Hyperemesis gravidarum - Clinical review

Differentiate HG from morning sickness. By Dr Ciaran Crowe

Hyponatraemia may be present (Photograph: Ian Hooton/Science Photo Library)
Hyponatraemia may be present (Photograph: Ian Hooton/Science Photo Library)

Section 1: Epidemiology and aetiology

Nausea and vomiting affects 70-85% of all gravid women during the early weeks of pregnancy and usually resolves by 16 weeks' gestation.1,2

The extreme end of this condition, hyperemesis gravidarum (HG), is a rare but severe form of intractable nausea and vomiting in pregnancy. This is differentiated from morning sickness because it may require hospital admission for specialist treatment of electrolyte imbalance, weight loss (of 5-10%) and eventually, malnutrition (table 1).

HG is estimated to affect up to 2% of pregnancies, but this is debatable because of its varying definitions and patients' varying tolerance of the symptoms. Although the peak incidence of HG occurs between the eighth and 12th week of pregnancy, it may persist, with symptoms severe enough to require hospital admission. Some studies suggest admission rates of 1%, with an average length of stay of 2.6 to four days.3

TABLE 1: MORNING SICKNESS OR HG?
Morning sickness Hyperemesis gravidarum
Little if any weight loss. Weight loss of 5-20lb or more (>5% of patient’s pre-pregnancy weight).
Nausea and vomiting do not interfere with the ability to eat or drink enough each day.  Nausea and vomiting cause reduced food intake. Dehydration from vomiting can occur if not treated.
Vomiting is infrequent. Nausea is episodic but not severe and may cause discomfort.    Vomiting often, possibly with bile or blood if not treated. Nausea is usually moderate to severe and constant.
Dietary and/or lifestyle changes are enough to help most of the time. Fluid hydration through a vein and/or medication to stop the vomiting will be required.
Typically improvement is seen gradually after the first trimester, but nausea may remain at times for the duration of the pregnancy. Improvement usually seen by the middle of the pregnancy, but nausea and/or vomiting may continue until late pregnancy.
Patient is able to work most days and care for family.   Patient is likely to be unable to work for weeks or months, and may need help caring for herself.
Source: www.helpher.org

Risk factors

The risk of HG decreases with rising maternal age, particularly over 30 years old. HG is associated with a strong family history. Other risk factors include low BMI, non-white ethnicity, a history of HG in previous pregnancies, migraine, hyperthyroidism, GI disorders, motion sickness and pregestational diabetes.4

Vitamin intake, beginning early in pregnancy, appears to be protective. Smoking also appears to be protective, but is clearly to be discouraged due to its potential harmful effects.5

Untreated HG can result in Wernicke's encephalopathy, central pontine myelinolysis and maternal death.6 It is also associated with higher rates of intrauterine growth restriction and lower birthweight.7

Pathophysiology
The pathophysiology of HG remains poorly understood. Several theories have been advanced, with the general consensus being that it may relate to the high levels of hCG and estradiol in the blood during pregnancy.

The peak level of hormones and HG have a correlation. Conditions such as hydatidiform moles are strongly associated with HG. Women with HG give birth to a higher proportion of female infants and have a higher rate of multiple pregnancies.8

Section 2: Making the diagnosis

HG is a diagnosis of exclusion. If nausea and vomiting occur in early pregnancy and are not responsive to simple measures, such as reassurance and dietary changes, HG should be suspected (table 2).

TABLE 2: POSSIBLE CAUSES TO EXCLUDE
  • UTI
  • Hepatitis
  • Miscarriage with associated choriamnionitis
  • Iron supplementation
  • Antibiotics
  • Appendicitis
  • Cholecystitis
  • Oesophageal pouch
  • Oesophageal stricture
  • Small bowel obstruction
  • Thyrotoxicosis
  • Hyperparathyroidism/hypercalcaemia
  • Diabetic ketoacidosis
  • Uraemia
  • Addison’s disease
  • Molar pregnancy
  • Gestational trophoblastic disease
  • Multiple pregnancy
  • Threatened miscarriage
  • Eating disorder
  • Psychosis

The onset of HG is always in the first trimester, so the onset of vomiting after nine weeks' gestation should prompt other causes to be investigated and excluded.

The patient may describe symptoms such as being unable to keep down any solids or liquids, ptyalism (inability to swallow saliva) and spitting (>60% of cases), and vomiting persisting throughout pregnancy.

Clinical features include signs of dehydration, tachycardia, postural hypotension, mood changes, insomnia, decreased concentration and feelings of anxiety and depression.6

Temperature, fever, rigors and onset of symptoms after 12 weeks should prompt the clinician to consider diagnoses other than HG.

Presenting complications
The most common complication is weight loss of up to 10%, associated with muscle wasting and constant lethargy. Persistent vomiting may result in a Mallory-Weiss tear in the oesophagus, causing the patient's first presenting symptom to be haematemesis. In this case, a gastric/duodenal ulcer should be excluded.

Malnutrition can result in thiamine (vitamin B1) deficiency, which may cause Wernicke's encephalopathy, characterised by nystagmus, diplopia, abnormal ocular movements, ataxia and confusion.

