Diagnostic Considerations

Important considerations

It is important to consider other diagnoses in cases of severe refractory nausea and vomiting during pregnancy, especially if the presentation is atypical or other symptoms are present.

It is vital to fully inform patients of the available evidence regarding potential risks and benefits of all treatments administered for hyperemesis gravidarum, 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.

Differential Diagnoses

Workup

Goodwin TM. Hyperemesis gravidarum. Obstet Gynecol Clin North Am. 2008 Sep. 35(3):401-17, viii.
Hay JE. Liver disease in pregnancy. Hepatology. 2008 Mar. 47(3):1067-76. [QxMD MEDLINE Link].
Tan JY, Loh KC, Yeo GS, et al. Transient hyperthyroidism of hyperemesis gravidarum. BJOG. 2002 Jun. 109(6):683-8. [QxMD MEDLINE Link].
Simon EP, Schwartz J. Medical hypnosis for hyperemesis gravidarum. Birth. 1999 Dec. 26(4):248-54. [QxMD MEDLINE Link].
Poursharif B, Korst LM, Macgibbon KW, et al. Elective pregnancy termination in a large cohort of women with hyperemesis gravidarum. Contraception. 2007 Dec. 76(6):451-5. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Bailit JL. Hyperemesis gravidarium: Epidemiologic findings from a large cohort. Am J Obstet Gynecol. 2005 Sep. 193(3 Pt 1):811-4. [QxMD MEDLINE Link].
Sherman PW, Flaxman SM. Nausea and vomiting of pregnancy in an evolutionary perspective. Am J Obstet Gynecol. 2002 May. 186(5 Suppl Understanding):S190-7. [QxMD MEDLINE Link].
Creasy RK, Resnik R. Gastrointestinal disease in pregnancy. Creasy RK, Resnik R, eds. Maternal-Fetal Medicine, Principles and Practice. 5th ed. Philadelphia, Pa: WB Saunders; 2004. 1109-22.
Kuscu NK, Koyuncu F. Hyperemesis gravidarum: current concepts and management. Postgrad Med J. 2002 Feb. 78(916):76-9. [QxMD MEDLINE Link].
Goodwin TM, Nwankwo OA, O'Leary LD, et al. The first demonstration that a subset of women with hyperemesis gravidarum has abnormalities in the vestibuloocular reflex pathway. Am J Obstet Gynecol. 2008 Oct. 199(4):417.e1-9. [QxMD MEDLINE Link].
Rodien P, Jordan N, Lefevre A, et al. Abnormal stimulation of the thyrotrophin receptor during gestation. Hum Reprod Update. 2004 Mar-Apr. 10(2):95-105. [QxMD MEDLINE Link].
Panesar NS, Li CY, Rogers MS. Are thyroid hormones or hCG responsible for hyperemesis gravidarum? A matched paired study in pregnant Chinese women. Acta Obstet Gynecol Scand. 2001 Jun. 80(6):519-24. [QxMD MEDLINE Link].
Murata T, Suzuki S, Takeuchi T, et al. Relation between plasma adenosine and serum TSH levels in women with hyperemesis gravidarum. Arch Gynecol Obstet. 2006 Mar. 273(6):331-6. [QxMD MEDLINE Link].
Leylek OA, Toyaksi M, Erselcan T, et al. Immunologic and biochemical factors in hyperemesis gravidarum with or without hyperthyroxinemia. Gynecol Obstet Invest. 1999. 47(4):229-34. [QxMD MEDLINE Link].
Hershman JM. Human chorionic gonadotropin and the thyroid: hyperemesis gravidarum and trophoblastic tumors. Thyroid. 1999 Jul. 9(7):653-7. [QxMD MEDLINE Link].
Lagiou P, Tamimi R, Mucci LA, et al. Nausea and vomiting in pregnancy in relation to prolactin, estrogens, and progesterone: a prospective study. Obstet Gynecol. 2003 Apr. 101(4):639-44. [QxMD MEDLINE Link].
Koch KL. Gastrointestinal factors in nausea and vomiting of pregnancy. Am J Obstet Gynecol. 2002 May. 186(5 Suppl Understanding):S198-203. [QxMD MEDLINE Link].
Kosus A, Kosus N, Usluogullari B, Hizli D, Namuslu M, Ayyildiz A. Gut satiety hormones and hyperemesis gravidarum. Arch Gynecol Obstet. 2015 Dec. 292 (6):1225-30. [QxMD MEDLINE Link].
Shekhar S, Diddi G. Liver disease in pregnancy. Taiwan J Obstet Gynecol. 2015 Oct. 54 (5):475-82. [QxMD MEDLINE Link].
Ergin M, Cendek BD, Neselioglu S, Avsar AF, Erel O. Dynamic thiol-disulfide homeostasis in hyperemesis gravidarum. J Perinatol. 2015 Oct. 35 (10):788-92. [QxMD MEDLINE Link].
Jarnfelt-Samsioe A, Eriksson B, Waldenstrom J, et al. Serum bile acids, gamma-glutamyltransferase and routine liver function tests in emetic and nonemetic pregnancies. Gynecol Obstet Invest. 1986. 21(4):169-76. [QxMD MEDLINE Link].
