baby is more likely to receive neonatal care OR 1.47

Question 29

What should women be advised regarding antenatal CTG and US fetal monitoring in ICP.

Answer 29

They do not predict stillbirth.
Several studies describe fetal death despite close surveillance and previously normal US scans including dopplers.
ICP is not associated with FGR therefore strategies for monitoring for placental insufficiency are unlikely to be beneficial for women with isolated ICP.

Question 30

What impact on symptoms, biochemistry and fetal outcome is there from medications in ICP.

Answer 30

No treatments improve outcome
Treatment to improve itching are of limited benefit.
Consider antihistamines at night although effectiveness is uncertain.

Question 31

What effect may urso have on preterm birth in ICP?

Answer 31

Those taking urso compared to placebo had a reduction in spontaneous late preterm birth OR 0.46 vs 0.86.
However there is no evidence that this reduction results in any benefit.

Question 32

Should vitamin K be used in women with ICP.

Answer 32

Most women with ICP do not have evidence of fat malabsorption.
If a woman has steatorrhoea, coagulation assessment should be performed and use of vit K treatment considered.
- menadiol sodium phosphate 10mg PO OD

Question 33

What monitoring should be offered in labour to women with ICP?

Answer 33

• Offer CEFM to women with BA >100
• Advise women that there is insufficient evidence for or against CEFM is BA <100. Consider co-morbidities and preferences.
• Advise those with co-morbidities that they increase the risk of adverse outcomes.
• Advise women that meconium stained liquor is more common in moderate and severe ICP and this may influence decision making.
• Those with isolated ICP and no other risk factors, intrapartum care can follow national guidelines.

Question 34

What advice should be offered regarding future contraception or HRT.

Answer 34

• ICP itself should not influence future contraception or HRT.
• If they have a hx of cholestasis secondary to oestrogen containing contraception then advise to use progesterone only or non hormonal methods.
• for women with previous ICP requesting HRT, offer if no other contraindications.

Question 35

What is the risk of ICP in subsequent pregnancies and should it be screened for?

Answer 35

The risk is increased but studies have been too small to calculate the precise magnitude of risk.

At booking baseline LFTs and BA should be tested to establish that they are normal.
Repeat testing is only if clinically indicated.