Hyperemesis gravidarum: Pathogenesis and the use of antiemetic agents

Expert Opinion on Pharmacotherapy

Volumn 12, Issue 5, 2011, Pages 737-748

  Sanu, Olaleye ^a   Lamont, Ronald F ^b  

^a IMPERIAL COLLEGE HEALTHCARE NHS TRUST   (United Kingdom)

^b HUTZEL HOSPITAL   (United States)

Author keywords

antiemetics; benefit; effectiveness; hyperemesis gravidarum; management; pathogenesis; safety

Indexed keywords

ANTIEMETIC AGENT; ANTIHISTAMINIC AGENT; BENDECTIN; BENZAMIDE DERIVATIVE; BUCLIZINE; BUTYROPHENONE DERIVATIVE; CHLORPROMAZINE; CHOLINERGIC RECEPTOR BLOCKING AGENT; DEBENDOX; DIAZEPAM; DIPHENHYDRAMINE; DOPAMINE RECEPTOR BLOCKING AGENT; DOXYLAMINE; GINGER EXTRACT; HYDROXYZINE; LEVOMEPROMAZINE; MEPYRAMINE; METHOPROMAZINE; METOCLOPRAMIDE; ONDANSETRON; PHENOTHIAZINE DERIVATIVE; PLACEBO; PROCHLORPERAZINE; PROMETHAZINE; PYRIDOXINE; SEROTONIN ANTAGONIST; STEROID; THIAMINE; TRIETHYLPERAZINE; UNINDEXED DRUG;

ACUPUNCTURE; ACUTE DISEASE; AGITATION; CENTRAL NERVOUS SYSTEM DISEASE; CONVERSION DISORDER; CYTOKINE PRODUCTION; DISEASE ASSOCIATION; DROWSINESS; DRUG BIOAVAILABILITY; DRUG EFFECT; DRUG EFFICACY; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG USE; DYSTONIC DISORDER; EXTRAPYRAMIDAL SYMPTOM; GASTROINTESTINAL TRANSIT; HORMONAL REGULATION; HUMAN; HYPEREMESIS GRAVIDARUM; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; MENTAL STRESS; MOTION SICKNESS; NONHUMAN; PATHOGENESIS; PATIENT COMPLIANCE; PLACENTA FUNCTION; PSYCHOLOGICAL ASPECT; PYRIDOXINE DEFICIENCY; REHYDRATION; REVIEW; SEROTONINERGIC TRANSMISSION; SIDE EFFECT; STIMULUS RESPONSE; STOMACH PARESIS; SYSTEMATIC REVIEW; TOTAL PARENTERAL NUTRITION; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; VITAMIN SUPPLEMENTATION; VOMITING; WERNICKE KORSAKOFF SYNDROME;

ANTIEMETICS; CENTRAL NERVOUS SYSTEM; CONTROLLED CLINICAL TRIALS AS TOPIC; FEMALE; GASTROINTESTINAL TRACT; HORMONES; HUMANS; HYPEREMESIS GRAVIDARUM; PLACEBOS; PLACENTA; PREGNANCY; VITAMIN B 6 DEFICIENCY;

EID: 79952598754     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656566.2010.537655     Document Type: Review

References (119)