Ustun Y, Engin-Ustun Y, Dokmeci F, et al. Serum concentrations of lipids and apolipoproteins in normal and hyperemetic pregnancies. J Matern Fetal Neonatal Med. 2004 May. 15(5):287-90. [QxMD MEDLINE Link].
Kocak I, Akcan Y, Ustun C, Demirel C, Cengiz L, Yanik FF. Helicobacter pylori seropositivity in patients with hyperemesis gravidarum. Int J Gynaecol Obstet. 1999 Sep. 66(3):251-4. [QxMD MEDLINE Link].
Lee RH, Pan VL, Wing DA. The prevalence of Helicobacter pylori in the Hispanic population affected by hyperemesis gravidarum. Am J Obstet Gynecol. 2005 Sep. 193(3 Pt 2):1024-7. [QxMD MEDLINE Link].
Black FO. Maternal susceptibility to nausea and vomiting of pregnancy: is the vestibular system involved?. Am J Obstet Gynecol. 2002 May. 186(5 Suppl Understanding):S204-9. [QxMD MEDLINE Link].
Heinrichs L. Linking olfaction with nausea and vomiting of pregnancy, recurrent abortion, hyperemesis gravidarum, and migraine headache. Am J Obstet Gynecol. 2002 May. 186(5 Suppl Understanding):S215-9. [QxMD MEDLINE Link].
Vikanes A, Skjaerven R, Grjibovski AM, et al. Recurrence of hyperemesis gravidarum across generations: population based cohort study. BMJ. 2010 Apr 29. 340:c2050. [QxMD MEDLINE Link]. [Full Text].
Zhang Y, Cantor RM, MacGibbon K, et al. Familial aggregation of hyperemesis gravidarum. Am J Obstet Gynecol. 2011 Mar. 204(3):230.e1-7. [QxMD MEDLINE Link].
Fejzo MS, Sazonova OV, Sathirapongsasuti JF, Hallgrímsdóttir IB, Vacic V, MacGibbon KW, et al. Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum. Nat Commun. 2018 Mar 21. 9 (1):1178. [QxMD MEDLINE Link].
Kaplan PB, Gucer F, Sayin NC, et al. Maternal serum cytokine levels in women with hyperemesis gravidarum in the first trimester of pregnancy. Fertil Steril. 2003 Mar. 79(3):498-502. [QxMD MEDLINE Link].
Kiyokawa Y, Yoneyama Y. Relationship between adenosine and T-helper 1/T-helper 2 balance in hyperemesis gravidarum. Clin Chim Acta. 2006 Aug. 370(1-2):137-42. [QxMD MEDLINE Link].
Sekizawa A, Sugito Y, Iwasaki M, et al. Cell-free fetal DNA is increased in plasma of women with hyperemesis gravidarum. Clin Chem. 2001 Dec. 47(12):2164-5. [QxMD MEDLINE Link].
Sugito Y, Sekizawa A, Farina A, et al. Relationship between severity of hyperemesis gravidarum and fetal DNA concentration in maternal plasma. Clin Chem. 2003 Oct. 49(10):1667-9. [QxMD MEDLINE Link].
Yoneyama Y, Suzuki S, Sawa R, et al. Plasma adenosine concentrations increase in women with hyperemesis gravidarum. Clin Chim Acta. 2005 Feb. 352(1-2):75-9. [QxMD MEDLINE Link].
Yoneyama Y, Suzuki S, Sawa R, et al. The T-helper 1/T-helper 2 balance in peripheral blood of women with hyperemesis gravidarum. Am J Obstet Gynecol. 2002 Dec. 187(6):1631-5. [QxMD MEDLINE Link].
Biberoglu EH, Kirbas A, Dirican AO, et al. Alterations in lipid peroxidation and T-cell function in women with hyperemesis gravidarum. J Obstet Gynaecol. 2015 Sep 14. 1-4. [QxMD MEDLINE Link].
Simpson SW, Goodwin TM, Robins SB, et al. Psychological factors and hyperemesis gravidarum. J Womens Health Gend Based Med. 2001 Jun. 10(5):471-7. [QxMD MEDLINE Link].
Buckwalter JG, Simpson SW. Psychological factors in the etiology and treatment of severe nausea and vomiting in pregnancy. Am J Obstet Gynecol. 2002 May. 186(5 Suppl Understanding):S210-4. [QxMD MEDLINE Link].
Morrow GR, Roscoe JA, Hickok JT, et al. Nausea and emesis: evidence for a biobehavioral perspective. Support Care Cancer. 2002 Mar. 10(2):96-105. [QxMD MEDLINE Link].
Mitchell-Jones N, Gallos I, Farren J, Tobias A, Bottomley C, Bourne T. Psychological morbidity associated with hyperemesis gravidarum: a systematic review and meta-analysis. BJOG. 2017 Jan. 124 (1):20-30. [QxMD MEDLINE Link].
Fell DB, Dodds L, Joseph KS, et al. Risk factors for hyperemesis gravidarum requiring hospital admission during pregnancy. Obstet Gynecol. 2006 Feb. 107(2 Pt 1):277-84. [QxMD MEDLINE Link].
Dodds L, Fell DB, Joseph KS, et al. Outcomes of pregnancies complicated by hyperemesis gravidarum. Obstet Gynecol. 2006 Feb. 107(2 Pt 1):285-92. [QxMD MEDLINE Link].
