Medical education

Lessons from practice

Jaundice and pregnancy

Clinical record
1  Pertinent blood test results on initial presentation
A 25-­year-­old woman presented with jaundice, vomiting Reference
and weight loss. She was 13 weeks’ pregnant (gravida Test Result range
2, para 1) and had lost 20 kg (from 85 kg to 65 kg) over
Haemoglobin, g/L 146 115–155
the course of the pregnancy. She had first noticed
the jaundice 3 weeks earlier. She denied abdominal
9
Platelet count, × 10 /L 285 150–400
pain and pruritus. In a previous pregnancy she had Total bilirubin, μmol/L 135 < 20
hyperemesis gravidarum and lost 30 kg during the
Conjugated bilirubin, μmol/L 71 < 4
first trimester. She denied any other medical history.
She was taking ondansetron as required for her nausea Alkaline phosphatase (ALP), 86 30–110
but denied taking any other medications, herbal U/L
remedies or over-­the-­counter products. She did not γ-­Glutamyl transferase (GGT), 64 < 38
drink alcohol. Her vital signs at presentation were: U/L
blood pressure in the sitting position 109/70 mmHg,
Alanine aminotransferase 727 < 34
blood pressure in the standing position 90/68 mmHg, (ALT), U/L
respiratory rate 18 breaths per minute and oxygen
Aspartate aminotransferase 197 < 31
saturation 98%, and she was afebrile. She was clinically
(AST), U/L
dehydrated, as evidenced by postural hypotension
and dry mucous membranes, which was further Sodium, mmol/L 126 135–145
supported by ketones present on bedside urinalysis. Potassium, mmol/L 2.8 3.5–5.2
She was visually jaundiced but, notably, her abdomen
was soft and non-­tender, and there was no evidence of
hepatosplenomegaly or peripheral stigmata of chronic
liver disease. Pertinent blood test results are shown in
Box 1. phosphatase 63 U/L (RR, 30–110 U/L). Blood tests
repeated one month later had normalised.
A viral, autoimmune, thyroid, coeliac and haemolysis
screen was unremarkable (Box 2).
Discussion
An abdominal ultrasound showed that the gallbladder
was filled with thick, immobile and echogenic Pregnancy-­related liver disease tends to be reserved
sludge (Box 3, arrow). There was no evidence of acute for patients after 20 weeks’ gestation. These disorders
cholecystitis or biliary duct dilatation. can be life-­threating if not identified and managed
correctly. They include acute fatty liver of pregnancy,
Her liver dysfunction was suspected to be related to
pre-­eclampsia, HELLP (haemolysis, elevated liver
hyperemesis gravidarum and she was managed with
enzymes and low platelet count) syndrome, and
antiemetics, rehydration, correction of electrolyte
cholestasis of pregnancy. During the first trimester,
abnormalities and supplemental nasogastric feeding
few pregnancy-­related liver conditions exist, but one
under the supervision of a dietitian. Follow-­up in
well described is related to hyperemesis gravidarum.
hepatology clinic a week later revealed that she
was gaining weight and her nausea was controlled. Hyperemesis gravidarum is characterised by nausea,
Her blood test results showed bilirubin 26 μmol/L vomiting and typically mild to moderate elevations
(reference range [RR], < 20 μmol/L), alanine in serum aminotransferases and bilirubin. It usually
aminotransferase 109 U/L (RR, < 34 U/L), aspartate manifests in the first trimester and abates by 20
aminotransferase 40 U/L (RR, < 31 U/L), γ-­glutamyl weeks’ gestation. If left untreated, complications of
transferase 31 U/L (RR, < 38 U/L), and alkaline micronutrient deficiency (Wernicke encephalopathy
Anthony M from vitamin B1 deficiency, bleeding from vitamin
Whitfield
Lessons from practice K deficiency), dehydration (renal injury, electrolyte
Ai Van B Tran disturbance) and malnutrition (immunosuppression,
Nguyen • Few pregnancy-related liver conditions exist in the first
muscle wasting) may manifest.
­trimester but hyperemesis gravidarum is an important one.
Kashif Sheikh
• Elevations in bilirubin and aminotransferases are typically mild The pathophysiology of jaundice in hyperemesis
to moderate but can also be severe. gravidarum is not well understood. The condition
MJA 2019

Gold Coast University

Hospital, Gold Coast, • When approaching jaundice in pregnancy, it is important not produces a state of ketosis that is known to cause
to overlook non-pregnancy causes such as viral infections,
QLD. slowing of biliary drainage, which is thought to be
alcohol and drug use, and biliary pathology.
in part related to the contraction of the sphincter
Anth.Whitfield@
gmail.com • Outcomes are generally favourable if managed appropriately
of Oddi. Pregnancy itself results in delayed gastric
for both mother and offspring, but recurrence in subsequent
pregnancies is likely. ◆ emptying, which promotes cholestasis. Histology 1
doi: 10.5694/mja2.50057 typically shows evidence of cholestasis and the
 Medical education

