Fetal Mortality Associated with Cholestasisof with Ursodeoxycholic
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580 Gut 1995; 37: 580-584 CASE REPORTS Fetal mortality associated with cholestasis of Gut: first published as 10.1136/gut.37.4.580 on 1 October 1995. Downloaded from pregnancy and the potential benefit of therapy with ursodeoxycholic acid M H Davies, R C M A da Silva, S R Jones, J B Weaver, E Elias Abstract partum, but cholestasis of pregnancy is Cholestasis ofpregnancy is associated with associated with significant fetal morbidity increased fetal morbidity and mortality and mortality.'-9 Cholestasis of pregnancy and should be treated actively. The signifi- typically develops during the third trimester of cance attached to pruritus in pregnancy is pregnancy, but occasionally presents before often minimal, but it is a cardinal symp- 20 weeks. By definition, dermatological tom of cholestasis of pregnancy, which disease should be absent, if a diagnosis is may have no other clinical features. Eight made on clinical criteria alone,9 but this is women with previous cholestasis of not necessary if biochemical evidence of pregnancy were referred to The Liver cholestasis is obtained. Most patients are not Unit within a 12 month period for advice jaundiced and many have normal standard concerning future pregnancies. Thirteen liver function tests. Serum alanine trans- pregnancies had been affected by chole- aminase (ALT) is the most sensitive of stasis of pregnancy and 12 had been the conventional liver function tests,10-12 treated expectantly with resultant peri- although serum bile acids are invariably natal morbidity or mortality in 11 (one increased.0"11 13 Symptoms vary from mild normal delivery), including; eight still- pruritus to intractable pruritus, associated births, two premature deliveries with fetal with gastrointestinal upset and icterus. distress (one died in perinatal period), and Symptoms almost invariably resolve within http://gut.bmj.com/ an emergency caesarean section for fetal one week of delivery. distress. The other pregnancy was treated Treatment of cholestasis of pregnancy varies actively and delivery was uncomplicated. widely. Despite evidence to the contrary, Subsequently, three of these cases with some obstetricians still perceive cholestasis of recurrent cholestasis of pregnancy were pregnancy as a benign condition and adopt an referred while pregnant. In each, chole- expectant policy. We report eight cases with a stasis developed with severe pruritus, gross history of cholestasis of pregnancy whose preg- on October 1, 2021 by guest. Protected copyright. increase of serum bile acids, and deranged nancies had mostly been treated conservatively. liver tests. Each was treated with the Three of these cases were pregnant at the time choleretic agent ursodeoxycholic acid, with of referral and treated with the choleretic rapid clinical improvement and resolution ursodeoxycholic acid. of deranged biochemistry. In conclusion, Birmingham Liver cholestasis of pregnancy continues to be Unit, Queen Elizabeth Hospital, Edgbaston, treated expectantly despite its association Case reports and previous obstetric Birmingham with increased morbidity and mortality histories (Table) M H Davies and evidence suggesting improved progno- R C M A da Silva E Elias sis with active treatment and the potential Case 1: 34 year old white woman of reducing the associated perinatal First pregnancy, 1986 - pruritus from 28 Department of Clinical mortality. In an uncontrolled series of weeks gestation. She was reassured. Spon- Chemistry, Queen Elizabeth Hospital, three patients with cholestasis of preg- taneous onset of labour at 37/40. Stillborn Edgbaston, nancy, ursodeoxycholic acid seemed to female. Pruritus settled within two days. Birmingham provide safe and effective therapy. Second pregnancy 1988 - pruritus from. S R Jones (Gut 1995; 37: 580-584) 27/40. Induction oflabour at 38/40, because of Birmingham previous intra-uterine death. No meconium Maternity Hospital, Keywords: cholestasis of pregnancy, fetal mortality, staining. Male baby, alive and well. Pruritus Edgbaston, prognosis, treatment, ursodeoxycholic acid. settled within Birmingham four days. J B Weaver Third pregnancy - pruritus from 26 weeks, without jaundice. Fetal movements were normal Correspondence to: Dr M H Davies, Cholestasis of pregnancy is a disease of and she was reassured. Liver functions tests Birmingham Liver Unit, unknown aetiology, which may cause severe became abnormal, with increased serum aspar- Queen Elizabeth Hospital, Edgbaston, Birmingham. and intractable pruritus. The maternal prog- tate transaminase (AST) (135). Spontaneous Accepted for publication nosis is excellent, with symptoms and bio- onset of labour at 39/40, with stillbom female. 