eMedicine Specialties > Emergency Medicine > Obstetrics & Gynecology

Pregnancy, Hyperemesis Gravidarum

Susan Renee Wilcox, MD, Resident, Department of Emergency Medicine, Harvard Medical School
Alison Edelman, MD, Assistant Professor, Department of Obstetrics and Gynecology, Oregon Health Sciences University; Judith R Logan, MD, MS, Assistant Professor, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University

Updated: Dec 10, 2008

Introduction

Background

Nausea and vomiting are common in pregnancy, occurring in 70-85% of all gravid women. Hyperemesis gravidarum is a severe and intractable form of nausea and vomiting in pregnancy. It is a diagnosis of exclusion and may result in weight loss; nutritional deficiencies; and abnormalities in fluids, electrolyte levels, and acid-base balance. The peak incidence is at 8-12 weeks of pregnancy, and symptoms usually resolve by week 20 in all but 10% of patients. Uncomplicated nausea and vomiting of pregnancy is generally associated with a lower rate of miscarriage, but hyperemesis gravidarum may affect the health and well-being of both the pregnant woman and the fetus.

Pathophysiology

The etiology of nausea and vomiting of pregnancy is unknown. Many have postulated that nausea and vomiting are protective in pregnancy to reduce exposures to potentially teratogenic materials. Some theories hold that elevated human chorionic gonadotropin (hCG) or estradiol levels could be causative, due to correlations in numerous studies between levels and symptoms, but this has not been demonstrated conclusively. Psychological theories of the etiology are falling out of favor, and the American College of Obstetrics and Gynecology warns that attributing vomiting to psychological disorders has likely impeded progress in understanding the true etiology of hyperemesis gravidarum.

Frequency

United States

Hyperemesis gravidarum occurs in 0.5-2% of pregnancies, with the variation in incidence arising from different diagnostic criteria and ethnic variations. Studies have found an admission rate of 0.8% for hyperemesis gravidarum and an average of 1.3 hospital admissions per hyperemesis patient, with an average hospital stay of 2.6-4 days.

Mortality/Morbidity

With mild-to-moderate vomiting, the patient and the fetus are unlikely to experience any increased morbidity or mortality. Before the advent of intravenous hydration, hyperemesis was a major cause of maternal death. Currently, mortality is exceedingly rare, but maternal morbidities may include Wernicke encephalopathy from vitamin B-1 deficiency, Mallory-Weiss tears, esophageal rupture, pneumothorax, and acute tubular necrosis. Hyperemesis is the second leading cause of hospitalization in pregnancy, second only to preterm labor. Additionally, many women experience significant psychosocial morbidity, occasionally interfering with assumption of the maternal role and rarely leading to termination of the pregnancy.

Race

Hyperemesis patients are more likely to be nonwhite.

Age

Patients younger than 30 years are more likely to experience hyperemesis.

Clinical

History

• Nausea and vomiting occur in early pregnancy and are nonresponsive to simple measures, such as reassurance and dietary changes.
• Fever and abdominal pain are not characteristic of hyperemesis gravidarum.
• If vomiting begins after 9 weeks' gestation, other causes should be investigated.

Physical

Findings at physical examination may include the following:

• Weight loss
• Dehydration
  • Decreased skin turgor
  • Postural changes in blood pressure (BP) and pulse
• Abdominal tenderness, fever, and goiter likely indicate another process.

Causes

• The cause of severe nausea and vomiting in pregnancy has not been identified. Hyperemesis may have a genetic component, as sisters and daughters of women with hyperemesis have a higher incidence.
• Hyperemesis is also associated with hyperemesis in prior pregnancy, female gestation, multiple gestation, triploidy, trisomy 21, current or prior molar pregnancy, and hydrops fetalis.
• Women with history of motion sickness, migraine headaches, psychiatric illness, pregestational diabetes, being underweight pregestation, hyperthyroidism, pyridoxine deficiency, and gastrointestinal disorders are also at an increased risk.
• Some studies have suggested that Helicobacter pylori infection may play a role in hyperemesis, but the data are inconclusive.
• Cigarette smoking and maternal age older than 30 years appear to be protective.

Differential Diagnoses

Other Problems to Be Considered

Pyelonephritis
Molar pregnancy
Pseudotumor cerebri
Acute fatty liver of pregnancy

Workup

Laboratory Studies

• Obtain electrolyte levels.
• Measure urine gravity and ketones.
• Perform liver function tests (LFTs) if hepatitis is a concern. Of note, LFTs can be slightly elevated with hyperemesis gravidarum.
• Perform a complete blood count and urinalysis to rule out other causes, with particular concern for pyelonephritis.
• Hyperthyroidism causing nausea and vomiting is rare, a T3 and T4 level should be drawn if this is a concern. (Thyroid-stimulating hormone [TSH] can be suppressed in hyperemesis gravidarum.)
• Obtain serum amylase-to-creatinine ratio if pancreatitis is a concern.
• Serum hCG levels are not clinically useful in a patient with a known intrauterine pregnancy (IUP) and hyperemesis.

