Background: In the United States, hyperemesis gravidarum is the most common cause of hospitalization during the first half of pregnancy and is second only to preterm labor for hospitalizations in pregnancy overall. In approximately 0.3-3% of pregnancies, hyperemesis gravidarum is prevalent and this percentage varies on account of different diagnostic criteria and ethnic variation in study populations. Despite extensive research in this field, the mechanism of the disease is largely unknown. Although cases of mortality are rare, hyperemesis gravidarum has been associated with both maternal and fetal morbidity. The current mainstay of treatment relies heavily on supportive measures until improvement of symptoms as part of the natural course of hyperemesis gravidarum, which occurs with progression of gestational age. However, studies have reported that severe, refractory disease manifestations have led to serious adverse outcomes and to termination of pregnancies. Summary: Despite extensive research in the field, the pathogenesis of hyperemesis gravidarum remains unknown. Recent literature points to a genetic predisposition in addition to previously studied factors such as infectious, psychiatric, and hormonal contributions. Maternal morbidity is common and includes psychological effects, financial burden, clinical complications from nutritional deficiencies, gastrointestinal trauma, and in rare cases, neurological damage. The effect of hyperemesis gravidarum on neonatal health is still debated in literature with conflicting results regarding outcomes of birth weight and prematurity. Available therapy options remain largely unchanged in the past several decades and focus on parenteral antiemetic medications, electrolyte repletion, and nutritional support. Most studies of therapeutic options do not consist of randomized control studies and cross-study analysis is difficult due to considerable variation of diagnostic criteria. Key Messages: Hyperemesis gravidarum carries a significant burden on maternal health and US health care. Most published research on pathogenesis is observational and suggests multifactorial associations with hyperemesis gravidarum. Precise, strictly defined criteria for clinical diagnosis are likely to benefit meta-analyses of further research studies regarding pathogenesis as well as therapeutic options.

Keywords:
Hyperemesis gravidarum, Nausea and vomiting of pregnancy, Therapeutic modalities
1.
Daniels J: Hyperemersis gravidarum: past hysteria and present needs. BJOG 2017;124:31.
2.
Bacon CS: The vomiting of pregnancy. Am J Med Sci 1898;115:680-683.
3.
Ping E, Virginia W: Causes and treatment modalities of Hyperemesis Gravidarum during the late nineteenth and early twentieth century in the United States and Great Britain. American Public University, 2010.
4.
American College of Obstetricians and Gynecologists: Practice Bulletin No. 153: nausea and vomiting of pregnancy. Obstet Gynecol 2015;126:e12-e24.
5.
Boelig RC, Barton SJ, Saccone G, Kelly AJ, Edwards SJ, Berghella V: Interventions for treating hyperemesis gravidarum. Cochrane Database Syst Rev 2016;5:1-147.
6.
Fejzo MS, Ingles SA, Wilson M, Wang W, MacGibbon K, Romero R, Goodwin TM: High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals. Eur J Obstet Gynecol Reprod Biol 2008;141:13-17.
7.
Patterson AM: Hyperemesis Gravidarum. Ferri's Clinical Advisor 2017;6:629-629i.
8.
Lee NM, Saha S: Nausea and vomiting of pregnancy. Gastroenterol Clin North Am 2011;40:309-334.
9.
Ebrahimi N, Maltepe C, Bournissen FG, Koren G: Nausea and vomiting of pregnancy: using the 24-hour pregnancy-unique quantification of emesis (PUQE-24) scale. J Obstet Gynaecol Can 2009;31:803-807.
10.
Loh KY, Sivalingam N: Understanding hyperemesis gravidarum. Med J Malaysia 2005;60:394-399.
11.
Eliakim R, Abulafia O, Sherer DM: Hyperemesis gravidarum: a current review. Am J Perinatol 2000;17:207-218.
12.
Niemeijer MN, Grooten IJ, Vos N, Bais JM, van der Post JA, Mol BW, Roseboom TJ, Leeflang NM, Painter RC: Diagnostic markers for hyperemesis gravidarum: a systematic review and metaanalysis. Am J Obstet Gynecol 2014;211:150.e1-e15.
13.
Kjeldgaard HK, Eberhard-Gran M, Benth JŠ, Nordeng H, Vikanes ÅV: History of depression and risk of hyperemesis gravidarum: a population-based cohort study. Arch Womens Ment Health 2017;20:397-404.
14.
Christodoulou-Smith J, Gold JI, Romero R, Goodwin TM, Macgibbon KW, Mullin PM, Fejzo MS: Posttraumatic stress symptoms following pregnancy complicated by hyperemesis gravidarum. J Matern Fetal Neonatal Med 2011;24:1307-1311.
15.
