Case 24 A 29-year-old woman woman with vomiting in early pregnancy

 Case 24 A 29-year-old woman with vomiting in

early pregnancy

Mrs Begum, a 29-year-old para 1, is referred to the

assessment unit at the maternity hospital by her GP on

account of persistent vomiting. She is approximately 7

weeks pregnant by dates, has been unable to keep anything

down because of ongoing vomiting. She feels exhausted

and unable to cope.

What differential diagnosis comes to

your mind?

• Hyperemesis gravidarum

• Gastritis/gastroenteritis

• Urinary tract infection

• Other rare causes of vomiting, e.g. thyrotoxicosis, pancreatitis, Addison ’ s disease, cholecystitis, hepatitis

Obstetric history

Details of previous pregnancy including a history of

hyperemesis.

Past medical history including allergies

Any medical problems, e.g. pancreatitis, Addison ’ s

disease, hyperthyroidism

Family history

• Anybody else in the family with similar symptoms

• Is there a history of twins in the family?

Mrs Begum states that her nausea and vomiting started a

week ago and has been getting progressively worse .She

now feels sick all the time, is unable to keep any food

down. She vomits small amounts approximately 10–12 times

a day. She also admits to having some heartburn but denies

any abdominal pain, diarrhoea or urinary symptoms. She has

been feeling low and is unable to cope any more.

She has had one pregnancy in the past and her daughter,

Ayesha, is now 2 years old. She has a history of two

admissions early in her first pregnancy with intractable

vomiting requiring intravenous fluids and antiemetics.

She gives no history of medical problems or allergies. She

has non-identical twin brothers and reports that no one else

in the family has experienced similar symptoms

Obstetrics and Gynaecology: Clinical Cases Uncovered.

By M. Cruickshank and A. Shetty. Published 2009 by Blackwell

Publishing. ISBN 978-1-4051-8671-1.

KEY POINT

Hyperemesis gravidarum (HG) is defined as persistent

vomiting in pregnancy, which leads to weight loss (>5%

body mass) and ketosis. Although over 50% of pregnant

women experience nausea and vomiting, HG affects 1%

of pregnancies.

What would you like to elicit from the

history?

Presenting complaints

• Duration, frequency and amount of vomiting

• Any heartburn, abdominal pain or diarrhoea

• Any urinary symptoms

• Mood changes

KEY POINT

Hyperemesis gravidarum: onset is always in first trimester,

commonly around 6–8 weeks.

What key features would you look for

during physical examination?

General examination

• Signs of dehydration, e.g. dry skin and mouth,

decreased skin turgor154 Part 2: Cases

PART 2: CASES

• Pulse, blood pressure and temperature recording:

tachycardia and postural hypotension suggest

dehydration

• Assess mood – e.g. unkempt appearance, tearfulness

Routine systemic examination

To assess general health and exclude medical problems.

Mrs Begum is very tearful during the consultation. She

appears tired and run down but not in any pain. Her skin

and lips appear dry and there is tenting of her skin. Her

pulse is 98 beats/minute, of low volume and she appears to

have postural hypotension as indicated by lying and standing

blood pressures. These vital parameters indicate that she is

moderately dehydrated (Table 24.1). Systemic examination is

unremarkable.

What would be the next step?

Obtain a sample of urine for dipstick analysis and urine

pregnancy test

• Confirm pregnancy

• Increased specific gravity (dehydration)

• Presence of ketones (dehydration)

• Presence of nitrites/leucocytes/blood (may suggest

urinary infection)

What investigations would you like to

carry out?

Blood tests

• Full blood count (FBC): an increased haematocrit suggests haemoconcentration

• Urea and electrolytes (U & E): to look for hyponatraemia, hypokalaemia, low serum urea, hypochloraemic

alkalosis

• Liver function test (LFT): LFTs are abnormal in up to

50% of women with HG

• Thyroid function test (TFT): there may be transient

biochemical hyperthyroidism (Box 24.1 ). Resolves

without treatment by 18 weeks

Mid-stream sample of urine (MSSU)

To exclude urinary tract infection.

