Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group

Abstract

aObjective To explore the clinical features of obstetric cholestasis pregnancies in UK white Caucasians.Design A questionnaire survey.Setting Study coordinated at Queen Charlotte's Hospital.Population Clinical features of 352 affected pregnancies in 227 Caucasian women identified via a patient support group. Methods Evaluation of the gestation at which prematurity and intrauterine death occur, and recording of additional clinical features in pregnancies complicated by obstetric cholestasis. Main outcome measures The timing of pregnancies complicated by intrauterine death and prematurity.Results Among the affected pregnancies, 23 (7%) were complicated by intrauterine death (20 singletons and 3 twins) and 133 (38%) were delivered prematurely (56 spontaneous and 77 iatrogenic). Eighteen of the 20 singleton intrauterine deaths occurred after 37 weeks. All three intrauterine deaths in twin pregnancies occurred before 37 weeks. Pruritus started earlier in pregnancies complicated by spontaneous prematurity, but not in those complicated by intrauterine death. Conclusions Intrauterine death in singleton pregnancies complicated by obstetric cholestasis death mainly occurs after 37 weeks. The gestation at which pruritus is first reported may help to predict spontaneous prematurity.

Inhibition of Na+-Taurocholate Co-transporting Polypeptide-mediated Bile Acid Transport by Cholestatic Sulfated Progesterone Metabolites

“…In addition, administration of oral micronized natural progesterone for prophylaxis of preterm labor causes increased rates of ICP (12). Moreover, there is experimental evidence demonstrating that cholestatic reproductive hormone metabolites can influence the major and minor bile acid uptake transporters, the sodium-dependent Na ϩ -taurocholate co-transporting polypeptide (NTCP), and the Na ϩ -independent organic anion transporting proteins (13,14), respectively, as well as the major canalicular bile salt export pump (BSEP) (14 - 4 The abbreviations used are: ICP, intrahepatic cholestasis of pregnancy; P4-S, sulfated progesterone metabolite; PHH, primary human hepatocyte; TC, taurocholate; PM4-S, allopregnanolone-sulfate; PM5-S, epiallopregnanolone-sulfate; NTCP, Na ϩ -taurocholate co-transporting polypeptide; GC-MS, gas chromatography-mass spectrometry; HPLC, high pressure liquid chromatography; MS/MS, tandem mass spectrometry; BSEP, bile salt export pump. …”

“…Approximately 25% of women with asymptomatic hypercholanemia of pregnancy subsequently develop intrahepatic cholestasis of pregnancy (ICP), 4 a liver disorder that presents with pruritus, raised serum bile acids, and liver transaminases (3). In pregnancies complicated by maternal serum bile acid levels of Ͼ40 M, there are increased rates of spontaneous preterm labor, fetal asphyxial events, and meconium-stained amniotic fluid (3).…”

Operative delivery rates following induction of labour for obstetric cholestasis

“…1 For the mother the disease is usually transient and resolves rapidly following delivery, but the condition is associated with spontaneous preterm labour, meconium-stained amniotic fluid and fetal asphyxial events, 1 -6 all of which have been reported to occur more commonly in pregnancies where the maternal fasting serum bile acid levels are greater than 40 mmol/L. 4,5,7 Unexplained intrauterine fetal death is thought to occur more commonly at later gestational weeks 1,8,9 and as a consequence many obstetricians deliver women with OC between 37 and 38 weeks gestation. 10 However, concerns over such 'active management' include the risk of failed induction and slow progress in the first or second stage of labour requiring operative delivery by caesarean section or instrumental assistance.…”

Intrahepatic Cholestasis of Pregnancy and Bile Acid Levels *

“…In the April issue of HEPATOLOGY, Marrero et al 1 reported that the Barcelona Clinic Liver Cancer (BCLC) "staging classification" provided the best prognostic stratification for patients with hepatocellular carcinoma (HCC). Their staging validation, however, is limited by critical shortcomings.…”

“…A recent study by Williamson et al 1 investigated fetal outcome in women with ICP, and they reported high fetal complication rates. However, in this study several confounding factors were present.…”