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

Maria C Estiú,Jose J G Marin,Rocio I R Macias,Catherine Williamson,Marcela Dericco,Maria A Frailuna,Carla Otero,Gianfranco D Alpini

doi:10.1371/journal.pone.0176504

Abstract

BackgroundIntrahepatic cholestasis of pregnancy (ICP) is the commonest gestational liver disease. The risk of adverse fetal outcome has been associated with the severity of maternal hypercholanemia after diagnosis.ObjectiveTo investigate whether there is a relationship between the severity and timing of onset of hypercholanemia and the risk of meconium-stained amniotic fluid (MSAF) and adverse neonatal events.Study designThe study included 382 pregnancies complicated by ICP managed at a referral hospital in Buenos Aires (Argentina) between June 2009 and December 2013. The patients were classified into three groups according to the severity of hypercholanemia at diagnosis; mild (10–19.9 μmol/L), moderate (20–39.9 μmol/L) and severe (≥40 μmol/L). Their clinical characteristics and pregnancy outcomes were investigated in a prospective observational study.ResultsHigher risk of MSAF was observed when ICP appeared early in gestation or when hypercholanemia was more severe. Taking both parameters into account an MSAF risk factor (MRF) was defined. Based on a model of positive/negative predictive values, a cut-off point of MRF = 3 was selected, which prioritized sensitivity versus specificity. In ICP patients with MRF>3, the probability of MSAF was enhanced 4-fold. An increase in the frequency of MSAF was also associated with higher serum levels at diagnosis of alanine transaminase, alkaline phosphatase and direct bilirubin.ConclusionsThe risk of MSAF is associated not only with the magnitude of hypercholanemia at diagnosis but also with the early gestational onset of raised maternal serum bile acids.

Highlights

Intrahepatic cholestasis of pregnancy (ICP) is usually diagnosed in the third trimester of gestation, it may present as early as the first trimester
The risk of adverse fetal outcome has been associated with the severity of maternal hypercholanemia after diagnosis
An increase in the frequency of meconium-stained amniotic fluid (MSAF) was associated with higher serum levels at diagnosis of alanine transaminase, alkaline phosphatase and direct bilirubin

Summary

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is usually diagnosed in the third trimester of gestation, it may present as early as the first trimester. It typically resolves without treatment after delivery [1]. As demonstrated in animal models, exposure to pathologically high levels of bile acids affects normal fetal development, in particular adversely impacting hepatobiliary function [6,7], with persistent abnormalities for several weeks after birth [8]. The risk of adverse fetal outcome has been associated with the severity of maternal hypercholanemia after diagnosis

Methods

Results

Conclusion