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Hyperemesis Gravidarum
Last Updated: October 5, 2004

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Synonyms and related keywords: HEG, nausea in pregnancy, vomiting in pregnancy, morning sickness, difficult pregnancy, pregnancy complications, ketosis, pregnancy, pregnancy weight loss, Helicobacter pylori, H pylori AUTHOR INFORMATION
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Author: Giulia A Michelini, MD, Associate Clinical Professor of Medicine, IMedicine, University of California at Los Angeles School of Medicine Giulia A Michelini, MD, is a member of the following medical societies: American College of Physicians, and Society of General Internal Medicine Editor(s): Suzanne R Trupin, MD, Clinical Professor, Department of Obstetrics and Gynecology, University of Illinois College of Medicine at Urbana-Champaign; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Richard S Legro, MD, Professor, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine; Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Assumption Community Hospital; and Lee P Shulman, MD, Professor of Obstetrics and Gynecology, Head, Section of Reproductive Genetics, Feinberg School of Medicine, Northwestern University; Distinguished Physician, Department of Obstetrics and Gynecology, Northwestern Memorial Hospital Disclosure INTRODUCTION
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Background: Nausea and vomiting in pregnancy is extremely common. Studies estimate nausea occurs in 66-89% of pregnancies and vomiting in 38-57%. The nausea and vomiting associated with pregnancy almost always begins by 9-10 weeks of gestation, peaks at 11-13 weeks, and resolves (in 50% of cases) by 12-14 weeks. In 1-10% of pregnancies, symptoms may continue beyond 20-22 weeks. The most severe form of nausea and vomiting in pregnancy is called hyperemesis gravidarum (HEG). A continuous spectrum of the severity of nausea and vomiting ranges from the nausea and vomiting that occurs in most pregnancies to the severe disorder of HEG.

http://www.emedicine.com/med/topic1075.htm HEG is characterized by persistent nausea and vomiting associated with ketosis and weight loss (>5% of prepregnancy weight). HEG may cause volume depletion, altered electrolytes, and even death. Hospitalization is not infrequent. Pathophysiology: The physiologic basis of HEG is controversial. The following theories have been proposed: Psychological abnormalities Early work on the cause of both nausea and vomiting in pregnancy and HEG suggested that women with these symptoms were unable to accept pregnancy, had problems with their relationships with their mothers, or had personality disorders and/or hysteria. However, nausea and vomiting in pregnancy is now recognized as affecting the majority of women. Retrospectively, many of the earlier studies appear flawed. Newer evidence is conflicting. Some cases of HEG may represent psychiatric illnesses, including Munchausen syndrome, conversion or somatization disorder, and major depression, or they may occur under situations of stress or ambivalence surrounding the pregnancy. However, HEG may occur in the absence of psychological illness or stress. Hormonal changes Homology exists between the human chorionic gonadotropin (HCG) molecule and its receptor and the thyroid-stimulating hormone (TSH) molecule and its receptor. HCG can physiologically stimulate the thyroid. HCG levels peak in the first trimester. Some women with HEG appear to have clinical hyperthyroidism. However, in a larger proportion (50-60%), TSH is transiently suppressed and the free thyroxine (T4) index is elevated (40-73%) with no clinical signs of hyperthyroidism, circulating thyroid antibodies, or enlargement of the thyroid. In some cases of HEG, some investigators have found a positive correlation between the level of serum HCG elevation and free T4 levels. In these studies, the severity of nausea also appeared to be related to the degree of thyroid stimulation. For these patients, HCG levels were linked to increased levels of immunoglobulin M, complement, and lymphocytes. An immune process may be responsible for increased circulating HCG or isoforms of HCG with a higher activity for the thyroid. Critics of this theory note that nausea and vomiting is not a usual symptom of hyperthyroidism, signs of biochemical hyperthyroidism are not universal in cases of HEG, and some studies have failed to correlate the severity of symptoms with biochemical abnormalities. Some studies link high estradiol levels to the severity of nausea and vomiting in patients who are pregnant, while others find no correlation between estrogen levels and the severity of nausea and vomiting in pregnant women. Previous intolerance to oral contraceptives is associated with nausea and vomiting in pregnancy.

