TWIN PREGNANCY AND INTRAEPATHIC CHOLESTASIS OF PREGNANCY: A COHORT STUDY ON 441 PREGNANCIES

INTRODUCTION Intrahepatic cholestasis of pregnancy (ICP) is a complication of pregnancy resulting in elevation of serum bile acid levels. Elevations in bile acids are associated with adverse pregnancy outcomes, namely meconium staining of amniotic fluid, fetal asphyxial, preterm delivery, both spontaneous and iatrogenic, and sudden intrauterine fetal demise. An increased incidence of ICP has been also demonstrated among twin pregnancies, due to elevated hormone levels. The aim of the present work was to determine maternal and fetal outcomes of intrahepatic ICP in twin pregnancies. METHODS This was a retrospective single-hospital cohort study of twin pregnancies complicated by ICP. All twin pregnancies receiving care at a regional tertiary medical center, Italy, from January 2013 to October 2016 were included in the study. Inclusion criteria were: dichorionic diamniotic (DCDA) pregnancy or monochorionic diamniotic (MCDA) pregnancy and patients receiving both outpatient and inpatient care at the University Hospital. Exclusion criteria were monochorionic monoamniotic pregnancy or triplet, patients with pre-pregnancy liver disease. Data on maternal demographics and obstetric complications together with fetal outcomes were collected for all patients. The risks of adverse maternal and fetal outcomes were determined in relation to serum bile acid levels > 40 micromol/L. Subgroup analysis focused on the effect of assisted reproductive technology (ART) and on the mode of delivery in twin pregnancies complicated by ICP. RESULTS A total of 441 twin pregnancies were included, of which 32 (7.3%) had intrahepatic cholestasis. Among pregnancies complicated by cholestasis the mean maternal age was 37.7 years old (SD = 4.7), 21 (65.6%) pregnancies were conceived by ART, one through egg donation. ICP was significantly more frequent in DCBA comparing to MCDA (29 vs 3, p < 0.001). Moreover there were significantly more MCDA among patients without ICP than in patients with ICP (22% vs 9.4%, p < 0.001). Cesarean section was performed significantly more (p < 0.001) in the ICP group (93.7%), compared to patients without ICP (82.3%). All vaginal deliveries in ICP patients were induced and the mean gestational age at delivery was 35+6 weeks. Three fetuses (4.7%) were born with cord blood pH ≤ 7. Interestingly, all these three fetuses were conceived by ART, and one of them by egg donation, and from three different pregnancies with early onset ICP. Finally, in the ICP group there was neither fetal demise nor perinatal death. CONCLUSIONS Twin gestation is believed to be associated with a higher incidence of ICP. Compared to an incidence of 0.1-1.5% in singletons as reported in literature, we found that 7.3% of twin gestation were complicated by ICP. Subgroup analysis revealed higher incidences of adverse outcomes in severe and early onset ICP and ART. ICP was also associated with iatrogenic preterm delivery. Notably, no intrauterine demises were registered.