Therapeutic plasma exchange as a novel treatment for severe intrahepatic cholestasis of pregnancy: Case series and mechanism of action.

INTRODUCTION: Intrahepatic cholestasis of pregnancy is characterised by pruritus and elevated serum bile acids. The pruritus can be severe, and pharmacological options achieve inconsistent symptomatic improvement. Raised bile acids are linearly associated with adverse fetal outcomes, with existing management of limited benefit. We hypothesised that therapeutic plasma exchange removes pruritogens and lowers total bile acid concentrations, and improves symptoms and biochemical abnormalities in severe cases that have not responded to other treatments. METHODS: Four women with severe pruritus and hypercholanemia were managed with therapeutic plasma exchange. Serial blood biochemistry and visual analogue scores of itch severity were obtained. Blood and waste plasma samples were collected before and after exchange; individual bile acids and sulfated progesterone metabolites were measured with HPLC-MS, autotaxin activity and cytokine profiles with enzymatic methods. Results were analysed using segmental linear regression to describe longitudinal trends, and ratio t tests. RESULTS: Total bile acids and visual analogue itch scores demonstrated trends to transiently improve following plasma exchange, with temporary symptomatic benefit reported. Individual bile acids (excluding the drug ursodeoxycholic acid), and the sulfated metabolites of progesterone reduced following exchange (P = .03 and P = .04, respectively), whilst analysis of waste plasma demonstrated removal of autotaxin and cytokines. CONCLUSIONS: Therapeutic plasma exchange can lower potentially harmful bile acids and improve itch, likely secondary to the demonstrated removal of pruritogens. However, the limited current experience and potential complications, along with minimal sustained symptomatic benefit, restrict its current use to women with the most severe disease for whom other treatment options have been exhausted.

Operative delivery rates following induction of labour for obstetric cholestasis.

The aim of this study was to determine whether women induced for obstetric cholestasis (OC) have increased rates of operative delivery compared with women without OC who are induced. This retrospective case-control study included 64 women with OC (singleton pregnancies), who had labour induced compared with two control groups (matched for parity and gestational week at delivery). The majority of women were induced at 37 weeks. We found no significant increase in the rate of operative or assisted delivery in OC cases compared with either control group. Women with OC who are induced between 36 and 40 weeks gestation do not have increased rates of assisted or operative delivery compared with induced controls.

Non-invasive fetal electrocardiography in singleton and multiple pregnancies.

OBJECTIVES: To document the duration of fetal cardiac time intervals in uncomplicated singleton pregnancies using a novel non-invasive fetal electrocardiography (fECG) system and to demonstrate this technique's ability to acquire recordings in twin and triplet pregnancies. DESIGN: Prospective cross sectional observational study. SETTING: Antenatal wards and clinics, day assessment unit and centre for fetal care at a tertiary referral hospital, London, UK. POPULATION OR SAMPLE: Three hundred and four singleton and multiple pregnancies, 15-41 weeks of gestation. METHODS: Using electrodes sited on the maternal abdomen, a fetal electrocardiography (fECG) system was developed and tested on 304 pregnant women from 15 to 41 weeks of gestation, of whom 241 were uncomplicated singletons, 58 had twin and 5 had triplet pregnancies. The composite abdominal signals were stored on a laptop computer and the fECG derived off-line using a digital signal processing technique. For singletons, linear regression was used to analyse PR, QRS, QT and QTc intervals, and construct time-specific reference ranges. MAIN OUTCOME MEASURE: Duration of fECG time intervals as a function of gestational age. Success of signal separation in singleton, twin and triplet pregnancies. RESULTS: For singletons, a total of 250 recordings was obtained from 241 individuals with a signal separation success rate of 85% (213/250). Success rates were significantly poorer between 27 and 36 weeks of gestation (2 x k chi(2), P < 0.0001), with 84% (31/37) of separation failures occurring during this period. P, Q, R and S waves were seen in all cases where fetal signals were separated and were used to generate fECG time interval reference ranges. In 22% (43/199) of analysed cases, no T waves were identified, 63% (27/43) of whom were < or =24 weeks of gestation. In twins and triplets, separate fetal signals were obtained in 78% (91/116) and 93% (14/15), respectively; P, Q, R and S waves were evident in all averaged fECGs, while T waves were identified in 59% (54/91) and 57% (8/14). CONCLUSIONS: This study provides reference ranges with gestation for fECG intervals derived non-invasively from normal singleton pregnancies and demonstrates the feasibility of obtaining complete fECG recordings non-invasively across a wide gestational range in pregnancies of all pluralities. The fECG time intervals described will enable the identification of pathological fECG recordings from high risk pregnancies where fECG abnormalities are suspected.