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

Abstract

Background: Intrahepatic 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.

Objective: To 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 design: The 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.

Results: Higher 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.

Conclusions: The 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.

Fig 1. Flow chart of ICP cases included in the study.

Flow chart showing the intrahepatic cholestasis of pregnancy (ICP) cases at the Mother’s and Children’s Hospital, Buenos Aires, from June 2009 to December 2013, and reasons for the exclusion of some patients from the study.

Fig 2. Flow chart of management of patients.

Flow chart showing distribution of women with intrahepatic cholestasis of pregnancy (ICP) depending on whether they were not treated or treated with ursodeoxycholic acid (UDCA), together with days of treatment.

Fig 3. Relationship between hypercholanemia and body weight at birth.

Gestational age and body weight of neonates born from women with intrahepatic cholestasis of pregnancy (ICP) with high or low weights at birth for their gestational age.

Fig 4. Relationship between hypercholanemia and the frequency of meconium-stained amniotic fluid (MSAF).

Frequency of the presence of MSAF in pregnancies complicated by cholestasis of pregnancy classified according to gestational age (GA) at diagnosis (A) or at delivery (B), severity of hypercholanemia (mild: 10–19.9 μmol/L; moderate: 20–39.9 μmol/L; severe: ≥40 μmol/L) at diagnosis in women not treated (C) or women treated with ursodeoxycholic acid (UDCA), (D), and at delivery in those treated with UDCA (E).

Fig 5. Evaluation of the index to predict the risk of meconium-stained amniotic fluid (MSAF).

Balance between sensitivity and specificity for different cut-off values of meconium risk factor (MRF), calculated taking into account the severity of hypercholanemia and gestational age at diagnosis (A). Proportion of cases of MSAF in pregnancies with complications due to cholestasis of pregnancy according to a MRF cut-off value of 3 in women not treated or treated with ursodeoxycholic acid (UDCA) (B).