Epidemiology

• Nausea and vomiting are common in pregnancy, affecting up to 70% to 85% of pregnant women.^[2]
• Nausea and vomiting in pregnancy are more common in:
  • Primigravidae.
  • Multiple pregnancy.
  • History of previous hyperemesis gravidarum.
• It is less common with increasing maternal age.
• It tends to be a disease of Western society and is less common in developing countries, especially in rural communities.

Presentation

• Symptoms usually start between 4 and 7 weeks of gestation and resolve by 16 weeks in about 90% of women.
• Check for signs of dehydration and any possible underlying cause.

Differential diagnosis

Other causes of nausea and vomiting should be considered:^[3]

• Gastrointestinal - eg, gastroenteritis, gastritis, cholecystitis, peptic ulceration, hepatitis, appendicitis, pancreatitis, gastrointestinal obstruction.
• Neurological - eg, migraine, raised intracranial pressure.
• Urinary tract infection.
• Ear, nose, and throat disease - eg, labyrinthitis, Ménière's disease, vestibular dysfunction.
• Drugs - eg, opioids, iron.
• Metabolic and endocrine disorders - eg, hypercalcaemia, diabetes, Addison's disease, uraemia (acute kidney injury, chronic kidney disease), and thyrotoxicosis.
• Psychological disorders - eg, bulimia.
• Pregnancy-associated conditions - eg, pre-eclampsia, gestational trophoblastic disease, twisted ovarian cyst, fatty liver of pregnancy.

Investigations

• These are only required if there is a possible alternative diagnosis or in the assessment of the well-being of mother and fetus.
• In cases of hyperemesis gravidarum: renal function and electrolytes, LFTs, midstream urine and ultrasound (exclude multiple or molar pregnancy).

Management

Most cases are mild and do not require treatment. Nausea and vomiting in pregnancy usually resolves spontaneously within 16 to 20 weeks and is not associated with a poor pregnancy outcome. However, persistent vomiting and severe nausea can progress to hyperemesis gravidarum if the woman is unable to maintain adequate hydration, and fluid and electrolyte balance. Nutritional status may be jeopardised.^[4]

Management options

• Advice:
  • There is no research-based evidence on the effectiveness of dietary treatment.^[5]
  • Advise the patient to rest; eat small, frequent meals that are high in carbohydrate and low in fat.
  • Avoid any foods or smells that trigger symptoms.

• Many different treatments are often used to help alleviate nausea and vomiting in pregnancy. A Cochrane review found that:^[5]

  • Evidence regarding the effectiveness of P6 acupressure, auricular (ear) acupressure and acustimulation of the P6 point was limited.
  • Acupuncture (P6 or traditional) showed no significant benefit to women in pregnancy.
  • The use of ginger products may be helpful to women, but the evidence of effectiveness was limited and not consistent.
  • There was only limited evidence from trials to support the use of pharmacological agents including pyridoxine (vitamin B6), and anti-emetic drugs to relieve mild or moderate nausea and vomiting.
• Anti-emetic drug treatment:^[3]
  • This should only be given when symptoms are persistent, severe and preventing daily activities.
  • Drug treatment options include cyclizine, metoclopramide, prochlorperazine, promethazine, chlorpromazine, domperidone and ondansetron (selective 5-hydroxytryptamine receptor antagonist), or combinations of these agents.
  • Proton pump inhibitors and histamine H2-receptor antagonists may be used in women who also have dyspepsia and may be a useful adjunctive treatment.
  • Ondansetron has shown benefits in patients with intractable hyperemesis gravidarum, with few side-effects and no reports of teratogenicity. One small study of women with severe disease found that ondansetron was no more effective than promethazine.
  • There is no evidence that any one anti-emetic is better than another.

Admission

• Women with severe symptoms should be referred for fluid, electrolyte and vitamin replacement (usually intravenously). Nutritional support (enteral or parenteral) is needed in women who have intractable symptoms and weight loss, despite appropriate therapy.
• Indications for referral to secondary care include:^[3]
  
  • Continued nausea and vomiting associated with ketonuria or weight loss (>5% body weight), despite oral anti-emetics.
  • Continued nausea and vomiting and inability to keep down oral anti-emetics.
  • Confirmed or suspected comorbidity (such as confirmed urinary tract infection and inability to tolerate oral antibiotics).

