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MRCOG PART 2 SBAs and EMQs

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ESSAY 181 - CHOLESTASIS

Posted by Vaani M.
These findings are suggestive of obstetric cholestasis of pregnancy. It is characterised by itching of the hands and feet in the third trimester of pregnancy usually not associated with a rash and resolves after delivery. Elevated bilirubin, bile acids, and liver enzymes are present. The other causes like viral infections, pre-eclampsia, acute fatty liver of pregnancy have been ruled out in this woman. The implications for this woman would be severe itching and sleep deprivation for her. Her fetus would be at increased risk of premature birth either spontaneous or induced, and at risk of intrauterine death. Her family members would also be at risk of having the same problem in their pregnancies. Her chance of having the same problem recurring in future pregnancies also would be high. There would be no long term implications for her or her child.

Weekly follow up of liver function tests, and tests of fetal wellbeing would be needed. There are no specific tests for fetal wellbeing as none including CTG, amniocentesis, doppler or amnioscopy are predictive of fetal condition. Severity of maternal disease is also not correlated to the fetal risk. Early induction of labour has no proven benefit. Evidence of risk of meconium stained liquor, caeserean section, and postpartum haemorrhage are not conclusive.

Topical emollients would be useful to relieve the itching and not for the biochemical abnormalities. S-adenosyl methionine is to be administered twice daily as intravenous infusion and is inconvenient for the woman,so would not be preferred. Uridyl deoxy cholic acid is used to relieve itching and correction of liver functions but evidence of benefit has not been proven. Dexamethasone could be used orally for its membrance stabilising effect and correction of liver functions but its long term use may be associated with maternal adverse effects and fetal neurological adverse effects although these have not been proven as its benefit.

Vitamin K has to be given to this woman orally as 10mg daily tablets till delivery. Raised bile salts would lead to loss of enterohepatic circulation and depletion of Vit. K and its dependent clotting factors as factor II, VII, IX, X. This would be corrected with oral water soluble vit. K and thus reduce risk of maternal and fetal haemorrhage.

Early delivery may be required if maternal condition worsens or with severe biochemical abnormalities or suspected fetal compromise although all of these could be sudden and unpredictable. Vaginal delivery would be preferred unless for an obstetric reason.