Hyponatraemia (plasma sodium <120mmol/L) causes lethargy, seizures and respiratory arrest. Severe hyponatraemia and its rapid reversal may precipitate central pontine myelinolysis.9 This condition is characterised by spastic quadriparesis, pseudobulbar palsy and impaired consciousness.

Other vitamin deficiencies in HG include B12 and B6, causing anaemia and peripheral neuropathy.

Investigations
Initial GP investigations include urine pregnancy beta hCG and urinalysis, looking particularly for increased specific gravity and significant ketonuria, usually 3+ ketones.

Urinalysis will also help to exclude UTI and other renal pathology.

A general inspection should include checking the patient's current weight against their booking weight or medical notes, checking for ketotic breath and noting if the patient appears lethargic and unwell.

Once the patient is referred to the specialist, a series of investigations will be performed to exclude other causes of her symptoms. These include:  

  • Sodium, potassium and urea (alternate days if on IV fluids)
  • LFTs, glucose (weekly)
  • TFTs and calcium if vomiting is persistent
  • FBC to exclude infection
  • Daily urinalysis to monitor change in ketotic state
  • MSU
  • Pelvic ultrasound to assess for multiple birth and exclude a hydatidiform mole or other gynaecological pathology causing vomiting and abdominal pain, for example, ovarian cyst

Section 3: Managing the condition

The mainstay of treatment is to correct hypovolaemia and prevent complications.

If mild or moderate with only some ketonuria, give dietary advice and do not rush oral intake. If sucking on ice cubes is tolerated, sips of flat carbonated drinks should be advised. If these are tolerated, carbohydrate meals should be eaten frequently in small portions when the symptoms are at their least prominent.

The patient should be told to start with a bland diet and avoid fatty/dairy foods and spicy or acidic foods. If these measures fail and symptoms worsen, more active treatment will be necessary (table 3).

Any woman who is heavily ketotic with continuing symptoms (dehydration) should be admitted to a specialist unit. Drugs that may cause nausea and vomiting should be temporarily discontinued.

Rehydration
Fluid replacement is as follows:

  • Normal daily requirement. Give 1L over six hours, another 1L over six hours, then eight-hourly.
  • Normal saline (with or without added potassium) or Hartmann's solution is the fluid of choice.
  • Do not give dextrose-containing fluids, which may precipitate encephalopathy and worsen hyponatraemia.
  • Ensure adequate electrolyte replacement: 40 mmol/L potassium is the normal daily requirement plus continuing loss by vomiting.
  • Double-strength saline solution should be avoided even in cases of severe hyponatraemia, because rapid correction of sodium depletion may cause central pontine myelinolysis.

Thiamine
Thiamine supplementation should be given if vomiting is prolonged. The daily requirement in pregnancy is 1.5mg.

  • Give thiamine hydrochloride tablets 25-50mg three times a day.
  • If the patient cannot tolerate the tablets, consider 100mg thiamine diluted in 100ml normal saline infused IV over one hour, or multivitamin injection IM.

Thromboprophylaxis
Any pregnant woman with dehydration and prolonged bed rest should receive thromboprophylaxis and wear compression stockings.

Reflux symptoms
Histamine receptor blockers (ranitidine) and the PPI omeprazole have been used successfully.

Severe HG management
If conventional management methods fail, this can result in significant psychological and physical morbidity. In these cases, corticosteroid treatment is instigated. The current regimen is hydrocortisone 100mg twice a day followed by 40mg prednisolone daily.10

The aim is to stop steroid treatment by 20 weeks. However, patients often require them beyond this, even for the duration of the pregnancy. This can have implications, including osteoporosis, hip necrosis, gestational diabetes and immunosuppression.

Long-term prednisolone use is not known to be associated with poor fetal outcome. If corticosteroids fail, a trial of total parenteral nutrition may be necessary.11 At all stages, patients need psychological support.

TABLE 3: ANTIEMETICS IN ORDER OF CHOICE
Medication  Dosage Route of administration
Cyclizine 50mg three times a day, oral Oral, IM or IV
Promethazine 25mg once a day at bedtime, oral Oral
Prochlorperazine 5mg three times a day, oral
12.5mg three times a day, rectal or IM
Oral
Rectal or IM
Metoclopramide 10mg three times a day, oral Oral, IM or subcutaneous
Domperidone 10mg four times a day, oral
30-60mg four times a day, rectal
Oral
Rectal
Chlorpromazine 10-25mg three times a day, oral
25mg three times a day, IM
Oral
IM

There is no evidence that these drugs are harmful in pregnancy

Ondansetron IV appears to be no better than promethazine IV

Section 4: Prognosis and follow-up

The outcome in the vast majority of cases is excellent, with most women making a full recovery by 20 weeks.

However, those with HG who gain less than 7kg throughout the pregnancy are more likely to give birth to low-birthweight infants and are thought to have an increased risk for preterm birth.12

After booking with the midwife, these patients should be referred early to the antenatal clinic and reviewed by a specialist.

