Evidence-Based Approaches to Managing Nausea and Vomiting in Early Pregnancy

Tekoa L. King, CNM, MPH; Patricia Aikins Murphy, CNM, DrPH

J Midwifery Womens Health. 2009;54(6):430-444.

Etiology of Nausea and Vomiting in Pregnancy

Although the fundamental trigger is pregnancy, NVP results from a complex interplay of influences that include endocrine, gastrointestinal, vestibular, and olfactory factors; possible genetic predisposition; and responses that are modified by behavioral cues, support (or lack thereof), and psychology.^[16] Proposed etiologies include high levels of β-hCG and estrogen due to the close temporal relationships between the average peaks of NVP and peak of β-hCG levels and the correlations between NVP and conditions with higher estradiol levels. Progesterone or corticosteroid deficiency related to the observed associations between NVP and lower levels of these hormones has been proposed. Thyroid dysfunction, infectious disease (specifically infection with Helicobacter pylori), and psychosocial, cultural, and psychogenic causes have all been theorized to play a role in the etiology of this condition. NVP is correlated with a transient biochemical hyperthyroidism related to β-hCG stimulation of the thyroid. Genetic causes are suggested by observations that NVP is more frequent in monozygotic twins; is more common in women whose siblings and mothers are affected; shows ethnic variation; and is correlated with other genetically determined conditions, such as taste sensation, anosmia, and glycoprotein receptor defects.^[16,17]

An infectious origin is suggested by 14 published case-control studies that found a significant association between the presence of H pylori and HG. However, there are no directed studies addressing the efficacy of antibiotic treatments for H pylori in resolving the symptoms of HG.^[18] The most likely relationship is that women with H pylori and gastritis experience a more severe end of the NVP spectrum.

There is little evidence that NVP represents a psychiatric, conversion, or psychosomatic disorder; most studies suggesting this association are older and have flawed methodologies that call the findings into question. However, other studies show that NVP and HG can result in anxiety and depression, and it appears that the psychological responses to this physiologic condition can become entrenched and/or conditioned. This possibility is supported by evidence that psychological treatments (e.g., hypnosis) may help some individuals.^[8,19,20]

In summary, the etiology of NVP is physiologic, and the cause of more extreme forms remains unclear. Therefore, assessment of the condition focuses on severity, and management is largely supportive.^[21]

1 2 3 4 5 6 7 8 9

Next Section

Cite this: Evidence-Based Approaches to Managing Nausea and Vomiting in Early Pregnancy - Medscape - Oct 30, 2009.

Abstract and Introduction
Etiology of Nausea and Vomiting in Pregnancy
Assessment: The Pregnancy Unique Quantification of Emesis/Nausea Score
Management: Safety and Efficacy
Dietary and Lifestyle Recommendations
Nonpharmacologic Treatments
Pharmacologic Therapies
Clinical Implications
Conclusion
References

Table 1. Doses of Antiemetics Used to Treat Nausea and Vomiting in Pregnancy
Drug Name (Trade Name)	Dose	Major SEs (Recommendations)	FDA Pregnancy Category
Antihistamines (H₁ antagonists)
Diphenhydramine (Benadryl)	50–100 mg q 4–6 h PO/IM/IV	May cause drowsiness (can be used to offset anxiety caused by metoclopramide or phenothiazines)	B
Dimenhydrinate (Dramamine)	50–100 mg q 4–6 h PO/PR^a; 50 mg (in 50 mL of saline over 20 min) q 4–6 h IV	May cause drowsiness (can be used to offset anxiety caused by metoclopramide or phenothiazines)	B
Doxylamine (Unisom)	12.5 mg twice a day PO or 12.5 mg in morning and 25 mg at night PO		A
Phenothiazines (central D₂ antagonists)
Prochlorperazine (Compazine)	5–10 mg q 4–6 h PO/IM/IV; 25 mg rectal suppository bid; maximum dose is 40 mg/day	Sedation, anticholinergic effects, mouth, EPS, hypotension if given IV too quickly	C
Promethazine (Phenergan)	12.5–25 mg q 4–6 h PO/IM/IV/PR	Sedation, anticholinergic effects, mouth, EPS, hypotension if given IV too quickly	C
Benzamides (central and peripheral D₂ antagonists)
Metoclopramide (Reglan)	5–10 mg PO q 8 h PO/IM; 1–2 mg/kg IV; continuous SQ dose regimens available^b	EPS, agitation, anxiety, acute dystonic reactions (give 50 mg diphenhydramine before dose to prevent EPS)	B
Serotonin antagonists
Ondansetron (Zofran)	4–8 mg PO 3–4 times per day 4–8 mg over 15 min IV q 12 h; may be given 1 mg/h continuously for 24 h	Headache	B
Butyrophenones
Droperidol^c (Inapsine)	0.625–2.5 mg IV over 15 min then 1.25 mg or 2.5 mg IM as needed; can be given IV continuously at 1–1.25 mg/h	EPS, prolonged QT syndrome (give 50 mg diphenhydramine before dose to prevent EPS; reserve for persons who have failed other regimens)	C

bid = Two times daily; EPS = extrapyramidal effects; FDA = US Food and Drug Administration; IM = intramuscular; IV = intravenous; PO = per os (orally); PR = per rectum (rectally); SE = side effect; SQ = subcutaneous.
^aMaximum dose is 200 mg/day if taken concomitantly with doxylamine, 400 mg/day if taken as a single agent.
^bContinuous dose regimens can be found in Buttino Jr et al.^[89]
^cTo be used only after medical consultation and if other medications have failed to resolve symptoms, secondary to risk for prolonged QT syndrome.

Table 2. US Food and Drug Administration Ratings for Drug Use in Pregnancy ^a
Category	Interpretation
A	Adequate, well controlled studies in pregnant women have not shown an increased risk of fetal abnormalities to the fetus in any trimester of pregnancy.
B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well controlled studies in pregnant women. OR Animal studies have shown an adverse effect, but adequate and well controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.
C	Animal studies have shown an adverse effect and there are no adequate and well controlled studies in pregnant women. ORNo animal studies have been conducted and there are no adequate and well controlled studies in pregnant women.
D	Adequate well controlled or observational studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective.
X	Adequate well controlled or observational studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities or risks. The use of the product is contraindicated in women who are or may become pregnant.

Source: US Food and Drug Administration (21 CFR §201.57).^[72]
^aNote that the US Food and Drug Administration has proposed changes to prescription drug labeling for use in pregnancy and lactation. (See www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm093311.htm for additional information.)

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.