Postnatally watch for postpartum haemorrhage and prompt treatment would be required. The neonate would be given vit. K as usual. Liver functions need to be repeated after 10 days as it would be normally raised in the puerperium initially. She needs follow up until liver functions are normalised to ensure the diagnosis. Contraceptives are advised with risk of recurrence with oestrogenic compounds which should be avoided. Information leaflets would be provided and the woman counselled at all stages during her treatment and follow up.
Posted by Sreekala S.
The most probable diagnosis is cholestasis of pregnancy. The other causes of elevated bile acids and transaminases have to be ruled out by performing an upper abdominal ultrasound to rule out gallstones, hepatitis screen(viral and auto immune hepatitis), antimitochondrial antibodies for primary biliary cirrhosis and anti smooth muscle antibodies for chronic active hepatitis. It was shown that women with hepatitis C infection have a higher prevalence of Obstetric cholestasis. In women with hepatitis C and obstetric cholestasis treatment with Interferon and ribavarin postnatally can be curative. Therefore, viral screening is important. The diagnosis of obstetric cholestasis is by exclusion.
There is an increased risk of preterm delivery, meconium staining of the liquor, fetal distress, fetal intracranial haemorrhage, intra uterine death and Post partum haemorrhage due to Vit K deficiency. In view of these risks, the woman should be counselled sympathetically about the need for close monitoring during her pregnancy and labour.
Ursodeoxy cholic acid 1000-1500mg given in 2-3 divided doses should be prescribed as it was shown to reduce the pruritus , improve the abnormal LFTs and probably reduce the risk of still birth although it is still unproven. Vitamin K 10mg should be given orally once the diagnosis has been made until delivery to reduce the risk of haemorrhage. Antihistamines can be given for symptomatic relief of pruritus. If she is unable to take ursodeoxycholic acid, then cholestyramine or prednisolone (12mg daily for 7 days and gradual tapering over 3 days )or S adenosyl methionine can be tried. Calamine lotion or aqueous cream with menthol can be used for pruritus.
LFTs have to be monitored on a weekly basis; although monitoring the disease activity with LFTs does not predict the outcome but ensures continued cholestasis.
CTG should be performed regularly, although it lacks sensitivity to predict fetal death.Ultrasound scan for fetal growth and if necessary Doppler should be done. The aim is to deliver by 37 weeks as it was shown that delivery after 38weeks increases the possibility of fetal death.
IOL should be considered at 37completed weeks if there is no sign of labour. Caesarean section is indicated only for obstetric indications. Continuous electronic monitoring should be done during labour and blood crossmatched as there is a high risk of PPH. Haematologist should be involved in the event of PPH. Paediatrician should be available at delivery and vit K administered to the Baby.
Postnatally the woman should be counselled that there is a recurrence rate of 90% in the subsequent pregnancies. Breast feeding is encouraged. COCP should be avoided as there is risk of 27%recurrence of symptoms due to the estrogen component.The other alternatives like condoms, IUCD can be considered. If the alternatives are unsuitable, then she needs close monitoring with serial LFTs , surveillance for pruritus and discontinue the COCP if she becomes symptomatic.
In the event of continued pruritus or abnormal LFTs postnatally, she needs referral to a hepatologist. Leaflets about cholestasis should be provided and information on support groups given.
Posted by Sarwat F.
Most likely diagnosis with these findings is cholestasis of pregnancy. Differential diagnosis include biliary obstruction viral hepatitis, skin disorders. Personal history of skin disorders, viral markers and ultrasound scan of upper abdomen will help in reaching to a conclusive diagnosis. Cholestasis is associated with increased risk of obstetric haemorrhage. Fetal risks include preterm labour, meconium staining of liquor, fetal distress, stillbirth and intracranial hemorrhage. It has a genetic basis of inheritance and family members are at risk of having the disease.
Regarding management of this pregnancy, mother will be explained about the disease and need for fetal survillance. Symptomatic treatment will be provided during pregnancy. Topical emollients can be given for itching. She can be given antihistamines, cholestyramine can also be helpful. There is insufficient data to support the use of s adenosyl methionine for cholestasis. Bile acids like ursodeoxycholic acid, although not licensed for use in pregnancy, are used extensively for cholestasis and there are no reported adverse effects. Steroids can also be used in resistant cases however repeated courses of steroids are associated with adverse fetal and neonatal neurological outcome. Vitamin k is given to mother weekly either intramuscularly or oral regimes. If oral regimens are used water-soluble ones are used daily, as cholestasis is associated with fat malabsorption. Her liver function tests are done weekly and coagulation profile is monitored. Any signs of preterm labour should be recognized and in that event in utero transfer to a unit with neonatal facilities considered.
Fetal surveillance will be carried out every 2 weeks. At each visit growth scans are carried out and Doppler done if there is any evidence of slow growth. This can be supplemented by doing cardiotocograph as well. However she will be counselled that no recent monitoring modality for prediction of antepartum stillbirth can be recommended. It has been a practice to induce labour between 36 to 38 weeks to prevent late stillbirths, however data is insufficient to support early induction. Decision is therefore made after careful assessment of clinical and biochemical factors and woman?s wishes. Baby is also given vitamin k after delivery. There is a risk of obstetric haemorrhage and delivery should take place in a unit well equipped with dealing obstetric hemorrhage. Group and hold is done during labour. Wide bore intravenous access is achieved.
After delivery liver function tests are deferred until 10 days. A follow-up appointment is arranged to discuss the sequelae of this condition. Contraception is discussed and oral contraceptives are better avoided because of their effect on liver function. Woman is counselled that this condition tends to recur in subsequent pregnancies. An information leaflet is provided and information regarding support groups is given.
Posted by Aroosha B.
The findings in this case are suggestive of obstetric cholestasis or intrahepatic cholestasis of pregnancy which typically presents in third trimester with itching mainly of palms of hands and soles of feet although rarely legs, arms, abdomen, arm back and breasts may be involved. Whenever a woman presents with itching at it is important to look for the presence of rash because in case the rash is present, then a dermatological referral may be required.
In this case a history of cyclical itching, a history of pruritus or oral intake of combined pills or family history further support the diagnosis of obstetric cholestasis. Before reaching a final diagnosis further investigations to rule out other causes of liver pathology must be done such as hepatitis A, hepatitis B, hepatitis C, CMV, Epstein Barr virus antimitochondrial antibodies,anti smooth muscle antibodies and USG for chronic active hepatitis and primary biliary cirrhosis.
The management of her pregnancy should be by explaining the condition to the patient Obstetric cholestasis is associated with increased risk of prematurity and even iatrogenic prematurity . There is reported increase incidence of meconium stained liquor , still birth, PPH and increased rate of caesarean section, although the incidence of still birth in patients with obstetric cholestasis is not very different from other patients.The management is symptomatic with aim to improve the symptoms
The patients can be given local applications like calcium lotion, Balneum Plus. Aqueous cream preprations with menthol 1-2 % can also provide help. The role of systemic cholestyramine to decrease prupritus is not well establish. Activated charcoal and guar gum do not help.
Ursodeoxyclolic use has been described to improve the pruritis and liver function but there is wide variety in Uk prarice and ther is insufficient evidence to prescribe its use for treatment in obstetric cholestasis. The use of S adenosyl methionine for relief of pruriris and improvement of LFT?s is not done as safety is not yet established.
The woman should be given oral water soluble Vit K from 34 weeks Gestation onwards as its poor absorption leads to decreased synthesis of factor 2, 7, 9, and 10 and increased risk of PPH.
The use of dexamethasone has been seen beneficial in a very few studies so its use should not be out of randomized controlled trials.
No method of fetal monitering have been proved to decrease still birth rate as there is no IUGR or Doppler chanes in fetal vessels in pregnancies effected by obstetric cholestasis CTG also give a snapshort view of fetal condition.
Elective delivery at 37 weeks is usually done by IOL but it is associated with increased risk of transient tachypnoea of new born and patient should be managed on individual basis.
Posted by Aroosha B.
LFTS should be done on weekl;y basis.Post natel follow up should be done to see that the condition has completely resolved and liver function should not be repeated before 10 days. The patient should be given detailed information that the disease has no long term consequences for mother or neonate, a high risk of recurrence, avoidance if possible of estrogen containing contraceptives and a high incidence of family history. The patient should be given information leaflets and also about obstetric cholestasis patient support group.