1. Goodwin TM. Hyperemesis gravidarum. Obstet Gynecol Clin N Am 2008;35:401-7
2. Department of Health, Welsh Office, Scottish Home and Health Department and Department of Health and Social Services, Northern Ireland. Confidential Enquiries into Maternal Deaths in the United Kingdom 1991-93. HMSO, London; 1996
3. Renee L, Eason, E, Melzack R Nausea and vomiting during pregnancy: a prospective of its frequency, intensity and patterns of change. Am J Obstet Gynecol 2000;182:931-7 (Pubitemid 30228470)
4. Kallen B. Hyperemesis during pregnancy and delivery outcome: a registry study. Eur J Obstet Gynecol Reprod Biol 1987;26:291-302 (Pubitemid 17163069)
5. Asking J, Eriandsson G, Kaijser M, et al. Sickness in pregnancy and sex of child. Lancet 1999;354:2053
6. Depue RH, Bernstein L, Ross R, et al. Hyperemesis gravidarum in relation to estradiol levels, pregnancy outcome, and other maternal factors: a seroepidemiologic study. Am J Obstet Gynecol 1987;156:1137-41 (Pubitemid 17075463)
7. Klebanoff M, Koslowe P, Kaslow R, Rhoads G. Epidemiology of vomiting in early pregnancy. Obstet Gynecol 1985;66:612-16 (Pubitemid 16216146)
8. Bailit JL. Hyperemesis gravidarum: epidemiologic findings from a large cohort. Am J Obstet Gynecol 2005;193:811-14 (Pubitemid 41261481)
9. Tan P, Jacob R, Queck K, Omar S. The fetal sex ratio and metabolic, biochemical, haematological and clinical indicators of severity of hyperemesis gravidarum. BJOG 2006;113:733-7 (Pubitemid 43781707)
10. Jordan V, Grebe S, Cooke R, et al. Acidic isoforms of chorionic gonadoptrophins in European and Samoan women are associated with hyperemesis gravidarum and may be tyrotrophic. Am J Obstet Gynecol 1999;50:619-27 (Pubitemid 29236339)
11. Fejzo MS, Ingles SA, Wilson M, et al. High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals. Eur J Obstet Gynecol 2008;141:13-17
12. Trogstad L, Stoltenberg C, Magnus P, et al. Recurrence risk in hyperemesis gravidarum. BJOG 2005;112:1641-5 (Pubitemid 43961217)
13. Einarson TR, Navioz Y, Maltepe C, et al. Existence and severity of nausea and vomiting in pregnancy (NVP) with different partners. J Obstet Gynecol 2007;27:360-2 (Pubitemid 47124323)
14. Grjibovski AM, Vikanes A, Stoltenberg C, Magnus P. Consanguinity and the risk of hyperemesis gravidarum in Norway. Acta Obstet Gynecol Scand 2008;87:20-5
15. Goodwin TM. Spectrum of nausea and vomiting in pregnancy. Clin Obstet Gynecol 1998;41:597-605
16. Poursharif B, Korst LM, Fejzo MS, et al. The psychosocial burden of hyperemesis gravidarum. J Perinatol 2008;28:176-81 (Pubitemid 351338607)
17. Fejzo MS, Poursharif B, Korst LM, et al. Symptoms and pregnancy outcomes associated with extreme weight loss among women with hyperemesis gravidarum. J Womens Health (Larchmt) 2009;18:1981-7
18. Goodwin TM. Nausea and vomiting of pregnancy: an obstetric syndrome. Am J Obstet Gynecol 2002;186:S186-189
19. Gwyn DG, Leslie RA, Hopkins DA. Gastric afferents to the nucleus of the solitary tract in the cat. Neurosci Lett 1979;14:13-17 (Pubitemid 10233988)
20. Ciriello J, Hrycyshyn AW, Calaresu FR Glossopharyngeal and vagal afferent projection to the brainstem of the cat. J Auton Nerv Sys 1981;4:63-79
21. Saito R, Suehiro Y, Ariumi H, et al. Antiemetic effects of a novel NK-1 receptor antagonist HSP-117 in ferrets. Neurosci Lett 1998;254:169-72 (Pubitemid 28459408)
22. Endo T, Minami M, Monma Y, et al. Vagotomy and ondasetron (5-HT3 antagonist) inhibited the increase of serotonin concentration induced by cytotoxic drugs in the area postrema of ferrets. Biogenic Amines 1992;9:163-75 (Pubitemid 23003446)
23. Stefanini E, Clement-Cormier Y. Detection of dopamine receptors in the area postrema. Eur J Pharmacol 1981;74:257-60 (Pubitemid 11002114)
