Diagnostic accuracy of bile acid detection via mass spectrometry for intrahepatic cholestasis of pregnancy (ICP): A systematic review and meta-analysis

Abstract

Background

The diagnosis of intrahepatic cholestasis of pregnancy (ICP) has traditionally relied on detecting elevated total bile acids. However, measuring total levels may not capture the full diagnostic picture. Mass spectrometry (MS) now allows precise measurement of individual bile acid subtypes. Yet, the clinical diagnostic value of this detailed profile remains unclear. This systematic review and meta-analysis therefore evaluates the diagnostic accuracy of MS-based bile acid analysis for ICP.

Methodology: Search Strategy and Study Selection

We systematically queried five databases: PubMed, Web of Science, the Cochrane Library, OVID, and CNKI. Our search strategy incorporated both keywords and Medical Subject Headings (MeSH) related to intrahepatic cholestasis of pregnancy, its diagnosis, and mass spectrometry. Two authors then independently screened the retrieved records, extracted the relevant data, and evaluated the risk of bias in the studies that were included.

Statistical Synthesis

The primary goal of our analysis was to determine how well mass spectrometry–based bile acid profiling identifies ICP. We therefore pooled the reported sensitivity and specificity from the selected studies. To present the overall diagnostic accuracy, we constructed a summary receiver operating characteristic (SROC) curve. All statistical work was completed using Stata 17.0, Review Manager 5.4, and Meta-Disc.

Results

The present systematic review and meta-analysis evaluated eight studies that focused on two clinical applications of mass spectrometry (MS) in bile acid profiling. For distinguishing ICP from healthy pregnancies (four studies), the assay showed excellent accuracy, with sensitivity at 0.95 (95% confidence interval [CI]: 0.89–0.98), and specificity at 0.95 (95% CI: 0.91–0.98). The diagnostic odds ratio was 332.18 (95% CI: 100.89–1093.71), and the area under the SROC curve reached 0.9860.

In the comparison between ICP and asymptomatic hypercholanemia of pregnancy (four studies), the method continued to perform well, showing a sensitivity of 0.93 (95% CI: 0.86–0.97) and specificity of 0.92 (95% CI: 0.84–0.97). The diagnostic odds ratio was 156.54 (95% CI: 47.07–520.55), and the SROC area was 0.9735.

Conclusion

These findings demonstrate that mass spectrometry-based bile acid profiling provides reliable diagnostic performance for intrahepatic cholestasis of pregnancy, clearly distinguishing it from healthy pregnancies and from asymptomatic hypercholanemia of pregnancy (AHP). Moving forward, key priorities will involve confirming these results in larger, multi-center studies, creating unified international guidelines for clinical application, and resolving the recognized shortcomings of current diagnostic approaches for ICP.