Basics
Description
Hyperemesis gravidarum is a condition of severe nausea and vomiting during pregnancy, leading to fluid, electrolyte, and acid-base imbalance, nutritional deficiency, and weight loss.
- Ketonuria and weight loss of >5% of pre-pregnancy body weight distinguish hyperemesis from normal nausea and vomiting of pregnancy.
- The symptoms often require hospitalization.
Epidemiology
- More common in Western populations
- Hyperemesis patients are more likely to be younger and nonwhite.
- Average 1.3 hospital admissions per patient with hyperemesis
- Estimated cost of treating a single patient in the US is $17,000.
Incidence
Hyperemesis gravidarum occurs in 0.3 " 1.5% of all live births.
Prevalence
- Nausea and vomiting occur in up to 80% of pregnant women.
- Usually improves by 16 weeks gestation
- In up to 20% of patients, symptoms persist throughout pregnancy.
Risk Factors
- Primigravida
- Family history of hyperemesis in the patient 's mother
- History of hyperemesis in previous pregnancy
- Multiple gestation
- Gestational trophoblastic disease
- Certain fetal anomalies
- Trisomy 21, hydrops fetalis
- Helicobacter pylori infection
Genetics
- A daughter is 2 " 3 times as likely to have hyperemesis if her mother also had hyperemesis, suggesting underlying genetic predisposition.
- There does not appear to be a paternal genetic contribution to hyperemesis.
General Prevention
- There is no prevention.
- Early intervention can improve symptoms and may decrease hospitalizations.
Etiology
- Exact cause is unknown.
- Hormones of pregnancy, including ²-HCG and estrogen, are felt to play a key role by directly causing or lowering the threshold for nausea and vomiting.
- Symptoms are most severe at the time of peak HCG levels.
- There are hormone-mediated alterations seen in gastric motility.
- There are measurable changes in the vestibulo-ocular reflex function.
Associated Conditions
- Gastroesophageal reflux
- Depression
- Suppression of TSH/mild hyperthyroidism
Diagnosis
Hyperemesis is a clinical diagnosis. Delineating hyperemesis from nausea and vomiting of pregnancy can be difficult. The proposed criteria are most widely accepted:
- Intractable nausea and vomiting with:
- Ketonuria
- Loss of >5% of pre-pregnancy body weight
History
- History of hyperemesis in prior pregnancy or in the patient 's mother
- Onset of nausea and vomiting in the first trimester, usually starting at 4 " 5 weeks gestation
- Vomiting that begins after 12 weeks gestation should not immediately be attributed to nausea and vomiting of pregnancy.
- Patients often report ptyalism (excessive saliva) and spitting.
- Assess for gastroesophageal reflux symptoms (retrosternal discomfort and heartburn) as this may precipitate nausea and vomiting.
- Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scoring system can be administered at each visit (1)[B].
- 3-question survey that measures the severity of nausea and vomiting
- Includes number of daily vomiting episodes, length of nausea per day in hours, and number of retching episodes per day
Physical Exam
- Weight
- Assess for weight loss (>5%) or inadequate weight gain
- Signs of volume depletion
- Tachycardia
- Postural hypotension
- Dry oral mucosa
- Muscle wasting and weakness
- Thyroid examination
- Assess for goiter or thyroid nodule
Tests
Lab
- Urinalysis
- Assess for ketones or infection
- Electrolytes and renal function
- Severe hyponatremia is a reported complication.
- Hypokalemia common
- Prealbumin
- TSH
- Exclude acute thyrotoxicosis
- Theα-subunit of ²- HCG is identical to TSH and interacts with the TSH receptor leading to reduced production of TSH.
- Free T4 may be slightly elevated, though these patients are clinically euthyroid.
- H. pylori serology (2)[B]
- A few studies have shown an association with H. pylori, and there are case reports of symptom improvement after eradication.
- Liver function tests
- Abnormal in up to 50% of patients hospitalized with hyperemesis
- Mild elevation in transaminases is most common (ALT " > AST).
