Post graduation IGMC shimla

1. Jaundice in pregnancy
Moderator -Dr.Meenakshi Kandoria
Presented by-Dr.Asha choudhary

2. Jaundice is hyperbilirubinemia that causes visible
yellowish discolouration of body tissues like
skin,mucous membrane and sclera[icterus].
When serum bilirubin level exceeds 2mg%[normal
range is 0.2 to 1.2mg%]
Overall incidence in India is 1 to 4 per 1000
deliveries.
Causes of jaundice in pregnancy are grouped as-

3. Specific to pregnancy Coincidental to
pregnancy
When pregnancy is
superimposed to
chronic liver disease
• ICP[obstetric
hepatosis]
Viral hepatitis:A-E,G Chronic hepatitis
• Severe pre
eclampsia,eclampsia,H
ELLP syndrome
Gallstone-obstructive
jaundice
Cirrhosis
• AFLP Drug induced-
isoniazid,phenothiazines
tumors
• Severe hyperemesis
graviderum
Hemolytic jaundice-
mismatched
BT,malaria,c.welchii
infection
• Endotoxic shock-DIC

4. Pregnancy induced physiological changes in liver :
• Size of liver remains normal .
• All liver enzymes decrease in pregnancy except :
serum alkaline phosphatase-increase
• Total alkaline phosphatase activity almost
doubles,but much of rise is attributable to heat
stable placental alkaline phosphatase isozymes.

5. Bilirubin metabolism

7. Intra hepatic cholestasis of pregnancy
Also k/a recurrent jaundice of pregnancy,cholestatic
hepatosis,icterus gravidarum[earlier].
ICP is the second most comman cause of jaundice in
pregnancy[in India],the first one being viral hepatitis.
Overall incidence is 0.2 -2% of pregnant women worldwide.
Associations are- more comman in multifetal pregnancy.
-women treated with vaginal progesterone
for preterm labor prophylaxis showed
increased ICP rate[x4 fold].
-changes diappear after delivery but often
recur in subsequent pregnancies or with
estrogen containing contraceptives.

8. Pathogenesis:
The cause of ICP is unclear ,but changes in various sex
steroid hormones level are implicated.
The stasis of bile in the bile canaliculi with rise in conjugated
bilirubin is probably due to excess circulating
estrogen,similar manifestation is also observed in women
taking contraceptive pills.
Genetic ,familial,and abnormal progesterone metabolism
have been observed.
Mutations in various genes that control hepatocellular
transport systems
-mutation in ABCB4 gene ,which
encodes MDR3 protein associated with

9. .
progressive familial intrahepatic cholestasis.
-mutation in ABCB11 gene,which encodes a bile salt
export pump.
-ATP8B1 gene encodes farnesoid X receptor and
transporting ATPase[drug induced cholestatic
jaundice in gravidas taking azathioprine following
renal transplantation].
 Following the inciting causes , bile acids[cholic and
chenodeoxycholic acid] are incompletely cleared and
accumulate in plasma and underneath the skin.
 Hyperbilirubinemia is due to retention of conjugated
bilirubin ,but total plasma conc.rarely exceed 4 to 5mg/dl
[jaundice rarely develops].

10.  ALP elevated
 AST & ALT levels normal to moderately elevated but seldum
exceed 200 U/L.
 Total serum bile acids raised [best investigation]
 Recurrence is comman[50 -60%].
 On liver biopsy –cholestasis
-no liver necrosis
-no liver inflamation

11. Clinical presentation:
ICP typically presents after 28 weeks of gestation.
Elevated total serum bile acid or transaminase levels plus
pruritis supports an ICP diagnosis.
Generalised pruritis that shows predilection for the palms
and soles.
Constitutional symptoms are absent ,and skin changes are
limited to excoriations from scratching[no rash].
Jaundice rarely.[10% cases].
The features subsides within 2wks postpartum.

12. INVESTIGATIONS
CHG
Viral markers
LFT’s
Serum bile acid [specific measure of the diagnosis and
monitoring]
Liver USG to exclude cholelithiasis.
Coagulation profile[PT]

13. Management
Antihistamines and topical emollients.
Ursodeoxycholic acid[UDCA]-preffered drug-oral dosing is
10-15mg/kg maternal body weight daily,which is divided
into two or three doses[available as 300mg capsules].
Cholestyramine [earlier].
Therapeutic plasma exchange .
Rifampin .