24. Palacios JM, Wamsley JK, Kuhar MJ. The distribution of histamine H1 receptors in the rat brain: an autoradiographic study. Neuroscience 1981;6:15-17
25. Wamsley JK, Lewis MS, Young WS III, Kuhar MJ. Autoradiographic localisation of muscarinic cholinergic receptors in rat brainstem. J Neurosci 1981;1:176-91 (Pubitemid 11028322)
26. Peroutka SJ, Snyder SH. Differential effects of neuroleptic drugs at brain Dopamine, serotonin, alpha-adrenergic and histamine receptors: relationship to clinical potency. Am J Psychiat 1980;137:1518-22 (Pubitemid 11196805)
27. Lei ZM, Rao CV, Kornyei JL, et al. Novel expression of human Chorionic gonadotrophin/luteinizing hormone receptor gene in brain. Endocrinology 1993;132:2262-70 (Pubitemid 23133280)
28. Saito R, Takano Y, Kamiya H. Roles of substance P and NK1 receptor in the brainstem in the development of emesis. J Pharmacol Sci 2003;91:87-94 (Pubitemid 36575559)
29. McRitchie D, Tork I. Distribution of substance P-like immunoreactive neurons and terminals throughout the nucleus of the solitary tract in the human brain stem. J Comp Neurol 1994;343:83-101 (Pubitemid 24129528)
30. Chelen W, Kabrisky M, Rogers S. Spectral analysis of the electroencephalographic response to motion sickness. Aviat Space Environ Med 1993;64:24-9 (Pubitemid 23049526)
31. Miller A, Rowley H, Roberts T, Kucharczyk J. Human cortical activity during vestibular and drug induced nausea detected using MSI. Ann N Y Acad Sci 1996;737:51-8
32. Vaknin Z, Halperin R, Schneider D, et al. Hyperemesis gravidarum and non-specific abnormal EEG findings: a preliminary report. J Reprod Med 2006;51:623-7 (Pubitemid 44300073)
33. Bailey TM, Dye L, Jones S, et al. Food cravings and aversions during pregnancy: relationships with nausea and vomiting. Appetite 2002;38:45-51 (Pubitemid 34412110)
34. Drachman DA. Memory and cognitive function in man: does the cholinergic system have a specific role? Neurology 1977;27:783-90 (Pubitemid 8171670)
35. Hummel T, Von Mering R, Huch R, Kolble N. Olfactory modulation of nausea during early pregnancy? BJOG 2002;109:1394-7 (Pubitemid 36026547)
36. Whitehead SA, Andrews PLR, Chamberlain GVP. Characterisation of nausea and vomiting in early pregnancy: a survey of 1000 women. J Obstet Gynecol 1992;12:364-9 (Pubitemid 23026065)
37. Goodwin T, Nwankwo O, Davis-O'Leary L, 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;199:417.e1-417.e9
38. Yanushpolsky E, Ozturk M, Polgar K, et al. The effects of cytokines on human chorionic gonadotrophin production by a trophoblast cell line. J Reprod Immunol 1993;25:235-47 (Pubitemid 24068742)
39. Kaplan P, Gucer F, Sayin N, et al. Maternal serum cytokine levels in women with hyperemesis gravidarum in the first trimester of pregnancy. Fertil Steril 2003;79:498-502 (Pubitemid 36293441)
40. 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;187:1631-5 (Pubitemid 36026699)
41. Woolf CJ. Generation ofacute pain: central mechanisms. Br Med Bull 1991;47:523-33
42. Yoneyama Y, Suzuki S, Sawa R, Araki T. Plasma adenosine concentrations increase in women with hyperemesis gravidarum. Clinica Chimica Acta 2004;342:99-103 (Pubitemid 38352918)
43. Minagawa M, Narita J, Tada J, et al. Mechanisms underlying immunologic states during pregnancy: possible association of the sympathetic nervous system. Cell Immunol 1999;196:1-13 (Pubitemid 29455421)
44. Carpenter DO. Neural mechanisms in emesis. Can J Physiol Pharmacol 1990;68:230-6
45. Goodwin TM, Hershman JM, Cole L. Increased concentration of the free (beta) Subunit of human chorionic gonadotrophin in hyperemesis gravidarum. Acta Obstet Gynecol Scand 1994;73:770-2
46. 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;101:639-44 (Pubitemid 36390049)
