Predictors of adverse neonatal outcomes in intrahepatic cholestasis of pregnancy

Am J Obstet Gynecol. 2015 Oct;213(4):570.e1-8. doi: 10.1016/j.ajog.2015.06.021. Epub 2015 Jun 10.


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).

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.

Keywords: bile acid; intrahepatic cholestasis of pregnancy; neonatal outcome; ursodeoxycholic acid.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Bile Acids and Salts / blood
  • Cholagogues and Choleretics / therapeutic use
  • Cholestasis, Intrahepatic / blood
  • Cholestasis, Intrahepatic / drug therapy
  • Cholestasis, Intrahepatic / epidemiology*
  • Cohort Studies
  • Female
  • Gestational Age
  • Humans
  • Hyperbilirubinemia / epidemiology*
  • Hypoglycemia / epidemiology*
  • Infant, Newborn
  • Intensive Care Units, Neonatal / statistics & numerical data
  • Logistic Models
  • Multivariate Analysis
  • Oxygen Inhalation Therapy / statistics & numerical data
  • Pneumonia / epidemiology*
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / drug therapy
  • Pregnancy Complications / epidemiology*
  • Pregnancy Outcome
  • Respiration, Artificial / statistics & numerical data
  • Respiratory Distress Syndrome, Newborn / epidemiology*
  • Retrospective Studies
  • Risk Factors
  • Stillbirth / epidemiology*
  • Transient Tachypnea of the Newborn / epidemiology*
  • Ursodeoxycholic Acid / therapeutic use
  • Young Adult


  • Bile Acids and Salts
  • Cholagogues and Choleretics
  • Ursodeoxycholic Acid
  • Aspartate Aminotransferases
  • Alanine Transaminase

Supplementary concepts

  • Intrahepatic Cholestasis of Pregnancy