Imaging
Ultrasound (abdominal and pelvic):
- Exclude gallbladder disease, multiple gestation, and hydatidiform mole
Differential Diagnosis
- Nausea and vomiting of pregnancy
- Acute thyroiditis
- Eating disorders
- Molar pregnancy
- Biliary tract disease
- Hepatitis
- Gastroesophageal reflux disease
Treatment
Medication
There is often anxiety and reluctance to prescribe antiemetic agents in pregnancy, but extensive data shows lack of teratogenesis and good fetal safety data with the following medications:
First Line
Patients who vomit pills may need to be treated with suppositories or IV formulations.
- Pyridoxine (Vitamin B6) alone or with doxylamine (10 " 12.5 mg PO q.i.d.) (3)[A]
- Phenothiazines
- Promethazine (12.5 " 25 mg PO q4h) and prochlorperazine (5 " 10 mg q6h)
- Antihistamines
- Doxylamine and dimenhydrinate
- Prokinetic drugs
- Metoclopramide (10 mg PO or IV q6h)
- Acid suppression
- H2 blockers
- Ranitidine (75 " 150 mg PO b.i.d.)
Second Line
- Antiemetics
- HT3 receptor antagonists
- Ondansetron: Widespread, off-label use (4 " 8 mg IV or PO q8h)
- Acid suppression
- Proton pump inhibitors
- Rabeprazole, esomeprazole, pantoprazole, lansoprazole " " all pregnancy category B
- Corticosteroids have been used.
- Discordant results in randomized controlled trials
- Should be considered unproven and used only as a last resort
- Only may be used after 10 weeks gestation
Additional Treatment
General Measures
- Maintain fluid and electrolyte balance
- Maintain adequate caloric intake
- Control nausea and vomiting
Issues for Referral
- Referral to a dietician for discussion of hyperemesis diet
- Initiation of tube feeds or parenteral nutrition should be done in conjunction with a nutritionist.
- Severe or complicated cases may be referred to a gastroenterologist or maternal fetal medicine specialist.
Complementary and Alternative Medicine
- Behavioral therapy
- May benefit patients who are depressed or experiencing anticipatory nausea and vomiting
- Ginger
- Acupressure
- Wrist bands marketed for treatment of motion sickness are available over the counter and may help some patients.
Surgery
- In cases of severe protein-calorie malnutrition, a duodenal or jejunal feeding tube placement may be necessary.
- A catheter for venous access may be placed in patients requiring prolonged IV therapy or total parenteral nutrition (TPN).
In-Patient Considerations
Initial-Stabilization
- Correct fluid and electrolyte imbalance
- Patients at risk for Wernicke 's encephalopathy should be treated with thiamine replacement. Any patient with prolonged vomiting requiring IV fluids or parenteral nutrition is at risk.
- Avoid dextrose-containing fluids
Admission Criteria
Any woman who is ketotic and unable to maintain hydration should be hospitalized.
IV Fluids
- Initially, avoid dextrose-containing fluids, which may precipitate Wernicke 's encephalopathy.
- Patients with severe symptoms and recurrent hospitalizations should be considered for outpatient IV therapy.
- Maintaining adequate hydration improves nausea
- Can be administered through a visiting nurse or patients may be taught to self-administer fluids and IV medications
- Iatrogenic complications may occur.
- Hypercoagulability of pregnancy and dehydration from hyperemesis result in high risk of thrombosis.
- Infection or thrombosis of indwelling catheters used for long-term fluid replacement or TPN occurs in up to 50%.
- Peripheral access is preferable.
Discharge Criteria
Patient should tolerate enough oral intakes to maintain hydration or plans for outpatient IV therapy should be in place.
Ongoing Care
Follow-Up Recommendations
Most women can continue to eat and drink enough to be treated as outpatients.
Patient Monitoring
- Patients with severe hyperemesis should be seen weekly with longer duration between visits as symptoms abate.
- Weight should be assessed at each visit.