47. Soules MR, Hughes CL Jr, Garcia JA, et al. Nausea and vomiting of pregnancy: role of human chorionic Gonadotrophin and 17-hydroxyprogesterone. Obstet Gynecol 1980;55:696-700 (Pubitemid 10068679)
48. Kauppila A, Huhtaniemi I, Ylikorkala O. Raised serum human chorionic Gonadotrophin concentrations in hyperemesis gravidarum. BMJ 1979;1:1670-1 (Pubitemid 9200312)
49. Jarnfelt-Samsioe A, Bremme K, Eneroth P. Steroid hormones in emetic and non-emetic pregnancy. Eur J Obstet Gynecol Reprod Biol 1986;21:87-99 (Pubitemid 16177492)
50. Masson GM, Anthony F, Chau E. Serum chorionic gonadotrophins (hCG), Schwangerschaftsprotein 1 (SP1), progesterone and oestradiol levels in patients with nausea and vomiting in earlypregnancy. BJOG 1985;92:211-15 (Pubitemid 15146694)
51. Goodwin TM, Montoro M, Mestman JH. Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects. Am J Obstet Gynecol 1992;167:648-52
52. Rodien P, Bremont C, Sanson ML, et al. Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotrophin. N Engl J Med 1998;339:1823-6 (Pubitemid 29005787)
53. Fejzo MS, Romero R, Goodwin TM. Patients with a history of hyperemesis gravidarum have similar symptoms during egg stimulation and develop ovarian hyperstimulation syndrome: case series. Fert Steril 2010;93:267.e1-11
54. Bagshawe KD, Orr AH, Rushworth AG. Relationship between concentrations of human chorionic gonadotrophin in plasma and cerebrospinal fluid. Nature 1968;217:950-1
55. Kumar D. In vitro inhibitory effect of progesterone on intrauterine human smooth muscle. Am J Obstet Gynecol 1962;34:1300-4
56. Milenov K, Kazakov L. Influence of ovarian hormones on electromyograms of uterus, stomach, and intestines in dogs. Endocrinologica 1973;7:163-9
57. Bruce LA, Behsudi FM, Danhof IE. Smooth muscle mechanical responses in vitro to betanechol after progesterone in male rats. Am J Physiol 1978;235:E422-428 (Pubitemid 9163014)
58. Maes BD, Spitz B, Ghoos YF, et al. Gastric emptying in hyperemesis gravidarum and non-dyspeptic pregnancy. Aliment Pharmacol Ther 1999;13:237-43 (Pubitemid 29090020)
59. El-Mallakh RS, Liebowitz NR, Hale MS. Hyperemesis gravidarum as conversion disorder. J Nerv Ment Dis 1990;178:655-9 (Pubitemid 20378886)
60. Fairweather DVI. Nausea and vomiting in pregnancy. Am J Obstet Gynecol 1968;102:135-75
61. Poursharif B, Korst LM, MacGibbon KW, et al. Elective pregnancy termination in a large cohort of women with hyperemesis gravidarum. Contraception 2002;76:451-5 (Pubitemid 350180739)
62. Simpson SW, Goodwin TM, Robins SB, et al. Psychological factors and hyperemesis gravidarum. J Womens Health Gend Based Med 2001;10:471-7 (Pubitemid 32677646)
63. Kauppila A, Ylikorkala O, Jarvinen PA. The function of the anterior pituitary-Adrenal cortex axis in hyperemesis gravidarum. BJOG 1976;83:11-16
64. Ditto A, Morgante G, la Marca A, De Leo V. Evaluation of treatment of hyperemesis gravidarum using parenteral fluid with or without diazepam. A randomised study. Gynecol Obstet Invest 1999;48:232-6
65. Sherman PW, Flaxman SM. Nausea and vomiting of pregnancy in an evolutionary Perspective. Am J Obstet Gynecol 2002;186:S190-197 (Pubitemid 34533873)
66. Pepper GV, Roberts SC. Rates of nausea and vomiting in pregnancy and dietary characteristics across populations. Proc R Soc B 2006;273:2675-9 (Pubitemid 44570370)
67. Heller S, Salkeld RM, Korner WF. Vitamin B6 status in pregnancy. Am J Clin Nutr 1973;26:1339-48
68. Schuster K, Bailey LB, Dimperio D, Mahan CS. Morning sickness and vitamin B6 status of pregnant women. Hum Nutr Clin Nutr 1985;39:75-9 (Pubitemid 15090325)
69. Sahakian V, Rouse D, Sipes S, et al. Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomised, double blind placebo-controlled study. Obstet Gynecol 1991;78:33-6