The risk of experiencing HG in subsequent pregnancies is 16-19%, a rate 29 times higher than it is for a woman who has never experienced the condition.5

Section 5: Case study

A 32-year-old Bangladeshi woman who is 12 weeks pregnant has just booked with the midwife. This is the woman's first pregnancy.

She states that she has been nauseated and vomiting frequently throughout the day.

The midwife says it is morning sickness and gives her dietary advice, as well as telling her to avoid foods that worsen the symptoms.

Two weeks later the patient visits her GP, who takes a history and establishes that the patient is vomiting hourly and is unable to go to work or do any normal daily activities. It is also revealed that all of her sisters had severe morning sickness.

The GP finds signs of dehydration. The patient is normotensive with a pulse of 90bpm. Her weight is 55kg.

Urine shows ++ketones, nitrites, +protein and a trace of leucocyte.

An MSU is sent.

The GP prescribes cyclizine 50mg three times a day and advises her to stay nil by mouth for 24 hours, followed by the introduction of flat lemonade. If this is tolerated, she can introduce a bland diet, but avoid fatty and spicy foods.

Dehydration

She returns two weeks later, weighing 48kg and showing signs of significant dehydration. She has a BP of 88/60mmHg, pulse 100bpm, dry tongue, and ++++ketones. She reports feeling weak and dizzy.

The GP arranges for her to go to the early pregnancy unit, suspecting HG. She is given IV cyclizine and metoclopramide and 3L of IV fluids. She feels much better, with ++ketones, and that evening she is discharged with thiamine and antiemetics.

A follow-up telephone consultation 24 hours later reveals her symptoms are worse than ever. She is admitted as an inpatient. Domperidone (rectal) and other antiemetics are tried, without success.

Following discussion, a steroid course is started. She improves but is now feeling low in mood. Her vomiting returns and a case conference decides to continue steroids and instigate total parenteral nutrition.

Her symptoms did not improve greatly until 34 weeks. By 36 weeks, her symptoms returned. She delivered a live female weighing 2.1kg by caesarean section. The patient was later commenced on antidepressants and required follow-up during her next pregnancy.

Section 6: Evidence base

Clinical trials

  • Nelson-Piercy C. Treatment of nausea and vomiting in pregnancy: when should it be treated and what can be safely taken? Drug Saf 1998; 19: 155-64.
  • Nelson-Piercy C, Fayers P, de Swiet M. Randomised, double-blind, placebo-controlled trial of corticosteroids for the treatment of hyperemesis gravidarum. BJOG 2001; 108: 9-15.

Online

Reflect on this article and add notes to your CPD Organiser on MIMS Learning

CPD IMPACT: EARN MORE CREDITS

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Where possible, identify women who are at high risk of HG when they book in and provide early advice at this stage.
  • Liaise with the local obstetrics department to write a joint management protocol for HG, defining the roles of primary and secondary care.
  • Review the management of patients with HG over the past two years and discuss how to improve future management.

References

1. Ogunyemi DA, Fong A. Hyperemesis gravidarum. eMedicine. Trupin SR et al (eds). Medscape 2 Nov 2009.

2. Bottomley C, Bourne T. Management strategies for hyperemesis. Best Pract Res Clin Obstet Gynaecol 2009; 23(4): 549-64.

3. Fell DB, Dodds L, Joseph KS et al. Risk factors for hyperemesis gravidarum requiring hospital admission during pregnancy. Obstet Gynecol 2006; 107(2 pt 1): 277-84.

4. Wilcox SR, Edelman A, Logan JR. Pregnancy, hyperemesis gravidarum. eMedicine. Sayah AJ et al (eds). 2008.

5. Goodwin TM. Hyperemesis gravidarum. Obstet Gynecol Clin N Am 2008; 35: 401-17.

6. Lewis G, Drife J. Why Mothers Die. Report on Confidential Enquiries into Maternal Deaths in the United Kingdom 1994-1996. London, The Stationery Office, 1998.

7. Vilming B, Nesheim BI. Hyperemesis gravidarum in a contemporary population in Oslo. Acta Obstet Gynecol Scand 2000; 79: 640-3.

8. Basso O, Olsen J. Sex ratio and twinning in women with hyperemesis or pre-eclampsia. Epidemiology 2001; 12: 747-9.

9. Tesfaye S, Achari V, Yang YC et al. Pregnant, vomiting, and going blind. Lancet 1999; 352: 1594.

10. Nelson-Piercy C, Fayers P, de Swiet M. Randomised double-blind, placebo-controlled trial of corticosteroids for the treatment of hyperemesis gravidarum. BJOG 2001; 108: 9-15.

11. Subramaniam R, Soh EB, Dhillon HK et al. Total parenteral nutrition (TPN) and steroid usage in the management of hyperemesis gravidarum. Aust NZ J Obstet Gynaecol 1998; 38: 339-41.

12. Dodds L, Fell DB, Joseph KS et al. Outcomes of pregnancies complicated by hyperemesis gravidarum. Obstet Gynecol 2006; 107: 285-92.

Contributed by Dr Ciaran Crowe, an ST4 in obstetrics and gynaecology, William Harvey Hospital, Ashford, Kent

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