Professional Documents
Culture Documents
Hyperemesis Gravidarum: - Obstetrics
Hyperemesis Gravidarum: - Obstetrics
Hyperemesis Gravidarum: - Obstetrics
Hyperemesis Gravidarum
Yat May Wong, MBCHB, MRCOG; Vallipuram Sivanesaratnam, MBBS, FRCOG
N
ausea and vomiting and anxiety experienced by been proposed to reduce the inci-
in pregnancy are patients. dence of hyperemesis gravidarum
common phenome- Many therapeutic agents, both include advanced maternal age and
na, occurring in Western and Eastern, have been cigarette smoking; a high body
approximately 70% of all preg- proposed with mixed results.5-12 weight, nulliparity and twin preg-
nancies.1-4 Hyperemesis gravi- This review will discuss the current nancy have been reported to be
darum, the extreme end of the knowledge of the condition, man- associated with an increased risk.14
spectrum, is characterised by agement strategies, and evidence for
severe nausea and intractable vom- an effect on pregnancy outcome. CLINICAL PRESENTATION
iting. It is a diagnosis of exclusion
when no other organic cause can EPIDEMIOLOGY Hyperemesis gravidarum tends to
be identified. begin in the first trimester of preg-
Various theories have been sug- The incidence of hyperemesis nancy and resolves by 20 weeks of
gested for its pathogenesis and gravidarum has been reported as 5 gestation.15 The nausea is generally
aetiology; there is no universal per 1000 pregnancies5 with a severe and the vomiting intractable.
consensus but it can be a grave reported range of 1 to 20 per Dehydration is not uncommon and
condition for both the mother and 1000.13 There is no clear dividing hospitalisation is necessary as
the fetus if it is not recognised and line that dictates when the ‘normal’ ketosis and electrolyte imbalance
treated early. Treatment thus nausea and vomiting of pregnancy may occur. Patients may report
remains non-specific, although (morning sickness) becomes hyper- weight loss, often more than 5% of
prompt rehydration and correction emesis gravidarum. The condition body weight; excessive salivation
of any electrolyte imbalance is poorly understood, a fact reflect- may also occur. Laboratory find-
remain the cornerstone of success- ed by the available studies that are ings include ketosis with increased
ful management. More specific generally small and non-ran- urinary specific gravity, raised
therapy may be considered if the domised. The low number of blood urea nitrogen and haema-
patient is not responding to basic patients obtained from these stud- tocrit, and decreased serum sodi-
supportive therapy. Hyperemesis ies reflects a lack of universal um, potassium and chloride.
gravidarum tends to be prolonged definition and diagnosis of this
and intractable in nature, so ade- condition; most studies are either DIFFERENTIAL DIAGNOSES
quate counselling and reassurance epidemiological or case reports.
are important to alleviate the fear Protective factors that have Differential diagnoses include gas-
non-pharmacological therapies. the patient is able to tolerate an intravenous and oral, in severe
(Table 2) Early diagnosis with oral diet, oral anti-emetics can be hyperemesis gravidarum has been
prompt hospital admission is nec- prescribed. Caution has to be exer- reported.5-7 The exact mechanism
essary to minimise complications. cised as extrapyramidal symptoms by which steroids suppress vomit-
Nutritional deficiencies have may occur with both these drugs ing is unclear; it may be via a direct
been recorded in patients with because of their anticholinergic effect upon the vomiting centre in
persistent prolonged vomiting.43 effects. the brain.7
Prolonged thiamine deficiency may Droperidol, a dopamine antag- Steroid therapy may be used in
lead to acute Wernicke’s encepha- onist, given by intravenous infusion these patients when other causes of
lopathy.43-44 Nasogastric feeding together with diphenhydramine, an vomiting have been excluded,
with nutritional supplements may antihistamine, have been used with when vomiting has persisted for
be necessary in severe cases.45 some success in the management of more than 4 weeks and is associat-
hyperemesis gravidarum that has ed with dehydration, and when the
Supportive Treatment not responded to conventional risks and benefits of treatment
Intravenous rehydration and cor- anti-emetics.9 The sedative and have been clearly explained to the
rection of any electrolyte imbal- anticholinergic effects of diphenhy- patient. As there is mixed data con-
ance is vital.15 Oral feeding should dramine help counteract the fre- cerning the safety of steroids in
be stopped to allow the gut to rest quency of anxiety and extrapyra- pregnancy, both to the mother
and parenteral anti-emetics pre- midal symptoms. However, con- and fetus,48-50 the use of steroids
scribed early on. Most patients will genital fetal anomalies have been should be confined to refractory
respond to this therapy; an oral noted in a minority of patients; it is cases.
