University of Baghdad

Student Report
Alkindy college of Medicine

Jaundice of pregnancy
A Report Submitted In Fulfillment Of The Requirements Of Fourth Year
Medical College, Obstetric Module Course, Department of Gynecology &
Obstetric / Alkindy College of Medicine

Submitted By the Student:

Ali Faris Abdulbaqi

Supervised By:
Dr. Thikra Najem

10 / September /2020

‫ علي فارس عبد الباقي عبد‬:‫اسم الطالب‬

‫ التوليد‬:‫المادة‬

‫ الرابع‬:‫الصف‬

:)21) ‫الدرجة النهائية‬

‫ ذكرى نجم‬.‫ د‬:‫اسم وتوقيع األستاذ المشرف‬

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 List of contents
Contents Page
numbering
Introduction 3

Signs & symptoms 3

Pathophysiology 4

Diagnosis 5

Treatment 5

Summary 6

References 7

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1. Introduction

Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric

cholestasis, cholestasis of pregnancy, jaundice of pregnancy, and prurigo
gravidarum, [1] is a medical condition in which cholestasis occurs
during pregnancy. It typically presents with itching[2] and can lead to
complications for both mother and baby. Pruritus (itching) is a common
symptom of pregnancy, affecting around 20% of women. [3] The majority of
times, itching is a minor annoyance caused by changes to the skin, especially
that of the abdomen. However, there are instances when itching may be a
symptom of ICP. Although typically noticed on the palms of the hands and the
soles of the feet, the itching can occur anywhere on the body. ICP occurs most
commonly in the third trimester, but can begin at any time during the
pregnancy[4] .
2. Signs and symptoms
Most women with this condition present in the third trimester (although it can present
as early as seven weeks) with itching without a rash. Typically, the itching is
localized to the palms of the hands and soles of the feet, but can be anywhere on the
body.
Hallmarks of ICP include the following symptoms:
Most common:

 Itching, in particular but not limited to that of the palms of the hands and soles of
the feet, without presence of a rash
 Itching that is more noticeable in the evening
 Darker urine
Less common:

 Lighter stools
 Increased clotting time (due to possibly associated vitamin K deficiency)
 Fatigue
 Increased nausea
 Decrease in appetite
 Jaundice (less than 10% of women)
 Upper right quadrant pain
Not all ICP sufferers have all of the above symptoms [4] .

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3. Pathophysiology

The causes of intrahepatic cholestasis of pregnancy are still not fully

understood.[4] Hormones, environmental and genetic factors are all thought to
contribute to the condition.[5]
 ICP commonly occurs in the third trimester at the time when hormone levels
are at their highest.
 Twin and triplet pregnancies, which are associated with higher hormone levels,
show a higher incidence of ICP.[6]
 ICP resolves quickly after delivery, when placental hormone production
ceases.
 Older high-dose estrogen oral contraceptive pills could cause features of ICP.
Estrogens
Estrogens, and particularly glucuronides such as estradiol-17β-D-glucuronide, have
been shown to cause cholestasis in animal studies, by reducing bile acid uptake
by hepatocytes.[7]
Progesterone
Treatment with progesterone in the third trimester of pregnancy has been shown to be
associated with the development of ICP, and levels of metabolites of progesterone,
particularly sulfated progesterone,[8] are higher in patients with ICP than unaffected
women, suggesting that progesterone also has a role in ICP. [5]
Genetic factors
Clustering of cases of ICP in families, geographic variation in rates of ICP, and
recurrence of ICP in 45-70% of subsequent pregnancies all suggest a genetic
component to the disease.[5] Genetic mutations in the hepatocellular transport
protein ABCB4 (MDR3), which controls secretion of phosphatidylcholine into bile,
have been found in cases of ICP.[9]
Genetic mutations affecting hepatic bile salt transport molecules have also been
found in patients with progressive familial intrahepatic cholestasis. It has been found
that mothers of patients with this disease have a higher incidence of ICP, suggesting
that heterozygote carriers of these mutations are also predisposed to ICP. [5]
In addition to genetic changes to bile salt transport molecules, high levels of estrogen
glucuronides have been shown to inhibit the bile salt export pump
(BSEP) ABCB11,[10] and high levels of progesterone to inhibit the ABCB4 (MDR3)
phospholipid transporter.[11]

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Consequently, both genetic mutations in hepatocyte proteins involved in bile
secretion together with inhibition of those proteins by high levels of hormone
metabolites in pregnancy may have roles in the pathogenesis of ICP. [4]
Environmental factors
A number of features of ICP suggest that environmental factors also have a role in the
disease:
 It has been reported that the incidence of ICP is higher in winter than
summer.[12]
 The incidence of ICP in Chile has dropped from 14% of pregnancies before
1975 to 4% in 2016.[13]
 ICP recurs in between 60% and 90% of subsequent pregnancies.
 Low serum selenium levels have been linked to ICP,[14] although the role of
selenium in bile secretion is not known.
4. Diagnosis
ICP is diagnosed by blood tests including a serum bile acid test and liver function
test. While most pregnant women experience some itch from time to time, itching on
the palms and soles without a visible rash, or persisting severe or extensive itch
symptoms should be reported to the midwife or obstetrician[14].
To obtain a diagnosis of ICP, there are two LFT (liver function tests) and Serum bile
acid test. The liver function tests (LFTs) is a simple blood test, the results of which
should be available by the next day. If the ALT level is elevated, this, plus pruritus of
palms and soles, could be considered as potentially diagnostic of ICP but only with
elevated bile acid levels (however LFTs are not always elevated in ICP patients). The
serum bile acid blood test for ICP is a quantitative measurement of bile acids [15].
Other problems with the liver that occur in pregnancy should be considered by the
treating clinician. These include preeclampsia, the HELLP syndrome, and acute fatty
liver of pregnancy. Furthermore, other causes of hepatitis, like hepatitis viruses,
cancer and certain medications, should also be considered [7].

