Dysregulation of bile acids increases the risk for preterm birth in pregnant women

Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications. Bile acids are recognized as signaling molecules regulating a myriad of cellular and metabolic activities but have not been etiologically linked to PTB. In this study, a hospital-based cohort study with 36,755 pregnant women is conducted. We find that serum total bile acid levels directly correlate with the PTB rates regardless of the characteristics of the subjects and etiologies of liver disorders. Consistent with the findings from pregnant women, PTB is successfully reproduced in mice with liver injuries and dysregulated bile acids. More importantly, bile acids dose-dependently induce PTB with minimal hepatotoxicity. Furthermore, restoring bile acid homeostasis by farnesoid X receptor activation markedly reduces PTB and dramatically improves newborn survival rates. The findings thus establish an etiologic link between bile acids and PTB, and open an avenue for developing etiology-based therapies to prevent or delay PTB.


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Ruitang Deng
March 23, 2020 No specific codes were used to collect data. Human serum bile acids, AST, ALT, total bilirubin, GGT levels were measured and collected by the automatic biochemical analyzer (AU2700, Olympus). The mouse serum bile acids and AST levels were measured and collected by the GloMax® 96 Microplate Luminometer (Promega).
IBM SPSS Statistics 25 and SAS software were used for statistical analyses. Total serum bile acids, serum AST, ALT, total bilirubin, GGT and Real-time PCR data were analyzed using Prism version 8 (Graphpad software).
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Sample size A minimal of 5 mice per group were based on power calculation with assumption that there is a minimal of 20% difference between the groups. The heterogeneity of the sample sizes from 5 to 13 mice per group in the study reflects the variation in synchronized pregnancy rates during each experiment.
Data exclusions No data were excluded for the analyses, but on rare occasion the newborn pups were eaten by the mother immediately after birth therefore

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Blinding the data on the rates of alive birth were not available (not included in the analyses). Also on rare occasion, limited amount of blood samples were collected due to technical issues from a mouse, the data on serum bile acids, AST concentrations or both were not available for the mouse (not included in the analyses).
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