http://www.emedicine.com/med/topic1075.htm Progesterone also peaks in the first trimester and decreases smooth muscle activity; however, studies have failed to show any connection between progesterone levels and symptoms of nausea and vomiting in pregnant women. Gastrointestinal dysfunction Elevations in female sex hormones during pregnancy may change esophageal, gastric, and small bowel motility. Although progesterone appears to decrease lower-esophageal sphincter pressure, a number of studies have found no decrease in lower-esophageal sphincter pressure during pregnancy. Studies on gastric emptying demonstrate that it is unchanged in pregnancy. However, some studies have correlated alterations in gastric myoelectrical activity in the first trimester of pregnancy with nausea. Small bowel transit time increases in pregnancy, but only in the second and third trimester. Hepatic dysfunction Many investigators have targeted changes in liver function as a possible cause of HEG. Patients with HEG often demonstrate abnormalities of liver enzymes. Liver disease can cause symptoms of nausea and vomiting, and abnormalities have been found on liver biopsy samples from patients with pregnancies complicated by HEG. Theories postulate either an increased sensitivity of the liver to the hormonal alterations of pregnancy or abnormalities in steroid inactivation; however, not all patients with HEG show liver abnormalities. In one study by Jarnfelt-Samsioe et al, pregnant women with vomiting had lower bilirubin and gamma-glutamyl transferase levels compared to women without vomiting. Lipid alterations In another study, Jarnfelt-Samsioe et al found higher levels of triglycerides, total cholesterol, and phospholipids in women with HEG compared to matched, nonvomiting, pregnant and nonpregnant controls. This may be related to the abnormalities in hepatic function in pregnant women. Infection Newer studies have found a relationship between infection with Helicobacter pylori and HEG. In a study by Kocak et al of 95 patients with HEG and 116 matched controls, H pylori infection was found in 91% of patients with HEG compared to 45% in controls. Frequency:

In the US: Of all pregnancies, 0.3-2% are affected with HEG (approximately 5 per 1000 pregnancies). Internationally: HEG appears to be more common in westernized industrialized societies and urban areas than rural areas.

http://www.emedicine.com/med/topic1075.htm Mortality/Morbidity: HEG was a significant cause of maternal death before 1940. Mortality from HEG in Great Britain decreased from 159 deaths per million births from 1931-1940 to 3 deaths per million births from 1951-1960. Charlotte Bront is thought to have died of HEG in 1855.

Many hours of productive work are lost because of nausea and vomiting during pregnancy. In one study of 200 pregnant women, 35% reported time lost from work. HEG is a debilitating illness that can cause severe suffering and profoundly affects both patients and their families. In one study of 140 women with HEG, 27% required multiple hospitalizations.

Race: No clear racial predominance is noted for HEG.


HEG is less common in American Indian and Eskimo populations. HEG is less common in African and some Asian populations (but not industrialized Japan).

Sex: HEG affects females. Age: The risk of HEG appears to decrease with advanced maternal age. CLINICAL
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History:

The defining symptoms of HEG are gastrointestinal in nature and include nausea and vomiting. Other common symptoms include ptyalism (excessive salivation), fatigue, weakness, and dizziness. Patients may experience the following:
o o o o

Sleep disturbance Hyperolfaction Dysgeusia Decreased gustatory discernment

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o o o o o

Depression Anxiety Irritability Mood changes Decreased concentration

When obtaining history from the patient, discuss present symptoms. Obtain information pertaining to the timing, onset, severity, pattern, and alleviating and exacerbating factors (eg, relationship to meals, medications, prenatal vitamins, stress, other triggers). A thorough review of systems for any symptoms that might suggest other gastrointestinal, renal, endocrine, and central nervous system disorders is vital. Review past medical history, placing emphasis on past medical conditions, surgeries, medications, allergies, adverse drug reactions, family history, social history (including support system), employment, habits, and diet. Obtaining a thorough gynecologic history of symptoms, such as vaginal bleeding or spotting, past pregnancies, past use of oral contraceptives, and response to oral contraceptives used, is important.

Physical:

The physical examination is usually unremarkable in patients with HEG. The physical examination findings may be more helpful if the patient has unusual complaints suggestive of other disorders (eg, bleeding, abdominal pain). Pay attention to the vital signs, including standing and lying blood pressure and pulse, volume status (eg, mucous membrane condition, skin turgor, neck veins, mental status), general appearance (eg, nutrition, weight), thyroid examination findings, abdominal examination findings, cardiac examination findings, and neurologic examination findings.

