Based on
Green top guideline 2022, Dewhurts, Evidence based algorithms
Background
⚫ 0.7% of pregnancies worldwide.
⚫ 1.4% in Asian population ( Risk is twice in the Asian Population) – Just like PCOS
Definition
Characterized by Pruritus in the absence of a primary skin condition, with abnormal maternal bile acid concentrations. Onset of symptoms mostly in third trimester –
⚫ Therefore all pruritus with rash + Cholestasis of pregnancy – T3 — Except Atopic Eruption in pregnancy
⚫ Pruritus and raised bile acid concentrations should return to normal after birth – At least by 6 weeks post-partum
⚫ If associated with rash is unlikely to be ICP
⚫ Bile acid concentrations are not associated with intensity of itching
⚫ BUT maternal total bile acid concentrations results are associated with the risk of stillbirth
⚫ Liver blood tests, such as ALT/AST are not associated with pregnancy outcome
Liver failure is not a typical feature of ICP – But (impaired synthetic function such as prolonged prothrombin time, or metabolic dysfunction such as hypoglycaemia) it is a feature of AFLP.
Pathology
Family History of OC shows it has a genetic component
- Oestrogen sulphation
- Bile acid transport
- Change in hepatocyte membrane fluidity.
History and Examination
⚫ Symptoms usually occur during the third trimester, but can occur earlier
Pruritus – typically worse at night, often widespread, is not specific to any single location and may involve the palms of the hands or the soles of the feet.
⚫
Persistent itch of normal skin and normal blood results, an initial diagnosis of gestational pruritus should be considered – Obstetric Cholestasis / Intrahepatic Cholestasis in Pregnancy – Pruritus with no rash
Pruritus in Pregnancy
⚫ Persistent itch of normal skin and normal blood results, an initial diagnosis of gestational pruritus should be considered
⚫ Women can go on to develop ICP up to 15 weeks after a diagnosis of gestational pruritus
⚫ Bile acid concentrations are not associated with severity of itching – but associated with risk of still birth
⚫ Consequent sleep deprivation
⚫ Evidence of cholestasis – pale stool, dark urine – Not very common
⚫ Steatorrhea – Usually due to Vit K malabsorption
⚫ Jaundice very rarely (<1%) – Even if it occurs, its very mild
⚫ Family history of OC – Autosomal Dominant Inheritance – Can have the gene but only 10% develop the disease
⚫ Skin inspection – no rash.
⚫ Skin trauma from intense scratching may be seen (excoriations).
Associations
⚫ 12.2% of women with ICP had pre-eclampsia compared with 3.4% of women without ICP (x4 risk of preeclampsia)
13.2% of women with ICP had already been diagnosed with gestational diabetes compared with 5.9% (GDM patients x2 likely to develop ICP)
⚫ Women who have had ICP had an increased likelihood of later being diagnosed with hepatobiliary disease
Theres an association between ICP and immune-mediated diseases later in life – Diabetes, Thyroid disease, Psoraisis, Crohns Disease but NOT ULCERATIVE COLITIS
Complications
Investigations
Remember that both bile acids and LFTs can be normal and it can rise later.
Diagnosis of ICP
- Pregnant women who have itching in skin of normal appearance
- and raised peak random total bile acid concentration of 19 micromol/L or more.
- The diagnosis is more likely if it is confirmed that itching and raised bile acids resolve after birth
- Offer repeat liver function tests and bile acid measurement (depending on gestation and clinical context) in women with normal blood results whose itch persists, and no other cause is apparent
- If resolution of itching is associated with normalisation of bile acids and liver function tests during pregnancy, the diagnosis of ICP is unlikely to be correct
- Additional laboratory and/or imaging investigations are not recommended in every woman, but could be considered on an individual basis.
- For many women with ICP, itching will stop very soon after birth; in the majority it stops in the first few hours or days
- Confirm the diagnosis of ICP in the postnatal period at least 4weeks after birth, with resolution of itching and liver function tests returning to normal (including bile acids)
Differential Diagnosis
Risks + Monitoring
In women with ICP and peak bile acids 40micromol/L or more, co-morbidities may be associated with a greater risk of stillbirth.
Pathophysiology of stillbirth
⚫ Bile acids may cause an acute fetal anoxic event possibly due to fetal arrhythmia
⚫ Acute placental vessel spasm
New Greentop guidance
For women with ICP, consider repeating liver function tests and bile acids after 1 week, and then determine frequency on an individual basis – Cater the monitoring as in the table above
Fetal Monitoring
⚫ Advise women with ICP to monitor fetal movements
⚫ Fetal ultrasound, biophysical profile and/or cardiotocography (CTG) do not predict or prevent stillbirth in ICP
ICP is NOT associated with fetal growth restriction (- but Pemphigoid Gestatonis is), with no difference in birthweight centiles
compared with babies born to women without ICP, and therefore strategies for antenatal monitoring for placental insufficiency are unlikely to be beneficial in women with isolated ICP
Role of Treatment
TREATMENT DOESN’T IMPROVE OUTCOME! –
There is no evidence that routine medical treatment improves maternal raised bile acid concentrations or perinatal outcomes.
Long sleeves, Cut nails
Topical Emollients
⚫ Consider topical emollients such as aqueous cream (with or without menthol added) to ameliorate skin symptoms
Antihistamines
⚫ Chlorphenamine has antihistamine properties and may have sedative side-effects in some women
Other common antihistamine agents including loratadine and cetirizine are also used in pregnancy for other indications but do not have sedative side-effects
Ursodeoxycholic acid – Reduces PTL before 37 weeks
Evidence from randomised controlled trials shows that there is no reduction in adverse perinatal outcomes in women prescribed ursodeoxycholic acid
⚫ Ursodeoxycholic acid had no impact on the primary endpoint
⚫ Spontaneous preterm birth under 37weeks’ gestation was reduced in women taking ursodeoxycholic acid compared with placebo
Other agents
Other agents
⚫ Don’t offer any other agents
An opinion from a specialist in ICP should be sought before considering rifampicin treatment – catherine nona said this. But it’s not in guidelines to offer this
⚫Vitamin K – If steatorrhea or Increased PT
Consider maternal vitamin K treatment only if
○ Reduced absorption of dietary fats (e.g. presence of steatorrhea) and/or
○ Abnormal prothrombin time if coagulation studies are performed
⚫ Should be prescribed as a water-soluble formulation such as menadiol sodium phosphate at a dose of 10 mg daily
There are no treatments that improve pregnancy outcome (or raised bile acid concentrations).
Time and mode of delivery
- As of the table above
- Offer continuous fetal monitoring during delivery – Fetus may have arrhythmias
Women with moderate and severe ICP are more likely to have meconium-stained liquor, and this will influence the need for continuous electronic monitoring in labour - Mode of birth should therefore be based on usual obstetric or medical indications
Advise women that the presence of risk factors (such as gestational diabetes, pre-eclampsia, multifetal pregnancy) appear to increase the risk of adverse perinatal outcomes and that these conditions themselves may necessitate monitoring during birth or - in conjunction with ICP may influence decision-making around monitoring in labour
Postnatal care
- No evidence of an increased risk of postpartum haemorrhage if they have uncomplicated ICP
- Infant – IM Vitamin K
LFTs may increase in the first 10 days of the puerperium; in a pregnancy complicated by OC, defer routine measurement of LFTs
beyond 10 days minimum. - For women who have uncomplicated ICP, follow-up should be arranged at least 4weeks after birth to confirm resolution of ICP.
If itching or biochemical abnormalities persist beyond 6weeks postpartum, consider other diagnoses depending upon the history and examination findings. Referral to a hepatologist may be require - Long term
- No long term sequalae or hepatic damage to mother
Risk of recurrence in subsequent pregnancies 45-90% more if
○ CVS disease,
○ Liver disease,
○ multiple pregnancy
This whole statement is from a previous guideline and the 2022 one doe snot know the recurrence risk. There is only a statement saying that there is an increase in the recurrence
At booking in subsequent pregnancies, baseline measurement of liver function tests and bile acid concentrations should be performed in order to establish that these are normal. They should only be repeated if clinically indicated.
Recurrence of symptoms with ( Just like Pemphigoid Gestatoinis)
○ Next pregnancy
○ OCP-Avoid Oestrogen containing contraceptives(recurrence)
○ Menstruation ( E2)
Contraception and hormone replacement – Avoid COCP
For women with ICP and previous cholestasis secondary to combined hormonal (oestrogen-containing) contraception, advise them to use progestogen only or non-hormonal methods
Combined hormonal contraception can be used in women with ICP (UKMEC 2) provided they do not also have a history of contraception related cholestasis.
Contraceptive Use advises that copper-bearing intra-uterine devices, levonorgestrel-releasing intra-uterine systems,
progestogen-only implant, progestogen-only injectable, and progestogen-only pill can be used without restriction in women with a history of ICP (UKMEC category 1)
So when discharging tell about
a. Review in 4 weeks with Bile Acids
b. Recurrence Risk in next Pregnancy
c. Avoid COCP – Give Family planning alternative
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