14. Perinatal outcomes:
Sudden Still births[fetal cardiotoxicity of bile acids].
Fetal distress.
Preterm births
Meconium stained liquor.
IOL-@37-38 wks of gestation.

15. Acute fatty liver of pregnancy[AFLP]
Uncomman but potentially fatal complication that occurs in third
trimester or early postpartum period.
Most frequent cause
of liver failure in
pregnancy.
Also k/a acute fatty
metamorphosis
or yellow atrophy of liver. .
 Accumulation of
microvesicular fat that
Literraly ‘crowds out’
normal hepatocytic
function.

16. .
Grossely liver is small,soft ,yellow and greasy.
Incidence 1per 10,000 births.
Recurrence rare.
a/w recessively inherited mitochondrial abnormality of fatty acid
oxidation
Missence mutation of the gene on chr. 2 that codes for
LCHAD enzyme that causes LCFA accumulation in fetus
[homogygous] ,that comes in maternal blood .
acute liver injury and endothelial cell activation.

17. endothelial cell activation
[leaky capillary endothelium]
haemoconcentration 3rd space accumulation of fluid
Renal failure decrease ascites and pulmonary oedema
uteroplacental
blood flow
fetal distress
fetal demise

18. Clinical findings:-
AFLP almost always manifests in the last trimester of the
pregnancy,mean gestational age of 37 weeks.
Persistant nausea and vomiting are major complaints.
Degree of malaise, anorexia, RUQ pain and progressive jaundice
vary.
In almost all sever cases ,acute liver injury causes profound
endothelial cell activation.
 Half of affected women have HTN,proteinuria,and oedema
alone or in combination,these signs also suggest
preeclampsia.[d/d pre–eclampsia].

19. Severe liver dysfunction
Hypo coagulopathy increased NH3, hypo
Albuminaemia Hypoglycaemia cholestrolemia
Ascites encephalopathy RBC memb.
damage
haemolysis

20. investigations
CHG & P/S:leukocytosis,neucleated red cells, mild to moderate
thrombocytopenia,echinocytosis, high or within normal
range of hematocrit,
LFT’S: s.bilirubin level <10 mg/dl,
s.transaminase levels are moderately elevated<1000U/L.
ALP raised.
all clotting factors decreased[hypofibrinogenenemia].
S.LDH: raised.
RFT’S: increased s.urea,uric acid,s.creatinine.
Coagulation profile: increased BT,CT,Prothrombin time.

21. D-dimer & FDP’S: elevated .
Coagulopathy: due to diminished hepatic procoagulant synthesis &
consumption coagulopathy.
Hepatoglobin: decreased .
Random blood sugar
urine routine & microscopy
viral markers
USG
Hypoglycemia & hypoalbuminemia & hepatic encephalopathy.

.

22. Swansea criteria for AFLP diagnosis: used as a screening tool &
predictor of severity,shows suitable sensitivity:-
Clinical features: vomiting,abdominal pain,enencepathy,
polydipsia/polyuria.
Lab.features: bilirubin>0.8 mg/dl, AKI or S.Cr.>1.7 mg/dl
glucose<72 mg/dl, ammonia>47 micromole/L
WBC>11000/microL, coagulopathy/PT>14 s
AST/ALT>42 U/L urea>340 microMOL/L
USG: ascites or echogenic liver .
Histologic features: microvesicular steatosis.
>= 6 features without another explanation supports a diagnosis
of AFLP.

23. AFLP Pre-eclampsia
hematocrit
Platelets count
Fibrinogen
PT
Normal
Normal [usually]
Hemolysis
Hyperammonemia
hypoglycemia
Marked
Favours the diagnosis
Mild

24. Management:
 Immediate concerns :
-asses for the severity of liver
dysfunction
-find out the cause
-Look out for associated
complications & signs of liver failure.
-close fetal survelliance.

25.  Delivery of the fetus is necessary in the treatment
of AFLP,& significant procrastination increases
maternal & fetal risks.
Immediate termination of pregnancy
mode of delivery -vaginal delivery if possible
within 24 hrs.
-LSCS after correction of
coagulation profile.

26. Recovery:
Hepatic function usually return to normal with in a week
postpartum,but in the interim,intensivee medical support
may be required.
 Complications seen in recovery phase are:
- transient dibetes insipidus.
[elevated vasopressinase]
-acute pancreatitis.