Verberg MF, Gillott DJ, Al-Fardan N, Grudzinskas JG: Hyperemesis gravidarum, a literature review. Hum Reprod Update 2005;11:527-539.
16.
Grooten IJ, Den Hollander WJ, Roseboom TJ, Kuipers EJ, Jaddoe VW, Gaillard R, Painter RC: Helicobacter pylori infection: a predictor of vomiting severity in pregnancy and adverse birth outcome. Am J Obstet Gynecol 2017;216:512.e1-e9.
17.
Li L, Li L, Zhou X, Xiao S, Gu H, Zhang G: Helicobacter pylori infection is associated with an increased risk of hyperemesis gravidarum: a meta-analysis. Gastroenterol Res Pract 2015;2015:278905.
18.
Golberg D, Szilagyi A, Graves L: Hyperemesis gravidarum and Helicobacter pylori infection: a systematic review. Obstet Gynecol 2007;110:695-703.
19.
Selitsky T, Chandra P, Schiavello HJ: Wernicke's encephalopathy with hyperemesis and ketoacidosis. Obstet Gynecol 2006;107:486-490.
20.
Chiossi G, Neri I, Cavazzuti M, Basso G, Facchinetti F: Hyperemesis gravidarum complicated by Wernicke encephalopathy: background, case report, and review of the literature. Obstet Gynecol Surv 2006;61:255-268.
21.
Giugale LE, Young OM, Streitman DC: Iatrogenic Wernicke encephalopathy in a patient with severe hyperemesis gravidarum. Obstet Gynecol 2015;125:1150-1152.
22.
Sutamnartpong P, Muengtaweepongsa S, Kulkantrakorn K: Wernicke's encephalopathy and central pontine myelinolysis in hyperemesis gravidarum. J Neurosci Rural Pract 2013;4:39-41.
23.
Baba Y, Morisawa H, Saito K, Takahashi H, Rifu K, Matsubara S: Intraperitoneal hemorrhage in a pregnant woman with hyperemesis gravidarum: vitamin K deficiency as a possible cause. Case Rep Obstet Gynecol 2016;2016:5384943.
24.
Lassey SC, Robinson JN: Rhabdomyolysis after hyperemesis gravidarum. Obstet Gynecol 2016;128:195-196.
25.
Buchanan GM, Franklin V: Hamman and Boerhaave syndromes - diagnostic dilemmas in a patient presenting with hyperemesis gravidarum: a case report. Scott Med J 2014;59:e12-e16.
26.
Poursharif B, Korst LM, MacGibbon KW, Fejzo MS, Romero R, Goodwin TM: Elective pregnancy termination in a large cohort of women with hyperemesis gravidarum. Contraception 2007;76:451-455.
27.
Simpson SW, Goodwin TM, Robins SB, Rizzo AA, Howes RA, Buckwalter DK, Buckwalter JG: Psychological factors and hyperemesis gravidarum. J Wones Health Gend Based Med 2001;10:471-477.
28.
Hizli D, Kamalak Z, Kosus A, Kosus N, Akkurt G: Hyperemesis gravidarum and depression in pregnancy: is there an association? J Psychosom Obstet Gynaecol 2012;33:171-175.
29.
Tan PC, Zaidi SN, Azmi N, Omar SZ, Khong SY: Depression, anxiety, stress and hyperemesis gravidarum: temporal and case controlled correlates. PLoS One 2014;9:e92036.
30.
Tan PC, Vani S, Lim BK, Omar SZ: Anxiety and depression in hyperemesis gravidarum: prevalence, risk factors and correlation with clinical severity. Eur J Obstet Gynecol Reprod Biol 2010;149:153-158.
31.
Saha S, Loranger D, Pricolo V, Degli-Esposti S: Feeding jejunostomy for the treatment of severe hyperemesis gravidarum: a case series. JPEN J Parenter Enteral Nutr 2009;33:529-534.
32.
Dodds L, Fell DB, Joseph KS, Allen VM, Butler B: Outcomes of pregnancies complicated by hyperemesis gravidarum. Obstet Gynecol 2006;107:285-292.
33.
Kuru O, Sen S, Akbayır O, Goksedef BP, Ozsürmeli M, Attar E, Saygılı H: Outcomes of pregnancies complicated by hyperemesis gravidarum. Arch Gynecol Obstet 2012;285:1517-1521.
34.
Koudijs HM, Savitri AI, Browne JL, Amelia D, Baharuddin M, Grobbee DE, Uiterwaal CS: Hyperemesis gravidarum and placental dysfunction disorders. BMC Pregnancy Childbirth 2016;16:374.
35.
Bolin M, Åkerud H, Cnattingius S, Stephansson O, Wikström AK: Hyperemesis gravidarum and risks of placental dysfunction disorders: a population-based cohort study. BJOG 2013;120:541-547.
36.
