Stillbirth in intrahepatic cholestasis of pregnancy and timing of severely elevated bile acid concentrations: an observational cohort study.

OBJECTIVE

To determine whether the gestation at which severe ICP (bile acids ≥100 µmol/L) developed or peaked is associated with the risk of stillbirth.

STUDY

DESIGN

Observational cohort study, including patients with singleton pregnancies and severe ICP, likely enriched for those experiencing stillbirths. The association between peak serum bile acid concentration and stillbirth risk was determined using logistic regression. Participants were dichotomized according to the gestation at which serum bile acid concentrations first became severe, or peaked, and stillbirth rates compared using Mann-Whitney and logistic regression.

RESULTS

Of 198 participants, 15 (7.6 %) pregnancies ended in stillbirth. The gestation of peak bile acid concentration was associated with stillbirth risk (OR 1.28 per advancing week, 95 %CI 1.06-1.56); patients with stillbirths first developed severely elevated bile acids later than those with livebirths (p = 0.029). Of those with first bile acid concentration ≥100 μmol/L after 28 weeks', 13/133 (9.8 %) babies were stillborn, whilst 2/65 (3.1 %) stillbirths occurred for those with severe disease onset before 28 weeks' (OR 3.47, 95 %CI 0.77-15.74). For 11/15 patients experiencing stillbirth, bile acids rose markedly in the five days prior to stillbirth.

CONCLUSIONS

A later gestation at which serum bile acids first rise over 100 μmol/L, and a later gestation at which bile acid concentration peaks, are both associated with a higher risk of stillbirth. A marked increase in bile acid concentration immediately prior to stillbirth may herald increased risk. These findings underline the benefit of repeat testing and surveillance of serum bile acids to support individualized recommendations regarding birth gestation.