Nausea and Vomiting of Pregnancy


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Nausea and vomiting of pregnancy affects nearly 75% of pregnant women. The exact cause is unknown. In most cases, it is a mild, self-limited condition that can be controlled with conservative measures and has no adverse fetal sequelae. About 1% of women develop hyper-emesis gravidarum, which may result in adverse outcomes for the mother and fetus. Patients with nausea and vomiting of pregnancy should be evaluated for other causes, particularly if symptoms are unremitting or presentation is atypical. Initial treatment is conservative and includes dietary changes, emotional support, and vitamin B6 supplementation. Several safe and effective pharmacologic therapies are available for women who do not improve with initial treatment. Women with hyperemesis gravidarum may require more aggressive interventions, including hospitalization, rehydration therapy, and parenteral nutrition.

Nausea and vomiting occur in up to 74% of pregnant women, and 50% experience vomiting alone.1,2 Although the term morning sickness is commonly used to describe nausea and vomiting of pregnancy, the timing, severity, and duration of symptoms vary widely. Approximately 80% of women report that their symptoms last all day, whereas only 1.8% report symptoms that occur solely in the morning.2

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Vitamin B6 should be prescribed as first-line treatment for nausea and vomiting of pregnancy.

A

32, 33

Physicians should consider prescribing doxylamine (Unisom SleepTabs) in addition to vitamin B6 for treatment of nausea and vomiting of pregnancy because the combination reduces symptoms by 70%.

C

34


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Vitamin B6 should be prescribed as first-line treatment for nausea and vomiting of pregnancy.

A

32, 33

Physicians should consider prescribing doxylamine (Unisom SleepTabs) in addition to vitamin B6 for treatment of nausea and vomiting of pregnancy because the combination reduces symptoms by 70%.

C

34


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

Women who are less educated, older, or black, and those who have lower incomes, multiple gestations, or increasing gravidity (including miscarriages) are at greater risk of nausea and vomiting of pregnancy.1 A personal history of motion sickness,3 migraine headaches,4 or nausea associated with the use of estrogen-containing contraceptives5 also increases the risk.

Hyperemesis gravidarum describes nausea and vomiting that is severe enough to cause fluid and electrolyte disturbances, and often requires hospitalization.6 It affects up to 1% of pregnant women and is associated with persistent vomiting (more than three episodes per day) that results in severe dehydration, ketonuria, electrolyte abnormalities such as hypokalemia, and weight loss of more than 5%.7,8 A personal history of hyperemesis gravidarum, gestational trophoblastic disease, fetal triploidy, fetal trisomy 21, hydrops fetalis, and multiple gestations increases the risk of this condition.9 The risk may be increased by as much as 50% if the fetus is female.10

Etiology and Pathophysiology

The causes of nausea and vomiting of pregnancy and of hyperemesis gravidarum are unknown. However, observational data indicate that these conditions correlate with levels of human chorionic gonadotropin (hCG) and the size of the placental mass, which suggests that placental products may be associated with the presence and severity of nausea and vomiting.11 Some women with complete hydatidiform molar pregnancies, in which no fetus is present, have significant nausea and vomiting, which indicates that placental factors, particularly hCG, are responsible. Women with higher hCG levels, such as those with multiple gestations, hydatidiform moles, or fetuses with Down syndrome, are at increased risk of nausea and vomiting.12

Levels of estrogen and progesterone may also be involved. Other potential etiologies include placental prostaglandins, serotonin levels, thyroid dysfunction, increased leptin levels, immune system dysregulation, Helicobacter pylori infection, and gastrointestinal dysmotility.11

Differential Diagnosis

In most pregnancies, nausea and vomiting is mild and self-limited. It usually starts within four weeks of the last menstrual period and peaks at nine weeks' gestation. An estimated 60% of cases resolve by the end of the first trimester, and 87% resolve by 20 weeks' gestation.13  Women who have atypical presentations (e.g., onset of symptoms after nine weeks' gestation, symptoms beyond the first trimester, severe symptoms, hyperemesis gravidarum) should be evaluated to exclude potentially serious causes (Table 1).

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Table 1.