27. Viral hepatitis:
Most comman cause of jaundice in pregnancy in tropics.
Causes are : a]. Hepatitis viruses –hepatitis-A[RNA]
hepatitis-B[DNA]
hepatitis-C[RNA]
hepatitis-D[RNA]
hepatitis-E[RNA]
hepatitis-G[RNA]
b]. CMV virus
c]. Herpes simplex virus

28. These viruses themselves probably are not hepatotoxic
the immunological response to them causes hepatocellular
necrosis .
acute infections: most often sub clinical and anicteric.
when the are clinically apparent,nausea,
vomiting,headache & malaise may
precede jaundice by 1-2 weeks.
low grade fever more comman with
hepatitis -A

29. By the time jaundice develops,symptoms usually are improving.
 serum transaminase levels vary,there peaks do not corresponds with
disease severity ,peak levels[400-4000U/L] are usually reached by the
time jaundice develops.
serum bilirubin values typically continue to rise ,5-20mg/dl despite
falling serum transaminase levels.
 sever features are persistant nausea vomiting ,prolonged PT,
low serum albumin,hypoglycaemia,high serum bilirubin levels,
CNS symptoms.
In most cases clinical & biochemical recovery complete within
1-2 months in all cases of hepatitis –A,in most cases of hepatitis-B,
but in only a small proportion of those caused by hepatitis –C

30.  Acute hepatitis has a case fatality rate of 0.1 %.
Most fatalities are due to fulminant hepatic necrosis,
which in later pregnancy resembles,AFLP.
Hepatic encephalopathy is usual presentation .
Mortality rate is 80%.
50% of cases have hepatitis-B infection ,and co infection
with delta agent is comman.
Most comman cause of viral hepatitis in pregnancy
is Hep-B.
Most comman cause of acute viral hepatitis related
mortality in pregnancy is Hep-E.
 .

31. Hepatitis-A
 RNA picorna virus[ not teratogenic].
 feco-oral route-food/water.
 IP-around 4 weeks.
 lacks a chronic stage.
 nonspecific symptoms.
 early serological Ig M anti –HAV antibody.
 during convalescent,IgG antibody predominates.
 vactination-inactivated hepatitis viral vaccine.
 unvaccinated gravida recentaly exposed by close
personal/sexual contact –provide passive
immunization 0.1ml/kg Ig & concurrently the first
dose of hep-A vaccine series given in separate arm.
Mx-: balanced diet and diminished physical activity.

32. Hepatitis -B
Double standed DNA virus.[not teratogenic]
Onset-incidious/acute
HBV-carcinogenic-chronic infection is a known risk of HCC.
Transmittion:-parenteral route,sexual contact,shared contaminated
needles, blood & other body fluids,vertical transmission[10 % risk in
1st trimester & 90% in third trimester] it is specially high[90%] from
those mothers who are seropositive to HBsAg & HBeAg,neonatal
transmission at time of delivery,rarely by breast milk[ACOG do not
consider maternal HBV infection a c/I of breast feeding].
IP-: 40-150 days.
After acute hepatitis-90% of adults recover completely;
remaining considered to have chronic hepatitis B.

33. Diagnosis/Serology :-
HBsAg:first marker,preceds
the rise in transaminase.
Anti-HBs:last Ab to appear,marks
complete d’s resolution.
Found in vaccinated
individuals also.
HBcAg: not detactable in serum.
Anti-HBc: first Ab to appear,IgM &
IgG.
HBeAg:high viral replication/DNA
load.
Anti-HBe:Good prognosis[active viral replication
stopped.

34. Screening:- all pregnant women should be screend at first ANC
& it should be repeated during the 3rd trimester for
‘high risk’ groups.
Management: -To curb vertical transmission,newborn of seropositive
mothers are given hepatitis B immune globulin[HBIG]
plus the first of a three dose hepatitis B recombinant
vaccine series very soon after birth;has lowered the
transmission drastically & prevented around 90% of
infections.
But women with high HBV viral loads-10^6-10^8 copies/ml or those
who are HBeAg still have at least a 10% vertical transmission
rate,regardless of immunoprophylaxis; there is recommendation
antiviral therapy to decrease viral levels[tenofovir & telbivudine].

35. Thank you