Beneficial effect of ursodeoxycholic acid on alterations induced by cholestasis of pregnancy in bile acid transport across the human placenta

Serrano, Maria A.; Brites, Dora; Larena, Monica G.; Monte, María J.; Bravo, Manuel; Oliveira, Nuno G.; Marin, José J.G.

doi:10.1016/s0168-8278(98)80234-1

Cited by 118 publications

(87 citation statements)

References 32 publications

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“…Recent studies suggest that oral use of Ursodeoxycholic acid improves maternal clinical and biochemical features and may [19][20][21][22][23][24] prevent the foetal effects of ICP . Careful foetal assessment and appropriate medical intervention have improved the 5 perinatal outcome .…”

Section: Introductionmentioning

confidence: 99%

Maternal and Foetal outcome in Cholestasis of Pregnancy

Sinha

Pandey

Das

2017

J. Nepalgunj Med. College

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Background: Obstetric cholestasis has been associated with an increased risk of preterm delivery, intrapartum meconium, foetal distress and intrauterine foetal death. Objectives: To know the perinatal outcome of cholestasis in pregnancy. Materials & Methods: This is a hospital based Observational study conducted in the department of Obstetrics & Gynaecology at Nepalgunj Medical College Teaching Hospital Kohalpur between August 2015 to January 2016.A total of 40 patients were included in the study with diagnosis of obstetric cholestasis. Data were recorded & analysed. Results: The study group of 40 mothers delivered 40 new born. Mean age group of women in the study was 24.9±5.5 years & 70% were primigravida. The mean gestational age at onset of pruritus was 30.33±4.24 weeks. The rate of caesarean section was 40%. Premature membrane rupture noted in 20% cases while 17.5% were postpartum haemorrhage. Regarding foetal outcome; meconium baby 32.5%, Intrapartum foetal distress 17.5%, preterm baby 10% while 37.5% were complication free. There was 2.5% of intrauterine foetal death, where pregnancy continued beyond 38 weeks. Thirteen new borns (32.5%) were admitted to neonatal intensive care unit. Conclusion: Cholestasis in pregnancy is high risk group with adverse perinatal outcomes.

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Section: Introductionmentioning

confidence: 99%

Maternal and Foetal outcome in Cholestasis of Pregnancy

Sinha

Pandey

Das

2017

J. Nepalgunj Med. College

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“…A variety of other medications have been tried to alleviate maternal symptoms, but have not been shown to alter fetal prognosis. UDCA has been shown to restore the impaired bile acid transport across the throphoblast [13] and decrease the delivery of bile acids to the fetus [6,14,24]. Up to now, no adverse effects on the fetus of UDCA therapy has been reported.…”

Section: Discussionmentioning

confidence: 99%

“…Ursodeoxycholic acid (UDCA) is the most commonly used medication to alleviate maternal pruritus and improve fetal prognosis [13][14]. However, the use of UDCA has been restricted for the last trimester of pregnancy and data are missing about the first-trimester usage of UDCA in case of atypical early onset ICPs as it is not clear whether it has embryotoxic effect [15].…”

Section: Ursodeoxycholic Acid Administration From the First Trimestermentioning

confidence: 99%

Ursodeoxycholic acid administration from the first trimester in case of a severe early-onset intrahepatic cholestasis of pregnancy

Berkes¹,

Nagy²,

Rigó³

2009

Clinical and Experimental Medical Journal

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Abbreviations CTG = cardiotocography; ICP = intrahepatic cholestasis of pregnancy; UDCA = ursodeoxycholic acid Intrahepatic cholestasis of pregnancy (ICP) usually presents in the third trimester and rarely before 25 weeks' gestation [1]. It is characterized by pruritus, mild jaundice [2], fat malabsorption and raised maternal liver enzymes and bile acids. The overall prevalence of the disease is estimated at 1/1000 to 1/10000 pregnancies [3]. Scandinavia (2%) and Chile (4%) have the highest prevalence [2,4]. There is no uniform agreement on the criteria for diagnosing ICP. Knox and Olans [5] assert the role of elevated liver enzymes, whereas Palma et al. [6] emphasise that the most sensitive laboratory signs are the elevated total serum bile acids. Intrahepatic cholestasis of pregnancy is characterized by pruritus, raised maternal liver enzymes and bile acids. It usually presents in the third trimester and rarely before 25 weeks. Ursodeoxycholic acid is the most promising therapy to alleviate symptoms and prevent fetal risk. However, its administration has been restricted for the last trimester as its embryotoxic effect is undetermined. We report here a case of an extremely rare, severe obstetric cholestasis with early onset treated by ursodeoxycholic acid from the 9 th week of pregnancy, the earliest ever reported in the literature. The treatment was well tolerated. At the 32 nd week urgent caesarean section was performed due to intolerable symptoms, worsening laboratory results and signs of fetal distress. A healthy newborn was delivered. It is concluded that ursodeoxycholic acid in case of a severe early-onset intrahepatic cholestasis may be started in the early pregnancy to improve maternal condition and prevent fetal complications.

