nausea%20-and-%20vomiting%20in%20pregnancy
NAUSEA & VOMITING IN PREGNANCY
Nausea & vomiting in pregnancy (NVP), commonly known as "morning sickness", affects 50-90% of pregnant women.
In most women, the condition manifests between the 4th-7th week after last menstrual period and resolves by the 16th week of gestation.
It manifests in a spectrum of severity from mild nausea to very rare life-threatening symptoms.
The etiology is multifactorial.
The pregnant woman's sense of well-being and her daily activities are greatly affected by nausea and vomiting; the physical and emotional impact often leads to anxiety and worry about the effect of the symptoms on the fetus and reduced job efficiency.

Pharmacotherapy

Pyridoxine with or without Doxylamine

  • Pyridoxine can be used as monotherapy or in combination with Doxylamine
  • Doxylamine/Pyridoxine combination is considered as the 1st-line of treatment based on evidence supporting its efficacy and safety
    • Improves mild to moderate nausea but does not significantly decrease vomiting
  • Doxylamine is an H1 receptor antagonist that has been shown to be effective for nausea and vomiting in pregnancy (NVP)
  • Pyridoxine is a co-enzyme in the transamination of amino acids and plays an important role in protein metabolism
    • Pyridoxine’s mode of action in alleviating NVP is not known; no clear association has been found between pyridoxine status and NVP
  • Pyridoxine has no known teratogenic effects and is less likely to cause adverse effects than antihistamine antiemetics; but evidence for its benefit in nausea and vomitng (N/V) in early pregnancy remains limited
    • Maximum dose is 200 mg/day in pregnant women but doses of up to 500 mg/day appear to be safe

Antihistamines

  • Diphenhydramine, Dimenhydrinate, Hydroxyzine, Meclizine, Promethazine and Trimethobenzamide have been used to control NVP and have been shown to be more effective than placebo
  • Directly inhibit the action of histamine at H1 receptor and indirectly affect the vestibular system, thereby decreasing the stimulation of vomiting center; also promotes antiemetic action by inhibiting muscarinic receptors
  • When used in therapeutic doses, these agents do not appear to be associated with an increased risk of congenital abnormalities

Phenothiazines

  • Phenothiazines (eg, Chlorpromazine, Prochlorperazine) have demonstrated significant therapeutic effect for severe NVP
    • Chlorpromazine may be given in refractory cases
  • Block postsynaptic mesolimbic dopamine receptors and depress the reticular activating system, thus affecting emesis
  • Studies of pregnant women exposed to various phenothiazines have failed to demonstrate an increased risk of fetal malformation

Propulsive Agent

  • Metoclopramide is a stimulant of upper gastrointestinal tract (GIT) motility
  • Increases lower esophageal sphincter tone and decreases transit time through the upper GIT, also blocks dopamine receptors at the chemoreceptor trigger zone of central nervous system (CNS)
  • NVP is associated with gastric dysrhythmia and the use of motility agents is a common practice
  • Effective and safe but used as 2nd-line agent due to risk of extrapyramidal effects
  • Studies have confirmed the lack of association between Metoclopramide exposure during the 1st trimester and congenital malformation

Other Agents Considered for Refractory Cases 

Corticosteroid

  • Eg Methylprednisolone (dose 15-20 mg IV 8 hourly)
  • Rationale for use is based on the theory that NVP is partly due to corticotropin deficiency
  • Only a few studies have shown some effectiveness in treating NVP
    • Reserved for treatment of refractory NVP or hyperemesis gravidarum
  • A small but significantly increased risk of oral clefting was noted with 1st trimester exposure
    • Routine use during 1st trimester is not recommended

Serotonin (5-HT3) Antagonist

  • Ondansetron, a 5-HT3 antagonist, has been tried for the treatment of hyperemesis gravidarum (dose 8 mg IV 12 hourly or 1 mg/hour continuously 24 hourly)
  • Evidence on its safety and efficacy for NVP remains limited
  • Use may be considered in women with refractory NVP or hyperemesis gravidarum if other interventions have failed and preferably after the first trimester

Adjunctive Therapy

Acid-suppressive Therapy

  • A study revealed that women with heartburn or acid reflux and NVP experienced significant improvement in symptoms after treatment with acid-reducing agents (eg antacids, H2-receptor antagonists, proton pump inhibitors) and anti-emetics

Non-Pharmacological Therapy

Acupuncture and Acupressure

  • Traditional Chinese medicine belief that stimulation of P6 acupressure point (Neiguan point) can relieve nausea
    • The point is located 3 fingerbreadths above the wrist on the volar surface
  • Data on the benefit of acupressure are equivocal

Ginger

  • Used in teas, preserves, ginger ale and pill form
  • May be used in mild to moderate nausea and vomiting in pregnancy
  • Has been demonstrated to be more effective than placebo in improving nausea but did not significantly reduce emesis
  • Safety data is lacking though many cultures use ginger as a spice with amounts similar to commonly prescribed therapy (125-250 mg orally 3-4x daily)
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