70. Vutyavanich T, Wongtra-ngan S, Ruangsri R Pyridoxine for nausea and vomiting of pregnancy: a randomised, double-blind placebo controlled trial. Am J Obstet Gynecol 1995;173:881-4
71. Tan PC, Yow CM, Omar SZ. A placebo-controlled trial of oral pyridoxine in hyperemesis gravidarum. Gynecol Obstet Invest 2009;67:151-7
72. Jarnfelt-Samsioe A, Eriksson B, Waldenstrom J, Samsioe G. Serum bile acids, gamma-glutamyltransferase and routine liver function tests in emetic and non emetic pregnancies. Gynecol Obstet Invest 1986;21:169-76 (Pubitemid 16083982)
73. Safari HR, Fassett MJ, Soutter IC, et al. The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomised, double blind, controlled study. Am J Obstet Gynecol 1998;179:921-4 (Pubitemid 28489281)
74. Fischer-Rasmusses W, Kjaer SK, Dahl C, et al. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1990;38:19-24 (Pubitemid 20327165)
75. Vickers AJ. Can acupuncture have specific effects on health? A systematic review of acupuncture emesis trials. J R Soc Med 1996;89:303-11 (Pubitemid 26188709)
76. Einarson A, Koren G, Bergman U. Nausea and vomiting in pregnancy: a comparative european study. Eur J Obstet Gynecol Reprod Biol 1998;76:1-3 (Pubitemid 28031973)
77. Yates BJ, Miller AD, Lucot JB. Physiological basis and pharmacology of motion sickness. Brain Res Bull 1998;47:395-406 (Pubitemid 29095346)
78. Tonini M, Cipollina L, Poluzzi E, et al. Review article:Clinical implications of enteric and central D2 receptor blockade by Antidopaminergic gastrointestinal prokinetics. Aliment Pharmacol Ther 2004;19:379-90 (Pubitemid 38297106)
79. Endo T, Minami M, Hirafuji M, et al. Neurochemistry and neuropharmacolgy of emesis-the role of serotonin. Toxicology 2000;153:189-201
80. Winters HS. Antiemetics in nausea and vomiting of pregnancy. Obstet Gynecol 1961;18:753-6
81. Newlinds JS. Nausea and vomiting in pregnancy: a trial of triethylperazine. Med J Aust 1964;51:234-6
82. Lask S. Treatment of nausea and vomiting of pregnancy with antihistamines. BMJ 1953;1:652-3
83. Erez S, Schifrin BS, Dirim O. Double blind evaluation of hydroxyzine as an antiemetic in pregnancy. J Reprod Med 1971;7:57-9
84. Diggory PLC, Tomkinson JS. Nausea and vomiting in pregnancy. A trial of meclozine dihydrochloride with and without pyridoxine. Lancet 1962;2:370-2
85. Conklin FJ, Nesbitt REL. Buclizine hydrochloride for nausea and vomiting of pregnancy. Obstet Gynecol 1958;11:214-19
86. Geiger CJ, Fahrenbach DM, Healey FJ. Bendectin in the treatment of nausea and vomiting in pregnancy. Obstet Gynecol 1959;14:688-90
87. Fitzgerald JPB. The effect of promethazine in nausea and vomiting of pregnancy. N Z Med J 1955;54:215-18
88. Wheatley D. Treatment of pregnancy sickness. Br J Obstet Gynecol 1997;84:444-7
89. Singleton CK, Martin PR Molecular mechanisms of thiamine utilization. Curr Mol Med 2001;1:197-207 (Pubitemid 33772043)
90. Goodwin TM, Poursharif B, Korst LM, et al. Secular trends in the treatment of hyperemesis gravidarum. Am J Perinatol 2008;25:141-7 (Pubitemid 351429723)
91. Ahlmark A, Werko L. Toxaemia of pregnancy. Ciba Foundation Symposium, Churchill, London; 1950
92. Kapeller-Adler R, Adler E. Further investigatios on the histidine and the histamine metabolism in normal and pathological pregnancy. BJOG 1943;50:177-83
93. Seto A, Einarson T, Koren G. Pregnancy outcome following first trimester exposure to antihistamines: Meta-analysis. Am J Perinatol 1997;14:119-24 (Pubitemid 27143335)
94. Watcha MF, White PF. Antiemetics. Bailliere's Clin Anaesthesiol 1995;9:119-36
95. Mazzotta P, Magee LA. A risk-benefit assessment of pharmacological and non-Pharmacological treatments for nausea and vomiting of pregnancy. Drugs 2000;59:781-800 (Pubitemid 30232320)
