[CG] Obstetric cholestasis

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Obstetric Cholestasis (OC) is an important disease unique to pregnancy

  • Multifactorial condition characterised by pruritus in the absence of a rash, with abnormal liver function tests (LFTs), in the absence of an alternative cause, both of which resolve after birth
  • Associated with increased perinatal mortality and maternal morbidity
  • The incidence appears to be increasing. It is not clear whether or not this is due to improved surveillance and diagnosis
  • In the UK, OC affects approximately 0.7% of pregnancies and 1.2–1.5% of those in women of Indian–Asian or Pakistani–Asian origin. The incidence appears to be higher during the winter months
  • Inform woman's consultant once diagnosis is made

Aetiology

  • Uncertain
  • Multi‐factorial
  • Oestrogen is implicated
  • More common in multiple pregnancies
  • Hepatitis C and gallstones are predisposing factors
  • Familial: +ve family history 30 – 35%
  • Possible autosomal dominant inheritance

Clinical features

Common:  

  • Severe pruritus which may cause insomnia. (Note that a degree of pruritus affects up to 25% of pregnancies: only in a small minority of cases will this be due to OC.)
  • Usually third trimester onset
  • Itch classically starts on soles of feet and palms and spreads to trunk/limbs
  • No associated rash 
  • Excoriation may be present

 Less common:  

  • Dark urine
  • Pale stools
  • Anorexia
  • Steatorrhoea
  • Jaundice (rare)

Maternal risks

  • Debilitating disease
  • Increased likelihood of undergoing caesarean section
  • Slightly increased risk of post partum haemorrhage due to reduced absorption of Vitamin K

Fetal risks

  • Increased risk of stillbirth. Quoted stillbirth rates (without intervention) up to 100 per 1000 births (10%), though other studies have found considerably lower rates 
  • Risk increases >37+0 weeks
  • Spontaneous (and iatrogenic) preterm birth
  • Increased intrapartum complications such as meconium staining of liquor (25 – 45%; incidence rises in proportion to maternal bile acids levels) and intrapartum fetal distress (12 – 22%)
  • Increased rate of intracranial haemorrhage secondary to Vitamin K deficiency 

A precise explanation of the fetal effects remains elusive. 

Diagnosis: by exclusion of other causes of symptoms/abnormal LFTs 

  • Past obstetric history, family history, or if similar problems when taking combined oral contraceptive pill
  • Exclude pre‐existing liver disease, usually on history
  • Check if taking medications which may cause deranged LFTs, e.g.methyldopa
  • Consider pre‐eclampsia and acute fatty liver of pregnancy as differential diagnoses in atypical cases
  • Identify risk factors for viral hepatitis

Investigations
LFTs (including AST and GGT) and bile acids

  • NOTE: AST and/or GGT may need to be ordered as separate tests, depending on your local laboratory's standard LFT set.
  • Typical 2–4 fold rise in transaminases.
  • Remember normal pregnancy changes: alkaline phosphatase will be elevated and is therefore not informative; normal upper limits for bilirubin, transaminases and GGT are 20% lower than non‐pregnant levels
  • Bilirubin may be slightly elevated in OC
  • Bile acid level should be measured. A fasting sample is not required. Our laboratory runs the assay daily on weekdays. A level of over 17 μmol/L is strongly suggestive of OC (in the absence of another explanation) and there is some evidence of progressively increasing fetal risk above this level. This risk increases markedly at >40 μmol/L. Results >30 μmol/L will be phoned to the ordering clinician by the laboratory. <7 μmol/L is certainly within the normal range, though this does not exclude the diagnosis. A result between 7 and 16 is equivocal and should not be construed as positive evidence for the diagnosis.

Women with persistent pruritus and normal/equivocal biochemistry should have blood tests repeated every 1–2 weeks: some women will have pruritus for days or weeks before the development of abnormal blood test results.

Hepatitis serology  

  • A, B, C, cytomegalovirus and Epstein Barr virus

Autoimmune liver disease screen

  • Anti‐smooth muscle antibodies (chronic active hepatitis)
  • Anti‐mitochondrial antibodies (primary biliary cirrhosis)

Hepatic/gallbladder ultrasound in selected patients

  • This is indicated if gallbladder disease is suspected. The presence of gallstones does not exclude OC: rather, it is a predisposing factor

Random blood glucose

 

Antenatal management

The principal intervention is planned delivery at 37 to 38 weeks.

