Hyperemesis Gravidarum

Nausea is the most common gastrointestinal symptom of pregnancy and it occurs in 80-85% of all pregnancies during the first trimester. 52% of women have associated vomiting. The symptoms are normal features of pregnancy, are self-limiting, and usually subside by 16-20 week gestation. 'Morning sickness' is the term usually given to nausea and vomiting in pregnancy but only 11-18% of woman have symptoms confined to the mornings.^1,2

Hyperemesis gravidarum occurs when vomiting becomes intractable in early pregnancy and causes fluid and electrolyte imbalances and nutritional deficiency. The woman usually needs to be admitted to hospital. The clinical features that define it are:³

• Persistent nausea and vomiting
• Dehydration
• Ketonuria
• Electrolyte imbalance
• Weight loss > 5% of pre-pregnancy weight

The exact cause is not known but raised levels of human chorionic gonadotrophin (HCG), thyroxine and oestrogen have been implicated. Hyperemesis gravidarum is more common in pregnancies associated with higher levels of HCG (molar pregnancies, multiple pregnancies).^4,5 Psychological factors have also been implicated.^5,6

Hyperemesis gravidarum occurs in 3.5/1000 deliveries.

Risk factors

Hyperemesis gravidarum is more common in:

• Trophoblastic disease
• Multiple pregnancies
• Those who have had hyperemesis gravidarum in a previous pregnancy⁷
• Those with a family history of hyperemesis gravidarum
• Nulliparity
• Female fetus^8,9
• Maternal obesity
• Age < 30 years¹⁰
• Non-smokers¹⁰

Symptoms

• Nausea
• Vomiting
• Ptyalism (excessive salivation)
• Spitting
• Fatigue
• Anorexia
• Weight loss

Signs

• Dehydration
• Muscle wasting
• Ketosis
• Weight loss > 5% of pre-pregnancy weight
• Postural hypotension
• Tachycardia
• Collapse

There are other causes of nausea and vomiting in pregnancy. Ask about associated abdominal pain, diarrhoea and assess for fever. Causes include:

• Pregnancy-related: e.g. pre-eclampsia, acute fatty liver of pregnancy
• Gastrointestinal: e.g. gastroenteritis, appendicitis, cholecystitis, peptic ulcer disease, intestinal obstruction, pancreatitis, hepatitis
• Genito-urinary: e.g. urinary tract infection, renal calculi, degenerating uterine fibroid, ovarian cyst torsion
• Ear, nose and throat: e.g. labyrinthitis
• Endocrine: e.g. hypercalcaemia, diabetic ketoacidosis, thyrotoxicosis
• Neurological: e.g. migraine, tumours
• Psychological: e.g. eating disorders
• Drug toxicity or intolerance: e.g. iron

• Urinalysis: Look for ketonuria and increased urine specific gravity. Send MSU to exclude UTI.
• Full blood count: Haematocrit is usually raised.
• Urea, electrolytes and creatinine: May show hyponatraemia, hypokalaemia, low serum urea, raised serum creatinine.
• Liver function tests: May show raised serum aminotransferases and total bilirubin and mildly raised amylase. Abnormalities should resolve once symptoms improve.
• Thyroid function tests: May show high free T₄ ± low TSH. High free T₃ is less common. The woman is clinically euthyroid. Abnormalities should resolve once symptoms improve.
• Ultrasound scan: To exclude multiple pregnancy and hydatidiform mole.

Other causes of nausea and vomiting should be excluded. Ketonuria should be managed with drug treatment. If raised ketones levels persist despite drug treatment, and/or the woman is unwell, she should be admitted to hospital.

Management of nausea and vomiting symptoms

NICE guidelines were published in 2003 on routine antenatal care and included advice on the management of common symptoms of pregnancy including nausea and vomiting.¹¹These recommendations are currently being updated and the update is due to be issued in March 2008.

General supportive measures

• Drink and eat little and often.
• Meals high in carbohydrate and lower in fat are better.
• Cold meals reduce smell-related nausea.
• Avoid caffeine and alcohol as these can enhance dehydration.