Causes: In some studies, women from low-to-middle socioeconomic class, women with lower levels of education, women with previous pregnancies with nausea and vomiting, women in their first pregnancies, and women with previous intolerance to oral contraceptives more commonly experience nausea and vomiting during pregnancy. Nausea and vomiting during pregnancy is also more common with multiple-gestation pregnancies.

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Risk factors for HEG may include the following:


o o o o o

Previous pregnancies with HEG Greater body weight Multiple gestations Trophoblastic disease Nulliparity

Cigarette smoking is associated with a decreased risk for HEG.


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DIFFERENTIALS

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Acute Renal Failure Addison Disease Appendicitis Biliary Disease Esophagitis Fatty Liver Gastroenteritis, Viral Gastroesophageal Reflux Disease Hepatitis, Viral Hyperparathyroidism Hyperthyroidism Ileus Nephrolithiasis Pancreatitis, Acute Peptic Ulcer Disease Porphyria, Acute Intermittent Preeclampsia (Toxemia of Pregnancy) Other Problems to be Considered: Intracranial lesions Eating disorders Gastroparesis

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Acute Renal Failure Addison Disease Appendicitis

http://www.emedicine.com/med/topic1075.htm Biliary Disease Esophagitis Fatty Liver Gastroenteritis, Viral Gastroesophageal Reflux Disease Hepatitis, Viral Hyperparathyroidism Hyperthyroidism Ileus Nephrolithiasis Pancreatitis, Acute Peptic Ulcer Disease Porphyria, Acute Intermittent Preeclampsia (Toxemia of Pregnancy)

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http://www.emedicine.com/med/topic1075.htm Center Pregnancy Overview Vomiting during Pregnancy Overview Vomiting during Pregnancy Causes Vomiting during Pregnancy Symptoms Vomiting during Pregnancy Treatment

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WORKUP

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Lab Studies:

Initial lab studies for HEG should include the following:


o

Urinalysis for ketones and specific gravity: A sign of starvation, ketones may be harmful to fetal development. High specific gravity occurs with volume depletion.

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Serum electrolytes: Assess electrolyte status to evaluate for low potassium or sodium, identify hyperchloremic metabolic alkalosis or acidosis, and evaluate renal function and volume status. Liver enzymes and bilirubin: Elevated transaminase levels may occur in as many as 50% of patients with HEG. Amylase: This is elevated in approximately 10% of patients with HEG. TSH: HEG is associated with hyperthyroidism and suppressed TSH levels in 50-60% of cases. Calcium level: Consider measuring Ca++ levels. Some rare cases have been reported of hypercalcemia being associated with HEG, resulting from hyperparathyroidism. Hematocrit: This may be elevated because of volume contraction.

o o

Imaging Studies:

An ultrasound is usually warranted in patients with HEG to evaluate for multiple gestations or trophoblastic disease. Additional imaging studies generally are not needed unless the clinical presentation is atypical (eg, nausea and/or vomiting beginning after 9-10 wk of gestation, nausea and/or vomiting persisting after 20-22 wk, acute severe exacerbation) or another disorder is suggested based on history or physical examination findings. If indicated clinically, performing an ultrasound to evaluate the pancreas and/or biliary tree appears to be a low-risk study.

Procedures:

In patients with abdominal pain or upper gastrointestinal bleeding, upper gastrointestinal endoscopy appears to be safe in pregnancy, although careful monitoring is suggested.
Section 6 of 10

TREATMENT

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Medical Care: Initial management should be conservative and may include reassurance, dietary recommendations, and support. Alternative therapies may include acupressure and hypnosis.

