Intrahepatic cholestasis of pregnancy: observational study of the treatment with low-dose ursodeoxycholic acid

Abstract

BackgroundTo exam the biochemical, obstetric management and pregnancy outcome in women with intrahepatic cholestasis of pregnancy (ICP) and treatment with ursodeoxycholic acid (UDCA).MethodsPregnancy outcome in patients with ICP (N = 307) was studied and patients treated with UDCA (N = 208) vs. no UDCA were compared. The data of the antenatal visits, deliveries and neonatal outcome of 307 pregnancies with ICP was collected from the hospital computerized delivery room log book. UDCA was used in 208 pregnancies. The diagnosis was made by maternal pruritus and elevation of total fasting bile acid (BA) (>6 μmol/l) and elevation of serum alanine aminotransferases (ALT) (>45 U/l). Maternal and neonatal data was analysed and data of the patients who used UDCA during pregnancy was analysed separately and compared with the data from patients without medication.ResultsUDCA was well tolerated. Mothers receiving UDCA had ICP diagnosed five weeks earlier than mothers without medication. At the diagnosis, levels of total BA and ALT were higher in the group using UDCA compared to the group without medication. Most deliveries were induced and perinatal outcome was good. Apgar scores at 5 min were significantly lower in UDCA group (p < 0.05), but fetal umbilical artery pH values were similar in both groups (p > 0.05). There were 30 patients with total BA > 40 μmol/l at diagnosis, 24 with UDCA and 6 without medication and those deliveries were induced soon after diagnosis. The preterm labour was also more common in these patents (p < 0.05). Women with preterm babies had significantly early onset pruritus and ICP was diagnosed earlier. Serum ALT and total BA levels were significantly higher in those pregnancies at diagnosis and also at first control.ConclusionsPreterm labour was associated in severe ICP (total BA > 40 μmol/l), ALT levels were also significantly higher and ICP was diagnosed earlier (p < 0.05). Apgar scores were lower in preterm babies (p < 0.05), but umbilical artery pHvalues were not significantly lower. UDCA was well tolerated by pregnant women. With low-dose UDCA treatment the obstetric outcome was good. We still recommend careful obstetrical follow-up.

Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis

“…However, co-treatment of TC with 1 μM of UDCA was effective in protecting against such CV slowing. Reflecting the clinical safety of UDCA in fetal and maternal hearts,[ 19 ] treatment of hearts with UDCA alone did not produce any adverse changes in this study. Furthermore, a significantly smaller decrease in CV (−7.4±1.8%; P <0.05) was observed in the maternal hearts compared to the decrease in the fetal hearts ( Fig 2A and 2B ).…”

Management of Intrahepatıc Cholestasıs of Pregnancy: Revıew of Lıterature

“…Currently, UDCA is the most promising treatment for ICP [38].First Palma et al reported UDCA improved significantly serum biochemistry in patients with ICP at 1992 [39].Initial pilot studies in ICP followed by controlled trials demonstrated that UDCA improved pruritus and liver tests and had no maternal or neonatal adverse effects [39,40].Since that time, there have been several studies and additional case series demonstrating that UDCA treatment results in clinical and biochemical improvement in ICP [41,42].Studies examining the bile acid pool composition have shown that, in addition to a reduction in the serum bile acid concentration, treatment with UDCA results in a normalization of the CA:CDCA ratios, and a reduction in urinary excretion that is associated with reduction in pruritus [43].The mechanism underlying the beneficial effect of UDCA is unclear. UDCA has been shown to correct the impaired bile acid transfer kinetics observed in ICP placentas and to reverse the morphological changes seen in the placentas of a rodent model of ICP.…”

Transport mechanism of ursodeoxycholic acid in human placental BeWo cells

“…Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-related liver disorder with a condition of severe pruritus combined with elevated liver function during the second or third trimester of pregnancy, and symptoms resolve spontaneously within 2-3 weeks after delivery (Joutsiniemi, Timonen, Linden, Suvitie, & Ekblad, 2015). The mother experiences intense, disturbing itching (Lammert, Marschall, Glantz, & Matern, 2000).…”

“…UDCA appears to be the most efficient pharmacologic treatment. It has been shown that UDCA ameliorates pruritus and restores elevated liver function during ICP (Joutsiniemi et al, 2015;Joutsiniemi, Timonen, Leino, Palo, & Ekblad, 2014;Kondrackiene, Beuers, & Kupcinskas, 2005), without interfering with fetoplacental estrogen production (Joutsiniemi et al, 2014). It was more effective than cholestyramine and dexamethasone at reducing bile acid concentration (Kondrackiene et al, 2005).…”