Nausea and Vomiting in Pregnancy & Hyperemesis GravidarumIona Berger - June 28, 2016

Pathophysiology:- The pathogenesis of NVP is poorly understood - Etiology is likely multifactorial- Observational data indicate that these conditions correlate with:

o Levels of human chorionic gonadotropin (hCG)o Size of the placental masso Levels of estrogen and progesteroneo Other potential etiologies include placental prostaglandins,

serotonin levels, thyroid dysfunction, increased leptin levels, immune system dysregulation, H. pylori infection, and GI dysmotility.

Risk factors:For nausea and vomiting:

- Less educated, older, or black, and those who have lower incomes, multiple gestations, or increasing gravidity (including miscarriages)

- A personal history of motion sickness, migraine headaches, or nausea associated with the use of estrogen-containing contraceptives

For hyperemesis gravidarum (HG):

- A personal history of hyperemesis gravidarum, gestational trophoblastic disease, fetal triploidy, fetal trisomy 21, hydrops fetalis, and multiple gestations

Clinical Presentation:- Most common medical condition in pregnancy, affecting 50%–90% of women - The most severe form of NVP is commonly referred to as hyperemesis gravidarum (HG)

o Defined as persistent vomiting that leads to weight loss greater than 5% of pre-pregnancy weight, with associated electrolyte imbalance and ketonuria

o Occurs in about 1% of pregnancies- Although the term morning sickness is commonly used to describe nausea and vomiting of pregnancy, the timing, severity,

and duration of symptoms vary widely. Only 1.8% report symptoms that occur solely in the morning… ~ 80% of women report that their symptoms last all day.

- N/V usually starts within 4 weeks of the last menstrual period and peaks at nine weeks’ gestation. An estimated 60% of cases resolve by the end of the first trimester, and 87% resolve by 20 weeks’ gestation

Diagnosis:

- Other causes of N/V must be ruled out, including GI, GU, CNS, and toxic/metabolic problems.

- Idiopathic NVP must be distinguished from NVP of known etiology

Differential Diagnosis of Nausea and Vomiting of PregnancyCommon causes: cholecystitis, gastroenteritis, GERD, migraine causes

Less common causes: biliary tract disease, drug toxicities or intolerances, hepatitis, hyperthyroidism, kidney stones, molar pregnancy, pancreatitis, PUD, preeclampsia, HELLP syndrome, pyelonephritis

Uncommon causes: acute fatty liver of pregnancy, Addison disease, appendicitis, CNS tumors, degenerating uterine leiomyoma, DKA, hypercalcemia, intestinal obstruction, Meniere disease, Ovarian torsion, porphyria, pseudotumor cerebri, uremia, vestibular lesions

Goals of therapy1) Decrease maternal morbidity (prevent HG, prevent weight loss associated with nausea and/or vomiting, preeclampsia,

esophageal rupture, elective termination of pregnancy (for sole reason of N/V))2) Decrease fetal morbidity (= fetal growth restriction, fetal mortality)3) Improve s/sx (= decrease feelings of nausea and vomiting)4) Improve quality of life (= avoid hospitalizations/additional office visits, time lost from work)

Non-pharm:

- Lifestyle changes: Sleep requirements increase in early pregnancy. Because fatigue seems to exacerbate NVP, women should be encouraged to increase their rest, especially while they are symptomatic.

- Dietary changes: no evidence to prove the effectiveness of dietary changes on relieving NVP symptoms o Recommendations have included separating solids and liquids; eating small, frequent meals consisting of bland

foods; avoiding fatty foods; and avoiding drinking cold, tart, or sweet beverages. Other advice has been to avoid sensory stimuli, particularly strong odours.

- Acupuncture and acupressure: stimulation of the P6 point. Efficacy is difficult to assess due to study design issues. Non-blinded RCTs demonstrated a decrease in “persistent nausea” by at least 50%.

Pharmacologic Therapies (OTC and Rx):Drug Mechanism of Action Adverse Effects NotesGinger

(typical dose: 250mg QID)

Unclear, but thought to inhibit serotonin receptors and to exert antiemetic effects at level of GI and in the CNS

Uncommon, but can include mild GI effects (=heartburn, diarrhea, and irritation of mouth).May require monitoring of INR if on warfarin (due to possible effect ginger has on fibrinolytic activity)

No evidence based studies have been published (to date) to exclude possibility of teratogenicity. A Cochrane review concluded that ginger was beneficial for N/V in pregnancy.

Doxylamine H1 receptor antagonist (vestibular system)

Drowsiness Currently sold in Canada as Diclectin (10mg doxylamine with 10mg pyridoxine (vit B6)).No risk to the fetus.

Other H1 receptor antagonists (e.g. dimenhydrinate, hydralazine)

H1 receptor antagonist(vestibular system)

Drowsiness, dizziness, headache, fatigue

No human teratogenic potential. Availability in parenteral and suppository formulations makes these agents a good choice for treatment of acute or breakthrough episodes of NVP

Pyroxidine (B6 vitamin) Unknown Paresthesias, headache, fatigue

Proven to be non-teratogenic in combo with doxylamine.

Metoclopramide Antagonizes both the dopamine (D1) and serotonin receptors (5-HT3) centrally and increases gastric emptying, lowers esophageal sphincter pressure.

Decreased energy, dizziness, drowsiness, insomniaContraindications: pheochromocytoma. Caution: parkinson’s, clinical depression

Avoid high dosages or treatment for longer than 12 weeks

Promethazine and Prochlorpemazine

Antagonize the dopamine (D2) receptor in the CNS chemoreceptor trigger zone and also have a modest effect on H1 receptors

Sedation More effective than antihistamines in preventing or alleviating vomiting

Ondansetron 5HT3 antagonist Hasn’t been shown to inc. risk of miscarriage, major malformations, or low birth wt

Not 1st line due to limited data of efficacy in pregnancy

Corticosteroids. Uncertain in NVP. Potential: Anti-inflammatory, interaction w/ serotonin, NK1 NK2, etc.

Wt gain, risk of infectionsFetal safety: increase risk of oral cleft

ACOG recommends against their use before 10 weeks GA. Last line.