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Hyperemesis Gravidarum
Emma Brooks, MD
image BASICS
DESCRIPTION
  • Hyperemesis gravidarum is persistent vomiting in a pregnant woman that interferes with fluid and electrolyte balance as well as nutrition:
    • Usually associated with the first 8 to 20 weeks of pregnancy
    • Believed to have biomedical and behavioral aspects
    • Associated with high estrogen and human chorionic gonadotropin (hCG) levels
    • Symptoms usually begin ~2 weeks after first missed period.
  • System(s) affected: endocrine/metabolic; gastrointestinal; reproductive
  • Synonym(s): morning sickness
Pregnancy Considerations
Common condition during pregnancy, typically in the 1st and 2nd trimesters but may persist into the 3rd trimester.
EPIDEMIOLOGY
Incidence
Hyperemesis gravidarum occurs in 1-2% of pregnancies.
Prevalence
Hyperemesis gravidarum is the most common cause of hospitalization in the first half of pregnancy and the second most common cause of hospitalization of pregnant women.
ETIOLOGY AND PATHOPHYSIOLOGY
  • Unknown
  • Possible psychologic factors
  • Hyperthyroidism
  • Hyperparathyroidism
  • Gestational hormones
  • Liver dysfunction
  • Autonomic nervous system dysfunction
  • CNS neoplasm
  • Addison disease
RISK FACTORS
  • Obesity
  • Nulliparity
  • Multiple gestations
  • Gestational trophoblastic disease
  • Gonadotropin production stimulated
  • Altered GI function
  • Hyperthyroidism
  • Hyperparathyroidism
  • Liver dysfunction
  • Female fetus
  • Helicobacter pylori infection (1)
GENERAL PREVENTION
Anticipatory guidance in 1st and 2nd trimesters regarding dietary habits in hopes of avoiding dehydration and nutritional depletion.
Pregnancy Considerations
  • 2% of pregnancies have electrolyte disturbances.
  • 50% of pregnancies have at least some GI disturbance.
COMMONLY ASSOCIATED CONDITIONS
Hyperthyroidism
image DIAGNOSIS
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Urinalysis: may see glucosuria, albuminuria, granular casts, and hematuria (rare); ketosis more common
  • Thyroid-stimulating hormone (TSH), T4
  • Electrolytes, BUN, creatinine:
    • Electrolyte abnormalities due to nausea and vomiting and subsequent dehydration
    • Acidosis
  • Calcium
  • Uric acid
  • Hypoalbuminemia
  • No imaging is indicated for the diagnosis of hyperemesis gravidarum unless there is concern for hydatidiform mole or multiple gestation, in which case ultrasound may be obtained.
Follow-Up Tests & Special Considerations
  • If hypercalcemia, consider checking parathyroid hormone (PTH) for hyperparathyroidism.
  • Drugs are unlikely to alter lab results.
Diagnostic Procedures/Other
Indicated only if it is necessary to rule out other diagnoses, as listed in the following section
DIFFERENTIAL DIAGNOSIS
Other common causes of vomiting must be considered:
  • Gastroenteritis
  • Gastritis
  • Reflux esophagitis
  • Peptic ulcer disease
  • Cholelithiasis
  • Cholecystitis
  • Pyelonephritis
  • Anxiety
  • Hyperparathyroidism
  • H. pylori infection
image TREATMENT
Pyridoxine and doxylamine (pregnancy Category A) are first-line treatments for hyperemesis gravidarum (2)[C]. This is followed by metoclopramide or ondansetron (pregnancy Category B), then prochlorperazine (pregnancy Category C), methylprednisolone (pregnancy Category C), or promethazine (pregnancy Category C).
GENERAL MEASURES
  • Patient reassurance
  • Bed rest
  • If dehydrated, IV fluids, either normal saline or 5% dextrose normal saline (with consideration for potential thiamine deficiency). Repeat if there is a recurrence of symptoms following initial improvement.
  • For severe cases, consider PO thiamine 25 to 50 mg TID or IV 100 mg in 100 mL of normal saline over 30 minutes once weekly and potential parental nutrition if needed.
  • Ondansetron carries an FDA warning regarding concerns for QT prolongation, but this is in the setting of high-dose IV administration and in patients with heart disease. It has unclear risk in the setting of pregnancy. The majority of the current studies appear to show no increased risk of fetal malformation with the use of ondansetron, but this is still an area of controversy (3)[C],(4)[B].
MEDICATION
  • Pyridoxine (vitamin B6) 25 mg PO or IV every 8 hours
  • Antihistamines (e.g., diphenhydramine [25 to 50 mg q4-6h] or doxylamine [12.5 mg PO BID]) (5)[C]
  • Combination product Diclegis (sustained-release pyridoxine 10 mg and doxylamine 10 mg) dosed (start 2 tabs PO q hs; if sx persist, increase to 1 tab in AM & 2 hs; if sx still persist, take 1 tab q AM, 1 mid day, and 2 hs; max 4 tablets/day)
  • P.507

  • Phenothiazines (e.g., promethazine or prochlorperazine):
    • Precautions: Phenothiazines are associated with prolonged jaundice, extrapyramidal effects, and hyper- or hyporeflexia in newborns.
