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Perinatal outcomes of intrahepatic cholestasis during pregnancy: An 8-year case-control study.

ABSTRACT: INTRODUCTION:Previous studies of fetal effects have suggested that intrahepatic cholestasis of pregnancy is associated with a higher rate of adverse neonatal outcomes including preterm birth, neonatal respiratory distress syndrome, meconium-stained amniotic fluid, neonatal intensive care unit admission, and stillbirth. The objective was to compare the neonatal and maternal consequences in pregnancies affected by intrahepatic cholestasis and normal pregnancies. MATERIAL AND METHODS:This case-control study compares pregnancies affected by intrahepatic cholestasis (pruritus and bile acid ? 10 ?mol/L) with low-risk pregnancies managed between December 2006 and December 2014 at a French university hospital center. RESULTS:There were 83 (59.3%) cases of mild cholestasis (10? BA ?39 ?mol/L), 46 (32.8%) of moderate cholestasis (40? BA ?99 ?mol/L), and 11 (7.9%) of severe cholestasis (BA ?100 ?mol/L). No in utero fetal deaths occurred in the 140 women with cholestasis or the 560 controls analyzed. The rate of respiratory distress syndrome was higher in neonates of women with intrahepatic cholestasis (17.1% vs. 4.6%, P<0.001; crude OR 4.46 (CI95% 2.49-8.03)). This risk was also significant after adjustment for gestational age at birth and mode of delivery, adjusted OR 2.56 (CI95%1.26-5.18). The postpartum hemorrhage rate was twice as high among the case mothers (25% versus 14.1% for controls, P = 0.002). CONCLUSION:After adjustment on the confounding factors we found a higher rate of respiratory distress syndrome and neonatal morbidity among neonates of the cholestasis group.

SUBMITTER: Arthuis C

PROVIDER: S-EPMC7029845 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Perinatal outcomes of intrahepatic cholestasis during pregnancy: An 8-year case-control study.

Arthuis Chloé C Diguisto Caroline C Lorphelin Henri H Dochez Vincent V Simon Emmanuel E Perrotin Franck F Winer Norbert N

PloS one 20200219 2

<h4>Introduction</h4>Previous studies of fetal effects have suggested that intrahepatic cholestasis of pregnancy is associated with a higher rate of adverse neonatal outcomes including preterm birth, neonatal respiratory distress syndrome, meconium-stained amniotic fluid, neonatal intensive care unit admission, and stillbirth. The objective was to compare the neonatal and maternal consequences in pregnancies affected by intrahepatic cholestasis and normal pregnancies.<h4>Material and methods</h4 ...[more]

PMID: 32074108

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Project description:BackgroundIntrahepatic cholestasis of pregnancy (ICP) can cause premature delivery and stillbirth. Previous studies have reported that mutations in ABC transporter genes strongly influence the transport of bile salts. However, to date, their effects are still largely elusive.MethodsA whole-exome sequencing (WES) approach was used to detect novel variants. Rare novel exonic variants (minor allele frequencies: MAF?<?1%) were analyzed. Three web-available tools, namely, SIFT, Mutation Taster and FATHMM, were used to predict protein damage. Protein structure modeling and comparisons between reference and modified protein structures were performed by SWISS-MODEL and Chimera 1.14rc, respectively.ResultsWe detected a total of 2953 mutations in 44 ABC family transporter genes. When the MAF of loci was controlled in all databases at less than 0.01, 320 mutations were reserved for further analysis. Among these mutations, 42 were novel. We classified these loci into four groups (the damaging, probably damaging, possibly damaging, and neutral groups) according to the prediction results, of which 7 novel possible pathogenic mutations were identified that were located in known functional genes, including ABCB4 (Trp708Ter, Gly527Glu and Lys386Glu), ABCB11 (Gln1194Ter, Gln605Pro and Leu589Met) and ABCC2 (Ser1342Tyr), in the damaging group. New mutations in the first two genes were reported in our recent article. In addition, compared to the wild-type protein structure, the ABCC2 Ser1342Tyr-modified protein structure showed a slight change in the chemical bond lengths of ATP ligand-binding amino acid side chains. In placental tissue, the expression level of the ABCC2 gene in patients with ICP was significantly higher (P?<?0.05) than that in healthy pregnant women. In particular, the patients with two mutations in ABC family genes had higher average values of total bile acids (TBA), aspartate transaminase (AST), direct bilirubin (DBIL), total cholesterol (CHOL), triglycerides (TG) and high-density lipoprotein (HDL) than the patients who had one mutation, no mutation in ABC genes and local controls.ConclusionsOur present study provide new insight into the genetic architecture of ICP and will benefit the final identification of the underlying mutations.

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Perinatal outcomes of intrahepatic cholestasis during pregnancy: An 8-year case-control study.

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Perinatal outcomes of intrahepatic cholestasis during pregnancy: An 8-year case-control study.

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