Risk of stillbirth in United States patients with diagnosed intrahepatic cholestasis of pregnancy

Abstract

Intrahepatic cholestasis of pregnancy is associated with a 4- to 10-fold increase in the risk of stillbirth in the absence of intervention, leading to recommendations for antenatal assessment, ursodiol use, and often preterm or early term delivery. This study aimed to determine whether current management strategies for intrahepatic cholestasis of pregnancy mitigate the elevated risk of stillbirth at a population level. This was a retrospective cohort study using the 2015-2020 National Readmissions Database, an administrative database developed by the United States Agency for Healthcare Research and Quality. Our study identified delivery hospitalizations, gestational age at delivery, occurrence of intrahepatic cholestasis of pregnancy and stillbirth, and comorbid conditions using the International Classification of Diseases diagnosis and procedure codes. Moreover, this study compared the timing of delivery and stillbirth rates of pregnant patients with intrahepatic cholestasis of pregnancy vs those without intrahepatic cholestasis of pregnancy at the time of delivery hospitalization. This study identified a cohort of 9,987,705 delivery hospitalizations in the National Readmissions Database, corresponding to a weighted national estimate of 18,609,207 births. Of these births, 152,040 (0.8%) were noted to have an intrahepatic cholestasis of pregnancy diagnosis. Patients with an intrahepatic cholestasis of pregnancy diagnosis were older, with small differences in comorbidities, such as a higher rate of gestational diabetes mellitus, than patients without an intrahepatic cholestasis of pregnancy diagnosis at delivery hospitalization. The overall rates of stillbirth were lower among those with intrahepatic cholestasis of pregnancy than among those without intrahepatic cholestasis of pregnancy (252 vs 386 per 100,000 deliveries; risk difference, 133 fewer per 100,000 deliveries; 95% confidence interval, 98-170), a finding that persisted after adjustment for insurance status, socioeconomic factors, and comorbid conditions (risk difference, 160 fewer stillbirths per 100,000 deliveries; 95% confidence interval, 127-194). Furthermore, although patients with intrahepatic cholestasis of pregnancy were more likely to deliver before term than those without intrahepatic cholestasis of pregnancy (30.1% vs 9.3%; P<.001), increased rates of stillbirth were not noted at any point after stratification of the cohort by gestational age at delivery. Patients with intrahepatic cholestasis of pregnancy diagnosis codes delivered earlier than those without intrahepatic cholestasis of pregnancy diagnosis codes, but the percentage of births affected by stillbirth was lower, even when stratifying for gestational age at birth. These results may provide reassurance to patients receiving an intrahepatic cholestasis of pregnancy diagnosis that current management does mitigate stillbirth risk in intrahepatic cholestasis of pregnancy.