Approach

The treatment of NVP depends on the severity and duration of the symptoms at the time of presentation. Treatment for common NVP can be divided into non-pharmacological and pharmacological treatments. Non-pharmacological therapies are most often recommended as first-line treatments out of concern for the developing fetus. If these methods fail, pharmacological options are considered.[2]

In dehydrated patients, intravenous fluids should be utilised. In patients with hyperemesis gravidarum, hospitalisation and treatment with parenteral nutrition may be required.

Without volume depletion

Initial non-pharmacological therapy includes dietary modification. Patients often find that they can better tolerate smaller, more frequent meals.[2] Foods that taste bland and are low in fat and high in carbohydrates are often best tolerated. Women often report that they can tolerate salty foods early in the day. Tart or sour liquids (e.g., lemonade) may be better tolerated than water. Eliminating supplemental iron, and substituting folic acid for iron-containing antenatal vitamins, may improve symptoms of nausea.[2]

If dietary modifications fail to improve symptoms, various alternative treatments (e.g., acupressure, acupuncture, ginger) have been evaluated in the treatment of NVP, and may be tried. Since there have been no head-to-head comparisons of the majority of these modalities, it is difficult to recommend a first-line treatment. Patients should be apprised of the various options and encouraged to try the one that they would prefer. Acupressure may improve symptoms.[2][15]​​ Acupressure may be applied to the P6 point (Neiguan point, located 3 finger-widths above the wrist on the volar surface). This may be applied using commercially available wrist bands. Ginger supplementation reduces symptoms of nausea.​​[2][15][16]​ Ginger may be used alone or with acupressure, and is considered safe to use in all trimesters of pregnancy. It can be taken raw, as a tea, or in tablet/capsule form.[17][18]

If non-pharmacological methods fail, drug therapy may be considered. First-line therapies include pyridoxine (vitamin B6) and/or doxylamine (an antihistamine).[2] One randomised controlled trial found that the combination was effective compared with placebo, but a re-analysis of the data queried the clinical significance of the findings.[19][20] The UK National Institute for Health and Care Excellence recommend doxylamine/pyridoxine in women with symptoms that have not responded to conservative management. However, there is no evidence to show how it compares with other first-line treatments.[21] Second-line therapies include alternative oral antihistamines (e.g., meclizine, dimenhydrinate, diphenhydramine) or antiemetics (e.g., chlorpromazine, prochlorperazine, metoclopramide, domperidone).[2][22][23]

With volume depletion

Patients with NVP who are unable to keep down liquids despite treatment with conservative measures and drug therapies will often become dehydrated and require treatment with intravenous fluids. Ringer's lactate may be used; normal saline or 5% dextrose-saline are alternatives if Ringer's lactate is not available.[24] One randomised controlled trial has demonstrated similar outcomes in patients hydrated with either normal saline or 5% dextrose solution.[25] If solutions containing glucose are considered, some physicians suggest giving thiamine (vitamin B1) prior to administration in order to prevent Wernicke's encephalopathy.[1][2]

In patients with volume depletion, parenteral (or rectal) anti-emetic therapy may be necessary. Evidence suggests that ondansetron may be more effective at controlling severe vomiting than metoclopramide.[26][27] However, in 2019 studies showed an increased risk of cleft palate following the use of ondansetron during the first trimester of pregnancy.[28] The European Medicines Agency's (EMA's) pharmacovigilance risk assessment committee (PRAC) has recommended limiting the use of ondansetron during the first trimester of pregnancy.[29] However, the UK Teratology Information Service (UKTIS), in collaboration with the European Network of Teratology Information Services (ENTIS), issued a joint statement in response to the recommendations from the EMA PRAC regarding the use of ondansetron in the first trimester of pregnancy. UKTIS and ENTIS suggest ondansetron should still be considered an option for patients with severe vomiting in pregnancy in whom first-line treatments have failed, noting in their statement that there is much more information available about safety during pregnancy for ondansetron than for other antiemetic drugs, with data now available from over 168,000 women treated during the first trimester.[30] The UK Medicines and Healthcare products Regulatory Agency also issued a drug safety update for ondansetron that provides similar advice.[31] Ondansetron should therefore be reserved as a second-line agent for the treatment of NVP.[32] Patients must be adequately counselled about the benefits of ondansetron, as well as the small increase in the risk of cleft palate that may exist.

Proton-pump inhibitors (PPIs) may be used as an alternative treatment option to parenteral or rectal anti-emetics, or in combination with them.[33] Data have demonstrated that PPIs are safe in pregnancy and are not associated with a significant increase in birth defects.[34] However, analysis of data derived from observational studies suggests that PPI use during pregnancy may be associated with a modest increased risk of asthma during childhood.[35]

Hyperemesis gravidarum is defined as persistent vomiting, volume depletion and electrolyte imbalance, ketosis, and >5% weight loss.[1] These patients will frequently require hospitalisation. For patients who have failed initial therapies, corticosteroids can be considered after the first trimester (their use has been associated with cleft palate in fetuses exposed in the first trimester).[2][36]​​ A randomised, double-blind, controlled study has demonstrated improvement in symptoms.[37] In extreme cases, patients may require enteral feeding or total parenteral nutrition to provide calories and replace electrolytes and nutrients. Enteral feeding has been shown to be effective in one small study utilising a nasogastric tube with infusion rates up to 100 mL/hour.[38]

Helicobacter pylori-positive patients

In severe cases, patients who test positive for Helicobacter pylori may be treated with appropriate eradication regimens.[7]

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