1. Ginger: Two randomised controlled trials (RCT) have shown beneficial effects of ginger in reducing the severity of nausea and vomiting. The first used ginger 250mg four times daily and the second used 1 tablespoon of ginger syrup in 4-8 fluid ounces of water four times daily.^12,13 A systematic review also reported on woman hospitalised for hyperemesis and ginger was shown to significantly reduce the degree of nausea and number of attacks of vomiting. There was no evidence of adverse effects on pregnancy outcome.^14,15
2. P6 acupressure: A number of systematic reviews have shown that P6 Neiguan point acupressure (located on the volar aspect of the forearm 3 fingerbreadths proximal to the wrist) improved nausea and vomiting symptoms.^14,15,16 Other RCTs have shown symptom improvement with the use of acupressure wristbands. Again, no adverse effects on pregnancy were shown.

1. Antihistamines (promethazine, prochlorperazine, metoclopramide): A meta-analysis showed a significant reduction in nausea in the treated group, although an increase in drowsiness was reported.¹⁴ Another review showed no significant increased risk of teratogenicity. A lack of safety data means that metoclopramide should not be used as first-line treatment.¹⁷
2. Phenothiazines: Again a systematic review found that phenothiazines reduced nausea and vomiting symptoms with no evidence of teratogenicity.¹⁸

• Pyridoxine (vitamin B6): NICE states that this is not currently recommended for use due to concerns about possible toxicity at high doses.
• Cyanocobalamin (vitamin B12): This was also shown to produce significant reduction in nausea and vomiting in two RCTs.¹⁸ However, when the research for the NICE guidelines was performed, no specific data about its safety were found.
• Corticosteroids: Short courses of intravenous pulsed hydrocortisone have been shown in one study to be an effective treatment for intractable hyperemesis gravidarum.¹⁹ However, another study showed that they did not reduce the need for rehospitalization for hyperemesis gravidarum later in the pregnancy.²⁰ They do not form part of the NICE 2003 recommendations for the management of nausea and vomiting in pregnancy.

Treatment in hospital

If raised ketones levels persist despite drug treatment, and/or the woman is unwell, she should be admitted to hospital.

• Parenteral fluid and electrolyte replacement: Normal saline or Hartmann's solution should be used as dextrose containing fluids that are rich in carbohydrate may precipitate Wernicke's encephalopathy. Potassium chloride may be added to the bags as needed. Urea, electrolytes and creatinine should be measured daily.
• Vitamin supplementation: Thiamine should be given routinely, orally or intravenously, to prevent Wernicke's encephalopathy.
• Management of nausea and vomiting symptoms: This should include the general supportive measures and NICE recommended drug treatment as detailed above. The intravenous or rectal route of drug administration may be needed initially.
• Parenteral nutrition: This should be commenced if the woman continues to lose weight.

• Wernicke's encephalopathy: This is due to thiamine deficiency. Clinical features include diplopia, nystagmus, ophthalmoplegia, ataxia and confusion. It can lead to irreversible Korsakoff's syndrome which can cause permanent neurological disability usually presenting as an inability to form new memories. Abnormal liver function tests are common and may play a role in its pathogenesis by decreasing the conversion of thiamine to its active metabolite.
• Other vitamin deficiencies: Vitamin B12 and vitamin B6 deficiency can cause anaemia, peripheral neuropathy and subacute combined degeneration of the spinal cord.
• Mallory-Weiss tears and oesophageal rupture.
• Hyperthyroxinaemia.
• Hyponatraemia: This can lead to lethargy, confusion, convulsions and respiratory arrest. Central pontine myelinolysis occurs if severe hyponatraemia is corrected too rapidly. This can cause progressive quadriparesis and bulbar palsy and can be fatal.
• Depression: This can occur in up to 60% of women. In the worst cases it may lead to women wanting to terminate their pregnancy.^21,4,5

Babies born to women who have had hyperemesis gravidarum have a higher incidence of low birth weight.²²

One study showed that adverse infant outcomes associated with hyperemesis were more likely to occur in women with poor weight gain during pregnancy. It showed that infants born to a mother with hyperemesis and pregnancy weight gain of < 7 kgs were more likely to have a low birth weight, be small for gestational age, be born before 37 weeks gestation and have a 5-minute Apgar score of < 7. Those with a pregnancy weight gain of > 7 kgs had no significant difference in pregnancy outcome than those without hyperemesis.²³

All women with nausea and vomiting in pregnancy should be reassured of its (usually) benign and normal nature. Self-help measures, dietary modifications and non-drug treatment should be initiated early. Any woman with ketonuria should be commenced on drug treatment with anti-emetics. Hopefully these measures will help to reduce the number of admissions to hospital of women with hyperemesis gravidarum.