Cholestasis: A Prospective Study of Perinatal Outcomes and Time to Symptom Improvement

Although intrahepatic cholestasis of pregnancy (ICP) remains poorly understood, there are several perinatal complications associated with this condition. This study aimed to examine perinatal outcomes of women with ICP, evaluate outcomes according to severity of disease, and monitor time to symptom improvement following diagnosis.

It involves a prospective, observational study of women with ICP at a single institution. Women with new-onset pruritus without rash were referred to a high-risk obstetrics clinic and evaluated with fasting total bile acids (TBA). Laboratory-confirmed ICP was defined as fasting TBA ≥10 µmol/L. Following diagnosis, a standardized protocol was utilized, including treatment with ursodeoxycholic acid (UDCA). Perinatal outcomes were compared amongst those with and without ICP, and to the general population. Women with ICP were further analyzed based on maximum TBA: 10 to 39, 40 to 99, and ≥100 µmol/L. A Kaplan-Meier survival curve was used to analyze time to symptom improvement.

A total of 404 patients were evaluated and 212 (52%) were diagnosed with ICP. The mean gestational age at diagnosis was 34.1 ± 3.3 weeks. When comparing those with ICP to those not confirmed, and to the general population, there were no differences in age, parity, mode of delivery, preeclampsia, or stillbirth (p > 0.05). Preterm birth was significantly associated with ICP (p < 0.01). This relationship was significant across increasing severity of TBA (p < 0.01) and persisted when examining rates of spontaneous preterm birth (p < 0.01). All women with fasting TBA ≥40 µmol/L delivered preterm due to premature rupture of membranes or spontaneous labor. Time to symptom improvement after diagnosis was over 2 weeks on average; however, this time increased with worsening severity of disease.

Despite treatment with UDCA, women with ICP are at increased risk for spontaneous preterm birth, and this risk significantly increased with severity of disease. Although not significant, a trend exists between increasing time to symptom improvement and worsening severity of disease.

· Preterm birth is significantly increased in patients diagnosed with intrahepatic cholestasis of pregnancy.. · The risk of preterm birth in women with ICP increases across increasing strata of disease.. · Following initiation of treatment in patients with ICP, symptom improvement takes more than 2 weeks..