Nausea and vomiting in pregnancy

Nausea and vomiting in pregnancy

Nausea and vomiting are both common in early pregnancy. There is no evidence of fetal damage as a result of the nausea and vomiting. Nausea and vomiting in pregnancy can occur at any time of the day and may be constant.

The causes of nausea and vomiting in early pregnancy are unknown. Nausea in later pregnancy may be due to reflux oesophagitis and it responds to antacids.

Nausea and vomiting are very common in pregnancy but are usually mild and only require reassurance and advice. However, persistent vomiting and severe nausea can progress to hyperemesis gravidarum. Hyperemesis gravidarum refers to persistent and severe vomiting leading to fluid and electrolyte disturbance, marked ketonuria, nutritional deficiency and weight loss. Without treatment, hyperemesis gravidarum may lead to central nervous system complications, liver failure and acute kidney injury but these complications are now rare in the developed world. See the section 'Hyperemesis gravidarum' at the end of this article.

Epidemiology¹

• Nausea and vomiting are common in pregnancy, affecting up to 90% of pregnant women. 35% of affected women are thought to have clinically significant symptoms.

• Nausea and vomiting in pregnancy are more common in:
  

  • Primigravidae.

  • Multiple pregnancy.

  • History of previous hyperemesis gravidarum or motion sickness.

  • Molar pregnancy.

  • Pregnancy where the fetus is female.

  • Younger women.

  • Obese women.

  • Women who are sero-positive for Helicobacter pylori.

• It tends to be a disease of Western society and is less common in developing countries, especially in rural communities.

Risk factors

In a 2020 cohort study of 2,411 women, a previous personal history of nausea, motion sickness (OR 3.17, 95% CI 1.81-5.56, p <0.0001) and nausea in migraine (OR 3.18, 95% CI 1.86-5.45, p <0.0001) are associated with severe nausea and vomiting in pregnancy² . Women with affected first-degree relatives had higher odds for moderate (OR 3.84, 95% CI 2.72-5.40) and severe (OR 3.19, 95% CI 1.92-5.28) NVP (p <0.0001). All these results remained significant after adjusting for parity, body mass index, smoking, employment and age.

Presentation

• In one UK cohort, nausea and vomiting symptoms usually start between 4 and 7 weeks of gestation (67% of women experienced symptoms between 11-20 days after ovulation³ ) and resolve by 16 weeks in about 90% of women.

• Check for signs of dehydration and any possible underlying cause.

• If symptoms begin after 12 weeks of pregnancy, there is usually another cause.

• A 2020 study found that there is a peak probability of nausea in the morning, a lower but sustained probability of nausea throughout the day, and a slight peak in the evening⁴ . It concluded that referring to nausea and vomiting in pregnancy as simply 'morning sickness' is inaccurate, simplistic and therefore unhelpful.

Differential diagnosis

Other causes of nausea and vomiting should be considered:

• 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 primary care, investigations are usually not required, unless there is concern that the mother is not maintaining adequate fluid intake. Check urine for ketones if this is a concern. If there are signs of dehydration, further investigation is usually undertaken in secondary care.

• In cases of hyperemesis gravidarum: renal function and electrolytes, LFTs, midstream urine (for infection and ketones) and ultrasound (exclude multiple or molar pregnancy).

Management

Most cases are mild and do not require treatment. Nausea and vomiting in pregnancy usually resolve spontaneously within 16-20 weeks and are 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.

Cochrane reviews have found no strong evidence for benefit of any one intervention, whether dietary, complementary medicine or traditional medication⁵ . Recent systematic reviews have found evidence however that ginger, antihistamines, metoclopramide (in mild disease) and vitamin B6 (mild to severe disease) are better than placebo^{6 7} .

General advice

Dietary suggestions which may help some women include:

• 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.

• The use of ginger products may be helpful. Evidence is limited and lacks consistency but there is some evidence of benefit over placebo.

• Try eating a dry biscuit first thing on waking in the morning before getting up.

Antiemetic medication

Medication should be avoided in pregnancy unless the benefit outweighs the potential risk, particularly in the first trimester. Antiemetics should only be used if dietary measures have failed and symptoms are persistent, severe and preventing daily activities. A Health Technology Assessment found that for severe nausea and vomiting in pregnancy, promethazine is as effective as metoclopramide, and ondansetron more effective than metoclopramide⁷ . If medication is required, National Institute for Health and Care Excellence Clinical Knowledge Summaries (NICE CKS) advice is to use:

• Promethazine or cyclizine first-line.

• Metoclopramide, prochlorperazine or ondansetron second-line:

  • Metoclopramide should not be used under the age of 20, due to the increased risk of extra-pyramidal side-effects, or for more than five days in line with the Medicines and Healthcare products Regulatory Agency (MHRA) recommendations.

  • Ondansetron is more expensive. Evidence suggests there is no significant risk of adverse fetal outcome when used in pregnancy⁸ .

Proton pump inhibitors and histamine H2-receptor antagonists may be used in women who also have dyspepsia, and may be a useful adjunctive treatment.

Admission

• Women with severe nausea and vomiting 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:
  

  • Continued nausea and vomiting associated with ketonuria or weight loss (>5% body weight), despite oral antiemetics.

  • Continued nausea and vomiting and inability to keep down oral antiemetics.

  • Confirmed or suspected comorbidity (such as confirmed urinary tract infection and inability to tolerate oral antibiotics, or diabetes).

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. Mild-to-moderate nausea and vomiting do not affect pregnancy outcome adversely; indeed there is some evidence that these symptoms are associated with a lower rate of miscarriage.

Potential medical complications of hyperemesis gravidarum are discussed below.

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.

Epidemiology

• Hyperemesis gravidarum affects 0.3-2% of pregnancies⁹ .

• 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 gravidarum¹⁰ .

• There is evidence that hyperemesis gravidarum is more common when the fetus is female¹¹ .

• 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 gravidarum¹² .

Hyperemesis gravidarum symptoms (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. See 'Differential diagnosis', above.

Hyperemesis gravidarum treatment and management⁹

• Advice, including dietary advice, and support.

• 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).

  • 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.

• Thromboprophylaxis:
  

  • Risk of venous thrombosis is increased due to dehydration and immobility, and consideration of prophylactic low molecular weight heparin is required.

• Antiemetic medication: see 'Management', above.

• Corticosteroids: may be used for intractable cases of severe hyperemesis gravidarum in secondary care.

Hyperemesis gravidarum 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.

Maternal

• Weight loss (10-20% of body weight).

• Dehydration.

• Acidosis.

• Hyponatraemia, from persistent vomiting (which may cause lethargy, headache, confusion, nausea, vomiting, seizures or respiratory arrest). Excessive correction of hyponatraemia can lead to central pontine myelinolysis.

• Hypokalaemia (which may cause muscle weakness or cardiac arrhythmias).

• Vitamin deficiencies:

  • Vitamin B1 (thiamine) deficiency (causing 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 due to repeated vomiting.

• Retinal haemorrhages.

• Splenic avulsion.

• Pneumothorax.

• Postpartum complications: persistence of symptoms and food aversions, postpartum gallbladder dysfunction and symptoms of post-traumatic stress disorder.

Fetal complications¹¹

• There is evidence that hyperemesis gravidarum is associated with a higher incidence of low birth weight (small-for-gestational-age and premature babies), particularly in low resource settings¹³ .

• Little is known about the long-term health effects of babies born to mothers whose pregnancies were complicated by hyperemesis gravidarum.