Clinical Review

Nausea and vomiting of pregnancy: Q&A with T. Murphy Goodwin

OBG Manag. 2004 August;16(8):54-67

References

1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Nausea and Vomiting of Pregnancy. Clinical management guidelines for obstetrician-gynecologists. No. 52. Washington, DC: ACOG: April 2004.

2. Klebanoff M, Koslone P, Kaslow R, Rhoads G. Epidemiology of vomiting in early pregnancy. Obstet Gynecol. 1985;66:612-616.

3. Mazzotta P, Stewart D, Atanackovic G, Koren G, Magee LA. Psychosocial morbidity among women with nausea and vomiting of pregnancy: prevalence and association with antiemetic therapy. J Psychosom Obstet Gynaecol. 2000;21:129-136.

4. Mazzota P, Magee L, Koren G. Therapeutic abortions due to severe morning sickness. Unacceptable combination. Can Fam Physician. 1997;43:1055-1057.

5. Goodwin TM. Nausea and vomiting of pregnancy: an obstetric syndrome. Am J Obstet Gynecol. 2002;186:S184-S189.

6. Goodwin TM, Montoro M, Mestman JH, Pekary AE, Hershman JM. The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. J Clin Endocrinol Metab. 1992;75:1333-1337.

7. Goodwin TM, Hershman JM. Hyperthyroidism due to inappropriate production of human chorionic gonadotropin. Clin Obstet Gynecol. 1997;40:32-44.

8. Depue RH, Bernstein L, Ross RK, et al. Hyperemesis gravidarum in relation to estradiol levels, pregnancy outcome, and other maternal factors: a seroepidemiologic study. Am J Obstet Gynecol. 1987;156:1137-1141.

9. Vellacott ID, Cooke EJ, James CE. Nausea and vomiting in early pregnancy. Int J Gynaecol Obstet. 1988;27:57-62.

10. Gadsby R, Barnie-Adshead AM, Jagger C. A prospective study of nausea and vomiting during pregnancy. Br J Gen Prac. 1993;43:245-248.

11. 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;182:931-937.

12. Boles RG, Williams JC. Mitochondrial disease and cyclic vomiting syndrome. Dig Dis Sci. 1999;44:103S-107S.

13. Czeizel AE, Dudas I, Fritz G, Tecsoi A, Hanck A, Kunovits G. The effect of periconceptional multivitamin-mineral supplementation on vertigo, nausea and vomiting in the first trimester of pregnancy. Arch Gynecol Obstet. 1992;251:181-185.

14. Emelianova S, Mazzotta P, Einarson A, Koren G. Prevalence and severity of nausea and vomiting of pregnancy and effect of vitamin supplementation. Clin Invest Med. 1999;22(3):106-110.

15. Jednak MA, Shadigian EM, Kim MS, et al. Protein meals reduce nausea and gastric slow wave dysrhythmic activity in first trimester pregnancy. Am J Physiol. 1999;277:G855-G861.

16. Sahakian V, Rouse D, Sipes S, Rose N, Niebyl J. Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled study. Obstet Gynecol. 1991;78:33-36.

17. Vutyavanich T, Wongtrangan S, Ruangsri R. Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol. 1995;173:881-884.

18. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Engl J Med. 1998;338:1128-1137.

19. Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000;62:385-392.

20. Simpson SW, Goodwin TM, Robins SB, et al. Psychological factors and hyperemesis gravidarum. J Womens Health Gend Based Med. 2001;10:471-477.

21. Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol. 1998;41:597-605.

Gastrointestinal disorders
Appendicitis
Biliary tract disease
Esophagitis
Gastroenteritis
Gastroparesis
Hepatitis
Intestinal obstruction
Pancreatitis
Peptic ulcer disease
Genitourinary disorders
Acute renal failure
Degenerating fibroid
Nephrolithiasis
Pyelonephritis
Torsion
Metabolic disorders
Addison’s disease
Diabetic ketoacidosis
Hyperparathyroidism
Hyperthyroidism
Porphyria
Pregnancy-related
Acute fatty liver of pregnancy
Preeclampsia
Pregnancy-induced hypertension
Miscellaneous
Central nervous system lesions
Drug toxicity/side effects
Eating disorder
Migraine
Pseudotumor cerebri
Vestibular lesions
Adapted from Goodwin TM²¹

Do vitamins, rest, diet, ginger, or acupuncture help?

Vitamins may help prevent NVP. For mild NVP, simple lifestyle changes or alternative remedies may suffice.

OBG MANAGEMENT: Would your first step with the patient described earlier be lifestyle and dietary adjustments?

GOODWIN: The first step in this case should have been prevention. Two studies have found that multivitamins given at conception help reduce the severity of NVP.^13,14

As for lifestyle changes, I would recommend rest and instruct the patient to avoid foods, activities, and other stimuli that exacerbate symptoms. Small, frequent meals are usually suggested to take the place of 3 large daily meals.