Imaging Studies

• The patient should have an ultrasonographic evaluation of her pregnancy to look for molar pregnancy or multiple gestations.

Treatment

Emergency Department Care

Early treatment of nausea and vomiting of pregnancy may prevent progression to hyperemesis gravidarum. First-line treatment often involves rest and avoidance of sensory stimuli that may act as triggers. Frequent small meals with avoidance of spicy or fatty foods and increasing high-protein snacks are recommended.

• Replace fluids and administer antiemetics, if required. Normal saline or Lactated Ringer solution is recommended.
• Consider the addition of glucose, multivitamins, magnesium, pyridoxine, and/or thiamine. For any patient in whom vitamin deficiency is a concern, thiamine 100 mg should be given before initiating dextrose-containing fluids.
• Dextrose solutions may stop fat breakdown.
• Continue treatment until the patient can tolerate oral fluids and until test results show little or no ketones in the urine.

Medication

The American College of Obstetrics and Gynecology recommends that first-line treatment of nausea and vomiting of pregnancy should start with pyridoxine (vitamin B-6) with or without doxylamine. Pyridoxine has been found to be effective in significantly reducing severe vomiting but is less effective with milder vomiting. Pyridoxine in combination with doxylamine 10 mg, the active ingredient in many over-the-counter sleep agents, has been showed in randomized, placebo-controlled trials to have a 70% reduction in nausea and vomiting. The combination of pyridoxine 10 mg and doxylamine 10 mg was available in the United States until 1983 as Bendectin, when it was voluntarily removed from the market by the manufacturer due to litigation. Multiple studies have shown no increased risk of birth defects with the pyridoxine-doxylamine combination.

If this is unsuccessful, adding or switching to PO, PR, or IV antiemetics may be required.

Typical antiemetics such as promethazine 12.5-25 mg every 4 hours or prochlorperazine 25 mg rectally every 12 hours are acceptable second-line agents.

Anticholinergics are supported by some data attesting to their safety, but they are not as well studied. Meclizine and dimenhydrinate have both been shown to be more effective than placebo in controlling nausea and vomiting of pregnancy. Metoclopramide, a promotility agent, has been demonstrated to be more effective than placebo in the treatment of hyperemesis gravidarum, and it has not been shown to be associated with increased incidence of congenital malformations. Ondansetron has limited safety and efficacy data, but it is increasing in use.

Corticosteroids have a possible benefit in the treatment of hyperemesis gravidarum. Steroids have been considered a last resort in patients who will require enteral or parenteral nutrition due to weight loss. The most common regimen is methylprednisolone 16 mg, orally or intravenously, every 8 hours for 3 days. Patients who do not respond within 3 days are not likely to respond. For those who do respond, the course may be tapered over 2 weeks. Some recent studies have demonstrated an association between oral clefts and methylprednisolone use in the first trimester. The current recommendation is that corticosteroids be used with caution and avoided before 10 weeks' gestation.

In addition to the medications mentioned below, ginger is a common remedy for nausea and vomiting in pregnancy. Ginger capsules of 250 mg taken 4 times a day have been demonstrated to be effective against nausea and vomiting of pregnancy as well as hyperemesis when compared with placebo, without evidence of significant side effects or adverse effects on pregnancy outcomes. However, no clinical or experimental data about adverse effects of ginger in pregnancy exist. The Food and Drug Administration (FDA) does not regulate ginger products.

Practitioners of traditional Chinese medicine believe that stimulation of acupuncture point P6 can relieve nausea. Acupressure can be used as an alternative or complement to Western medications. However, the data about acupressure for nausea are equivocal. Sea Band is an easy over-the-counter product that stimulates the P6 site.

Nutritional supplements

Pyridoxine deficiency may have an etiologic role. Severe nutritional deficiencies may lead to thiamine deficiency and result in Wernicke encephalopathy.

Pyridoxine (Vitamin B6, Hexa-Betalin)

Some use pyridoxine with doxylamine (active ingredients in Benedictine, an antiemetic no longer available in the United States but still widely used in Europe). In the United States, doxylamine can be found in the over-the-counter medication Unisom (effective dose is half tablet).

Dosing

Adult

10-20 mg PO qd for up to 3 wk or 10 mg IV qd for 3 d

Pediatric

Not established

Interactions

May decrease levodopa, phenytoin, and phenobarbital serum levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

>200 mg/d may precipitate withdrawal effects when discontinued

Thiamine (Vitamin B1, Thiamilate)

Used in the treatment of thiamine deficiency including Wernicke encephalopathy syndrome.