Mullin PM, Bray A, Schoenberg F, MacGibbon KW, Romero R, Goodwin TM, Fejzo MS: Prenatal exposure to hyperemesis gravidarum linked to increased risk of psychological and behavioral disorders in adulthood. J Dev Orig Health Dis 2011;2:200-204.
37.
Tan P, Norazilah MJ, Omar SZ: Dextrose saline compared with normal saline rehydration of hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol 2013;121(2 pt 1):291-298.
38.
Spruill SC, Kuller JA: Hyperemesis gravidarum complicated by Wernicke's encephalopathy. Obstet Gynecol 2002;99(5 pt 2):875-877.
39.
Longo L: Delayed-Release Doxylamine-Pyridoxine Drug Monograph. VA Pharmacy Benefits Management, 2015.
40.
Madjunkova S, Maltepe C, Koren G: The delayed-release combination of doxylamine and pyridoxine (diclegis®/diclectin®) for the treatment of nausea and vomiting of pregnancy. Pediatr Drugs 2014;16:199-211.
41.
Maltepe C, Koren G: Preemptive treatment of nausea and vomiting of pregnancy: results of a randomized controlled trial. Obstet Gynecol Int 2013;2013:1-8.
42.
Smith HS, Cox LR, Smith BR: Dopamine receptor antagonists. Ann Palliat Med 2012;1:137-142.
43.
Tan PC, Khine PP, Vallikkannu N, Omar SZ: Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol 2010;115:975-981.
44.
Bsat FA, Hoffman DE, Seubert DE: Comparison of three outpatient regimens in the management of nausea and vomiting in pregnancy. J Perinatol 2003;23:531-535.
45.
Sanofi-Aventis: Phenergan Product Information, 2012.
46.
Maina A, Arrotta M, Cicogna L, Donvito V, Mischinelli M, Todros T, Rivolo S: Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised control trial: CLONEMESI. BJOG 2014;121:1556-1562.
47.
American Society of Health - System Pharmacists, Metoclopramide Hydrochloride Drug Monograph. AHFS DI Essentials, 2017.
48.
Pasternak B, Svanström H, Mølgaard-Nielsen D, Melbye M, Hviid A: Metoclopramide in pregnancy and risk of major congenital malformations and fetal death. JAMA 2013;310:1601-1611.
49.
American Society of Health - System Pharmacists, Zofran Drug Monograph. AHFS DI Essentials, 2017.
50.
Pasternak B, Svanstrom H, Hviid A: Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med 2013;368:814-823.
51.
Einarson A, Maltepe C, Navioz Y, Kennedy D, Tan MP, Koren G: The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study. BJOG 2004;111:940-943.
52.
Abramowitz A, Miller ES, Wisner KL: Treatment options for hyperemesis gravidarum. Arch Womens Ment Health 2017;20:363-372.
53.
Abas MN, Tan PC, Azmi N, Omar SZ: Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomimzed controlled trial. Obstet Gynecol 2014;123:1272-1279.
54.
Reichmann JP, Kirkbride MS: Reviewing the evidence for using continuous subcutaneous metoclopramide and ondansetron to treat nausea & vomiting during pregnancy. Manag Care 2012;21:44-47.
55.
Omay O, Einarson A: Is mirtazapine an effective treatment for nausea and vomiting of pregnancy?: a case series. J Clin Psychopharmacol 2017;37:260-261.
56.
Anttila S, Leinonen EV: A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev 2001;7:249-264.
57.
Winterfeld U, Klinger G, Panchaud A, Stephens S, Arnon J, Malm H, Te Winkel B, Clementi M, Pistelli A, Maňáková E, Eleftheriou G, Merlob P, Kaplan YC, Buclin T, Rothuizen LE: Pregnancy outcome following maternal exposure to mirtazapine: a multicenter, prospective study. J Clin Psychopharmacol 2015;35:250-259.
58.
Smit M, Dolman KM, Honig A: Mirtazapine in pregnancy and lactation - a systematic review. Eur Neuropsychopharmacol 2016;26:126-135.
59.
Yost NP, McIntire DD, Wians FH Jr, Ramin SM, Balko JA, Leveno KJ: A randomized, placebo-controlled trial of corticosteroids for hyperemesis due to pregnancy. Obstet Gynecol 2003;102:1250-1254.
60.
Bondok RS, El Sharnouby NM, Eid HE, Abd Elmaksoud AM: Pulsed steroid therapy is an effective treatment for intractable hyperemesis gravidarum. Crit Care Med 2006;34:2781-2783.
61.
Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L, Friesen MH, Jacobson S, Kasapinovic S, Chang D, Diav-Citrin O, Chitayat D, Nulman I, Einarson TR, Koren G: Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology 2000;62:385-392.
© 2017 S. Karger AG, Basel
2017
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.