5. Treatment
Upon diagnosis, many providers will prescribe ursodeoxycholic acid. While
there is no cure for ICP, and no way to guarantee a successful outcome, studies
have shown a slightly better fetal and maternal outcome from administration of
ursodeoxycholic acid, whereas cholestyramine appears to only relieve
itching.[7][15If additional blood tests to check clotting function identify a problem,
giving Vitamin K may help avoid the risk of hemorrhage at delivery.

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Delivery by 35–37 completed weeks may be important to fetal outcome as a
recent study demonstrated that in severe ICP (defined as bile acids greater than
40 umol/L) the risk of stillbirth was 1.5% compared to 0.5% of uncomplicated
pregnancies. This risk rose further if bile acids doubled.[16] The most recent
research, published in The Lancet, suggests that around 90% of women with ICP
could wait until 39 weeks of pregnancy to be induced. However, this relies on
regular bile acid testing with rapid return of results.[17]

Summary
Intrahepatic cholestasis of pregnancy is a common disorder of pregnancy
manifested by pruritus and elevated bile acids. The etiology of cholestasis is
poorly understood and management is difficult due to the paucity of data
regarding its diagnosis, treatment, and related adverse outcomes. Jaundice
affects a small percentage (1-4 per 1000) of pregnant women, yet is an important
medical disorder especially in developing countries. Jaundice in pregnancy
carries adverse outcomes for both the fetus and the mother. It accounts for 60%
perinatal and 14% of maternal deaths. Causes peculiar to pregnancy are HELLP
syndrome, Acute fatty liver of pregnancy, intrahepatic cholestasis, severe
hyperemesis and toxemia of pregnancy. Causes concurrent with pregnancy are
viral hepatitis, gallstones, hemolytic jaundice or due to drugs administered
during pregnancy.

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References:

1. Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-
Volume Set. St. Louis: Mosby.
2. Tunzi M, Gray GR (January 2007). "Common skin conditions during pregnancy".
American Family Physician. 75 (2): 211–8.
3. Bergman, H.; Melamed, N.; Koren, G. (2013). "Pruritus in pregnancy: Treatment
of dermatoses unique to pregnancy". Canadian Family Physician. 59 (12): 1290–
1294.
4. Jump up to:a b Pusl T, Beuers U (2007). "Intrahepatic cholestasis of pregnancy".
Orphanet Journal of Rare Diseases. 2: 26.
5. Jump up to:a b c d Lammert F, Marschall HU, Glantz A, Matern S (December
2000). "Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis
and management". J. Hepatol. 33 (6): 1012–21.
6. Gonzalez MC, Reyes H, Arrese M, et al. (July 1989). "Intrahepatic cholestasis of
pregnancy in twin pregnancies". Journal of Hepatology. 9 (1): 84–90.
7. Jump up to:a b Reyes H, Sjövall J (March 2000). "Bile acids and progesterone
metabolites in intrahepatic cholestasis of pregnancy". Annals of Medicine. 32 (2):
94–106.
8. Abu-Hayyeh, S (2015). "Prognostic and mechanistic potential of progesterone
sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum".
Hepatology. 63 (4): 1287–1298.
9. Dixon, PH (2017). "An expanded role for heterozygous mutations of ABCB4,
ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy".
10. Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ (2000). "Drug- and
estrogen-induced cholestasis through inhibition of the hepatocellular bile salt
export pump (Bsep) of rat liver". Gastroenterology. 118 (2): 422–30.
doi:10.1016/S0016-5085(00)70224-1. PMID 10648470.
11. Debry P, Nash EA, Neklason DW, Metherall JE (January 1997). "Role of
multidrug resistance P-glycoproteins in cholesterol esterification". Journal of
Biological Chemistry. 272 (2): 1026–31.
12. Williamson, Catherine; Geenes, Victoria (2014). "Intrahepatic cholestasis of
pregnancy". Obstetrics and Gynecology. 124 (1): 120–33.

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13. Ovadia, Caroline; Williamson, Catherine (2016). "Intrahepatic cholestasis of
pregnancy: recent advances". Clinics in Dermatology. 34 (3): 327–34
14. Kauppila A, Korpela H, Mäkilä UM, Yrjänheikki E (January 1987). "Low serum
selenium concentration and glutathione peroxidase activity in intrahepatic
cholestasis of pregnancy". British Medical Journal (Clinical Research
Edition). 294 (6565): 150–2.
15. Walker, Kate F.; Chappell, Lucy C.; Hague, William M.; Middleton, Philippa;
Thornton, Jim G. (27 July 2020). "Pharmacological interventions for treating
intrahepatic cholestasis of pregnancy". The Cochrane Database of Systematic
Reviews. 7: CD000493.
16. Geenes, V.; Chappell, L.C.; Seed, P.T.; Steer, P.J.; Knight, M.; Williamson, C.
(April 2014). "Association of severe intrahepatic cholestasis of pregnancy with
adverse pregnancy outcomes: a prospective population-based case-control
study". Hepatology. 59 (4): 1482–91.
17. Ovadia, Caroline (2019). "Association of adverse perinatal outcomes of
intrahepatic cholestasis of pregnancy with biochemical markers: results of
aggregate and individual patient data meta-analyses". Lancet. 393 (10174): 899–
909.