Nurmi M, Rautava P, Gissler M, Vahlberg T, Polo-Kantola P. Incidence and risk factors of hyperemesis gravidarum: A national register-based study in Finland, 2005-2017. Acta Obstet Gynecol Scand. 2020 Aug. 99 (8):1003-13. [QxMD MEDLINE Link].
Fossum S, Vikanes ÅV, Naess Ø, Vos L, Grotmol T, Halvorsen S. Hyperemesis gravidarum and long-term mortality: a population-based cohort study. BJOG. 2016 Dec 15. [QxMD MEDLINE Link].
Boelig RC, Barton SJ, Saccone G, Kelly AJ, Edwards SJ, Berghella V. Interventions for treating hyperemesis gravidarum. Cochrane Database Syst Rev. 2016 May 11. CD010607. [QxMD MEDLINE Link].
Rosen T, de Veciana M, Miller HS, et al. A randomized controlled trial of nerve stimulation for relief of nausea and vomiting in pregnancy. Obstet Gynecol. 2003 Jul. 102(1):129-35. [QxMD MEDLINE Link].
Borrelli F, Capasso R, Aviello G, et al. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol. 2005 Apr. 105(4):849-56. [QxMD MEDLINE Link].
McParlin C, O'Donnell A, Robson SC, Beyer F, Moloney E, Bryant A, et al. Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review. JAMA. 2016 Oct 4. 316 (13):1392-1401. [QxMD MEDLINE Link].
Liu AT, Chen S, Jena PK, Sheng L, Hu Y, Wan YY. Probiotics improve gastrointestinal function and life quality in pregnancy. Nutrients. 2021 Nov 3. 13 (11):[QxMD MEDLINE Link]. [Full Text].
Safari HR, Alsulyman OM, Gherman RB, et al. Experience with oral methylprednisolone in the treatment of refractory hyperemesis gravidarum. Am J Obstet Gynecol. 1998 May. 178(5):1054-8. [QxMD MEDLINE Link].
US Food and Drug Administration. FDA approves Diclegis for pregnant women experiencing nausea and vomiting. April 8, 2013. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm347087.htm. Accessed: April 15, 2013.
Lowes R. FDA approves Diclegis as first morning sickness drug in 30 years. Medscape Medical News. April 9, 2013. Available at http://www.medscape.com/viewarticle/782212. Accessed: April 15, 2013.
Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010 Dec. 203(6):571.e1-7. [QxMD MEDLINE Link].
Koren G, Maltepe C. Preemptive Diclectin therapy for the management of nausea and vomiting of pregnancy and hyperemesis gravidarum (abstract). ClinicalTrials.gov. Available at http://clinicaltrials.gov/show/NCT00293644. Accessed: April 10, 2013.
Matok I, Gorodischer R, Koren G, Sheiner E, Wiznitzer A, Levy A. The safety of metoclopramide use in the first trimester of pregnancy. N Engl J Med. 2009 Jun 11. 360(24):2528-35. [QxMD MEDLINE Link].
Holmgren C, Aagaard-Tillery KM, Silver RM, et al. Hyperemesis in pregnancy: an evaluation of treatment strategies with maternal and neonatal outcomes. Am J Obstet Gynecol. 2008 Jan. 198(1):56.e1-4. [QxMD MEDLINE Link].
ACOG. ACOG (American College of Obstetrics and Gynecology) Practice Bulletin: nausea and vomiting of pregnancy. Obstet Gynecol. 2004 Apr. 103(4):803-14. [QxMD MEDLINE Link].
Fejzo MS, Magtira A, Schoenberg FP, et al. Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol. 2013 Sep. 170(1):71-6. [QxMD MEDLINE Link].
Fox S. Morning sickness: antihistamines linked to poor outcomes. Medscape Medical News from WebMD. June 14, 2013. Available at http://www.medscape.com/viewarticle/806282. Accessed: June 19, 2013.
Goodwin TM. Nausea and vomiting of pregnancy: an obstetric syndrome. Am J Obstet Gynecol. 2002 May. 186(5 Suppl Understanding):S184-9. [QxMD MEDLINE Link].
Hsu JJ, Clark-Glena R, Nelson DK, et al. Nasogastric enteral feeding in the management of hyperemesis gravidarum. Obstet Gynecol. 1996 Sep. 88(3):343-6. [QxMD MEDLINE Link].
Jarnfelt-Samsioe A, Eriksson B, Mattsson LA, et al. Serum lipids and lipoproteins in pregnancies associated with emesis gravidarum. Gynecol Endocrinol. 1987 Mar. 1(1):51-60. [QxMD MEDLINE Link].
Larimore WL, Petrie KA. Drug use during pregnancy and lactation. Prim Care. 2000 Mar. 27(1):35-53. [QxMD MEDLINE Link].
Scott JR. Medical and surgical complications of pregnancy. Danforth DN, De Saia PJ, Hammond CB, Scott JR, eds. Danforth's Obstetrics and Gynecology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008. 282-6.
Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018 Jan. 131 (1):e15-e30. [QxMD MEDLINE Link].

