Predictors of adverse neonatal outcomes in intrahepatic cholestasis of pregnancy

Abstract

Objective-We sought to determine predictors of adverse neonatal outcomes in women with intrahepatic cholestasis of pregnancy (ICP).Study Design-This study was a multicenter retrospective cohort study of all women diagnosed with ICP across 5 hospital facilities from January 2009 through December 2014. Obstetric and neonatal complications were evaluated according to total bile acid (TBA) level. Multivariable logistic regression models were developed to evaluate predictors of composite neonatal outcome (neonatal intensive care unit admission, hypoglycemia, hyperbilirubinemia, respiratory distress syndrome, transient tachypnea of the newborn, mechanical ventilation use, oxygen by nasal cannula, pneumonia, and stillbirth). Predictors including TBA level, hepatic transaminase level, gestational age at diagnosis, underlying liver disease, and use of ursodeoxycholic acid were evaluated.Results-Of 233 women with ICP, 152 women had TBA levels 10-39.9 μmol/L, 55 had TBA 40-99.9 μmol/L, and 26 had TBA ≥100 μmol/L. There was no difference in maternal age, ethnicity, or prepregnancy body mass index according to TBA level. Increasing TBA level was associated with higher hepatic transaminase and total bilirubin level (P < .05). TBA levels ≥100 μmol/L were associated with increased risk of stillbirth (P< .01). Increasing TBA level was also associated with earlier gestational age at diagnosis (P< .01) and ursodeoxycholic acid use (P = . 02). After adjusting for confounders, no predictors were associated with composite neonatal morbidity. TBA 40-99.9 μmol/L and TBA ≥100 μmol/L were associated with increased risk of meconium-stained amniotic fluid (adjusted odds ratio, 3.55; 95% confidence interval, 1. 45-8.68 and adjusted odds ratio, 4.55; 95% confidence interval, 1.47-14.08, respectively).Corresponding author: Tetsuya Kawakita, MD. tetsuya.x.kawakita@gunet.georgetown.edu. The authors report no conflict of interest.Presented at the 35th annual meeting of the Society for Maternal-Fetal Medicine, San Diego, CA, Feb. 2-7, 2015. Conclusion-In women with ICP, TBA level ≥100 μmol/L was associated with increased risk of stillbirth. TBA ≥40 μmol/L was associated with increased risk of meconium-stained amniotic fluid. HHS Public AccessKeywords bile acid; intrahepatic cholestasis of pregnancy; neonatal outcome; ursodeoxycholic acid Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease in pregnancy characterized by pruritus, elevated total serum bile acids, and elevated liver enzymes. ICP is associated with increased risk of preterm birth (19-60%), meconium passage <37 weeks (17.9%), intrapartum nonreassuring fetal heart tracing (22-41%), respiratory distress syndrome (RDS) (29%), and stillbirth (0.75-7%). 1-4 Based on high rates of stillbirth and neonatal morbidity, early delivery is often advocated to reduce the risk of term stillbirth. In the absence of evidence-based guidelines for optimal timing of delivery, induction of labor at 36-37 weeks of gestation or after documenting fetal lung maturity is freque...

Polish Gynecological Society Recommendations for Labor Induction

“…The incidence of intrauterine fetal death increases with the duration of pregnancy and the concentration of bile acids. Observational studies indicate an increased risk after 37 weeks of gestation in cases of severe cholestasis with bile acid concentration greater than 100 mmol/L [44]. Meconium-stained amniotic fluid also often occurs in pregnancies complicated by cholestasis and bile acid concentration greater than 40 mmol/L, which is often attributed to fetal hypoxia.…”

Relationship between early onset severe intrahepatic cholestasis of pregnancy and higher risk of meconium-stained fluid

“…High bile acid levels have also been associated with increased risk of MSAF [14]. This is very relevant because the exposure of fetal lung to toxic levels of these molecules can result in lung injury, through alteration of secretory phospholipase A2 [15,16].…”

Intrahepatic Cholestasis of Pregnancy with Severe Elevation of Bile Acids in the Setting of Acute Hepatitis C Infection

“…A positive linear correlation exists between bile acid levels and adverse fetal outcomes including meconium staining of amniotic fluid, fetal asphyxial events, spontaneous preterm delivery, iatrogenic preterm delivery, and sudden intrauterine fetal demise [1, 13]. Several studies have delineated levels of bile acids in terms of severity and subsequent fetal complication rates.…”

“…This is equivalent to a 10% risk of stillbirth if bile acids are greater than 100 micromol/L [14]. Comparably, a 2015 retrospective cohort study by Kawakita et al reaffirmed that bile acid levels greater than 40 micromol/L were associated with increased risk of meconium-stained amniotic fluid (OR 3.55, CI 1.45–8.68), as well as the association between bile acids greater than 100  μ mol/L and an increased risk of stillbirth [13]. …”