2  Laboratory tests to be requested when investigating jaundice in pregnancy

Investigation Rationale

Non-­pregnancy-­related tests

Pre-­hepatic causes

Reticulocyte count, haptoglobin, haemoglobin Evaluate for haemolytic anaemia

Hepatic causes

CMV IgM and EBV IgM Exclude acute cytomegalovirus and Epstein–Barr virus, respectively

HAV IgM Exclude acute hepatitis A

HBsAg, HBc IgM Exclude active/chronic hepatitis B

HCV antibody Exclude chronic hepatitis C

ANA Often elevated in cases of autoimmune liver disease, SLE

Antismooth-­muscle antibody and anti-­LKM Presence raises suspicion of autoimmune hepatitis

antibodies

Antimitochondrial antibody If present, suggestive of primary biliary cholangitis

Immunoglobulins Total IgG often elevated in the setting of autoimmune hepatitis

Anti-­tTG IgA Exclude coeliac disease, which can manifest as weight loss and rarely cause
liver dysfunction

TFTs Exclude thyrotoxicosis or hypothyroidism, which can rarely cause liver disease

Cu/Ceruloplasmin Evaluate for evidence of Wilson disease if the patient has cirrhosis or there is
a high index of suspicion

α-­1-­Antitrypsin Deficiency can predispose to liver disease; consider if patient has cirrhosis or
family history of cirrhosis

Post-­hepatic causes

Abdomen ultrasound Evaluate for stones or biliary pathology

Lipase Evaluate for evidence of acute pancreatitis or biliary pathology

Pregnancy-­related (after 20 weeks’ gestation) tests

Bile acid salts Elevated in setting of cholestasis of pregnancy

Coagulation studies Disseminated intravascular coagulation in the third trimester may be part of
acute fatty liver of pregnancy. Assess synthetic function of liver

Reticulocyte count, haptoglobin, haemoglobin Haemolysis can be a feature of HELLP syndrome

ANA = antinuclear antibody. Anti-­L KM = anti-­liver/kidney microsomal antibody. Anti-­tTg IgA = antitissue transglutaminase IgA antibody. CMV = cytomegalovirus.
Cu = copper. EBV = Epstein–Barr virus. HAV = hepatitis A virus. HBc = hepatitis B virus core antibody. HBsAg = hepatitis B surface antigen. HCV = hepatitis C virus.
HELLP = haemolysis, elevated liver enzymes and low platelet count. SLE = systemic lupus erythematosus. TFTs = thyroid function tests. ◆

occasional necrotic hepatocyte.1 More recently,

3  Abdominal ultrasound showing the gallbladder filled with an association has been described between
thick, immobile and echogenic sludge (arrow) jaundice in hyperemesis gravidarum and the
presence of biliary sludge, as evident in our
case.2 Formation of biliary sludge has been
hypothesised to result from a combination of
the above described mechanisms, with the
addition of dehydration. Intermittent movement
of sludge within the biliary tree causing
blockage of bile flow is a possible mechanism
contributing to jaundice formation.
Management includes fluids to restore
MJA 2019

euvolaemia, replacement of electrolytes,

supplemental nutrition (enteral and, in severe
intractable cases, parenteral) and antiemetics.
Medications need to be safe for mother and
fetus, and typically ondansetron intravenously
2 followed by glucocorticoid therapy are

indicated for intractable cases. Outcomes tend to be
favourable for both mother and fetus when patients
are managed promptly.3 Recurrence in subsequent
pregnancies is common and, as such, patients should
be closely monitored to allow early intervention in
future pregnancies.
When approaching jaundice in pregnancy, it is
important not to overlook exacerbation of existing liver
diseases and common causes for liver injury, including
viral infections, alcohol, drugs (most commonly
antibiotics such as erythromycin, amoxicillin or
Medical education
clavulanic acid), toxins, and biliary pathology. It is
important to be systematic and consider pre-­hepatic
(haemolytic anaemia), hepatic (intrinsic liver disease)
and post-­hepatic (stones, biliary pathology) causes in
addition to pregnancy-­specific liver conditions.
Competing interests: No relevant disclosures.
Provenance: Not commissioned; externally peer reviewed. ■
© 2019 AMPCo Pty Ltd
References are available online.
MJA 2019
3
 Medical education
1 Larrey D, Rueff B, Feldmann, et al.
Recurrent jaundice caused by recurrent
hyperemesis gravidarum. Gut 1984; 25:
1414–1415.
MJA 2019
2 Matsubara S, Kuwata T, Kamozawa C, et
al. Connection between hyperemesis grav-
idarum, jaundice or liver dysfunction, and
biliary sludge. J Obstet Gynaecol Res 2012;
38: 446–448.
3 Nulman I, Rovet J, Barrera M, et at.
Long-­term neurodevelopment of children
exposed to maternal nausea and vomiting
of pregnancy and diclectin. J Pediatr 2009;
2: 45–50. ■

3.e1
4