Pelvic ultrasound

• Confirms viability of the pregnancy

• Diagnoses twin gestation

• Excludes molar pregnancy

Mrs Begum is not anaemic but has a raised haematocrit

along with hyponatraemia and hypokalaemia. Her LFTs and

TFTs are within the normal range. A urine dipstick shows the

presence of +++ ketones but is negative for nitrites,

leucocytes and blood. The clinical features along with

ketonuria and high urine specific gravity confirm

dehydration. A pelvic ultrasound scan shows a dichorionic

twin pregnancy of 7 weeks’ gestation.

Table 24.1 Clinical signs of dehydration.

Dehydration Mild Moderate Severe

Skin turgor Normal Dry Clammy

Buccal

mucosa/lips

Moist Dry Parched/

cracked

Pulse Regular Slightly increased Increased, low

volume

Urine output Normal Decreased Anuric

Box 24.1 Gestational hyperthyroidism

• Biochemical hyperthyroidism found in approximately

60% women with HG

• Self-limiting

• Patient clinically euthyroid

• Findings: ↑ free thyroxine (T4), ↓ thyroid stimulating

hormone (TSH), negative thyroid antibodies

• Mechanism:

• human chorionic gonadotrophin (HCG) shares α subunit

with TSH

• increased secretion of HCG/HCG oversensitive

thyrotrophin receptors/secretion of variant of HCG

• Thyroid function tests provide an index of severity of HG

• More common in Asian women

• Rarely, Graves disease may present in pregnancy. The

absence of TSH receptor, antiperoxidase, and

antithyroglobulin autoantibodies supports the diagnosis

of HG

KEY POINT

Hyperemesis gravidarum is a diagnosis of exclusion. There

is no single confirmatory test.

Thus, by a focused history, thorough clinical examination

and relevant investigations other causes of vomiting are

excluded. We can conclude that the likely diagnosis in Mrs

Begum’s case is that of hyperemesis gravidarum (Box 24.2).Case 24 155

PART 2: CASES

The diagnosis is explained to Mrs Begum, who is very

anxious, as her symptoms are much worse in her present

pregnancy. She wonders if it could lead to any harm to

herself or to her babies.

What are the complications associated

with hyperemesis gravidarum?

Maternal complications of hyperemesis

gravidarum

• Can lead to serious morbidity

• Mallory – Weiss tears of oesophagus and haematemesis

because of persistent vomiting and retching

• Malnutrition

• Weight loss (up to10 – 20% of body mass), muscle

wasting, weakness

• Hyponatraemia (plasma sodium <120 mmol/L):

 can cause lethargy, seizures and respiratory arrest

 severe hyponatraemia and its rapid correction can

precipitate central pontine myelinolysis

• Vitamin deficiency:

 thiamine (B1) – acute deficiency causes Wernicke ’ s

encephalopathy (Box 24.3 ) Residual impairment leads

to Koraskoff ’ s psychosis

 vitamin B12 and pyridoxine (B6) – anaemia and

neuropathy

• Thrombosis: the combination of dehydration and bed

rest increase the risk of thrombosis

• Psychological problems: these are often

underestimated

Fetal complications of hyperemesis gravidarum

• Severe HG is associated with low birth weight babies

• HG leading to Wernicke ’ s encephalopathy is associated with fetal death in 40% of cases

How will you manage this woman, who

has been diagnosed with hyperemesis

at 7 weeks’ gestation?

Box 24.2 Pathophysiology of hyperemesis

gravidarum

• Poorly understood, multifactorial

• Temporal relationship exists between level of human

chorionic gonadotrophin (HCG) and severity of

symptoms

• HCG peaks between 6 and 12 weeks coinciding with

peak symptomatology

• Correlation with high HCG levels explains the increased

incidence of HG in women with multiple pregnancy and

hydatiform mole, both conditions associated with very

high HCG levels

• Mechanical factors, e.g. decreased peristalsis and

delayed gastric emptying, exacerbate the symptoms, but

are not thought to be causative

• Psychological and behavioural theories exist but are not

proven

• Risk factors: multiparity, past history of HG and eating

disorder, multiple gestation, hydatiform mole

• Cigarette smoking and maternal age >30 years appear

to be protective

• Evidence suggests infection with Helicobacter pylori may

have a role

Box 24.3 Wernicke’s encephalopathy

• Syndrome characterized by diplopic abnormal ocular

movements, ataxia and confusion

• Precipitated by administration of IV dextrose/glucose in

thiamine deficiency

• Residual impairment is common despite replacement

• Koraskoff’s psychosis is characterized by amnesia,

impaired ability to learn and confabulation (invented

memories which are then taken as true because of gaps

in the memory)