Differential Diagnosis of Nausea and Vomiting of Pregnancy

Common causes

Cholecystitis

Gastroenteritis

Gastroesophageal reflux

Migraine headaches

Less common causes

Biliary tract disease

Drug toxicities or intolerances

Hepatitis

Hyperthyroidism

Kidney stones

Molar pregnancy

Pancreatitis

Peptic ulcer disease

Preeclampsia/HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count)

Pyelonephritis

Uncommon causes

Acute fatty liver of pregnancy

Addison disease

Appendicitis

Central nervous system tumors

Degenerating uterine leiomyoma

Diabetic ketoacidosis

Hypercalcemia

Intestinal obstruction

Meniere disease

Ovarian torsion

Porphyria

Pseudotumor cerebri

Uremia

Vestibular lesions

Table 1.

Differential Diagnosis of Nausea and Vomiting of Pregnancy

Common causes

Cholecystitis

Gastroenteritis

Gastroesophageal reflux

Migraine headaches

Less common causes

Biliary tract disease

Drug toxicities or intolerances

Hepatitis

Hyperthyroidism

Kidney stones

Molar pregnancy

Pancreatitis

Peptic ulcer disease

Preeclampsia/HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count)

Pyelonephritis

Uncommon causes

Acute fatty liver of pregnancy

Addison disease

Appendicitis

Central nervous system tumors

Degenerating uterine leiomyoma

Diabetic ketoacidosis

Hypercalcemia

Intestinal obstruction

Meniere disease

Ovarian torsion

Porphyria

Pseudotumor cerebri

Uremia

Vestibular lesions

In women with straightforward nausea and vomiting of pregnancy, physical examination findings are generally unremarkable. Abnormal findings (e.g., abdominal tenderness, peritoneal signs, fever) suggest another cause. In the absence of other physical findings, significant dehydration, with or without orthostasis, is consistent with hyperemesis gravidarum.

No laboratory tests are necessary in patients with normal examination findings and no evidence of dehydration. If not already performed, ultrasonography may be used to evaluate for the presence of a molar pregnancy or multiple gestation if there is clinical suspicion or abnormally elevated hCG levels.

If laboratory tests are ordered because of clinical suspicion that symptoms are not caused by straightforward nausea and vomiting of pregnancy, a basic approach should include a complete blood count; urinalysis; metabolic panel including transaminase levels; and measurement of thyroid-stimulating hormone, quantitative hCG, and amylase levels. An abnormally high hCG level suggests a multiple gestation, molar pregnancy, or, in rare cases, a twin pregnancy with both a normal fetus and a molar gestation.

Maternal and Fetal Outcomes

In pregnancies with uncomplicated nausea and vomiting, there is a decreased risk of miscarriage, as well as lower rates of preterm delivery, fetal death, and growth restriction.14,15 However, infants of women who lost weight early in the pregnancy, particularly in the setting of hyperemesis gravidarum, are at increased risk of growth restriction or low birth weight.16 Women with nausea and vomiting that is refractory to treatment or complicated by weight loss have increased risks of fetal growth restriction and fetal death, as well as preeclampsia and maternal complications associated with vomiting (e.g., esophageal rupture, retinal hemorrhage, Mallory-Weiss syndrome, pneumothorax).17,18

Treatment

Treatment should be directed toward reducing symptoms while posing the least amount of risk to the fetus and mother. Various modalities have been used, some without evidence of benefit.

NONPHARMACOLOGIC THERAPIES

Traditional first-line therapy for nausea and vomiting of pregnancy and for hyperemesis gravidarum includes dietary modifications such as avoidance of large meals and consumption of low-fat, low-fiber, bland foods (e.g., breads, crackers, cereals, eggs, tofu, lean meat, peanut butter, fruits, vegetables). Avoidance of foods with strong smells and those with increased protein and liquid content is often recommended.19 However, there is little evidence to support these recommendations.

Although nausea and vomiting of pregnancy and hyperemesis gravidarum have been linked with a variety of psychological conditions, including depression and stress-related disorders, more recent data have not shown a definitive association.20 Evidence shows that women appreciate acknowledgment of the distress caused by nausea and vomiting of pregnancy and hyper-emesis gravidarum.21

A variety of other nonpharmacologic therapies for nausea and vomiting of pregnancy are listed in Table 2.2231 Although commonly used by patients and recommended by health care professionals, most of these treatments have only limited evidence supporting their benefit.