diet may be gradually reintroduced unclear if the abnormalities were
when the vomiting is under con- due to a drug effect. Until larger Anti-thyroid drugs
trol, preferably starting with low studies are available, this regimen As hyperthyroidism has been noted
fat foods.46 cannot be recommended as a rou- in patients with hyperemesis gravi-
A protracted hospital stay and tine management for hyperemesis darum, it is tempting to prescribe
multiple hospital re-admissions are gravidarum. anti-thyroid medication in an
common. A minority of patients Intravenous ondansetron, a attempt to suppress symptoms.
may elect to terminate the preg- serotonin antagonist has also been However, the role of anti-thyroid
nancy as a treatment of symp- tried.8 It has been beneficial in the drugs in management remains
toms.47 Hence, psychological, med- treatment of chemotherapy- unclear. A short course of anti-thy-
ical and supportive therapies are induced nausea and vomiting.37 roid drugs may be beneficial and
essential components of manage- However, a preliminary study com- can be discontinued once the vom-
ment. paring ondansetron with prome- iting has settled.51 Other researchers
thazine showed no benefit. As it is however, have reported no benefits
Anti-emetics an expensive drug, its routine use with anti-thyroid drugs as the
Metoclopramide and prochlorper- in the management of hyperemesis hyperthyroidism is transient and
azine are common first-line anti- gravidarum cannot be justified. self limiting.28,52 Until more evi-
emetics. They should be adminis- dence is available, anti-thyroid
tered regularly in the first instance Steroids drugs should not be routinely pre-
and by a parenteral route. When The successful use of steroids, both scribed.
therapies have been found to be Rhoads GG. Epidemiology of vomiting in early Helicobacter pylori. Lancet 1992;339:893-895.
pregnancy. Obstet Gynecol 1985;66:612-616. 32. Veenendaal RA, Pena AS, Meijer JL, et al.
useful, but the results of these stud- 15. Abell TL, Riely CA. Hyperemesis gravidarum. Long term serological surveillance after treatment
ies must be cautiously interpreted. Gastroenterol Clin North Am 1992;21:835-849. of Helicobacter pylori infection. Gut 1991;32:
16. Kauppila A, Ylikorkala O, Jarvinen PA, 1291-1294.
A multidisciplinary approach Harapalahti J. The function of anterior pituitary 33. Blecker U, Lanciers S, Hauser B, Metha DI,
might be necessary in certain cases adrenal cortex axis in hyperemesis gravidarum. Br Vandenplas Y. Serology as a valid screening test
J Obstet Gynaecol 1976;95:624-625. for Helicobacter pylori infection in asymptomatic
to ensure an optimal outcome for 17. Goodwin TM, Hershman JM, Cole L. subjects. Arch Pathol Lab Med 1995;119:30-32.
these patients. Increased concentration of the free beta-subunit of 34. Feldman RA, Deeks JJ, Evans SJW. Multi-lab-
human chorionic gonadotropin in hyperemesis oratory comparison of eight commercially avail-
gravidarum. Acta Obstet Gynecol Scand 1994;73: able Helicobacter pylori serology kits.
770-772. Helicobacter pylori serology study group. Eur J
REFERENCES 18. Glick MM, Dick EL. Molar pregnancy pre- Microbiol Infect Dis 1995;14:428-433.
senting with hyperemesis gravidarum. J Am 35. Lerang F, Moum B, Mowinckel P, et al.
1. Brandes JM. First trimester nausea and vomit- Osteopath Assoc 1999;99:162-164. Accuracy of seven different tests for diagnosis of
ing as related to the outcome of pregnancy. Obstet 19. Hershman JM. Human chorionic gonado- Helicobacter pylori infection and the impact of
Gynecol 1967;30:427-431. tropin and the thyroid: hyperemesis gravidarum H2-receptor antagonists on test results. Scand J
2. Midwinter A. Vomiting in pregnancy. and trophoblastic tumours. Thyroid 1999; 9:653- Gastroenterol 1998;33:364-369.
Practitioner 1971;206:743-750. 657. 36. Hasler WL. Serotonin receptor physiology:
3. Jarnfelt-Samsioe A, Samsioe G, Velinder GM. 20. Mori M, Amino N, Tamaki H, Miyai K, relation to emesis. Dig Dis Sci 1999;44:108-111S.
Nausea and vomiting in pregnancy – a contribu- Tanizawa O. Morning sickness and thyroid func- 37. Pritchard JF, Wells CD. Relationships between
tion to its epidemiology. Gynecol Obstet Invest tion in normal pregnancy. Obstet Gynecol ondansteron systemic exposure and anti-emetic
1983;16:221-229. 1988;72:355-359. efficacy and safety in cancer patients receiving cis-
4. Weigel MM, Weigel RM. The association of 21. Pekonen F, Alfthan H, Stenman UH, plastin. Pharmacology 1992;45:188-194.
reproductive history, demographic factors, alcohol Ylikorkala O. Human chorionic gonadotropin 38. Borgeat A, Faithi M, Valiton A. Hyperemesis
and tobacco consumption with the risk of devel- (hCG) and thyroid function in early human preg- gravidarum: is serotonin implicated? Am J Obstet
oping nausea and vomiting in early pregnancy. nancy, circadian variation and evidence for intrin- Gynecol 1997;176:476-477.