16 February 1995 chemical derangements resolving rapidly post Pruritus settled almost immediately. Fetal mortality associated with cholestasis ofpregnancy 581 Case reports UDCA A/N Otnset Mode of Mecomiiumti Cessationi Case Pregnancy Onset RX Ictenus clinlic labour Gestationi delivety AST stainizng Olutcolme (fpruritus 1 1st 28/40 No No Yes SPONT 37/40 Vaginal 243 Yes Stillbirth 2 Days 2nd 27/40 No No Yes Induced 38/40 Vaginal 129 No Normal 4 Days 3rd 26/40 No No Yes SPONT Term Vaginal 135 Yes Stillbirth 1 Day Gut: first published as 10.1136/gut.37.4.580 on 1 October 1995. Downloaded from 4th 25/40 Yes No Yes C/s 35/40 ELEC C/s 213 No Normal 2 Days 2 1st 35/40 No No Yes SPONT 38/40 EMERG C/s N/D Yes Fetal distress 3 Days 2nd 35/40 No No Yes SPONT Term Vaginal 82 Yes Stillbirth 1 Day 3rd 28/40 Yes No Yes C/s 35/40 ELEC C/s 42 No Normal 0 Days 3 1st 28/40 No No Yes SPONT 36/40 Vaginal N/D N/K Perinatal death 7 Days 2nd None No No Yes SPONT Term Vaginal N/D No Normal N/A 3rd 32/40 No No Yes SPONT 37/40 Vaginal N/D No Normal 7 Days 4th 30/40 Yes No Yes Induced 38/40 Vaginal 205 No Normal 2 Days 4 1 st None No N/A Yes SPONT Term Vaginal N/D No Normal N/A 2nd 30/40 No No Yes SPONT 36/40 Vaginal N/D ? Fetal distress 1 Week 3rd 31/40 No No Yes SPONT Term Vaginal N/D Yes Stillbirth 2 Days 5 1 st None No N/A Yes SPONT 35/40 Vaginal N/D Yes PREM+NIL N/A* 2nd None No N/A Yes SPONT Term Vaginal N/D No Normal N/A 3rd 25/40 No No Yes SPONT 32/40 Vaginal N/D Yes Stillbirth 1 Day 6 1st 31/40 No No Yes SPONT Term Vaginal N/D Yes Stillbirth 7 Days 7 1st 28/40 No No Yes SPONT 37/40 Vaginal N/D Yes Stillbirth 7 Days 8 1st 32/40 No No Yes SPONT 37/40 Vaginal 172 Yes Stillbirth 1 Day A summary of details of all pregnancies of eight females referred subsequently to The Liver Unit. A total of 13 pregnancies were affected by cholestasis of pregnancy, resulting in two normal deliveries, two premature deliveries with fetal distress (1 perinatal death), one emergency caesarean section at 38 weeks for fetal distress, and eight stillbirths occurred. *First baby of case 5 was born premature, but with no other complications. UDCA RX=ursodeoxycholic acid therapy; N/D=liver function tests not done before delivery; A/N CLINIC=antenatal clinic; N/A=not applicable; N/K=not known; SPONT=spontancous; EMERG/ELEC C/s=emergency or elective caesarean section. Case 2: 29 year old white woman Third pregnancy - pruritus from 25 weeks First pregnancy - pruritus from 35/40. gestation, without jaundice and liver function Spontaneous onset of labour, at 38+ weeks tests were not monitored. Fetal movements gestation. Emergency caesarean section for were normal and she was reassured. Onset of fetal distress. Baby discharged alive and well. labour was spontaneous at 32 weeks, with a Pruritus settled within three days. stillborn baby delivered vaginally. Pruritus Second pregnancy - pruritus from 35/40, settled within one day. without jaundice. Fetal movements were normal, she was reassured, and the pregnancy was treated routinely. Serum AST was Case 6: a 35 year old white woman increased at 82 lU/l. Spontaneous onset of First pregnancy - pruritus from 31 weeks, labour at term, with a stillborn baby delivered without jaundice. Fetal movements normal vaginally. Pruritus settled within one day. and the pregnancy was treated routinely. Liver function tests were not monitored. http://gut.bmj.com/ Spontaneous onset of labour at term, with a Case 3: 30 year old white woman stillborn baby delivered vaginally. Pruritus First pregnancy - pruritus from 28 weeks. settled within seven days. Spontaneous labour at 36/40, with fetal dis- tress. The baby was transferred to special care baby unit (SCBU). The baby was discharged Case 7: a 28 year old white woman home, but readmitted with recurrent con- Firstpregnancy - pruritus from 28 weeks ges- on October 1, 2021 by guest. Protected copyright. vulsions and died in the perinatal period. tation, without jaundice. Liver function tests Second pregnancy - normal. were not monitored and pregnancy was treated Third pregnancy - pruritus from 32/40. routinely. Spontaneous onset of labour at Spontaneous onset of labour at 37/40, with 37/40, with a stillborn baby delivered vaginally. delivery of healthy baby. Pruritus settled within seven days. Case 4: 30 year old white woman Case 8: a 27year old white woman First pregnancy - normal. First pregnancy - pruritus from 32 weeks, Second pregnancy - pruritus from 30 weeks without jaundice. Serum AST increased at 172 gestation. Early labour, at 36/40, with fetal dis- IU/l, but fetal movements were normal and she tress. Baby discharged alive and well. was reassured. Spontaneous labour at 37 Third pregnancy - pruritus from 31 weeks weeks gestation, with a stillborn baby delivered gestation, without jaundice. The pregnancy vaginally. Relief of pruritus occurred immedi- was treated routinely. Liver function tests were ately post partum. not monitored and she was reassured. Spontaneous onset of labour at term, with stillborn baby.