Posted by Srivas  P.
Intrahepatic Cholestasis of Pregnancy is a likely diagnosis if itching is not associated with skin rashes. Cholelithiasis, liver diseases, Hepatitis and lymphomas can cause generalized itching and should be ruled out before coming to this diagnosis. Fifty percent of woman may give family history of this condition. If rashes are present the diagnosis could be dermatoses of pregnancy.

ICP shows deranged liver tests. Post prandial elevation of serum bile acids is a sensitive marker for cholestasis of pregnancy and correlates with severity of pruritis. Serum alanine aminotransferase and aspartate aminotransferase may be raised, and bilirubin can be raised too. A new marker of hepato cellular damage, Glutathione-S-tranferase alpha (GST alpha) can differentiate cholestasis of pregnancy from pruritis gravidarum. Woman should have Hepatitis profile (Hepatitis A, B, C, EBV and CMV) and auto antibody screen for primary biliary cirrhosis. Woman with Hepatitis C have higher incidence of cholestasis. USG scan of liver and biliary tree should be done to rule out cholilithiasis.

In the absence of skin rashes, absence of positive findings for liver damage, cholelitiasis and pruritis appearing first time in third trimester?ICP is the most likely diagnosis, by exclusion.

It is important to counsel the woman regarding the fetal and maternal implications of the condition and the refractory nature of treatment. Maternal risks include psychological distress by persistent itching and risk of obstetric hemorrhage. Fetal risks are due to preterm delivery, 15% incidence of stillbirths, 25 % incidence of fetal distress and meconium staining of liquor.

The principle of management involves close fetal surveillance, correct timing of delivery and control of maternal symptoms. Once the diagnosis of Obstetric cholestasis is made, woman should be delivered between 37-38 weeks to reduce risks of IUD. The risk of IUD may be reduced to 05-1 % by maternal treatment with ursodeoxycholic acid (UDCA) and dexamethasone but maynot be totally prevented. UDCA also improves maternal symptoms of pruritis. Other symptomatic treatments include cool baths, antihistamines and cholestyramine?each with variable results.

She should get oral Vit K 10 mg daily once obstetric cholestasis is diagnosed to reduce risk of haemorrhage by deficiency of Vit K dependent clotting factors and baby should receive vit K at delivery. She should also be told about 90 % recurrence risk of Obstetric Cholestasis in next pregnancy and also recurrence of similar symptoms with use of oral contraceptives. She may be given COC if she insists on it but should have regular LFTs and it should be stopped if the LFT gets deranged.