Dosing

Adult

100 mg IV/IM qd for up to 2 wk

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Sensitivity reactions can occur (intradermal test-dose recommended in suspected sensitivity); deaths have resulted from IV use; sudden onset or worsening of Wernicke encephalopathy, following glucose administration, may occur in thiamine-deficient patients; administer before or with dextrose-containing fluids in suspected thiamine deficiency

Antiemetics

No drug has been approved by the FDA for the treatment of nausea and vomiting in pregnancy since Benedictine. Any antiemetic must be prescribed with caution.

Promethazine (Phenergan)

Antidopaminergic agent effective in treating emesis. Blocks postsynaptic mesolimbic dopaminergic receptors in brain and reduces stimuli to the brainstem reticular system. Not to be administered SC or intra-arterially, because necrotic lesions may develop.

Dosing

Adult

12.5 mg PO/PR tid and 25 mg hs
25 mg IV/IM, and repeat prn in 2 h; switch to PO as soon as possible

Pediatric

0.25-1 mg/kg PO/IV/IM/PR 4-6 times/d prn

Interactions

May have additive effects when used concurrently with other CNS depressants or anticonvulsants; coadministration with epinephrine may cause hypotension

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, impaired liver function, seizures, sleep apnea, asthma, and acute-angle glaucoma; may cause drowsiness

Prochlorperazine (Compazine)

Antidopaminergic drug that may relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors with its anticholinergic effects and by depressing the reticular activating system.

Dosing

Adult

5-10 mg PO/IM tid/qid, not to exceed 40 mg/d
2.5-10 mg IV q3-4h prn; not to exceed 10 mg/dose or 40 mg/d
25 mg PR bid

Pediatric

>12 years: Administer as in adults

Interactions

Coadministration with other CNS depressants or anticonvulsants may cause additive effects; with epinephrine may cause hypotension

Contraindications

Documented hypersensitivity; bone marrow suppression; narrow-angle glaucoma; severe liver or cardiac disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Drug-induced Parkinson syndrome or pseudoparkinsonism occurs frequently; akathisia is the most common extrapyramidal reaction in elderly patients; lowers seizure threshold; caution with history of seizures

Metoclopramide (Reglan)

Works as an antiemetic by blocking dopamine receptors in chemoreceptor trigger zone of the CNS. Usually reserved for use when other therapies fail to control symptoms. Stimulates intestinal motility and is metabolized in the kidneys.

Dosing

Adult

10 mg PO up to qid 30 min before meals and at hs

Pediatric

>12 years: Administer as in adults

Interactions

Anticholinergics may antagonize effects; opiate analgesics may increase toxicity in CNS

Contraindications

Documented hypersensitivity; pheochromocytoma or GI hemorrhage, obstruction, or perforation; history of seizure disorders

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Avoid with medications that can cause extrapyramidal reactions; caution in a history of mental illness and Parkinson disease

Dimenhydrinate (Dramamine)

Used as an antimotion sickness agent, dimenhydrinate has been demonstrated to be effective in reducing hyperemesis and is an acceptable second-line agent.

Dosing

Adult

50-100 mg PO q4-6h; not to exceed 400 mg/d; not to exceed 200 mg/d if also taking doxylamine

Pediatric

>12 years: Administer as in adults

Interactions

Caution advised when using with other anticholinergic agents or sedating agents, may have additive effect

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Previously linked to increased rate of birth defects, recent case-control study found no evidence of teratogenicity
May cause drowsiness, headaches, fatigue, paradoxical CNS stimulation

Diphenhydramine (Benadryl)

Used for the treatment and prophylaxis of vestibular disorders that may cause nausea and vomiting.

Dosing

Adult

25-50 mg PO q6-8h prn; not to exceed 400 mg/d
10-50 mg IV/IM q6-8h prn; not to exceed 400 mg/d

Pediatric

12.5-25 mg PO tid/qid, 5 mg/kg/d, or 150 mg/m²/d divided tid/qid; not to exceed 300 mg/d
5 mg/kg/d IV/IM or 150 mg/m²/d divided qid; not to exceed 300 mg/d

Interactions

Potentiates effect of CNS depressants; alcohol in syrup form may interact with medications that can cause disulfiramlike reactions

Contraindications

Documented hypersensitivity; MAOI use

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction

Meclizine (Antivert, Antrizine, Meni-D, Dramamine, Marezine)

Decreases excitability of the middle-ear labyrinth and blocks conduction in middle-ear vestibular-cerebellar pathways. These effects are associated with relief of nausea and vomiting.