Prognosis

• Most cases are self-limiting and settle without complication as pregnancy progresses.
• However, nausea and vomiting may cause significant psychosocial difficulties, time off work and a restriction of domestic and leisure activities.

Hyperemesis gravidarum

Different definitions of hyperemesis gravidarum exist, but the important features are intractable vomiting associated with weight loss of more than 5% of pre-pregnancy weight, dehydration, electrolyte imbalances, ketosis, and the need for admission to hospital.^[3] 

Epidemiology

• Hyperemesis gravidarum occurs in less than 1% of pregnancies.^[3]
• One study found that a moderate intake of water and adherence to a healthy diet that includes vegetables and fish before pregnancy are associated with a lower risk of developing hyperemesis gravidarum.^[6]
• There is evidence that hyperemesis gravidarum is associated with a higher female/male ratio.^[7] 
• A Canadian study found that hyperthyroid disorders, psychiatric illness, previous molar pregnancy, pre-existing diabetes, gastrointestinal disorders and asthma were all risk factors for hyperemesis gravidarum, whereas maternal smoking and maternal age older than 30 were associated with decreased risk. Singleton female pregnancies, pregnancies with multiple male fetuses, and male and female combinations were associated with increased risk of hyperemesis gravidarum.^[8]

Presentation

Vomiting that begins after 12 weeks of gestation is unlikely to be caused by hyperemesis gravidarum, and other pathological causes should always be considered before attributing nausea and vomiting in pregnancy to hyperemesis gravidarum.^[3]  See 'Differential diagnosis', above.

Management^[3]

• Advice, including dietary advice, and support: see 'Epidemiology', above.
• Fluid and electrolyte replacement:
  
  • Women who are severely dehydrated and ketotic need to be assessed in secondary care, with intravenous fluid and electrolyte replacement (with normal saline or Hartmann's solution).
  • Infusions of dextrose-containing fluids may precipitate Wernicke's encephalopathy.
  • Fluid and electrolyte balance must be reassessed frequently.
  • Potassium must be replaced appropriately.
• Nutritional support (enteral or parenteral) may be required.
• Vitamin supplements:
  • Thiamine supplements should be given routinely - orally if tolerated, or intravenously - to all pregnant women admitted to hospital as a result of prolonged vomiting.
  • Pyridoxine supplements should also be considered.
• Thromboprophylaxis:
  • Risk assessment for venous thrombosis and consideration of prophylactic low molecular weight heparin while dehydrated, unwell, or immobile are essential.
• Anti-emetic drugs: see 'management', above.
• Corticosteroids: may be used for intractable (failure to respond to conventional treatment) cases of severe hyperemesis gravidarum in secondary care.

Complications

In severe cases, dehydration, weight loss, electrolyte disturbance (eg, ketosis) and nutritional deficiency can occur. Hyperemesis gravidarum is rarely associated with death, but may lead to serious complications, including Wernicke's encephalopathy, central pontine myelinolysis and spontaneous oesophageal rupture.^[9]

Maternal:^[3]

• Weight loss (10-20% of body weight).
• Dehydration.
• Electrolyte abnormalities.
• Hyponatraemia, from persistent vomiting (leading to lethargy, headache, confusion, nausea, vomiting, and seizures), or overzealous correction of hyponatraemia, which can lead to central pontine myelinolysis.
• Hypokalaemia (skeletal muscle weakness, cardiac arrhythmias).
• Vitamin deficiencies: vitamin B1 deficiency (Wernicke’s encephalopathy, which may also be precipitated by high concentrations of dextrose); vitamin B12 and vitamin B6 deficiencies may cause anaemia and peripheral neuropathies.
• Mallory-Weiss tears of the oesophagus.
• Postpartum complications: persistence of symptoms and food aversions, postpartum gallbladder dysfunction, and symptoms of post-traumatic stress disorder.

Fetal complications:^[7]

• There is evidence that hyperemesis gravidarum is associated with a higher incidence of low birth weight (small for gestational age and premature babies).
• Little is known about the long-term health effects of babies born to mothers whose pregnancies were complicated by hyperemesis gravidarum.^[7]