Symptoms usually subside 48 hrs after delivery but if it persists after 7 days, alternate diagnosis should be thought about and she should have a postnatal biliary tract USG and a review by a gastroenterologist. She should be given information booklets to take home and read.

Posted by SUNIL P.
The diagnosis is most likely obstetric cholestasis. The implications for mother are - discomfort due to itch, possible development of jaundice, potential for vitamin k deficiency with coagulation derangement.
For baby, there is the risk of IUD which is unpredictable, of increased CTG abnormalities during labour and meconium staining of liquor, and increased iatrogenic prematurity and caesarean section rates. Baby has increased risk of haemorrhagic disease of newborn.
Future pregnancies, 75% chance of recurrence and cholestasis with the OCP.
I would explain the condition to the mother in terms she understands and give information leaflets on the condition.
I would commence her on vitamin K injections as oral vitamin K may not be well absorbed.
I would consider administering steroids, even though the number needed to treat to prevent 1 case of RDS is 96 at 34 weeks; in case of urgent delivery within the next fortnight.
I would moniter LFT?s, even though worsening LFT?s do not influence fetal outcome, and also coagulation on a weekly basis.
I would be alert to the possibility of diagnosies such as gall bladder pathology, and request US billiary tract.
I would review risk factors or hx to suggest viral or autoimmune hepatitis and request hep A/B/C serology and antibodies for autoimmune liver disease.
I would continue to moniter BP/ and symptoms for PET, even though diagnosis is strongly suggestive of cholestasis.
I would initiate increased fetal surveillance with growth scans, alternate day CTG?s, twice weekly BPP, even though the evidence is lacking that IUD can be predicted.
I would induce at 38weeks gestation or earlier if evidence of fetal compromise in an effort to avoid IUD.
At the start of induction I would inform the aneathatist of the patient, check coagulation and plan for anaesthetic/analgesic requirements.
The labour would be high risk and require continuous electronic fetal monitering.
Regarding maternal symptoms: antihistamines would be my 1st line choice. Ursodeoxycholic acid could be used but it is unlicensed. Alternatives include cholestyramine. The use of a gastroenterologist is helpful.
I would explain that the symptoms resolve following delivery, that it is likely to recur and that the OCP is contraindicated. I would recommend breast feeding and give alternative advice on contraception: POP is ok for example.
I would recommend neonatal vitamin K, if this were given orally and the mother was breast feeding, the dose should be 2mg at birth, then 2mg at one week, then monthly till weaned.
Posted by hala M.
The most likely diagnosis in this case is Obstetric Cholestasis (OC) and this is associated with risk to the mother (due to worsening, itching leading to insomnia and lack of sleep and due to vitamin K deficiency with its associated risk of haemorrhage) and to the foetus (still birth, prematurity, meconium stained amniotic fluid and caesarean section).
Although the question stated that there is no hypertension or proteinurea, but HELLP syndrome is still a possible diagnosis and this has its own complications of maternal/ foetal morbidity and mortality. Acute fatty liver of pregnancy (AFLP) can give the same picture or might coincide with OC.

The management of this pregnancy is by taking a detailed history asking about the severity of itching, rash association and its distribution and associated systemic symptoms (fatigue, fever, malaise, abdominal pain and jaundice).
Medical history is of relevance to ascertain the risk of autoimmune diseases (chronic active hepatitis CAH and primary billiary cirrhosis PBC). Asking about drug history is important because some drugs cause itching and an abnormal liver function test such as: methyldopa, penicillins, anti-thyroids and paracetamol. A family history of OC or similar personal history on combined oral contraceptive (COC) gives a strong clue to the possibility of OC.
On examination we need to check for a skin rash (scratch marks in OC) and its distribution. Polymorphic Eruption of pregnancy (PEP), Purigo, Pruitic follicullitis and pemphegoid gestationes can cause an itchy rash with a specific distribution. We need to check for temperature, jaundice, BP and abdominal tenderness (RUQ pain in Billiary Obstruction and Cholecystitis).
The investigation needed would be the liver USScan, viral hepatitis screening (ABC), CMV and EBV antibodies. Auto antibodies such as anti smooth muscle antibodies and anti mitochondrial antibodies are important for the diagnosis of CAH and PBC. Blood film for Haemolysis and full blood count for platelet blood count helps with the diagnosis of HELLP. Hypoglycaemia is found in AFLP.
Regarding foetal monitoring in OC none of the known methods (USScan, CTG, BPP and Doppler) showed a difference in the outcome.