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In some studies, acupressure has been shown to have a beneficial effect on nausea and vomiting during pregnancy; however, it has not been studied in patients with HEG. More controversy surrounds the benefit of hypnosis, but it has been studied in some cases of HEG and may be beneficial. Psychological counseling may be considered. Reserve pharmacologic therapy for severe and refractory cases. First-line outpatient drug therapy can include oral pyridoxine. If vomiting persists, doxylamine may be added to the pyridoxine or conventional antiemetics may be administered. Initiate a full laboratory workup in cases of severe refractory HEG (weight loss or the presence of more than trace urine ketones). Outpatient or home intravenous hydration should be considered. If medications and outpatient hydration fail or if severe electrolyte disturbances persist, inpatient admission for intravenous hydration may be necessary.
o

If hypokalemia is severe or symptomatic, calcium should be replaced parenterally. Before administering intravenous potassium, renal function should be evaluated. Potassium is usually added to intravenous fluid to achieve a concentration of 40 mEq/L (and not >80 mEq/L). An infusion rate of 10 mEq of potassium per hour should be safe as long as urine output is adequate. When administrating intravenous hydration to a patient who has severe volume depletion in an effort to prevent the development of Wernicke encephalopathy, avoid intravenous glucose until intravenous thiamine has been administered. If vomiting is recurrent with intravenous hydration and conventional medications fail, a trial of oral corticosteroids is appropriate. Failure of this regimen necessitates consideration of enteral nutrition (either central or peripheral total parenteral nutrition).

Surgical Care: In some refractory severe cases of HEG or if maternal survival is threatened, termination of the pregnancy should be considered as a last resort. Consultations:

Patients with HEG should be under the care of an obstetrician who is familiar with this disorder. Consultation with a psychiatrist or psychologist may be warranted because psychological assessment may be needed. In some cases, even supportive or focal

http://www.emedicine.com/med/topic1075.htm psychotherapy or psychiatric medications may be indicated. Behavioral therapy may be beneficial early in the course of HEG.

When certain disorders are considered the cause of nausea and vomiting (see Differentials), referral to a gastroenterologist or surgeon may be necessary.

Diet: Initial suggestions for dietary modification in patients with nausea and vomiting associated with pregnancy include the following:

Eat when hungry, regardless of normal meal times. Eat frequent small meals. Avoid foods high in fat and protein. Avoid emetogenic foods or smells. Increase intake of foods containing dry carbohydrates. Increase intake of carbonated beverages. Other suggested foods include herbal teas containing peppermint or ginger, other ginger-containing beverages, broth, crackers, unbuttered toast, gelatin, or frozen desserts. Preconception use of prenatal vitamins may decrease nausea and vomiting associated with pregnancy; however, in patients with HEG, vitamins (especially those containing iron) can sometimes exacerbate the symptoms.

Activity: Some patients note improvement of nausea and vomiting with decreased activity and increased rest. Other patients suggest that fresh outdoor air may improve symptoms.

MEDICATION

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Antihistamines, antiemetics of the phenothiazine class, and promotility agents (eg, metoclopramide) have been used in the treatment of nausea and vomiting during pregnancy. Vitamin B-6 (pyridoxine) has also been studied in the treatment of nausea and vomiting during pregnancy. In one study, nausea decreased but vomiting did not. In another study, pyridoxine significantly reduced nausea scores, but only in patients with the most severe symptoms. A number of randomized studies have been performed on drug treatment for HEG.

http://www.emedicine.com/med/topic1075.htm Ondansetron (Zofran), a serotonin-receptor antagonist, showed no benefit over the antiemetic promethazine (Phenergan), at much greater cost. Intramuscular adrenocorticotropic hormone showed no benefit over placebo. A randomized, doubleblind, crossover trial showed ginger extract to be more beneficial for reducing symptoms than placebo. Promethazine (Phenergan) has also been compared to methylprednisolone in a randomized, double-blind, controlled trial. Methylprednisolone appeared to decrease the rate of readmission for HEG; however, the patients randomized to promethazine had a significantly longer duration of symptoms prior to treatment. Diazepam (Valium) was used in one randomized study and appeared to shorten hospitalization, significantly reduce nausea, and decrease incidents of readmission for HEG. No significant adverse effects or fetal abnormalities were observed.