Am J Epidemiol 1988;127:562-570. sic thyrotropic activity of hCG. J Clin End Metab 39. Adams RH, Gordon J, Combes B. Hyperemesis
5. Safari HR, Alsulyman OM, Gherman RB, 1988;66:853-856. gravidarum. Evidence of hepatic dysfunction.
Goodwin TM. Experience with oral methylpred- 22. Montoro M, Mestman JH. Transient hyper- Obstet Gynecol 1968;31:659-664.
nisolone in the treatment of refractory hypereme- thyroidism and hyperemesis gravidarum: Clinical 40. Jarnfelt-Samsioe A, Eriksson B, Waldenstrom
sis gravidarum. Am J Obstet Gynecol 1998;178: aspects. Am J Obstet Gynecol 1992;167:648-652. J, Samsioe G. Serum bile acids, gamma-glutamyl-
1054-1058. 23. Bouillon R, Nassens M, Vanassche FA, et al. transferase and routine liver function tests in
6. Nelson-Piercy C, de Sweit M. Corticosteroids Thyroid function in patients with hyperemesis emetic and non-emetic pregnancies. Gynecol
for the treatment of hyperemesis gravidarum. Br J gravidarum. Am J Obstet Gynecol 1982;143:922- Obstet Invest 1986;21:169-176.
Obstet Gynaecol 1994;101:1013-1015. 926. 41. Tsoi PT, Chin RK, Chang AM. Psychogenic
7. Taylor R. Successful management of hyper- 24. Jeffcoate WJ, Bain C. Recurrent pregnancy factors in hyperemesis gravidarum. Asia Oceania J
emesis gravidarum using steroid therapy. Q J Med induced thyrotoxicosis presenting as hyperemesis Obstet Gynaecol 1988;14:457-460.
1995;89:103-107. gravidarum. Br J Obstet Gynaecol 1985;92:413- 42. La Ferla J. Psychologic and behavioural fac-
8. Sullivan CA, Johnson CA, Roach H, Martin 415. tors in hyperemesis gravidarum (letter). Am J
RW, Stewart DK, Morrison JC. A pilot study of 25. Valentin BH, Jones C, Tyack AJ. Hyperemesis Obstet Gynecol 1988;159:532-533.
intravenous ondansetron for hyperemesis gravi- gravidarum due to thyrotoxicosis. Postgrad Med J 43. van Stuijvenberg ME, Schabort I, Labadarios
darum. Am J Obstet Gynecol 1996;174:1565- 1980;56:746-747. D, Nel JT. The nutritional status and treatment of
1568. 26. Tareen AK, Baseer A, Jaffry HF, Shafiq M. patients with hyperemesis gravidarum. Am J
9. Nageotte MP, Briggs GG, Towers CV, Asrat T. Thyroid hormones in hyperemesis gravidarum. J Obstet Gynecol 1995;172:1585-1591.
Droperidol and diphenhydramine in the manage- Obstet Gynaecol 1995;21:497-501. 44. Gardian G, Voros E, Jardanhazy T, Ungurean
ment of hyperemesis gravidarum. Am J Obstet 27. Yoshimura M, Hershman JM. Thyrotropic A, Vecsei L. Wernicke’s encephalopathy induced
Gynecol 1995;174:1801-1806. action of human chorionic gonadotropin. Thyroid by hyperemesis gravidarum. Acta Neurol Scand
10. Jewell D, Young G. Interventions for nausea 1995;5:425-434. 1999;99:196-198.
and vomiting in early pregnancy (Cochrane 28. Caffrey TJ. Transient hyperthyroidism of 45. Hsu JJ, Clark-Glena R, Nelson DK, Kim CH.
review). In: The Cochrane Library 1999, Issue 3. hyperemesis gravidarum: a sheep in wolf’s cloth- Nasogastric enteral feeding in the management of
Oxford: Update Software. ing. J Am Board Fam Pract 2000;13:35-38. hyperemesis gravidarum. Obstet Gynecol 1996;
11. Brinker F. Herb contraindications and drug 29. Frigo P, Lang C, Reisenberger K, Kolbl H, 88:343-346.
interactions. Sandy, Oreg: Eclectic Institute, Inc Hirschl AM. Hyperemesis gravidarum associated 46. Signorello LB, Harlow BL, Wang S, Erick MA.
