Manzotti C
Manzotti Cristina, MD
Department of Pathophysiology and Transplantation
University of Milan
Via Francesco Sforza 35
20122 Milan, Italy
Email: cristina.manzotti@unimi.it
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific
liver disorder known to be associated with fetal adverse events, in
particular stillbirth. At present, an effective treatment to reduce the
risk of stillbirth, does not exist. Ursodeoxycholic acid (UDCA) is often
given in clinical practice to reduce maternal symptom of pruritus but
without strong evidence (Walker KF et al. Pharmacological interventions
for treating intrahepatic cholestasis of pregnancy. Cochrane Database
Syst Rev. 2020 Jul 27;7(7):CD000493), and iatrogenic preterm birth is
induced when the risk of stillbirth is thought to be higher (Ovadia C et
al. Association of adverse perinatal outcomes of intrahepatic
cholestasis of pregnancy with biochemical markers: results of aggregate
and individual patient data meta-analyses. Lancet. 2019 Mar
2;393(10174):899-909).
Total serum bile acid (TSBA) have been used as the most reliable marker
for the diagnosis, follow-up and prognosis of ICP, but their diagnostic
accuracy has been questioned (Manzotti C et al. Total serum bile acids
or serum bile acid profile, or both, for the diagnosis of intrahepatic
cholestasis of pregnancy. Cochrane Database of Systematic Reviews 2019,
Issue 7. Art. No.: CD012546).
In this context, the paper by Mitchell A et al presents three different
studies.
The first study measured fasting and non fasting TSBA levels in women
with and without ICP, to assess diurnal TSBA variation. Authors found
that TSBA increased markedly postprandially in both groups of women:
this means that using a fasting sample, as most often occurs in clinical
practice, the majority of women with severe ICP may not be diagnosed.
The second study determined TSBA non-fasting reference interval for in
the third trimester of pregnancy in healthy pregnant women, by
retrospective analysis of non-fasting serum samples from a local
database. They found that the upper limits for normal reference interval
were 10.4,15.5 and 18.3 μmol/l for white, asian and black women
respectively. Applying as the threshold to diagnose ICP 19μmol/l, a
higher limit than used in clinical practice, some affected women with
mild disease would not have been diagnosed.
However, the third study found that there was no higher risk of adverse
events in this group of women, compared to a healthy pregnant
population, except from iatrogenic preterm birth.
Nowadays clinical practice with pregnant women affected by ICP is still
far from being evidence based, mostly because of low quality and
underpowered studies published in the past, leading to heterogeneous
management in antenatal clinics. Some publications of the last three
years added new insights into ICP management. The paper by Mitchell A et
al, even if with limits of low number of patients with ICP enrolled and
unclear participant selection, seems a further contribution in this
direction.
Appling post-prandial testing for pregnant women suspected to have ICP
could give a more attendible sight over TSBA concentration to which
foetus is exposed, improving diagnostic accuracy for ICP and
understanding which pregnant women need more attention. The higher TSBA
upper limit proposed of 19 μmol/L may avoid overdiagnosis and
over-medicalization without losing potential adverse events. New high
quality and large population based clinical research is needed to reach
more solid evidence.