Introduction
Intrahepatic cholestasis of
pregnancy (ICP) is the most common pregnancy-associated liver disease.
It classically presents in the third trimester, the cardinal clinical
symptom is pruritus, and the specific laboratory examination is an
elevated total serum bile acids (TSBA) level1,2.
The prevalence of the condition is 0.2%-2%, but varies greatly among
ethnic groups and geographic regions. The pathogenesis is
multifactorial: increased reproductive hormones synthesis, environmental
factors, genetic predisposition and underlying liver disease are all
considered contributions to disease development and
severity1,3-5. ICP is a relatively nonthreatening
condition to the mother, but it is associated with fetal complications
such as spontaneous preterm delivery, meconium passage, and, in severe
cases, intrauterine death7. The increased risk of
stillbirth is possibly due to bile acids toxicity on fetal
cardiomyocytes or to vasoconstriction of chorionic
vessels22-24.
Internationally, there is lack of consensus regarding the diagnostic
criteria for ICP. Most guidelines agree on the requirement of pruritus
accompanied by otherwise unexplained abnormal liver function, both of
which resolve rapidly after delivery. TSBA are the most often used
biomarker for the diagnosis9-11.
The Royal College of Obstetricians and Gynaecologists (RCOG) guideline
recommends that the upper limit of pregnancy-specific ranges of TSBA
should be used for diagnosis25. Nevertheless,
reference ranges used in clinical laboratories are most often fasting
values measured in nonpregnant subjects, a result of extremely limited
data for pregnancy-specific reference
ranges4,11,17,29. Consequently, there is a wide range
of diagnostic criteria for ICP. Most guidelines recommend the use of
TSBA values of 10 to 15 µmol/L as a diagnostic threshold, but this may
be reduced to 6-10 µmol/L in fasting women1,9,10. In
clinical practice, the most widely used threshold is non-fasting 10
µmol/L, despite not being supported by strong
evidence9,29.
Recently, only extremely high TSBA levels (100 µmol/L or higher) were
shown to markedly increase the risk of stillbirth8.
Nevertheless, since no pharmacological treatment has been shown to
reduce adverse perinatal outcomes12,27,30, early
delivery is still often recommended to prevent the subsequent risk of
stillbirth2,7,8. Policies of active management result,
however, in increased intervention, caesarean-section rate and
iatrogenic prematurity that must be balanced against possible reductions
in perinatal mortality. The diagnosis of ICP has serious implications
for maternal, and especially fetal and neonatal
health18, therefore a correct diagnosis is essential.
The aim of this study was to investigate values of fasting and
postprandial TSBA in healthy pregnant women and to establish the
reference standard in pregnancy.