It is thought that nausea and vomiting of pregnancy (NVP) affects up to 80% of pregnant women and that about 35% of these women have clinically significant symptoms. Nausea and vomiting in pregnancy usually begins between the fourth and seventh weeks of gestation, peaks between the ninth and sixteenth weeks, and resolves by around the 20th week of pregnancy. Hyperemesis gravidarum (HG) is the severe form of NVP, which affects about 0.3–3.6% of pregnant women.

NVP is primarily thought to be associated with rising levels of beta human chorionic gonadotrophin (hCG) hormone, and conditions with higher hCG levels, such as trophoblastic disease and multiple pregnancy, have been associated with increased severity of NVP.

Risk Factors

Risk factors include:

• Increased placental mass (for example advanced molar gestation, multiple gestation)
• History of hyperemesis gravidarum in previous pregnancies
• History of motion sickness
• History of migraines
• Family history (first-degree relatives) of nausea and vomiting in pregnancy
• History of nausea with oestrogen-containing oral contraceptives
• First pregnancy.
• Obesity
• Stress
• Being seropositive for Helicobacter pylori

Clinical features

Hyperemesis gravidarum is a diagnosis of exclusion characterised by:

• Severe, protracted nausea and vomiting
• Weight loss of more than 5% of prepregnancy weight
• Dehydration
• Electrolyte imbalances
• Ketosis

Complications

Complications of hyperemesis gravidarum include:

• Metabolic complications
  • Weight loss
  • Dehydration
  • Hyponatraemia or hypokalaemia
  • Hypochloraemic metabolic alkalosis (if severe, metabolic acidaemia can occur)
  • Abnormal liver function test results
  • Vitamin deficiencies (for example thiamine [vitamin B1] which may cause Wernicke's encephalopathy)
• Mechanical complications
  • Retinal haemorrhage
  • Splenic avulsion
  • Mallory–Weiss tears or oesophageal rupture
  • Pneumothorax or pneumomediastinum
• Venous thromboembolism (combination of immobility and dehydration)

Differential diagnosis

Other pathological causes of nausea and vomiting include peptic ulcers, cholecystitis, gastroenteritis, hepatitis, pancreatitis, genitourinary conditions such as urinary tract infection or pyelonephritis, metabolic conditions, neurological conditions and drug-induced nausea and vomiting.

Investigations

• Urine dipstick:
  • quantify ketonuria as 1+ ketones or more
  • infection
• Urea and electrolytes:
  • hypokalaemia/hyperkalaemia
  • hyponatraemia
  • dehydration
  • renal disease
• Full blood count:
  • infection
  • anaemia
  • raised haematocrit
• Blood glucose monitoring:
  • exclude diabetic ketoacidosis if diabetic
• Ultrasound scan:
  • confirm viable intrauterine pregnancy
  • exclude multiple pregnancy and trophoblastic disease
• In refractory cases or history of previous admissions, check:
  • TFTs: hypothyroid/hyperthyroid
  • LFTs: exclude other liver disease such as hepatitis or gallstones, monitor malnutrition
  • calcium and phosphate
  • amylase: exclude pancreatitis
  • ABG: exclude metabolic disturbances to monitor severity

Management

• Antiemetics:
  • Prescribe oral cyclizine or promethazine (antihistamines), prochlorperazine or chlorpromazine (phenothiazines), or the combination drug doxylamine/pyridoxine (Xonvea®) first-line, and reassess the woman after 24 hours.
  • If first-line treatment is ineffective, switch to a second-line antiemetic from a different drug class, such as oral metoclopramide or domperidone (dopamine receptor antagonists), or ondansetron (a 5-HT3 receptor antagonist), and reassess the woman after 24 hours.
  • If second-line treatment is ineffective, seek specialist advice. Corticosteroids should be reserved for cases of HG where standard therapies have failed.
• Women who have vomiting but are not dehydrated can be managed in the community with antiemetics, support, reassurance, oral hydration and dietary advice.
• Ambulatory daycare management should be used for suitable patients when community/primary care measures have failed, for parenteral fluids, parenteral vitamins (multi and B-complex) and antiemetics.
• Inpatient management should be considered if there is at least one of the following:
  • continued nausea and vomiting and inability to keep down oral antiemetics
  • continued nausea and vomiting associated with ketonuria and/or weight loss (greater than 5% of body weight), despite oral antiemetics
  • confirmed or suspected comorbidity (such as urinary tract infection and inability to tolerate oral antibiotics).
• Normal saline with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration.
• Urea and serum electrolyte levels should be checked daily in women requiring intravenous fluids.
• Histamine H2 receptor antagonists or proton pump inhibitors may be used for women developing gastro-oesophageal reflux disease, oesophagitis or gastritis.
• Thiamine supplementation (either oral or intravenous) should be given to all women admitted with prolonged vomiting, especially before administration of dextrose or parenteral nutrition.
• Women admitted with HG should be offered thromboprophylaxis with low-molecular-weight heparin unless there are specific contraindications such as active bleeding. Thromboprophylaxis can be discontinued upon discharge.
• When all other medical therapies have failed, enteral or parenteral treatment should be considered with a multidisciplinary approach.