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

Abstract

Objective 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. Study Design 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. Results 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. Conclusion 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. Key Points

Evaluation of perinatal outcomes in intrahepatic cholestasis of pregnancy

“…However, in our study, a significant relationship was found between the gestational week at the time of diagnosis and only preterm birth, one of the adverse perinatal outcomes. In another study, although the gestational week at the time of diagnosis was found to be 34.1±3.3, higher than our study, it was found to be significantly associated with the rate of preterm birth, similar to ours [25] . In light of this information, knowing the gestational week at which ICP was diagnosed may help manage the disease and determine the negative consequences that may occur.…”

How Do Serum Zonulin Levels Change in Gestational Diabetes Mellitus, Pregnancy Cholestasis, and the Coexistence of Both Diseases?

“…According to the outcomes of the current study, pregnant women with ICP had higher rates of meconium-stained amniotic fluid, lower gestational weeks of delivery and due to this, lower birth weight APGAR scores, in agreement with the existing literature, and higher Caesarean delivery rates and similar NICU admission rates with those of the control group, in contrast with other study results [ 30 , 31 , 32 ]. However, similarly to other investigation results, patients with GDM had higher NICU admission rates and lower APGAR scores, but similar gestational weeks of delivery to the control group [ 33 , 34 ].…”

Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species‐mediated activation of placental GCN2/eIF2α pathway

“…Its typical manifestations are the presence of pruritus in combination with hepatic injury and elevated serum total bile acid (TBA) levels 1 . Gestational cholestasis was related to increased risks of pregnancy complications, such as gestational diabetes mellitus, later‐life cardiovascular diseases, later‐life autoimmune‐mediated conditions and later‐life biliary tree cancer 2,3 . Additionally, many of the findings in humans and animals showed that gestational cholestasis can lead to severe adverse fetal events, including spontaneous and iatrogenic preterm delivery, stillbirth, fetal death, and even neonatal death 4,5 .…”