KEY POINT

Hyperemesis is a leading cause of hospitalization in early

pregnancy.

Rehydration

Appropriate and adequate parentral fluid along with

electrolyte replacement forms the mainstay of treatment.

Rehydration with normal saline (0.9% saline, 150 mmol/L

sodium) or Hartman ’ s solution (0.6% saline, 132 mmol/L

!RED FLAG

Management should be early and aggressive in view of

increased risk of complications for mother and her fetus in

the absence of treatment.

If tolerating orally the management includes rest, small

but frequent carbohydrate meals along with adequate

fluids orally. However, if she is unable to maintain hydration she should be admitted to hospital.156 Part 2: Cases

PART 2: CASES

sodium) is recommended. Add potassium chloride to

fluid bags as directed by electrolyte levels. Check U & E

daily while on intravenous fluids.

The patient should be weighed twice weekly for objective assessment of dehydration. Continue treatment until

the patient can tolerate oral fluids and until test results

show little or no ketones in the urine.

Thiamine (vitamin B1) supplementation

Thiamine deficiency leads to Wernicke ’ s encephalopathy.

Thiamine supplementation is recommended in HG. If

the patient is unable to tolerate this orally thiamine is

administered as an infusion once a week.

Thromboprophylaxis

Table 24.2 Antiemetic agents.

Antihistamines Cyclizine H1 receptor antagonist

Promethazine Commonly used

Good safety profile

Phenothiazines Cholpromazine Side-effects: drowsiness,

extrapyramidal effects,

Prochlorperazine oculogyric crisis

Dopamine

antagonist

Metclopramide Promotility agents

Domperidone Oculogyric crisis and

extrapyramidal effects

Selective

serotonin

(5-HT3)

antagonist

Ondansetron Used for refractory HG

Limited safety data

Routine use not

recommended

!RED FLAG

An infusion of dextrose-containing fluid can precipitate

Wernicke’s encephalopathy and is not recommended.

Double strength saline should be avoided as rapid

correction of hyponatraemia can cause central pontine

myelinolysis.

Antiemetics

Antiemetics are recommended if rehydration and electrolyte replacement fail to improve the symptoms. Antiemetics should be prescribed on regular basis rather than as

required. The intravenous or rectal route can be used

initially and changed to oral route when tolerating orally

(Table 24.2 ).

KEY POINT

The commonly used antiemetics, e.g. antihistamines,

phenothiazines and dopamine antagonists, are not known

to be associated with teratogenesis.

!RED FLAG

Dehydration, bed rest and reduced mobility and pregnancy

are risk factors for thrombosis.

Women requiring hospitalization with HG should receive

thromboprophylaxis. Prophylactic doses of low molecular weight heparin along with thromboembolic deterrent

stockings (TEDS) should be used.

Psychological support

Emotional support from the medical team and the family

aid the medical treatment. Psychotherapy, hypnotherapy

and behavioural therapy have been reported to be of

benefit.

Alternative therapies

Pyridoxine (vitamin B6) has been reported to reduce the

severity of nausea. Ginger, available as capsules, is helpful

with nausea and vomiting with no apparent side - effects.

Acupuncture is thought to reduce the symptoms and

encourages weight gain.

Mrs Begum is commenced on 0.9% saline IV along with

prochlorperazine (Stemetil) IM on a regular basis. She is

given thromboprophylaxis in the form of low molecular

weight heparin and TEDS. Her fluid therapy is monitored

with daily U&E and urinary ketones. Thiamine is prescribed

as a weekly infusion.

