INTRAHEPATIC CHOLESTASIS OF PREGNANCY
Prevalence is influenced by genetic and environmental aspects and varies
between populations.
Intrahepatic cholestasis of pregnancy is a multifactorial condition. It is
characterised by
Pruritus in the absence of a primary skin condition
Abnormal maternal bile acid concentrations.
The onset of symptoms is most common in the third trimester, but can be
earlier in pregnancy. Alternative diagnoses (such as pre- eclampsia) should
always be considered before a diagnosis of ICP is made.
Pruritus and raised bile acid concentrations should return to normal after birth.
Ideally, all women with ICP should have liver function tests (including bile
acids) checked after birth, as a proportion may have persistent abnormalities
suggestive of additional or alternative comorbidities (such as non- alcoholic
fatty liver.
Diagnosis of ICP requires elevated maternal bile acid concentrations, and that
women and pregnant people with itching and isolated raised transaminases
alone (with normal bile acid concentrations) should not be given a diagnosis of
ICP.
CLINICAL FEATURES
Itching Generalized/ palms and soles More at night
Symps of Cholestasis dark urine and pale stools
Steatorrhea (due to fat malabsorp leading to deficiency of Fat
soluble vits, VIT K)
Clinical issues for women with ICP
The clinical issues for women and pregnant people with ICP may include coping
with the itching, monitoring options during the pregnancy, options for
controlling maternal symptoms, reducing fetal risk, preterm birth, difficulty
sleeping, anxiety about the condition, and optimal timing of birth.
Liver failure (impaired synthetic function such as prolonged prothrombin time,
or metabolic dysfunction such as hypoglycaemia) is not a typical feature of ICP.
DIAGNOSIS OF ICP
The diagnosis of ICP should be considered in pregnant women who have
itching without rash + raised peak random total bile acid concentration of 19
micromol/L or more. The diagnosis is more likely if it is confirmed that itching
and raised bile acids resolve after birth.
If a diagnosis of ICP is suspected, carry out a structured history and
examination, so that other causes of itching and liver dysfunction can be
excluded.
Offer repeat liver function tests and bile acid measurement (depending on
gestation and clinical context) in women with normal blood results whose
itch persists, and no other cause is apparent.
If resolution of itching is associated with normalisation of bile acids and liver
function tests during pregnancy, the diagnosis of ICP is unlikely to be correct.
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New onset pruritus in pregnant women, if associated with rash is unlikely to be
ICP. If the itchy skin looks abnormal (other than excoriations) then another
cause should be considered. Liver function tests and bile acids are not required
routinely. Clinicians should be aware however, that skin conditions (e.g.
eczema) and ICP can co-exist.
Drug reactions, allergic reactions, and urticaria should form part of the
differential diagnosis.
RECONSIDER DIAGNOSIS !!!!!
Pruritus and biochemical abnormalities usually persist throughout pregnancy
in women with ICP, although it is very common for them to fluctuate.
However, in a few women, pruritus and biochemical abnormalities will resolve
completely for the remainder of the pregnancy; clinicians may then need to
reconsider the cause of the original symptoms and why resolution has
occurred. There are many causes of transient liver function test abnormalities,
such as drug reactions (e.g. to antibiotics) or non- specific viral illnesses. When
resolution occurs during pregnancy, it is unlikely that the original diagnosis was
correct.
OTHER INVESTIGATIONS
Coagulation testing PT APTT is therefore not recommended routinely for
women and pregnant people with uncomplicated ICP. It should be considered
on an individual basis especially when failure of liver synthetic function or
failure of fat absorption (which causes Steatorrhea fat containing oily
bulky foul smelling stools that are difficuilt to pass) is suspected.
HEPATOLOGIST CONSULT
Women who develop severe ICP in the first or second
trimester and especially in the first trimester are more likely
to have an underlying genetic predisposition or an alternative
or additional diagnosis.
POSTNATAL RESOLUTION???
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MATERNAL RISKS
PRE-ECLAMPSIA
The incidence of pre- eclampsia was higher in women with ICP.
12.2% of women with ICP had pre- eclampsia.
Blood pressure and urinalysis screening for pre- eclampsia should be
done alongside review for ICP.
GESTATIONAL DIABETES
Risk assessment and testing for gestational diabetes should follow
national guidelines.
HEPATOBILIARY DISEASE
Women who have had ICP had an increased likelihood of later being
diagnosed with hepatobiliary disease predominantly due to gallstone
disease. However gallstones are common, affecting 5– 25% of adults
in high income countries and it is unclear whether gallstone disease
predates ICP in such women.
IMMUNE-MEDIATED DISEASES
Develop later in life
Diabetes
Thyroid disease
Psoriasis
Inflammatory polyarthropathies
Crohn's disease
RISK OF STILLBIRTH
Pathophysiology: it is thought that bile acids may cause an acute fetal anoxic
event possibly due to fetal arrhythmia or acute placental vessel spasm.
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Advise women with Isolated ICP and a Singleton pregnancy that the risk of
stillbirth only increases above population rate once their serum bile acid
concentration is 100 micromol/L or more.
In women with peak bile acids 19–39micromol/L and no other risk
factors, advise them that the risk of stillbirth is similar to the background
risk.
In women with peak bile acids 40–99micromol/L and no other risk
factors, advise them that the risk of stillbirth is similar to the background
risk until 38– 39 weeks' gestation.
In women with peak bile acids 100 micromol/L or more, advise them
that the risk is higher than the background risk.
Advise women with ICP with Risk factors (such as gestational diabetes and/or
pre- eclampsia and/ or multifetal pregnancy) appear to increase the risk of
stillbirth and may influence decision-making around timing of planned birth.
Women with ICP and a Twin pregnancy, the risk of stillbirth is higher
compared with a twin pregnancy without ICP. Stillbirths with ICP in twin
pregnancies occurred between 33– 35 weeks’ gestation, compared to 36– 38
weeks’ gestation among singletons.
PERINATAL RISKS
In Moderate and Severe ICP there is an increased risk of
Preterm birth( both spontaneous and Iatrogenic)
MS amniotic fluid during labour and birth more common at
35-38 weeks.
Need for NICU care ( d/t PT birth, respiratory problems, MSA
fluid).
MONITORING
MATERNAL MONITORING
Consider repeating LFTs and BAs after 1 week, and then determine frequency
on an individual basis, more frequent if required.
Maternal itch appears to be poorly correlated to the level of biochemical
abnormality. For women with ICP, ongoing monitoring of symptoms and
biochemical monitoring may show:
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Rising bile acid concentrations
Fall in bile acids concentrations into a more reassuring category, such
that frequency of monitoring and/or care can be altered accordingly,
Spontaneous resolution of itch and biochemical abnormalities returning
to normal levels, in which case the diagnosis should be reconsidered .
Fluctuating bile acid concentrations but peak concentrations within the
boundaries for their current diagnosis.
FETAL MONITORING
Fetal ultrasound BPP, (CTG) and Doppler studies DO NOT predict or prevent
stillbirth in ICP.
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