2. General objective
At the end of this teaching learning session, students will be able to
explain jaundice during pregnancy and its management.
3. Specific objectives
• Explain normal physiology of liver during pregnancy .
• Define jaundice during pregnancy.
• State the causes of jaundice during pregnancy Explain the physiology
of bilirubin production.
• Define obstetric cholestasis.
• State the diagnosis measure of OC.
• State the maternal and fetal effect of OC.
• State the complication of OC.
• Enumerate the preventive measure of jaundice.
• Explain the management of OC.
5. NORMAL LIVER PHYSIOLOGY IN PREGNANCY
• Outside pregnancy , liver receives upto 25-35 % of cardiac output
which does not change significantly during pregnancy
• Size of the liver does not increase
• Postero-superior displacement by the enlarging uterus.
• Palpably enlarged liver is abnormal in pregnancy.
• Metabolic ,synthetic & excretory functions of liver affected by
increased levels of estrogen & progesterone in pregnancy.
• The biochemical tests in the last trimester show the moderate increase in
alkaline phosphate, cholesterol and serum globulin.
• Hemoglobin , Serum albumin ,urea and uric acid concentration are
• About 10% to 15 % of normal women may be bilirubin level of over
1.0mg% due to delayed excretion of bilirubin which may cause pruritis
• Decreased Gallbladder contractility.
• Worldwide jaundice occur in about 1 out of every 1500
• Overall incidence in india is 1-4/1000 deliveries (Datta D.C.)
8. INTRODUCTION OF JUNDICE
• Jaundice is the clinical manifestation of raised bilirubin levels in
blood .Detected clinically at bilirubin concentration of 2 mg %
or more ( normal being 0.2 – 0.8 mg % )
• Jaundice may be coincidental to the pregnancy or due to a
condition that is specific to the pregnancy.
10. • Following the destruction of red blood cell ,the released
hemoglobin is broken down into globin and heme.
• The heme is broken down to biliverdin,which is reduced to form
bilirubin usually amounting to 250 to 300mg daily .(this is not
change by pregnancy)
• This bilirubin is unconjugated and water -insoluble and usually
carried to the liver bond to albumin.
• At the hepatocyte membrane, unconjugated bilirubin is actively
taken up and conjugated to two molecule of glucuronide, by the
action of uridine diphosphoglucurosyl (UDP) transferese.
• This conjugated bilirubin is water soluble and usually remain in
• Hepatocyte damage allows it to enter the blood , and the part
that remains unbound passes into urine and cause the dark
urine of cholestatic jaundice
12. Cont …
• The protein-bound conjugated bilirubin contributes to the yellow
discoloration of skin and mucus membrane.
• From the hepatocyte, bilirubin is actively taken up by the bile
• From the canaliculus conjugated bilirubin drains into the extra
hepatic bile ducts, common bile duct and finally the small intestine.
• The conjugated bilirubin is too large to be absorbed from the location
so it passes to the terminal ileum where bacterial action hydrolyzes it
free bilirubin which is then reduced to urobilinogen.
• Some of these undergoes further bacterial action in the stool,
changing it to stercobilinogen, which contribute to dark color of feces-
reduced entry of bilirubin into the gut accounts for the pale stool of
• The rest of urobilinogen is absorbed and returned to the liver via the
enterohepatic circulation, from there it is re-excreted into the bile.
• These urobilinogen is water soluble, in normal circumstances, a small
amount passes into the urine.
• Urinary urobilinogen is increased either there is an increased load of
bilirubin, in which case the hepatic capacity to re-excrate the
urobilinogen maybe over-whelmed, or if hepatic damage empairs re-
15. Causes of jaundice during pregnancy
Jaundice specific to pregnancy
• Hyperemesis gravidarum
• Intrahepatic cholestasis of pregnancy
• Pre-eclampsia/ eclampsia
• HELLP Syndrome
• Acute fatty liver of pregnancy
16. Jaundice unrelated to pregnant state
• Acute viral hepatitis
• Drug induced hepatitis
• Chronic hepatitis
-viral (HBV, HCV)
• Wilson’s disease
• Cirrhosis of liver
• Hemolytic anemia
• Common bile duct stone/
17. OBSTETRIC CHOLESTASIS
• Also called as recurrent jaundice of pregnancy, cholestatic jaundice of
pregnancy, jaundice of late pregnancy, and hepatosis of pregnancy. It
is a form of intrahepatic cholestasis associated with pruritus, elevated
serum bile acid levels, and the findings of bland cholestasis on liver
• It is more common in certain parts of the world. For example, in some
countries in South America, especially Chile and Bolivia, up to 1 in 20
or more pregnant women develop this condition
• OC affects 0.7% of pregnancies in whites in the United Kingdom and
approximately double this proportion of women of South Asian
• incidence being 1.24 % of all pregnancies in Indian population.