Media Gallery

of 0

Author

Dotun A Ogunyemi, MD Vice Chair of Patient Safety and Quality, William Beaumont Hospital; Professor, Oakland University, William Beaumont School of Medicine; Clinical Services Professor of Obstetrics and Gynecology, University of California, Los Angeles, David Geffen School of Medicine

Dotun A Ogunyemi, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, National Medical Association, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Richard S Legro, MD Professor, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Pennsylvania State University College of Medicine; Consulting Staff, Milton S Hershey Medical Center

Richard S Legro, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Society of Reproductive Surgeons, American Society for Reproductive Medicine, Endocrine Society, Phi Beta Kappa

Disclosure: Received honoraria from Korea National Institute of Health and National Institute of Health (Bethesda, MD) for speaking and teaching; Received honoraria from Greater Toronto Area Reproductive Medicine Society (Toronto, ON, CA) for speaking and teaching; Received honoraria from American College of Obstetrics and Gynecologists (Washington, DC) for speaking and teaching; Received honoraria from National Institute of Child Health and Human Development Pediatric and Adolescent Gynecology Research Thi.

Chief Editor

Christine Isaacs, MD Associate Professor, Department of Obstetrics and Gynecology, Division Head, General Obstetrics and Gynecology, Medical Director of Midwifery Services, Virginia Commonwealth University School of Medicine

Christine Isaacs, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists

Disclosure: Nothing to disclose.

Additional Contributors

Suzanne R Trupin, MD, FACOG Clinical Professor, Department of Obstetrics and Gynecology, University of Illinois College of Medicine at Urbana-Champaign; CEO and Owner, Women's Health Practice; CEO and Owner, Hada Cosmetic Medicine and Midwest Surgical Center

Suzanne R Trupin, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, International Society for Clinical Densitometry, AAGL, North American Menopause Society, American Medical Association, Association of Reproductive Health Professionals

Disclosure: Nothing to disclose.

Alex Fong, MD Staff Physician, Obstetrics and Gynecology Department, Cedars-Sinai Medical Center

Alex Fong, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Tiffany Chen Herrero, MD Resident Physician, Department of Obstetrics and Gynecology, Cedars Sinai Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Drugs & Diseases gratefully acknowledge the contributions of previous author Giulia A Michelini, MD, to the development and writing of this article.