Drug Category: Vitamins -- Essential for normal DNA synthesis and play a role in
various metabolic processes. Pyridoxine (Nestrex) -- Marketed in combination formulations with doxylamine (Benedectin, Dilectin). Benedectin was taken off the market in the United States in the 1980s because of liability issues, but it is available in Canada. Doxylamine is probably not teratogenic and can be used in combination with pyridoxine at a dose of 10-12.5 mg PO qd/bid. 10-50 mg PO bid/qid (often 30-100 mg/d) Not established May decrease levodopa, phenytoin, and phenobarbital serum levels A - Safe in pregnancy >200 mg/d may precipitate withdrawal effects when medication is discontinued

Drug Name

Adult Dose Pediatric Dose

Contraindications Documented hypersensitivity Interactions Pregnancy Precautions

Drug Category: Herbal medications -- Not approved by the US Food and Drug
Administration but are remedies believed to improve symptoms. Ginger -- A randomized, double-blind, crossover trial of a ginger extract was shown to be more beneficial for reducing symptoms than placebo.

Drug Name

http://www.emedicine.com/med/topic1075.htm Adult Dose Pediatric Dose Interactions Pregnancy 250 mg PO qid (powdered ginger root) Not established None reported C - Safety for use during pregnancy has not been established. Not recommended in pregnancy because no conclusive data are available; potential effect on testosterone binding and thromboxane synthetase activity are current concerns

Contraindications Documented hypersensitivity

Precautions

Drug Category: Antiemetics -- Useful in the treatment of symptomatic nausea.


Prochlorperazine (Compazine) -- May relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and depressing reticular activating system. In a placebo-controlled study, 69% of patients given prochlorperazine reported significant symptom relief, compared to 40% of patients in the placebo group. PO: 5-10 mg tid/qid; not to exceed 40 mg/d IV: 2.5-10 mg q3-4h prn; not to exceed 10 mg/dose or 40 mg/d IM: 5-10 mg q3-4h PR: 25 mg bid Not established

Drug Name

Adult Dose

Pediatric Dose

Documented hypersensitivity; bone marrow Contraindications suppression; coma; narrow-angle glaucoma; severe liver or cardiac disease Interactions Pregnancy Precautions Coadministration with other CNS depressants or anticonvulsants may cause additive effects; with epinephrine, may cause hypotension C - Safety for use during pregnancy has not been established. Drug-induced Parkinson syndrome or pseudoparkinsonism occurs quite frequently; akathisia is most common extrapyramidal reaction in elderly patients; lowers seizure threshold; may lower convulsive threshold; adverse effects can include hypotension,

http://www.emedicine.com/med/topic1075.htm sedation, and extrapyramidal and anticholinergic symptoms; data are conflicting regarding teratogenicity; crosses placenta and appears in breast milk Promethazine (Phenergan) -- For symptomatic treatment of nausea in vestibular dysfunction. Antidopaminergic agent effective in treating emesis. Blocks postsynaptic mesolimbic dopaminergic receptors in brain and reduces stimuli to brainstem reticular system. PO: 12.5-25 mg q4-6h prn (syr or tab) PR: 12.5-25 mg q4-6h prn IV/IM: 12.5-25 mg q4-6h; use caution with IV administration, concentration not to exceed 25 mg/mL, rate not to exceed 25 mg/min; do not administer SC or intra-arterially Not established May have additive effects when used concurrently with other CNS depressants or anticonvulsants; coadministration with epinephrine may cause hypotension C - Safety for use during pregnancy has not been established. Caution in cardiovascular disease, impaired liver function, seizures, sleep apnea, and asthma Chlorpromazine (Thorazine, Ormazine) -Mechanisms responsible for relieving nausea and vomiting include blocking postsynaptic mesolimbic dopamine receptors, anticholinergic effects, and depression of RAS. Blocks alpha-adrenergic receptors and depresses release of hypophyseal and hypothalamic hormones. PO: 10-25 mg q4-6h prn PR: 50-100 mg q6-8h prn IM: 12.5-25 mg once; if no hypotension, may administer 25-50 mg q3-4 h prn; caution with parenteral administration because of the potential for hypotension Not established

Drug Name

Adult Dose

Pediatric Dose

Contraindications Documented hypersensitivity Interactions

Pregnancy Precautions

Drug Name

Adult Dose

Pediatric Dose

http://www.emedicine.com/med/topic1075.htm Documented hypersensitivity; bone marrow Contraindications suppression, narrow-angle glaucoma, severe liver or cardiac disease Interactions Other CNS depressants, anticholinergics, or anticonvulsants; antihypertensives may cause additive effect; coadministration with epinephrine may cause hypotension C - Safety for use during pregnancy has not been established. May cause pseudoparkinsonism; akathisia is a common extrapyramidal reaction in elderly patients; lowers seizure threshold and increases risk of seizures in patient with history of seizures Methylprednisolone (Medrol) -- May improve symptoms of nausea and vomiting. 16 mg PO tid (48 mg/d) for 3 d initially, taper over 12 d; may be restarted or prior dose resumed if vomiting recurs during taper Not established Documented hypersensitivity; viral, fungal, or tubercular skin infections Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking concurrently with diuretics C - Safety for use during pregnancy has not been established. Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, osteoporosis, hypokalemia, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Pregnancy