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“…Thus, in the control group there was a moderate gradient in the foetal-to-maternal direction, with the placenta placed in between. The rise in maternal bile acids concentrations in ICP produces a reversal in the direction of the transplacental gradient of these molecules from the maternal blood towards the foetal circulation, which affects the placenta-mediated detoxification pathway [33]. The results regarding bile acid contents in placental tissue provide useful information to understanding the handling of bile acids under these circumstances of altered homeostasis.…”

Section: Concentration (Mm)mentioning

confidence: 99%

Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother‐placenta‐foetus trio during cholestasis of pregnancy

Estiú¹,

Monte

Rivas

et al. 2015

Brit J Clinical Pharma

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AIMIntrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and elevated bile acid concentrations in maternal serum. This is accompanied by an enhanced risk of intra-uterine and perinatal complications. High concentrations of sulphated progesterone metabolites (PMS) have been suggested to be involved in the multifactorial aetiopathogenesis of ICP. The aim of this study was to investigate further the mechanism accounting for the beneficial effect of oral administration of ursodeoxycholic acid (UDCA), which is the standard treatment, regarding bile acid and PMS homeostasis in the mother-placenta-foetus trio. METHODUsing HPLC-MS/MS bile acids and PMS were determined in maternal and foetal serum and placenta. The expression of ABC proteins in placenta was determined by real time quantitative PCR (RT-QPCR) and immunofluorescence. RESULTSIn ICP, markedly increased concentrations of bile acids (tauroconjugates > glycoconjugates >> unconjugated), progesterone and PMS in placenta and maternal serum were accompanied by enhanced concentrations in foetal serum of bile acids, but not of PMS. UDCA treatment reduced bile acid accumulation in the mother-placenta-foetus trio, but had no significant effect on progesterone and PMS concentrations. ABCG2 mRNA abundance was increased in placentas from ICP patients vs. controls and remained stable following UDCA treatment, despite an apparent further increase in ABCG2. CONCLUSIONUDCA administration partially reduces ICP-induced bile acid accumulation in mothers and foetuses despite the lack of effect on concentrations of progesterone and PMS in maternal serum. Up-regulation of placental ABCG2 may play an important role in protecting the foetus from high concentrations of bile acids and PMS during ICP. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Intrahepatic cholestasis of pregnancy (ICP) is characterized by an increase in maternal serum concentrations of bile acids and sulphated progesterone metabolites. WHAT THIS STUDY ADDS• The accumulation of sulphated progesterone metabolites in the serum of ICP patients is associated with enhanced concentrations of progesterone. Although these compounds may be involved in the aetiopathogenesis of ICP, the magnitude of this accumulation does not correlate with the degree of hypercholanaemia in ICP patients.• The beneficial effect of ursodeoxycholic acid (UDCA) treatment includes a reduction of maternal hypercholanaemia, which is not dependent on the correction of progesterone metabolites accumulation.• In spite of marked increases in maternal serum concentrations of sulphated progesterone metabolites and bile acids in ICP patients, the concentrations of these compounds in foetal serum remain normal or are only moderately elevated, respectively. The latter can be corrected by treatment with UDCA.• The ABCG2 export pump located at the apical membrane of trophoblast cells plays an important role in the placental barrier for sulphated progesterone metabolites and bile acids. ABCG2 up-regulation during ICP, and further by UDCA treatment, ...

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Beneficial effect of ursodeoxycholic acid on alterations induced by cholestasis of pregnancy in bile acid transport across the human placenta

Cited by 118 publications

References 32 publications

Maternal and Foetal outcome in Cholestasis of Pregnancy

Maternal and Foetal outcome in Cholestasis of Pregnancy

Ursodeoxycholic acid administration from the first trimester in case of a severe early-onset intrahepatic cholestasis of pregnancy

Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother‐placenta‐foetus trio during cholestasis of pregnancy

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