  • Meclizine 25 mg PO q6h
  • Metoclopramide 10 mg PO q6 to 8h
  • Methylprednisolone 16 mg PO/IV q8h for 2 to 3 days, then taper over 2 weeks if initial 3-day treatment is effective.
  • Ondansetron 4 to 8 mg PO q8h
Pregnancy Considerations
All medications taken during pregnancy should balance the risks and benefits both to the mother and the fetus.
COMPLEMENTARY & ALTERNATIVE MEDICINE
  • Ginger 350 mg PO TID may help (6)[A].
  • Motion sickness wristbands are another nonpharmacologic intervention that may improve symptoms. Evidence is mixed regarding the impact of acupressure and acupuncture in treating hyperemesis gravidarum (7)[C].
  • Medical hypnosis may be a helpful adjunct to the typical medical treatment regimen, but further study is needed (8)[C].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Typically outpatient therapy
  • In some severe cases, parenteral therapy in the hospital or at home may be required.
  • Enteral volume and nutrition repletion may be indicated.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Activity as tolerated after improvement
Patient Monitoring
  • In severe cases, follow-up on a daily basis for weight monitoring.
  • Special attention should be given to monitor for ketosis, hypokalemia, or acid-base disturbances due to hyperemesis.
DIET
  • NPO for first 24 hours if patient is ill enough to require hospitalization.
  • For outpatient: a diet rich in carbohydrates and protein, such as fruit, cheese, cottage cheese, eggs, beef, poultry, vegetables, toast, crackers, rice. Limit intake of butter. Patients should avoid spicy meals and high-fat foods. Consider cold foods. Encourage small amounts at a time every 1 to 2 hours.
PATIENT EDUCATION
  • Attention should be given to psychosocial issues, such as possible ambivalence about the pregnancy.
  • Patients should be instructed to take small amounts of fluid frequently to avoid volume depletion.
  • Avoid individual foods known to be irritating to the patient.
  • Wet-to-dry nutrients (sherbet, broth, gelatin to dry crackers, toast)
PROGNOSIS
  • Self-limited illness with good prognosis if patient's weight is maintained at >95% of prepregnancy weight.
  • With complication of hemorrhagic retinitis, mortality rate of pregnant patient is 50%.
REFERENCES
1. Li L, Li L, Zhou X, et al. Helicobacter pylori infection is associated with an increased risk of hyperemesis gravidarum: a meta-analysis. Gastroenterol Res Pract. 2015;2015:278905.
2. Maltepe C, Koren G. The management of nausea and vomiting of pregnancy and hyperemesis gravidarum—a 2013 update. J Popul Ther Clin Pharmacol. 2013;20(2):e184-e192.
3. Doggrell SA, Hancox JC. Cardiac safety concerns for ondansetron, an antiemetic commonly used for nausea linked to cancer treatment and following anaesthesia. Expert Opin Drug Saf. 2013;12(3):421-431.
4. Pasternak B, Svanström H, Hviid A. Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med. 2013;368(9):814-823.
5. Boelig RC, Berghella V, Kelly AJ, et al. Interventions for treating hyperemesis gravidarum. Cochrane Database of Syst Rev. 2013;(6):CD010607.
6. Viljoen E, Visser J, Koen N, et al. A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting. Nutr J. 2014;13:20.
7. Xu J, MacKenzie IZ. The current use of acupuncture during pregnancy and childbirth. Curr Opin Obstet Gynecol. 2012;24(2):65-71.
8. McCormack D. Hypnosis for hyperemesis gravidarum. J Obstet Gynaecol. 2010;30(7):647-653.
9. Veenendaal MV, van Abeelen AF, Painter RC, et al. Consequences of hyperemesis gravidarum for offspring: a systematic review and meta-analysis. BJOG. 2011;118(11):1302-1313.
Additional Reading
&NA;
  • Abas MN, Tan PC, Azmi N, et al. Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2014;123(6):1272-1279.
  • Anderka M, Mitchell AA, Louik C, et al. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth Defects Res A Clin Mol Teratol. 2012;94(1):22-30.
  • Jarvis S, Nelson-Piercy C. Management of nausea and vomiting in pregnancy. BMJ. 2011;342:d3606.
  • Matthews A, Haas DM, O'Mathúna DP, et al. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2014;(3):CD007575.
  • McCarthy FP, Lutomski JE, Greene RA. Hyperemesis gravidarum: current perspectives. Int J Womens Health. 2014;6:719-725.
  • Tan PC, Omar SZ. Contemporary approaches to hyperemesis during pregnancy. Curr Opin Obstet Gynecol. 2011;23(2):87-93.
Codes
&NA;
ICD10
  • O21.9 Vomiting of pregnancy, unspecified
  • O21.0 Mild hyperemesis gravidarum
  • O21.1 Hyperemesis gravidarum with metabolic disturbance
Clinical Pearls
&NA;
  • Do not allow patients to become volume depleted. Once this occurs, it is more difficult to interrupt the process.
  • Do not be hesitant to use medications to assist the patient, as this may help avoid volume depletion.
  • Consider secondary causes of hyperemesis if it develops after 12 weeks of gestation.