Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations.

BACKGROUND & AIMS: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of stillbirth. This study aimed to assess the relationship between bile acid concentrations and fetal cardiac dysfunction in patients with ICP who were or were not treated with ursodeoxycholic acid (UDCA). METHODS: Bile acid profiles and NT-proBNP, a marker of ventricular dysfunction, were assayed in umbilical venous serum from 15 controls and 76 ICP cases (36 untreated, 40 UDCA-treated). Fetal electrocardiogram traces were obtained from 43 controls and 48 ICP cases (26 untreated, 22 UDCA-treated). PR interval length and heart rate variability (HRV) parameters were measured in 2 behavioral states (quiet and active sleep). RESULTS: In untreated ICP, fetal total serum bile acid (TSBA) concentrations (r = 0.49, p = 0.019), hydrophobicity index (r = 0.20, p = 0.039), glycocholate concentrations (r = 0.56, p = 0.007) and taurocholate concentrations (r = 0.44, p = 0.039) positively correlated with fetal NT-proBNP. Maternal TSBA (r = 0.40, p = 0.026) and alanine aminotransferase (r = 0.40, p = 0.046) also positively correlated with fetal NT-proBNP. There were no significant correlations between maternal or fetal serum bile acid concentrations and fetal HRV parameters or NT-proBNP concentrations in the UDCA-treated cohort. Fetal PR interval length positively correlated with maternal TSBA in untreated (r = 0.46, p = 0.027) and UDCA-treated ICP (r = 0.54, p = 0.026). Measures of HRV in active sleep and quiet sleep were significantly higher in untreated ICP cases than controls. HRV values in UDCA-treated cases did not differ from controls. CONCLUSIONS: Elevated fetal and maternal serum bile acid concentrations in untreated ICP are associated with an abnormal fetal cardiac phenotype characterized by increased NT-proBNP concentration, PR interval length and HRV. UDCA treatment partially attenuates this phenotype. LAY SUMMARY: The risk of stillbirth in intrahepatic cholestasis of pregnancy (ICP) is linked to the level of bile acids in the mother which are thought to disrupt the baby's heart rhythm. We found that babies of women with untreated ICP have abnormally functioning hearts compared to those without ICP, and the degree of abnormality is closely linked to the level of harmful bile acids in the mother and baby's blood. Babies of women with ICP who received treatment with the drug UDCA do not have the same level of abnormality in their hearts, suggesting that UDCA could be a beneficial treatment in some ICP cases, although further clinical trials are needed to confirm this.

Development and validation of a knowledge, attitudes and practices questionnaire in the dietary management of irritable bowel syndrome.

OBJECTIVE: To develop and validate a questionnaire assessing knowledge, attitudes and practices in the dietary management of IBS. SUBJECTS/METHODS: An initial pool of 151 questions was generated addressing three domains (knowledge, attitudes, practices). Academic/senior clinical dietitians (n = 5) provided written feedback and a focus group (n = 4 gastroenterology dietitians) was undertaken to evaluate content and face validity of the question-items. Items considered irrelevant were removed and the refined questionnaire was administered to dietitians with different levels of IBS experience (n = 154) for further psychometric testing. Item reduction analysis was assessed by item difficulty index, discrimination index and point-biserial correlation. Construct validity was assessed via principal component analysis (PCA) and the 'known-groups' method. Internal reliability was assessed by Kuder-Richarson Formula 20 and Cronbach's alpha coefficient and external reliability by interclass correlation coefficient among participants who completed the instrument at baseline and two weeks later (n = 28). RESULTS: Face and content validity resulted in the removal of 61 items from the initial 151 items. Psychometric testing was applied to the refined 90-item questionnaire administered to participating dietitians, resulting in the final 46-item questionnaire. Six factors were extracted by PCA with varimax rotation explaining 59.2% of the total variance. Partial confirmatory factor analysis showed an acceptable model fit (χ2/df = 2.11, CFI = 0.97, TLI = 0.96, RMSEA = 0.08, SRMR = 0.05). Significant differences were found in sum scores among dietitians with different levels of IBS experience. Internal reliability was >0.7 for each factor. External reliability was >0.6 for each factor and >0.7 for overall items of each domain. CONCLUSION: A validated questionnaire to use in practice and research to assess knowledge, attitudes and practices in the dietary management of IBS has been developed.