Eur J Obstet Gynecol Reprod Biol. 2026 Sep 7;327:115423. doi: 10.1016/j.ejogrb.2026.115423. Online ahead of print.

ABSTRACT

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse perinatal outcomes, including stillbirth. While computerized cardiotocography (cCTG) is a standard tool for fetal surveillance, the specific impact of maternal biochemical severity on cCTG parameters remains poorly defined. Specifically, the qualitative aspects of fetal heart rate accelerations-rather than just their frequency-may provide deeper insights into fetal wellbeing under conditions of metabolic stress induced by elevated bile acids.

OBJECTIVE(S): To evaluate the association between maternal bile acid levels and cCTG parameters in pregnancies complicated by ICP, with a primary focus on the quality and distribution of accelerations (small vs. large) as a potential marker of fetal status.

STUDY DESIGN: We conducted a retrospective observational cohort study pooling two tertiary referral centers. The pooled cohort included 94 pregnancies with ICP, contributing 368 Sonicaid cCTG recordings across gestation (50 at <32 weeks, 55 at 32 to <34 weeks, and 263 at ≥34 weeks). For each pregnancy, peak bile acids (peak BA), defined as the maximum total serum bile-acid concentration recorded during pregnancy, were used as a proxy of biochemical severity and modeled as log2(peak BA), so effects represent a doubling in bile acids; a sensitivity analysis used peak BA ≥ 40 μmol/L. From each Sonicaid™ cCTG tracing we extracted short-term variability (STV), acceleration counts, and software-defined small and large accelerations. Acceleration quality was summarized as Small-share = small/(small + large) and Small/Large = small/large. Associations were tested using generalized linear models with robust standard errors clustered by pregnancy, stratified by gestational age (<32 weeks, 32 to < 34 weeks, and ≥ 34 weeks) and adjusted for gestational age within each band.

RESULTS: Across the 368 cCTG recordings, bile acids were not consistently associated with STV or total acceleration rate. A gestational-age-specific signal emerged for acceleration quality: in the 32 to less than 34-week window, higher bile acids were associated with a shift toward smaller accelerations (OR 1.146 per bile-acid doubling; 95% CI 1.029-1.275; p = 0.013), whereas no clear associations were observed at <32 weeks or ≥34 weeks. The association remained directionally consistent in sensitivity analyses using peak BA ≥40 micromol/L (OR 1.406; 95% CI 1.073-1.843; p = 0.014). Neonatal outcomes were variably available and were summarized descriptively.

CONCLUSIONS: In ICP, higher maternal bile acids are associated with a qualitative shift toward smaller cCTG accelerations specifically between 32 and 34 weeks. Acceleration quality may represent an underexplored cCTG dimension for risk stratification in ICP, but prospective validation with time-matched biochemistry and complete neonatal outcomes is needed.

PMID:42715676 | DOI:10.1016/j.ejogrb.2026.115423