Once OC is diagnosed, weekly LFTs, BP, urinalysis and general review until delivery, for monitoring of the condition and exclusion of other diagnoses. If LFTs return to normal, OC is unlikely. If LFTs escalate very rapidly, additional diagnoses need to be considered, coagulation screen performed and the frequency of monitoring increased: although this situation can be consistent with OC, it is not typical.

Fetal surveillance until planned delivery

There is no proven, useful monitoring regime. This is analogous to the situation in women with IDDM.  Fetal growth problems are not a feature of this condition and therefore any monitoring considered should be bio‐physical e.g. CTG, amniotic fluid volume, fetal umbilical artery Doppler (FUAD).

The following plan is suggested: 

  • Baseline assessment of AC, FUAD, amniotic fluid volume. Refer to consultant for review and determination of individual management
  • Ask women to report reduced fetal movements promptly. CTG should then be performed. There is no evidence to support routine CTG assessments

Drug therapy

  • Discuss with senior obstetrician before initiating this
  • Inform woman’s consultant and GP

First line treatments

Ursodeoxycholic Acid (UDCA)

  • There is strong evidence that this improves pruritus and liver function
  • Robust data does not exist regarding beneficial effects on fetal outcome
  • Weigh patient
  • Dose: 8‐12 mg/kg per day divided into 2 doses (round dose to nearest formulation strength, pharmacy stocks 150mg and 250mg preparations)

Vitamin K

All patients with prolonged prothrombin time should receive menadiol sodium phosphate 10mg daily, orally. (If unavailable prescribe phytomenadione 10mg daily orally (unlicensed)). BNF cautions relate to historical data. RCOG guideline supportive of use of Vitamin K. 

With normal prothrombin time vitamin K in low doses should be used only after careful counselling about the likely benefits but small theoretical risk. 

A degree of further symptomatic relief may be obtained by addition of:

  • Chlorphenamine: 4mg 4 times daily OR
  • Promethazine: 10mg 3 times daily initially (may be increased to 20mg)
  • Topical emollients, which may provide slight temporary relief

Second line treatment, to be initiated only by a consultant

Dexamethasone

  • Limited and somewhat conflicting evidence regarding its benefits and potential adverse effects, but use may be warranted where symptoms are severe and refractory
  • Should not be initiated without a thorough consultation with the woman by a consultant
  • 12mg orally daily in divided doses for 7 days, then reduced over 3 days and then stopped

The key intervention is a planned delivery at 37-38 weeks

  • A careful discussion should be had with the patient regarding this. From around 37 weeks onwards, the risk of stillbirth is likely to outweigh the risks to baby and mother of preterm delivery, particularly in those cases where bile acids/transaminases are severely abnormal. However, the evidence base for this is not particularly sound. Should a woman opt for conservative management, it is important to stress the inability to predict stillbirth
  • Steroids if < 36+0 weeks and elective delivery. Steroids if < 39+0 weeks and elective caesarean
  • IV access and continuous fetal monitoring in labour
  • Active management of third stage (PPH risk)
  • Caesarean section only for other obstetric complications

Resolution in postnatal period

  • Generally resolves soon after delivery (hours/days)
  • Rarely worsens in postnatal period
  • Postnatal resolution of pruritus and abnormal LFTs should be confirmed in order to secure the diagnosis. Defer confirmatory blood tests until 10 days post‐delivery
  • Recommend alternative to combined oral contraceptive pill. Progesterone‐only preparations are appropriate

Next pregnancy  

Recurrence risk is > 50%. For some women, every pregnancy is affected.

References

RCOG Green‐top Guideline 43  Obstetric Cholestasis April 2011 accessed 1.4.15 https://www.rcog.org.uk/globalassets/documents/guidelines/gtg43obstetriccholestasis.pdf

RCOG patient leaflet Obstetric Cholestasis May 2012  accessed 1.4.15  https://www.rcog.org.uk/globalassets/documents/patients/patientinformationleaflets/pregnancy/piobstetriccholestasis.pdf

Last reviewed: 16 April 2015

Next review: 31 May 2018

Author(s): Dr A Duncan, Consultant Obstetrician. (Lead Author); Dr A Archibald, Specialist Trainee O&G on behalf of GONEC

Version: 2

Approved By: A.M. Mathers, Clinical Director