• Obstetric cholestasis occurs in less than 1 in 100 pregnancies in the
UK. It is more common in women carrying twins, triplets, or more
• Cholestasis is a complication of pregnancy where pregnancy
hormones (particularly oestrogen) affect the liver by preventing the
flow of bile into the intestines. Bile usually aids with the breakdown
and absorption of food after digestion, but when a women has
obstetric cholestasis, bile and other toxins accumulate in the
• Affected individuals have a defect involving the excretion of bile
salts, which leads to increased serum bile acids. These are
deposited within the skin, causing intense pruritus.
• Up to 15% of OC cases are associated with the adenosine
triphosphate binding cassette, subfamily B, member 4
(ABCB4/abcb4) gene. This gene, also known as multidrug resistant
protein 3 (MDR3), encodes the transporter for phospholipids
across the canaliculi membrane of hepatocytes.
• Up to 10 different MDR3 mutations have been identified and
any one of these mutations may result in loss of function and,
therefore, raise bile acid levels. MDR3 is also associated with
progressive familial intrahepatic cholestasis.
• Therefore, a careful and focused family history of a patient
diagnosed with ICP, looking for a personal or family history of ICP
or gallstones and cholestasis with oral contraceptive pill (OCP)
use is important.
22. Cont ….
• Changes induced by these genetic mutations lead to an increased
sensitivity to estrogen. Estrogen has a known role in causing
cholestasis, and thus, cholestasis can arise from estrogen-
• The hepatic transport mechanisms for biliary excretion can be
altered by estrogen and progesterone .
• Which all contribute for obstetric cholestasis.
• Previous history of OC and taking OCP.
• Genetically susceptible women.
• Women with hepatitis C more commonly develop OC than those who
do not have the virus.
• An enhanced sensitivity to estrogen .(Mostly during third trimester)
24. • Molecular mechanism show many gene mutations that control
hepatocellular transport systems
Multidrug resistance 3 (MDR3) gene found with progressive familial
Decrease canalicular transport of bile acids .
25. SIGN AND SYMPTOMS
• Pruritus associated with abnormal liver transaminase or raised bile
acid . More than 70% of cases usually involves the trunk and the
extremities, including the palms and the soles of the feet.Disappears
24-48 hours postpartum (but biochemical and histological
abnormalities take longer to resolve)
26. • Malaise & insomnia
• Dark urine, anorexia, steatorrhoea .
• 10% to 25% patients develop obvious jaundice, and this is usually
• Abdominal pain, biliary colic, fever, anorexia, nausea, vomiting, are
• Ask about medical and family history to aid diagnosis. If close female
family members have been affected by OC/ICP then there may be at
• It is also important to exclude all other possible causes of itching,
such as allergies or eczema (but it is possible to have a skin condition
and OC/ICP). Other signs such as pale stools or dark urine may
indicate a problem with liver, including OC/ICP.
• OC can be diagnosed from blood tests called liver function
tests (LFTs) and a serum bile salt test. Liver function tests are
performed to gain an idea of how liver is functioning.
• levels of the liver enzymes alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) should be checked.
• The most specific test involves measuring serum bile salts. Raised
levels would be a measurement of greater than 14µmol/L
• Raised bilirubin may occur but this is not only marker of OC.
• Ultrasound scan of liver and biliary can exclude other problem.
• PT should be checked once a week.
• If symptoms or biochemical abnormalities persist more than 3 month
postpartum , women should refer to hepatologist.
30. FETAL EFFECT
• Intrauterine fetal death
• Spontaneous preterm delivery
• Intra partum fetal distress
• Meconium stained liquor
• The risk of still birth greatest after 37 weeks
• Maternal morbidity is low.
• The importance of this disorder is the effects on the fetus.
• It can lead to chronic placental insufficiency which may result in
anoxia, prematurity, perinatal death, fetal distress and stillbirth.
1. A Healthy Diet:
Eating healthy and hygienic food throughout pregnancy will help you
keep jaundice and other health issues at bay.
2. Healthy Weight:
Maintain a healthy weight and regulate the cholesterol levels in the
blood by keeping fat intake under check. Follow diet chart strictly.