After 72 hours of aggressive fluid and regular antiemetic

therapy Mrs Begum’s condition shows marked improvement.

Her symptoms settle and her urine is negative for ketones.

She is commenced on oral antiemetics along with small

frequent meals, which she tolerates well. She is keen to go

home, as she feels much better. She is therefore discharged

home with dietary advice on antiemetic therapy.

However, over the course of next few weeks she has

several admissions with similar symptoms, which appear not

to respond to conventional therapy. The doctor tells her she

has ‘refractory hyperemesis’.Case 24 157

PART 2: CASES

What would be the next step?

Ondensetron

This strong antiemetic is mostly used to treat nausea and

vomiting postoperatively and following chemotherapy. It

is an option for managing refractory HG. There are

limited data on its safety in pregnancy.

Corticosteroids

Steroid therapy reported to be of benefit with dramatic

improvement of symptoms with a significant reduction

in readmission rates. Hydrocortisone IV followed by oral

prednisolone are the preferred preparations. Dosage is

gradually reduced to a maintenance dose of 5 – 10 mg/day

by 20 weeks. No adverse fetal effects have been reported.

Total parentral nutrition and enteral feeding

This is expensive but can be life - saving in severe cases.

Total parenteral nutrition (TPN) requires monitoring

and protocol as can lead to infectious and metabolic

complications.

Mrs Begum’s consultant suggests a trial of ondensetron and

steroids, to which she responds dramatically. She is

eventually discharged home a week later on oral steroids

with a follow-up plan. Her steroid dose is gradually reduced

to a maintenance dose by 16 weeks’ gestation and

eventually stopped at 23 weeks.

The rest of her pregnancy was uneventful and she

delivered the twins spontaneously at 37 weeks. The babies

had normal Apgar scores and birth weights. She was

advised that her symptoms could recur in subsequent

pregnancies.

KEY POINT

• HG refractory to conventional therapy is a difficult

condition to treat

• Refractory HG is associated with multiple hospital

admissions and psychological morbidity

• Women may request termination of pregnancy in

extreme cases

CASE REVIEW

This 29 - year - old para 1 presented with vomiting and dehydration in early pregnancy. After excluding the other causes

of vomiting the diagnosis was that of HG. The mainstay of

management of this condition is rehydration by means of

intravenous fluids containing adequate sodium and potassium along with regular antiemetics. HG is associated with

increased risk of venous thrombosis, therefore thromboprophylaxis is recommended. Thiamine is prescribed to

prevent Wernicke ’ s encephalopathy.

Mrs Begum responded well to conventional treatment;

however, she experienced recurrence of her symptoms,

which were refractory to hydration and antiemetics. She

responded well to ondensetron and corticosteroids, drugs

reserved for refractory HG. Corticosteroids were stopped

at 23 weeks after a gradual dosage reduction.

The twins born at 37 weeks gestation, were of normal

weight and did not require admission to neonatal unit.

Thus, with appropriate management there was no evidence

of long - term effects of hyperemesis or its treatment for the

mother and her babies. In view of her history, Mrs Begum

was counselled about the risk of recurrence of symptoms

in subsequent pregnancies.

KEY POINTS

• HG is a diagnosis of exclusion

• Onset is usually around 6–8 weeks’ gestation

• Transient but self-limiting hyperthyroidism may occur in up

to 60% of cases

• Early, aggressive and appropriate fluid and electrolyte

replacement is the mainstay of management

• Antiemetics should be prescribed on a regular basis

• Common antiemetics are not teratogenic

• Thromboprophylaxis and thiamine replacement are

important components of management

• Serious complications are rare

• Ondensetron and short-term corticosteroids have a role

in managing refractory HG158 Part 2: Cases

PART 2: CASES

Further reading

Kuscu NK , Koyuncu F . Hyperemesis gravidarum: current concepts and management . Postgrad Med J 2002 ; 78 : 76 – 79 .

Neill AM , Nelson - Piercy C . Hyperemesis gravidarum review .

The Obstetrician and Gynaecologist 2003 ; 5 : 204 – 207 .