Bile acids and gestation

McIlvride, Saraid; Dixon, Peter H.; Williamson, Catherine

doi:10.1016/j.mam.2017.05.003

Cited by 62 publications

(53 citation statements)

References 158 publications

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“…Normal pregnancy is characterized by an increase in serum bile acid levels with increasing gestational age [ 32 ]. In some cases, serum bile acid levels rise sharply, leading to intrahepatic cholestasis of pregnancy (ICP) [ 33 ], which was associated with elevated risk of GDM [ 34 , 35 ]. Ursodeoxycholic acid (UDCA) is effective and safe in the treatment of ICP, with significantly modulated levels of total bile acids (TBA), alanine aminotransferase, aspartate aminotransferase and total bilirubin and without adverse drug reactions [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Bile acid metabolites in early pregnancy and risk of gestational diabetes in Chinese women: A nested case-control study

Huo

Cao

et al. 2018

EBioMedicine

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Background Bile acid metabolism plays an important role in metabolism but it is uncertain whether bile acid metabolites in early pregnancy are associated with risk of gestational diabetes mellitus (GDM). Methods We organized a 1:1 case-control study nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in China: 243 women with GDM were matched with 243 non-GDM controls on age (±1 year). Conditional logistic regression and restricted cubic spline were used to examine full-range associations of bile acid metabolites with GDM. Findings All the 9 detectable bile acids were inversely associated with the risk of GDM, among them, 8 in nonlinear and one in largely linear manners in multivariable analysis. Glycoursodeoxycholic acid (GUDCA) at ≤0.07 nmol/mL and deoxycholic acid (DCA) at ≤0.28 nmol/mL had threshold effects and their decreasing levels below the cutoff points were associated with rapid rises in the risk of GDM. In traditional risk factor model, the stepwise procedure identified that GUDCA ≤ 0.07 nmol/mL and DCA ≤ 0.280 nmol/mL were still significant (OR: 6.84, 95%CI: 1.10–42.48 & 2.06, 1.26–3.37), while other bile acids were not. Inclusion of the two bile acids in the model increased the area under operating characteristic's curve from 0.69 to 0.76 (95% CI: 0.71–0.80) ( P < .05). Interpretation Serum GUDCA ≤ 0.07 nmol/mL and DCA ≤ 0.28 nmol/mL in early pregnancy were independently associated with increased risk of GDM in Chinese pregnant women. Funding Talent Recruitment Scheme grant of Tianjin Medical University and National Key Research and Development Program, etc.

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Section: Discussionmentioning

confidence: 99%

Bile acid metabolites in early pregnancy and risk of gestational diabetes in Chinese women: A nested case-control study

Huo

Cao

et al. 2018

EBioMedicine

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“…The incidence of ICP ranges from 0.4% to 15% in different countries, ethnic populations and climatic conditions 3,4 . The majority of studies had demonstrated that ICP was associated with adverse maternal outcomes, including 3-fold increased risks of gestational diabetes mellitus and pre-eclampsia [5][6][7] . A large cohort study from Sweden showed that women with ICP had increased risks of later liver and biliary tree cancer, later specifically diabetes mellitus, later autoimmune-mediated and cardiovascular diseases after childbirth 8 .…”

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confidence: 99%

Continuous association of total bile acid levels with the risk of small for gestational age infants

Chen

et al. 2020

Sci Rep

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The association between maternal serum total bile acid (TBA) levels and small-for-gestational-age (SGA) infants is unclear. We investigated the association between various degrees of serum TBA levels and the risk of SGA infants in a Chinese population. The current study performed a cohort study among 11811 mothers with singleton pregnancy. Subjects were divided into seven categories according to maternal serum TBA levels. Interestingly, birth sizes were reduced, whereas the rate of SGA infants was increased across increasing categories of serum TBA. Compared to category 1, adjusted ORs (95%CI) for SGA infants were 0.99 (0.82-1.21) in category 2, 1.22 (0.97-1.53) in category 3, 1.99 (1.53-2.58) in category 4, 2.91 (2.16-3.93) in category 5, 4.29 (3.33-5.54) in category 6, and 9.01 (5.99-13.53) in category 7, respectively. Furthermore, adjusted ORs (95%CI) for SGA infants for each 1-SD increase in serum TBA levels were 1.36 (1.29-1.43) among all subjects, 2.40 (1.82-3.45) among subjects without cholestasis, and 1.13 (1.06-1.22) among subjects with cholestasis, respectively. These results suggest that gestational cholestasis increases the risk of SGA infants. Additionally, our results indicate strong, continuous associations of serum TBA levels below those diagnostic of cholestasis with a decreased birth sizes and an increased risk of SGA infants.

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“…This was largely due to an increase in taurine-conjugated CA and DCA. Although the fetus synthesizes bile acids from early pregnancy onward, maternal bile acids can also cross the placenta and contribute to the fetal bile acid pool ( 29 ). Unconjugated and, at much lower levels, taurine-conjugated CA and DCA were also raised in the serum of CA-fed mothers.…”

Section: Discussionmentioning

confidence: 99%

Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia

Pataia

McIlvride

Papacleovoulou

et al. 2020

American Journal of Physiology-Gastrointestinal and Liver Physi

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Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated maternal circulating bile acid levels and associated dyslipidemia. ICP leads to accumulation of bile acids in the fetal compartment and the elevated bile acid concentrations are associated with an increased risk of adverse fetal outcomes. The farnesoid X receptor agonist, obeticholic acid (OCA) is efficient in the treatment of cholestatic conditions such as primary biliary cholangitis. We hypothesized that OCA administration during hypercholanemic pregnancy will improve maternal and fetal bile acid and lipid profiles. Female C57BL/6J mice were fed either: a normal chow diet, a 0.5% cholic acid (CA)-supplemented diet, a 0.03% OCA-supplemented diet, or a 0.5% CA + 0.03% OCA-supplemented diet for 1 week prior to mating and throughout pregnancy until euthanization on day 18. The effects of CA and OCA feeding on maternal and fetal morphometry, bile acid and lipid levels, and cecal microbiota were investigated. OCA administration during gestation did not alter the maternal or fetal body weight or organ morphometry. OCA treatment during hypercholanemic pregnancy reduced bile acid levels in the fetal compartment. However, fetal dyslipidemia was not reversed, and OCA did not impact maternal bile acid levels or dyslipidemia. In conclusion, OCA administration during gestation had no apparent detrimental impact on maternal or fetal morphometry and improved fetal hypercholanemia. As high serum bile acid concentrations in ICP are associated with increased rates of adverse fetal outcomes, further investigations into the potential use of OCA during cholestatic gestation are warranted.

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Bile acids and gestation

Cited by 62 publications

References 158 publications

Bile acid metabolites in early pregnancy and risk of gestational diabetes in Chinese women: A nested case-control study

Bile acid metabolites in early pregnancy and risk of gestational diabetes in Chinese women: A nested case-control study

Continuous association of total bile acid levels with the risk of small for gestational age infants

Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia

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