Scientifically, however, almost nothing is known about these common recommendations, though 1 study showed protein liquid meals reduced nausea and gastric-motility abnormalities more than carbohydrate or fatty meals with the same caloric content.¹⁵

OBG MANAGEMENT: Do you ever recommend alternative remedies such as ginger powder or stimulation of the P6 acupuncture point (eg, via acupuncture, Sea-Band, or ReliefBand)?

GOODWIN: As the ACOG guidelines point out, they are worth a try. When the patient wants to take ginger, I recommend 250 mg by mouth 3 to 4 times daily.

When to start drug therapy

Pyridoxine (vitamin B₆) is the first choice, followed by a combination of pyridoxine and doxylamine, which together form the drug Bendectin (no longer available in the US).

OBG MANAGEMENT: When do you opt for drug therapy?

GOODWIN: When symptoms interfere with daily life and the remedies already mentioned fail or patients choose not to use them. In such cases, pyridoxine (vitamin B6) is my first choice. I recommend 10 to 25 mg 3 or 4 times daily. In 1 randomized, controlled trial,¹⁶ 25 mg of pyridoxine every 8 hours led to a significant reduction in severe vomiting. In another, 10 mg of pyridoxine every 8 hours decreased both nausea and vomiting compared to placebo.¹⁷

When pyridoxine alone fails to ease NVP, I add doxylamine (see “Stepwise drug treatment of nausea and vomiting of pregnancy”). When it was commercially available, Bendectin contained the pyridoxine-doxylamine combination (10 mg of each) in 1 pill and was the most commonly prescribed agent, but it is no longer offered in the US. In Canada, it is sold as Diclectin.

The teratogenicity of Bendectin has never been proven despite extensive study, and a 1998 review described the agent’s safety.

Although the manufacturer voluntarily removed the drug in the early 1980s because of lawsuits alleging birth defects, teratogenicity has never been proven despite extensive study. A 1998 review described Diclectin’s safety.¹⁸

Fortunately, the combination of pyridoxine and doxylamine is still available—though not in a single pill. Some pharmacies will compound it, or the patient can be given pyridoxine in combination with the over-the-counter sleep aid Unisom, which contains 25 mg doxylamine succinate per tablet.

If pyridoxine alone is ineffective, I generally add 12.5 mg of doxylamine (half a Unisom tablet) to each dose. The patient should be instructed to buy Unisom in tablet form, rather than gel caps, as the active ingredient in the latter is not doxylamine.

Stepwise drug treatment of nausea and vomiting of pregnancy

Before starting drug therapy, rule out other causes of nausea and vomiting.

STEP 1

Try monotherapy. Start with pyridoxine (vitamin B6), 10 to 25 mg, 3 or 4 times daily.

STEP 2

Add doxylamine (Unisom tablet), 12.5 mg, 3 or 4 times daily, and adjust dosage as necessary according to severity of symptoms. (Note: Half of a 25-mg Unisom tablet = 12.5 mg.)

STEP 3

Add promethazine (Phenergan), 12.5 to 25 mg every 4 hours, orally or rectally, or dimenhydrinate (Dramamine), 50 to 100 mg every 4 to 6 hours, orally or rectally. Not to exceed 400 mg/day; if the patient is taking doxylamine, limit to 200 mg/day.

STEP 4

If the patient is sufficiently hydrated, add any of the following (listed alphabetically):

metoclopramide (Reglan), 5 to 10 mg every 8 hours, intramuscularly or orally, or promethazine, 12.5 to 25 mg every 4 hours, intramuscularly, orally, or rectally, or trimethobenzamide (Tigan), 200 mg every 6 to 8 hours, rectally.

If the patient is dehydrated, give intravenous fluids. For women who require intravenous hydration and have been vomiting for 3 or more weeks, intravenous thiamine, 100 mg daily for 2 to 3 days, followed by intravenous multivitamins, is recommended. (No study has compared different fluid replacements for NVP.) and add any of the following intravenous agents (listed alphabetically): dimenhydrinate, 50 mg (in 50 mL saline over 20 minutes) every 4 to 6 hours, or metoclopramide, 5 to 10 mg every 8 hours, or promethazine, 12.5 to 25 mg every 4 hours.

STEP 5

In refractory cases: Add methylprednisolone (Medrol), 16 mg every 8 hours, orally or intravenously, for 3 days. Taper over 2 weeks to the lowest effective dose. Limit total therapy to 6 weeks. (If given in the first 10 weeks of gestation, corticosteroids may increase risk for oral clefts.) or add ondansetron (Zofran), 8 mg over 15 minutes, every 12 hours, intravenously. Safety, particularly in first trimester, not determined. (Used mainly for emesis; less effect on nausea.)

AT ANY STEP

Consider parenteral nutrition for dehydration or persistent weight loss. Stop nutrition once the patient achieves relief.
Consider alternative therapies such as ginger capsules (250 mg 3 times daily) and stimulation of the P6 acupuncture point (via wrist bands or acustimulation).

Adapted from Goodwin TM and American College of Obstetricians and Gynecologists¹