3. Active Lifestyle:
Consult doctor on safe exercises during pregnancy . It will help you
ensure a proper supply of blood and oxygen to different parts of the
body, including the liver.
4. Vaccinate Regularly:
Avoid hepatitis infections. Follow gynecologist’s advice and accordingly
get yourself vaccinated against the disease.
5. Limit Your Drug Intake:
Avoid the intake of medications or compounds that may be toxic to the
liver. Avoid the overuse of OTC drugs. Consult your doctor before taking
any medication during pregnancy.
5.Be On Guard While Traveling:
• Avoid traveling to regions that have breakout of diseases like malaria.
If must visit , always use preventive measures.
• Do not worry about having jaundice during pregnancy. Early
detection guarantees that mother and baby will be safe. Seek
medical opinion as soon as the symptoms of jaundice appear to avail
early treatment and ensure a speedy recovery.
• If previous history of OC ,advice about recurrent risk(90%).
• obtain biliary tract ultrasonography to exclude other pathology.
• Regular antenatal check up should be done.
• Conform the diagnosis with serum bile acid,ALT and AST
• Monitor serum bile acid in women with a proven diagnosis of OC.
36. • Exclude viral infection , including hepatitis C , autoimmune hepatitis
and other cause of bilary obstruction.
• Treat meternal symptoms with simple topical measures e.g. aqueous
cream with menthol.
• Consider ursodoxycholic acid 500 mg BID women with sever
37. • Consider oral vitamin K to reduce the risk of PPH.
• Dexamethamethasone 12mg daily for 7 days with gradual reduction
of dose over subsequent 3 days.to improvement in clinical symptoms
• Monitor fetal well being.
• Blood test should be done before discharged from hospital to check
LFTs and bile salts are reducing, however, LFTs can be raised for the
first 10 days after birth in normal pregnancy.
• Vitamin k supplement for baby.
• Use oral contraceptives only with close clinical and biochemical
• Consider referral to hepatologist if symptoms persist.
39. LOOKING AFTER YOURSELF/PATIENT TEACHING
• There are no special foods to eat or to avoid. As with all pregnant
women, eat a well-balanced diet which includes lots of vegetables,
fruit and whole wheat cereals, including bread.
• As the flow of bile into the gut is reduced, patient cannot tolerate the
same amount of fat as normal , therefore mother should lower fat
40. • To help with itching you may give the following suggestions .
Have frequent tepid baths.
Try not to get too hot.
Use lotions such as calamine and aqueous cream with menthol
Wear loose cotton clothing.
41. • Few women report what is known as ‘cyclical itching’ during the
menstrual cycle. This can happen just before ovulation or just prior to
a period but the itching is usually only mild and stops either when
ovulation has taken place or period has started.
• OC do not influence mother’s ability to breastfeed.
43. General objectives
• At the end of this classroom session students will be
able to explain jaundice related to pregnancy.
44. Specific objectives
• Define acute fatty liver of pregnancy.
• State the etiology of acute fatty liver of pregnancy.
• List sign and symptoms of AFLP.
• State diagnosis measure of AFLP.
• List the Complication of AFLP.
• Explain the management of AFLP.
• Describe eclampsia , hyperemesis graviderum and
HELLP in relation with jaundice.
45. Acute fatty liver of pregnancy
• AFLP is a form of microvesicular fatty liver disease
unique to human gestation that presents late in
pregnancy, often as fulminant hepatic failure with
sudden onset of coagulopathy and encephalopathy
in a woman without a prior history of liver disease .
• it is also known as Acute Yellow atrophy/ Acute Fatty
• Acute fatty liver of pregnancy (AFLP) is a serious
complication unique to pregnancy first described by
Sheehan in 1940. It is characterized by microvesicular
steatosis in the liver.
• It is a rare condition with an incidence of 5 in 100,000
pregnancies.Acute fatty liver of pregnancy (AFLP)
tends to occur in late pregnancy.
• AFLP is diagnosed in approximately 1 of 10,000
pregnancies / third trimester.
• Maternal mortality 10-15%
• Perinatal mortality 15-20%
• The exact pathophysiology of AFLP is unknown. AFLP is
unique to pregnancy.
• It appears to occur more commonly in primiparous
women than multiparous women.
• Women who develop AFLP are more likely to have a long-
chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD)
•LCHAD is found on the mitochondrial membrane
and is involved in the beta oxidation of long-chain
• This gene mutation is recessive; therefore, outside
of pregnancy under normal physiological conditions,
women have normal fatty acid oxidation.