- Periodic monitoring of prealbumin and electrolytes is advisable.
Diet
- Hyperemesis diet should be recommended:
- Eat small portions frequently
- Avoid an empty stomach, which may aggravate nausea
- Separate solids and liquids
- Eat primarily high-carbohydrate foods
- Avoid fatty foods, dairy and high-fiber foods
- Limit spicy or highly seasoned foods
- Vitamin supplementation
- Prenatal vitamins containing iron may aggravate symptoms.
- Patients may substitute non-iron formulations or children 's chewable vitamins, which may be better tolerated.
Prognosis
- Mild-to-moderate nausea and vomiting in pregnancy is not associated with adverse fetal outcomes.
- In most patients with hyperemesis, pregnancy outcome is favorable.
- Symptoms generally abate as the pregnancy progresses and resolve in most by 18 weeks gestation.
- When weight loss >5%, infants may be born earlier, weigh less, and be small for gestational age.
Complications
- Wernicke 's encephalopathy
- Mallory " Weiss tears of the esophagus
- Low infant birth weight
- Maternal or fetal death
- Severe depression
- Termination of pregnancy
- Esophageal perforation
- Retinal hemorrhage
References
1Koren G, Boskovic R, Hard M. Motherisk-PUQE (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy. Am J Obstet Gynecol. 2002;186:S228 " S231. [View Abstract]2Mansour GM, Nashaat EH. Role of Helicobacter pylori in the pathogenesis of hyperemesis gravidarum. Arch Gynecol Obstet. 2011;284(4):843 " 847. [View Abstract]3Walsh JW, Hasler WL, Nugent CE. Progesterone and estrogen are potential mediators of gastric slow-wave dysrhythmias in nausea of pregnancy. Am J Physiol. 1996;270(3 Pt 1):G506 " G514. [View Abstract]
Additional Reading
1Abell T, Riely C. Hyperemesis gravidarum. Gastroenterol Clin North Am. 1992;21:835 " 849. [View Abstract]2Bailit JL. Hyperemesis gravidarium: Epidemiologic findings from a large cohort. Am J Obstet Gynecol. 2005;193(3 pt 1):811 " 814. [View Abstract]3Findings from the First international Conference on Nausea and Vomiting in Pregnancy. Available at http://www.nvp-volumes.org/4Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol. 1998;41:597 " 605. [View Abstract]5Goodwin TM, Nwankwo O, O 'Leary LD. The first demonstration that a subset of women with hyperemesis gravidarum has abnormalities in the vestibuloocular reflex pathway. Am J Obset Gynecol. 2008;199:417.e1 " 417.e9.6Niebyl JR. Nausea and vomiting in pregnancy. N Engl J Med. 2010;363(16):1544 " 1550. [View Abstract]7Verberg MFG, Gillot DJ, Al-Fardan N. Hyperemesis gravidarum, a literature review. Hum Reprod Update. 2005;11:527 " 539.8Vikanes A, Skjaerven R, Grjibovski. Recurrence of hyperemesis gravidarum across generations: Population based cohort study. BMJ. 2010;340:c2050. [View Abstract]
Codes
ICD9
- 643.0 Mild hyperemesis gravidarum
- 643.1 Hyperemesis gravidarum with metabolic disturbance
ICD10
- O21.0 Mild hyperemesis gravidarum
- O21.1 Hyperemesis gravidarum with metabolic disturbance
SNOMED
- 14094001 excessive vomiting in pregnancy (disorder)
- 129598007 severe hyperemesis gravidarum (disorder)
- 129597002 moderate hyperemesis gravidarum (disorder)
- 19569008 mild hyperemesis gravidarum (disorder)
Clinical Pearls
- Hyperemesis occurs in 0.3 " 1.5% of live births
- Pharmacologic therapy is beneficial for severe or protracted symptoms and does not have negative effects on the fetus.
- In most patients, pregnancy outcome is favorable, but severe, untreated disease may result in significant maternal and fetal morbidity.