No abstract

Background: Intrahepatic cholestasis of pregnancy (ICP) affects approximately 0.7% of pregnancies in the UK and is associated with prematurity, fetal distress, and intrauterine death. Homozygous mutations in the ATP8B1 gene cause cholestasis with a normal serum gamma-glutamyl transpeptidase (c-GT), and have been reported in two forms of cholestasis: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC). Aims: To establish whether mutations in ATP8B1 are associated with ICP in British cases Patients: Sixteen well phenotyped women with ICP without raised c-GT were selected for sequence analysis. Subsequently, 182 patients and 120 controls were examined for the presence of the variants detected. Methods: All coding exons were sequenced in 16 cases. Eight ICP cases, including two women carrying a mutation, were investigated using in vivo hepatic 31 P magnetic resonance spectroscopy (MRS) Results: Two heterozygous ATP8B1 transitions (208G.A and 2599C.T) that resulted in amino acid substitutions were identified; 208G.A was identified in three cases. MRS revealed an increased phosphodiester signal (Mann-Whitney U test, p = 0.03) and a decreased phosphomonoester/ phosphodiester ratio (p = 0.04) in ICP cases compared with controls. Conclusions:We were able to demonstrate ATP8B1 mutations in ICP. MRS studies suggest that susceptibility to ICP is associated with a relative rise in biliary phospholipid. These data also suggest that MRS may be used for non-invasive assessment of the liver and biliary constituents in cholestasis.

Objectives To compare maternal cardiac function between pregnancies complicated by normotensive and pre-eclamptic intrauterine growth restriction (IUGR). Methods

Changes in left ventricular long-axis performance during pregnancy occur earlier than do measures of transverse function.