•However, if the fetus is homozygous for this
mutation, it will be unable to oxidize fatty acids.
•These acids are passed to the mother, who,
because of diminished enzyme function, cannot
metabolize the additional fatty acids.
•This results in hepatic strain leading to the
development of AFLP, which can be relieved by
delivery of the infant.
•Associated with inherited mitochondrial abnormalities of
beta oxidation of fatty acid .
•Genetic mutations .
The most common are the G1528C( and E474Q mutations
of the gene on chromosome 2 that code for long chain-3-
54. CLINICAL PRESENTATION
•Rarely may present after delivery.
•Severe nausea , repeated vomiting and upper
•Leukocytosis and thrombocytopenia are common.
• Fragmented RBC are seen in those with disseminated
• Have signs of co existent preeclampsia (50%)
• In severe cases progression over hours or days to
fulminant hepatic failure and death.
•The condition is diagnosed by the clinical picture.
•The women’s liver is tender but no enlarged and USG and
CT demonstrate the fatty infiltration.
•The liver enzyme is moderately high and women will
quickly show the sign of renal failure and become
• Liver function test.
• Raised serum bilirubin.
• Abnormal clotting with coagulopathy (prolongation of
prothrombin and partial thromboplastin times with
depression of fibrinogen levels).
• Liver biopsy is strongly contraindicated.
59. Fetal risk
• Intrauterine fetal death with a perinatal
mortality rate of 15-65%
• Neonatal risks include transient derangement
in LFT ‘s and hypoglycemia
AFLP is a life-threatening condition with a reported
1.8% maternal and 23% fetal mortality rate.Serious
• Disseminated intravascular coagulation (DIC ) and
• Hepatic coma.
• Acute kidney injury.
• If previous AFLP , check baseline LFT.advice to report
any new symptoms.
• Start home testing for urinary protein from 24 week of
• Monitor BP every two weeks.
• Proper stablish diagnosis.
63. LABOUR AND DELIVERY
•Maternal resuscitation by correction of hypoglycemia,
fluid balance and coagulopathy.
•Use multidisciplinary approach ideally in liaison with liver
unit to manage liver failure.
•Use intensive fetal monitoring.
•Perform urgent delivery when maternal condition is
stabilized, vaginal delivery preferable for mother.
•Maintain meticulous hemostasis.
• Continue intensive care management.
• Watch for postpartum wound hematoma formation
• Alert for possible PPH.
• Recurrence risk is difficult to estimate, perhaps as high
as 10% to 20%.
• Support contraceptive measure.
• Full hepatic recovery expected without further sequel
.occasionally emergency liver transplant needed.
•Pediatricians to consider screening baby for LCHAD
• Prenatal diagnosis of LCHAD possible by amniocentesis if
previous baby affected.
66. HYPEREMESIS GRAVIDARUM
Hyperemesis gravidarum (HG) is defined as
intractable nausea and vomiting during
pregnancy that often leads to fluid and
electrolyte imbalance, weight loss of 5% or
greater, and nutritional deficiency requiring
hospital admission .
• Liver involvement is seen in about 50%-60% of patients
with HG .
• Most commonly seen are mild serum
aminotransferases elevations, but there are reported
cases of severe transaminase elevations (alanine
aminotransferase (ALT) levels 400 to over 1000 U/L).
• Mild hyperbilirubinemia with mild jaundice can be seen
Preeclampsia defined by the triad of hypertension,
edema, and proteinuria. It affects about 5%-10% of
all pregnant women and usually occurs late in the
second trimester or in the third trimester.
Abnormal laboratory values include a 10- to 20-fold
elevation in aminotransferases, elevations in alkaline
phosphatase levels that exceed those normally observed
in pregnancy, and bilirubin elevations of less than 5 mg/dL
Liver histology generally shows hepatic sinusoidal
deposition of fibrin along with periportal
hemorrhage, liver cell necrosis, and in severe cases,
infarction; these changes are likely due to
vasoconstriction of hepatic vasculature
71. HEMOLYSIS, ELEVATED LIVER TESTS AND LOW
HELLP syndrome is a multisystemic disorder of
pregnancy involving hemolysis, elevated liver tests, and
low platelets. About 70% of cases occur antenatally,
during the last trimester of pregnancy
A dehydrogenase (LCHAD) has also been described,
suggesting a possible overlap of HELLP syndrome and
acute fatty liver of pregnancy. Laboratory findings
include hemolysis with increased bilirubin levels
(usually less than 5 mg/ dL)