1997. with Helicobacter pylori seropositivity. Obstet Saturated fat intake and the risk of severe hyper-
12. Fischer-Rasmussed W, Kjaer S, Dahl C, Asping Gynecol 1998;91:615-617. emesis gravidarum. Epidemiology 1998;9:636-
U. Ginger treatment for hyperemesis gravidarum. 30. Jacoby EB, Porter KB. Helicobacter pylori 640.
Eur J Obstet Gynecol Reprod Biol 1991;38:19-24. infection and persistent hyperemesis gravidarum. 47. Nelson-Piercy C. Treatment of nausea and
13. Fairweather DVI. Nausea and vomiting in Am J Perinatol 1999;16:85-88. vomiting in pregnancy. When should it be treated
pregnancy. Am J Obstet Gynecol 1968;102:135- 31. Kosunen TU, Seppala K, Sparma S, Sipponen and what can be safely taken? Drug Saf 1998;19:
175. P. Diagnostic value of decreasing IgG, IgA and 155-164.
14. Klebanoff MA, Koslowe PA, Kaslow R, IgM antibody titres after eradication of 48. Schaltz M, Patterson R, Zeitz S. Corticos-
teroid therapy for the pregnant asthmatic. JAMA 55. Backon J. Ginger in preventing nausea and JNCI 1986;76:1035-1039.
1975;233:804-807. vomiting of pregnancy: a caveat due to its throm- 61. Kullander S, Kallen B. A prospective study of
49. Vender RJ, Spiro HM. Inflammatory bowel boxane synthetase activity and effect on testos- drugs and pregnancy. II. Anti-emetic drugs. Acta
disease in pregnancy. J Clin Gastroenterol 1982;4: terone binding. Eur J Obstet Gynecol Reprod Biol Obstet Gynecol Sand 1976;55:105-111.
231-249. 1991;42:163-164. 62. Kricker A, Elliot J, Forrest J, McCredie J.
50. Lockshin MD, Druzin ML, Qamar T. 56. El Younis CM, Abulafia O, Sherer DM. Rapid Congenital limb deficiencies: Maternal factors in
Prednisolone does not prevent recurrent fetal marked response of severe hyperemesis gravi- pregnancy. Aust NZ J Obstet Gynaecol 1986;26:
death in women with antiphospholipid antibody. darum to oral erythromycin. Am J Perinatol 272-275.
Am J Obstet Gynecol 1989;160:439-443. 1998;15:533-534. 63. Klebanoff MA, Mills JL. Is vomiting during
51. Leylek OA, Cetin M, Toyaksi M, Erselcan T. 57. Zechnich R, Hammer T. Brief psychotherapy pregnancy teratogenic? BMJ 1986;292:724-726.
Hyperthyroidism in hyperemesis gravidarum. Int J for hyperemesis gravidarum. Am Fam Physician
Gynecol Obstet 1996;55:33-37. 1982;26:179-181.
52. Chong W, Johnston C. Unsuspected thyrotox- 58. Long MA, Simone SS, Tucher JJ. Outpatient
icosis and hyperemesis gravidarum in Asian treatment of hyperemesis gravidarum with stimu-
women. Postgrad Med J 1997;73:234-242. lus control and imagery procedures. J Behav Ther
53. Bone ME, Wilkinson DJ, Young JR, McNeil Exp Psychiatry 1986;17:105-109.
J, Charlton S. Ginger root – a new antiemetic: the 59. Jarnfelt-Samsioe A, Eriksson B, Waldenstrom
effect of ginger root on postoperative nausea and LA, Samsioe G. Some new aspects of emesis gravi-
About the Authors
vomiting after major gynaecological surgery. darum. Relations to clinical data, serum elec-
Anaesthesia 1990;45:669-671. trolytes, total protein and creatinine. Gynecol Dr Wong is a Lecturer and Dr Sivanesaratnam is a
54. Backon J. Ginger: inhibition of thromboxane Obstet Invest 1985;19:174-186. Professor and Head of Department. Both are in
synthetase and stimulation of prostacyclin: rele- 60. Bernstein L, Depue RH, Ross RK. Higher the Department of Obstetrics and Gynaecology
vance for medicine and psychiatry. Med Hypoth maternal levels of free estradiol in first compared at the University Malaya Medical Centre, Kuala
1986;20:271-278. to second pregnancy: early gestational differences. Lumpur, Malaysia.
JPOG welcomes papers from doctors anywhere in Asia, on all aspects of paediatrics, obstetrics and gynaecology,
with a focus on therapeutics and patient management. Our criteria for acceptance are simple: quality and
relevance to Asia. All articles undergo an independent peer-review process.
For more information, please contact: