Approach

The management of ICP aims to reduce risks of adverse perinatal outcomes, particularly stillbirth, and improve maternal pruritus. With a greater understanding of the aetiology of ICP, it may be possible to target treatments to the underlying pathology.

Fetal surveillance

ICP-associated stillbirth is not thought to be caused by placental insufficiency, with appropriately grown babies and no pathognomic ultrasound abnormalities.[65][66] It is thought instead that stillbirth occurs following a sudden catastrophic event, with case reports of stillbirth occurring within a short interval of normal fetal monitoring.[67] Thus, antenatal fetal surveillance with, for example, cardiotocography, is of benefit only during the monitoring period. Despite this, it is often offered for patient reassurance, although without consistent evidence of benefit.

See Monitoring.

Pharmacological treatment

With the exception of ursodeoxycholic acid, most trials in ICP are small (typically fewer than 100 women per arm), so evidence for pharmacological treatment is limited.[90]

Ursodeoxycholic acid

Ursodeoxycholic acid reduces the severity of pruritus (although to a small degree and inconsistently), alters the composition of the bile acid pool (enriching it with hydrophilic ursodeoxycholic acid and reducing hydrophobic bile acid concentrations), and reduces alanine aminotransferase concentrations.[90][91] [ Cochrane Clinical Answers logo ] ​​​ In a large placebo-controlled trial, which included more than 600 women, ursodeoxycholic acid did not reduce the frequency of a composite of adverse pregnancy outcomes that included preterm birth, stillbirth, and neonatal unit admission, although it did reduce meconium-staining of the amniotic fluid.[92] Reassuringly, however, ursodeoxycholic acid use was not associated with adverse side effects compared with placebo.

A subsequent individual participant data meta-analysis found that treatment with ursodeoxycholic acid was associated with a reduction in preterm birth (most clearly, spontaneous preterm birth) in singleton pregnancies in women whose bile acid concentrations at diagnosis or randomisation were ≥40 micromol/L.[93] Thus, ursodeoxycholic acid is recommended in particular for women with ICP before 37 gestational weeks who have bile acid concentrations ≥40 micromol/L.

Although the Royal College of Obstetricians and Gynaecologists recommends against routine use of ursodeoxycholic acid due to lack of evidence for maternal or fetal benefit, the more recent European and joint Australian and New Zealand guidelines cite the new data and suggest ursodeoxycholic acid may be considered for women with mild ICP (bile acids <40 micromol/L).[14][79][94]​ Decisions about treatment should be individualised.

Alternative treatments

Evidence for alternative agents is insufficient, and they should not be used outside of consultant care.

  • Colestyramine binds bile acids in the intestine; treated women may experience gastrointestinal side effects and consideration should be given to the fact that it may prevent absorption of ursodeoxycholic acid or vitamin K.[13] In a comparison with ursodeoxycholic acid, colestyramine showed no benefit within the treatment of pruritus or liver biochemistry.[95]

  • Results from trials on the impact of S-adenosylmethionine (SAMe) on pruritus in ICP are inconsistent, and no benefit was seen compared with ursodeoxycholic acid.[90][96][97]

  • A case series of women treated with rifampicin reported improved bile acids and pruritus for more than half, although its use within a clinical trial is awaited.[98]

  • Dexamethasone showed no benefit over ursodeoxycholic acid, and there is insufficient evidence to determine benefits for treatment with guar gum, activated charcoal, yinchenghao decoction, Danxiaoling pill, or Yiganling.[90][99]

Therapeutic plasma exchange

By replacing maternal plasma with 5% albumin solution, pruritogens and bile acids can be removed by therapeutic plasma exchange (TPE). Case series and reports have demonstrated variable short-term benefits.[100] However, TPE is invasive, with side effects including coagulopathy from the removal of clotting factors, and so should be reserved for women with severe disease at early gestations.

Timing of delivery

There is no evidence that any pharmacological treatment can prevent stillbirth; thus, timed early delivery on the basis of disease severity (determined by the measurement of serum bile acid concentrations) is recommended to reduce the risk of late stillbirth.[76]

Evidence shows that the stillbirth rate (3.4%, 95% CI 2.1% to 5.4%) is significantly elevated for women with ICP who have peak bile acid concentrations of ≥100 micromol/L, compared with the background population, and the stillbirth rate increases in the 35th gestational week particularly.[2] Previous research, without disease stratification, suggested delivery between 36 and 37 gestational weeks, using an assumption of overall increased stillbirth rate compared with the local population.[101][102]​ The balance of risk between early delivery and stillbirth should be discussed with women with ICP, and, for those with elevated serum bile acid concentrations ≥100 micromol/L, delivery by induction of labour or elective caesarean section (based on obstetric indications) should be offered from the 35th gestational week.[76][79]​ By contrast, for women with ICP who have peak bile acid concentrations <100 micromol/L, there is no increased risk of stillbirth compared with the background population, and thus early delivery to prevent stillbirth is not clearly indicated.[2] However, it is important to continue to measure maternal serum bile acid concentrations because they may increase with advancing gestation. The relative paucity of outcome data from pregnancies extending past 40 gestational weeks means that delivery is typically offered from 38 to 39 gestational weeks for women with moderate or even mild disease.[14][76]

In a prospective study of more than 700 women with moderate or severe disease (bile acid concentrations of ≥40 micromol/L), 7 of the 10 women who experienced stillbirth had additional gestational pathology, such as gestational diabetes or pre-eclampsia.[103] Thus, decisions about delivery gestation should be individualised according to bile acid concentrations and co-existent pathology.

For some women, the psychological impact of severe pruritus and fatigue associated with ICP may render iatrogenic early delivery necessary for maternal reasons. Liver dysfunction rarely deteriorates to the extent that there is concern about acute hepatic failure, and, should this occur, alternative diagnoses may need to be considered.

Prevention of vitamin K deficiency

Although there is no overall increased risk of bleeding (coagulopathy or postnatal haemorrhage) for women with ICP, supplementary vitamin K is recommended for women with steatorrhoea or taking bile acid-binding resins (such as colestyramine) because of the risk of vitamin K deficiency with fat malabsorption.[82][104]

Other supportive measures

Current management of pruritus is limited to topical creams (e.g., aqueous cream with menthol) and emollients, and sedating antihistamines (maternal itch is not thought to be secondary to histamine, so their use is purely aimed to improve sleep).[14]

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