96. Bendectin Peer Group. Bio/Basics International Peer Group Report. Merrell Dow Pharmaceuticals, Inc., March 14, 1975:559-637
97. Kubo N, Shirakawa O, Kuno T, Tanaka C. Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay. Japan J Pharmacol 1987;43:277-82 (Pubitemid 17034958)
98. Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2003;(4):CD000145
99. Nageotte MP, Briggs GG, Towers CV, Asrat T. Droperidol and diphenhydramine in the management of hyperemesis gravidarum. Am J Obstet Gynecol 1996;174(6):801-6
100. Lacasse A, Lagoutte A, Ferreira E, Berard A. Metoclorpramide and Diphenhdramine in the treatment of hyperemesis gravidarum: effectiveness and predictors of rehospitalisation. Eur J Obstet Gynecol Reprod Biol 2009;143:43-9
101. Isaacs B, Macarthur JG. Influence of chlorpromazine and promethazine on vomiting induced with apomorphine in man. Lancet 1954;267:570-2
102. Rumeau-Rouquette C, Goujard J, Huel G. Possible teratogenic effect of phenothiazines in human beings. Teratology 1976;15:57-64
103. Bsat FA, Hoffman DE, Seubert DE. Comparison of three outpatient regimens in the management of nausea and vomiting in pregnancy. J Perinatol 2003;23:531-5 (Pubitemid 37428160)
104. Tan PC, Khine PP, Vallikkannu N, Omar SZ. Promethazine compared with Metoclopramide for hyperemesis gravidarum. Obstet Gynecol 2010;115:975-81
105. Sullivan CA, Johnson CA, Roach H, et al. A pilot study of intravenous ondasetron for hyperemesis gravidarum. Am J Obstet Gynecol 1996;174:1565-8 (Pubitemid 26165279)
106. Einarson A, Maltepe C, Navioz Y, et al. The safety of ondasetron for nausea and vomiting of pregnancy: a propective comparative study. BJOG 2004;111:940-3 (Pubitemid 39223043)
107. Matok I, Gorodischer R, Koren G, et al. The safety of metoclopramide use in the first trimester of pregnancy. N Engl J Med 2009;360:2528-35
108. Milkovich L, Van den Berg BJ. An evaluation of the teratogenicity of certain antinauseant drugs. Am J Obstet Gynecol 1976;125:244-8
109. Buttino Louis Jr, Coleman SK, Bergauer NK, et al. Home subcutaneous metoclopramide therapy for hyperemesis gravidarum. J Perinatol 2000;20:359-62
110. Yamahara J, Huang Q, Li Y, et al. Gastrointestinal motility enhancing effect of ginger and its active constituents. Chem Pharm Bull 1990;38:430-1 (Pubitemid 20161708)
111. Backon J. Ginger in preventing nausea and vomiting of pregnancy: a caveat due to its thromboxane synthetase activity and effect on testosterone binding. Eur J Obstet Gynecol Reprod Biol 1991;42:163-4
112. Neri I, Allais G, Schiapparelli P, et al. Acupuncture versus pharmacological approach to reduce hyperemesis gravidarum discomfort. Minerva Ginecol 2005;57:471-5 (Pubitemid 41503754)
113. 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;34:2781-3 (Pubitemid 44610943)
114. Yost NP, McIntire DD, Wians Jr FH, et al. A Randomised, placebo-controlled trial of corticosteroids for hyperemesis due to Pregnancy. Obstet Gynecol 2003;102:1250-4 (Pubitemid 37518403)
115. Carmichael SL, Shaw GM, Ma C, et al. Maternal corticosteroid use and orofacial clefts. Am J Obstet 2007;197:585.e1-585.e7
116. Koren G, Maltepe C. Pre-emptive therapy for severe nausea and vomiting of pregnancy and hyperemesis gravidarum. J Obstet Gynaecol 2004;24:530-3 (Pubitemid 39233730)
117. Zhang Y, Cantor RM, Macgibbon K, et al. Familial aggregration of hyperemesis gravidarum. Am J Obstet Gynecol 2010. [Epub ahead ofprint]
118. Levichek Z, Atanacckovic G, Oepkes D, et al. An evidence-based treatment algorith m for nausea and vomiting of pregnancy. The Motherisk Programme, Toronto, 2000. Can Fam Phys 2002;48:267-8
119. Neutel CL, Johansen HL. Measuring drug effectiveness by default: the case of Bendectin. Can J Public Health 1995;86:66-70