Controlling the itching by emollient creams has a soothing effect and anti-histamines might offer some sedation to allow sleeping at night. S adenosylmethionine does not show to be effective in controlling maternal symptoms or improving foetal outcome. UDCA is not licensed in pregnancy. Giving vitamin K to the mother antenataly and to the neonate will reduce the risk of haemorrhage.
Planned delivery at 37-38 weeks is reasonable due to the fear of still birth and this needs to be discussed with the patient with reference to the risks/benefits of early delivery and the paediatric team should be aware of the situation. Breast feeding is not contraindication.
The patient needs to have a follow up at 10 days for the check of normalization of LFT and needs to be advised about the risk of reoccurrence more than 50%. Contraceptive advice is necessary as COC is contraindicated. The patient needs to be aware of the OC support group.

Posted by BAHAA-Uddin BOR B.
The diagnosis is most likely Obstetric Cholestasis, which has been suggested through the symptoms and clinical investigations. It is associated with maternal risks including vitamin K deficiency,increased risk of postpartum haemorrhage problems and significant morbidity including intense pruritis and consquent sleep deprivation and insomnia.It does not lead to chronic liver disease, but associated with high recurrence rate 75-90% .Obstetric Cholestasis in the mother carries a significant risk for her fetus ,including spontaneous prematurity, intrauterine fetal death ,Meconium stained liquor,intrapartum fetal distress and fetal intracranial haemorrhage secondary to vitamin K deficiency.The positive family history of this condition is about 33-50%.
The diagnosis is confirmed by excluding other causes of abnormal liver function such as cholelithiasis or extra-hepatic obstruction by liver ultrasound examination,serum hepatitis screen and antimitochondrial antibodies.
Once a diagnosis of Obstetric cholestasis is made , the mother should be counseled concerning the risks and need for fetal surveillance. Maternal Liver function tests including prothrombin time should be regularly monitored.
Maternal symptomatic control may be achieved by the use of anti-histaminics ,such as clorphenramine which may provide some sedation at night but do not make significant impact on pruritis,while topical emollients are safe in pregnancy , they provide slight temporary relief of pruritis.
Ursodeoxycholic acid ( UDCA ) is commonly used for relief of pruritis ,although it is not licensed for use in pregnancy .At present no definitive treatment for Obstetric Cholestasis resulting in resolution of the disease. S-Adenosyl methionine ( S-AME ) is given intravenously and may improve maternal symptoms and liver function especially when infused in combination with ( UDCA )., but is not widely used. Dexamethazone may reduce the itching and lower the bile acids and transaminases if used in dose ( 12 mg orally for 7 days with a reducing dose for 3 days.). There is no evidence that any of these drugs alters fetal outcome.
Water-soluble vitamin K ( 10 mg orally daily ) given to the mother may reduce the risk of the postpartum haemorrhage and fetal or neonatal bleeding. It should be commenced from the diagnosis .Maternal intra-muscular vitamin K may preferable to oral Fat-soluble vitamin K as malabsorption occurs.
Prediction of fetal outcome in this condition is difficult .Cardiotocographic monitoring of the fetus and umbilical artery Doppler studies are used but are not usually found to be abnormal. Fetal growth scans , liquor volume estimation are performed weekly,but these poor predictors of outcome .
The balance of risks and poor predictive value of tests of fetal welfare suggest that elective induction of labour from 36-38 weeks. No expectant management is the rule.
The place for amniocentesis for meconium stained liquor is unproven.,Corticosteroids may be given at 36 weeks gestation for the risk of preterm delivery. Continuous electronic fetal monitoring as risk of intra-partum fetal distress. Caesarean section is reserved for obstetric indications and fetal compromise.Blood sample should be taken and cross-matched for increased risk of PPH.
Complete recovery is usual following delivery.Itching may persist for up to 2 weeks post-partum. Postnatal LFT should be deferred for at least 10 days.
Vitamin K supplement should be given to the baby.The woman should be counselled that the risk of recurrence in future pregnancies is at least 75%.She should also be advised to avoid oral contraceptives containing oestrogen.,as LFT may become abnormal with COCP.The woman should be offered follow-up to ensure that LFTs have returned to normal . The patient be given complete informations about investigations carried for her, the implications of the Obstetric Cholestasis.
Information leaflet should be given to the patient ( The British Liver Trust )., Follow-up appointment should be arranged.. She should be given address of support group
(Obstetric Cholestasis Patient Support Group ).