Precautions

Drug Name Adult Dose Pediatric Dose Contraindications

Interactions

Pregnancy

Precautions

Drug Category: Antihistamines -- Studied in nausea and vomiting during pregnancy


and in small numbers of patients with HEG, providing relief in 82% of patients. Appears to be as efficacious as pyridoxine in another study. Drug Name Meclizine (Antivert) -- Decreases excitability

http://www.emedicine.com/med/topic1075.htm of middle ear labyrinth and blocks conduction in middle ear vestibular-cerebellar pathways. These effects are associated with relief of nausea and vomiting. Adult Dose Pediatric Dose 25-50 mg PO qid Not established May increase toxicity of CNS depressants, neuroleptics, and anticholinergics B - Usually safe but benefits must outweigh the risks. Caution in angle-closure glaucoma, prostatic hypertrophy, pyloric or duodenal obstruction, and bladder neck obstruction; should not be used when operating heavy machinery or driving; does not appear to be teratogenic
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Contraindications Documented hypersensitivity Interactions Pregnancy

Precautions

FOLLOW-UP

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Further Inpatient Care:

Inpatient care may be necessary if outpatient treatment fails or if severe fluid and/or electrolyte imbalance and nutritional compromise exist (see Treatment).

Further Outpatient Care:

Monitor patients regularly, paying attention to symptoms and to the state of mind of the patient and family. Monitor weight and urinary ketones at each visit.

In/Out Patient Meds:

See Treatment.

Complications:

Case reports describe the following maternal complications of HEG:


o o o

Esophageal rupture or perforation Pneumothorax and pneumomediastinum Wernicke encephalopathy or blindness

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Hepatic disease Seizures, coma, or death

Others complications include renal failure, pancreatitis, deep venous thrombosis, pulmonary embolism, central pontine myelinolysis, rhabdomyolysis, vitamin K deficiency and coagulopathy, and splenic avulsion. Complications associated with central hyperalimentation include sepsis, fungemia, tamponade, local infection, venous thrombosis, fatty infiltration of the placenta, and transaminitis. Interestingly, nausea and vomiting during pregnancy is associated with a lower risk of miscarriage, premature birth, low birth weight, and perinatal mortality. However, HEG may be associated with fetal complications of growth restriction and even fetal death, although this is controversial. One study found that in women with HEG and weight loss, 32% of children were below the 10th percentile for gestational weight at birth, versus only 6% of children in women with HEG and no weight loss. In most studies, an increase in congenital birth defects does not appear to be correlated with HEG.

Prognosis:

HEG is self-limited and, in most cases, improves by the end of the first trimester. However, symptoms may persist through 20-22 weeks of gestation and, in some cases, until delivery.

Patient Education:

Early patient education about the signs and symptoms of pregnancy may be beneficial. One study found an association between nausea and vomiting and insufficient knowledge about pregnancy, stress, doubts regarding the pregnancy, and poor communication with the doctor and spouse. Early interventions may include reassurance and dietary counseling, including directing the patient to eat small meals, to avoid high-fat or spicy foods, to follow hunger cues, and to increase the intake of dry carbohydrates and carbonated beverages. For excellent patient education resources, visit eMedicine's Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Pregnancy and Pregnancy, Vomiting.
Section 9 of 10

MISCELLANEOUS

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http://www.emedicine.com/med/topic1075.htm Medical/Legal Pitfalls:

Considering other diagnoses in cases of severe refractory nausea and vomiting is important during pregnancy, especially if the presentation is atypical or other symptoms are present. Fully informing patients of the available evidence regarding potential risks and benefits of all treatments administered for HEG is vital, especially regarding the effects of medications on the fetus. If not emergently required, avoid the administration of drugs during the first 10 weeks of gestation if possible.
Section 10 of 10

BIBLIOGRAPHY

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Abell TL, Riely CA: Hyperemesis gravidarum. Gastroenterol Clin North Am 1992 Dec; 21(4): 835-49[Medline]. Aikins Murphy P: Alternative therapies for nausea and vomiting of pregnancy. Obstet Gynecol 1998 Jan; 91(1): 149-55[Medline]. Broussard CN, Richter JE: Nausea and vomiting of pregnancy. Gastroenterol Clin North Am 1998 Mar; 27(1): 123-51[Medline]. Creasy RK, Resnik R: Thyroid disease and pregnancy. In: Creasy RK, Resnik R, eds. Maternal-Fetal Medicine, Principles and Practice. 4th ed. Philadelphia, Pa: WB Saunders; 1998: 1005-52. Ditto A, Morgante G, la Marca A, De Leo V: Evaluation of treatment of hyperemesis gravidarum using parenteral fluid with or without diazepam. A randomized study. Gynecol Obstet Invest 1999; 48(4): 232-6[Medline]. El Younis CM, Abulafia O, Sherer DM: Rapid marked response of severe hyperemesis gravidarum to oral erythromycin. Am J Perinatol 1998; 15(9): 5334[Medline]. Goodwin TM: Hyperemesis gravidarum. Clin Obstet Gynecol 1998 Sep; 41(3): 597-605[Medline]. Hershman JM: Human chorionic gonadotropin and the thyroid: hyperemesis gravidarum and trophoblastic tumors. Thyroid 1999 Jul; 9(7): 653-7[Medline]. Jarnfelt-Samsioe A, Eriksson B, Waldenstrom J, Samsioe G: Serum bile acids, gamma-glutamyltransferase and routine liver function tests in emetic and nonemetic pregnancies. Gynecol Obstet Invest 1986; 21(4): 169-76[Medline]. Jarnfelt-Samsioe A, Eriksson B, Mattsson LA, Samsioe G: Serum lipids and lipoproteins in pregnancies associated with emesis gravidarum. Gynecol Endocrinol 1987 Mar; 1(1): 51-60[Medline]. Kocak I, Akcan Y, Ustun C: Helicobacter pylori seropositivity in patients with hyperemesis gravidarum. Obstet Gynecol Sur 2000; 55 (4): 198-9. Lacroix R, Eason E, Melzack R: Nausea and vomiting during pregnancy: A prospective study of its frequency, intensity, and patterns of change. Am J Obstet Gynecol 2000 Apr; 182(4): 931-7[Medline]. Larimore WL, Petrie KA: Drug use during pregnancy and lactation. Prim Care 2000 Mar; 27(1): 35-53[Medline].

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Leylek OA, Toyaksi M, Erselcan T, Dokmetas S: Immunologic and biochemical factors in hyperemesis gravidarum with or without hyperthyroxinemia. Gynecol Obstet Invest 1999; 47(4): 229-34[Medline]. Safari HR, Fassett MJ, Souter IC, et al: The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double-blind, controlled study. Am J Obstet Gynecol 1998 Oct; 179(4): 921-4[Medline]. Safari HR, Alsulyman OM, Gherman RB, Goodwin TM: Experience with oral methylprednisolone in the treatment of refractory hyperemesis gravidarum. Am J Obstet Gynecol 1998 May; 178(5): 1054-8[Medline]. Scott JR: Normal Pregnancy and Prenatal Care, Medical and Surgical Complications of Pregnancy. In: Danforth DN, De Saia PJ, Hammond CB, Scott JR, eds. Danforth's Obstetrics and Gynecology. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999: 79, 333-6. Simon EP, Schwartz J: Medical hypnosis for hyperemesis gravidarum. Birth 1999 Dec; 26(4): 248-54[Medline]. Sorensen HT, Nielsen GL, Christensen K, et al: Birth outcome following maternal use of metoclopramide. The Euromap study group. Br J Clin Pharmacol 2000 Mar; 49(3): 264-8[Medline]. Sullivan CA, Johnson CA, Roach H, et al: A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol 1996 May; 174(5): 1565-8[Medline]. Wolkomir MS: Managing nausea and vomiting in pregnancy. Consultant 1996; 298-307.

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