Dosing

Adult

25-50 mg PO q12-24h; not to exceed 100 mg/d

Pediatric

>12 years: Administer as in adults

Interactions

May increase toxicity of CNS depressants, neuroleptics, and anticholinergics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in angle-closure glaucoma, prostatic hypertrophy, pyloric or duodenal obstruction, bladder-neck obstruction

Ondansetron (Zofran)

Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally, used in the prevention of nausea and vomiting. It is metabolized in the liver with P-450 mechanism.

Dosing

Adult

2-4 mg IV q6-8h

Pediatric

>12 years: Administer as in adults

Interactions

CYP450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) can change half-life and clearance of (dose adjustment usually not required)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Medication is for prevention of nausea and vomiting, not for rescue of nausea and vomiting

Follow-up

Further Inpatient Care

• Admit pregnant patients with any of the following:
  • Persistently abnormal vital signs
  • Severe dehydration and inability to tolerate oral fluids
  • Severe electrolyte abnormality
  • Acidosis
  • Infection
  • Malnutrition
• Weight loss
• Patients who continue to lose weight may require supplemental nutrition. Several care reports demonstrate that enteral tube feedings may be well tolerated and are a reasonable first attempt in admitted patients. Rarely, some women require total parenteral nutrition. Peripherally inserted central catheter (PICC) lines have been shown to have a high complication rate in these patients and should not be considered a routine therapy.

Further Outpatient Care

• Reassurance
• Frequent small meals with high-carbohydrate or high-protein content (Avoid offensive odors, fatty foods, spicy foods, iron supplements.)
• Some patients may require pyridoxine, pyridoxine, and doxylamine, or other antiemetics.
• For women infected with H pylori, case reports have suggested improvement in symptoms with eradication of the infection.
• Some women may find benefit in counseling.

Inpatient & Outpatient Medications

• As an outpatient, trial of pyridoxine (vitamin B-6) with/without doxylamine
• Oral or parenteral antiemetics if the patient's condition is unresponsive to fluids, dietary restrictions, and pyridoxine/doxylamine

Complications

• Complications of vomiting rarely occur; however, Mallory-Weiss tears and esophageal perforations have been reported.
• Women with hyperemesis and poor weight gain have lower average birth weights and are more likely to have a small for gestational age infant and may be at higher risk for preterm birth.
• In severe cases, without thiamine supplementation, Wernicke encephalopathy may occur (ie, diplopia, nystagmus, disorientation, confusion, coma).
• If treatment is unsuccessful, complications of prolonged dehydration and starvation may occur.

Prognosis

• One study has demonstrated that adverse fetal outcomes are mostly limited to poor maternal weight gain. Women who gained less than 7 kg in pregnancy were more likely to have fetal complications, but those with hyperemesis and greater than 7 kg weight gain had no increased risk. This research indicates that treating hyperemesis gravidarum such that the patient is able to gain weight portends a better prognosis.

Patient Education

• For excellent patient education resources, visit eMedicine's Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Pregnancy and Pregnancy, Vomiting.

Miscellaneous

Medicolegal Pitfalls

• No drugs are approved by the FDA for the treatment of nausea and vomiting in pregnancy, and the expected benefits of treatment should outweigh the risks.

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Keywords

hyperemesis gravidarum, nausea and vomiting in pregnancy, pernicious vomiting in pregnancy, uncontrollable vomiting in pregnancy, severe nausea and vomiting in pregnancy, morning sickness, miscarriage

Contributor Information and Disclosures

Author

Susan Renee Wilcox, MD, Resident, Department of Emergency Medicine, Harvard Medical School
Susan Renee Wilcox, MD is a member of the following medical societies: Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Alison Edelman, MD, Assistant Professor, Department of Obstetrics and Gynecology, Oregon Health Sciences University
Alison Edelman, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists
Disclosure: Organon Honoraria Speaking and teaching

Judith R Logan, MD, MS, Assistant Professor, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University
Judith R Logan, MD, MS is a member of the following medical societies: American Medical Informatics Association
Disclosure: Nothing to disclose.

Medical Editor

Assaad J Sayah, MD, Chief, Department of Emergency Medicine, Cambridge Health Alliance
Assaad J Sayah, MD is a member of the following medical societies: National Association of EMS Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Mark Zwanger, MD, MBA, Assistant Professor, Department of Emergency Medicine, Thomas Jefferson University
Mark Zwanger, MD, MBA is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and American Medical Association
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Pamela L Dyne, MD, Professor of Clinical Medicine/Emergency Medicine, David Geffen School of Medicine at UCLA; Attending Physician, Department of Emergency Medicine, Olive View-UCLA Medical Center
Pamela L Dyne, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

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