In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.
Levels of evidence (Ia-IV) and grading of recommendations (A-C) are defined at the end of the "Major Recommendations" field.
How is Obstetric Cholestasis Diagnosed?
C - Pregnancy-specific reference ranges for liver function tests (LFTs) should be used.
C - Other causes of itching and of liver dysfunction should be excluded.
C - Postnatal resolution of pruritus and LFTs should be confirmed.
In obstetric cholestasis, the pruritus is typically worse at night, is often widespread, and may involve the palms of the hands or the soles of the feet. Other causes of pruritus must be excluded. The skin should be inspected and care must be taken to differentiate dermatographia artefacta (skin trauma from intense scratching), which may be seen in obstetric cholestasis, from other common skin conditions such as eczema and pruritic eruption of pregnancy. Other evidence of cholestasis should be sought, including pale stool, dark urine, and family history of obstetric cholestasis.
In clinical practice, abnormalities in transaminases, gamma glutamyl transferase, bilirubin, and/or bile salts are considered sufficient to support the diagnosis of obstetric cholestasis.
If, in routine practice, bile salt assessment is not easily available, it would be reasonable, at present, only to obtain levels in women with pruritus who have persistently normal LFTs.
Other causes of abnormal LFTs should be excluded. A viral screen for hepatitis A, B, and C, Epstein Barr, and cytomegalovirus, a liver autoimmune screen for chronic active hepatitis and primary biliary cirrhosis (for example, anti-smooth muscle and antimitochondrial antibodies), and liver ultrasound should be carried out before the diagnosis is confirmed.
How Should Obstetric Cholestasis be Monitored?
C - Once obstetric cholestasis is diagnosed, it is reasonable to measure LFTs weekly.
C - Postnatal LFTs should be deferred for at least 10 days.
What is the Risk of Stillbirth for Pregnancies Complicated by Obstetric Cholestasis?
B - Obstetricians should be aware (and should advise women) that the current stillbirth rate for obstetric cholestasis is comparable to that in the general population. The risk of stillbirth in "untreated" obstetric cholestasis is unclear.
What Additional Risks are Associated with Pregnancies Complicated by Obstetric Cholestasis?
B - Obstetricians should be aware (and should advise women) that the incidence of premature birth is increased, both spontaneous and iatrogenic.
B - Obstetricians should be aware (and should advise women) that the evidence for an increased risk of meconium-stained liquor, caesarean section, or postpartum haemorrhage is inconclusive.
Can Fetal Death be Predicted and Prevented?
B - Delivery decisions should not be based on the degree of abnormality of biochemical tests, as current data are not robust enough to demonstrate or exclude a correlation between maternal levels of liver enzymes or bile salts and intrauterine death.
C - No specific fetal monitoring modality for the prediction of fetal death can be recommended.
B - Ultrasound is not a reliable method for preventing fetal death in obstetric cholestasis.
Should Women with Obstetric Cholestasis be Offered Elective Early Delivery?
B - Obstetricians should be aware that there are insufficient data to support or refute the popular practice of "early" (37 weeks of gestation) induction of labour aimed at reducing late stillbirth.
What Treatment, if any, Should be Used to Treat Obstetric Cholestasis and What Benefit Can be Expected?
There is no evidence that any specific treatment improves maternal symptoms or neonatal outcomes. All such therapies should be discussed with the individual woman with this in mind.
Topical Emollients
C - Topical emollients are safe but their efficacy is unknown.
S-Adenosyl Methionine
A - There is insufficient evidence to show whether S adenosyl methionine is effective for either control of maternal symptoms or for improving fetal outcome.
Ursodeoxycholic acid
A - There are insufficient data to support the widespread use of ursodeoxycholic acid (UDCA) outside of clinical trials. Women should be aware of the lack of robust data concerning improvement in pruritus, protection against stillbirth, and safety to the fetus or neonate.
Dexamethasone
B - Dexamethasone should not be first-line therapy for obstetric cholestasis, nor should it be used outside of a randomised controlled trial (RCT) without a thorough consultation with the woman.
What is the Role of Vitamin K?
C - It is reasonable to offer a daily supplement of water-soluble vitamin K to all women from diagnosis of obstetric cholestasis. If there is frank steatorrhoea or prolongation of the prothrombin time, the clinical case for the use of vitamin K is stronger.
What Follow-up Should be Offered to Women Who Have Had a Pregnancy Affected by Obstetric Cholestasis?
As a minimum, healthcare practitioners must ensure that LFTs return to normal, pruritus resolves, all investigations carried out during the pregnancy have been reviewed, and the mother had fully understood the implications of obstetric cholestasis. The latter will include reassurance about the lack of long-term sequelae for mother and baby, the high recurrence rate, discussion of contraceptive choices (usually avoiding oestrogen-containing methods), and the increased incidence of obstetric cholestasis in family members. Local policy will dictate how this is best organised.
Definitions:
Grading of Recommendations
Grade A - Requires at least one randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation (evidence levels Ia, Ib)
Grade B - Requires the availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendations (evidence levels IIa, IIb, III)
Grade C - Requires evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates an absence of directly applicable clinical studies of good quality (evidence level IV)
Levels of Evidence
Ia: Evidence obtained from meta-analysis of randomised controlled trials
Ib: Evidence obtained from at least one randomised controlled trial
IIa: Evidence obtained from at least one well-designed controlled study without randomisation
IIb: Evidence obtained from at least one other type of well-designed quasi-experimental study
III: Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies, and case studies
IV: Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities