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Table 2.

Nonpharmacologic Treatments for Nausea and Vomiting of Pregnancy

TreatmentComment

Acupuncture and acupressure

Auricular acupressure

Found to be ineffective22

P6 acupressure

Pressure applied with fingers or a device to the P6 acupressure point (located two or three finger breadths proximal to the wrist crease, midline on the forearm between the large flexor tendon); commonly used but found to be ineffective vs. placebo23

P6 acupuncture

Found to be ineffective vs. no treatment24

Sham acupuncture

Found to be ineffective vs. no treatment24

Traditional acupuncture

Found to be ineffective vs. no treatment or placebo24,25

Herbal therapies

Ginger

Two trials show symptom improvement vs. placebo,26,27 and four trials show symptom improvement similar to that with vitamin B62831; ginger extract (125 to 250 mg every six hours) should be considered; ginger tea or ginger ale can also be used as adjunctive treatment


Information from references 22 through 31.

Table 2.

Nonpharmacologic Treatments for Nausea and Vomiting of Pregnancy

TreatmentComment

Acupuncture and acupressure

Auricular acupressure

Found to be ineffective22

P6 acupressure

Pressure applied with fingers or a device to the P6 acupressure point (located two or three finger breadths proximal to the wrist crease, midline on the forearm between the large flexor tendon); commonly used but found to be ineffective vs. placebo23

P6 acupuncture

Found to be ineffective vs. no treatment24

Sham acupuncture

Found to be ineffective vs. no treatment24

Traditional acupuncture

Found to be ineffective vs. no treatment or placebo24,25

Herbal therapies

Ginger

Two trials show symptom improvement vs. placebo,26,27 and four trials show symptom improvement similar to that with vitamin B62831; ginger extract (125 to 250 mg every six hours) should be considered; ginger tea or ginger ale can also be used as adjunctive treatment


Information from references 22 through 31.

PHARMACOLOGIC THERAPIES

Vitamin B6 and Doxylamine. Vitamin B6 (10 to 25 mg every eight hours) is more effective than placebo in improving symptoms of nausea, although the reduction in vomiting is less clear32,33 (Table 3). Combination therapy with vitamin B6 and doxylamine (Unisom SleepTabs) reduces nausea and vomiting by 70%.34 Although there have been concerns about teratogenicity, a large meta-analysis showed that combination therapy with vitamin B6 and doxylamine is safe for use in the first trimester,35 and it is recommended for treatment of nausea and vomiting of pregnancy by the American College of Obstetricians and Gynecologists.34 In 2013, the U.S. Food and Drug Administration approved a delayed-release formulation of doxylamine and pyridoxine hydrochloride (Diclegis).

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Table 3.

Pharmacologic Treatments for Nausea and Vomiting of Pregnancy

AgentDosageAdverse effectsNotes

Primary therapies

Vitamin B6

10 to 25 mg every eight hours

Paresthesias, headache, fatigue

First-line therapy

Doxylamine (Unisom SleepTabs)

12.5 to 25 mg every eight hours

Drowsiness

May use lower dose in the morning and at midday, and larger dose at night

Secondary therapies

Dimenhydrinate

50 to 100 mg every four to six hours

Drowsiness, dizziness, headache, fatigue

Diphenhydramine (Benadryl)

25 to 50 mg every eight hours

Drowsiness, dizziness, headache, fatigue

Hydroxyzine (Vistaril)

50 mg every four to six hours

Drowsiness, dizziness, headache, fatigue

Meclizine (Antivert)

25 mg every six hours

Drowsiness, dizziness, headache, fatigue

Metoclopramide (Reglan)

10 mg every six hours

Tardive dyskinesia

Avoid high dosages or treatment for longer than 12 weeks

Ondansetron (Zofran)

4 to 8 mg every six hours

Headache, diarrhea, constipation, fatigue

Available as oral disintegrating tablet

Promethazine

12.5 to 25 mg every four to six hours

Sedation, extrapyramidal symptoms

Avoid intravenous administration (associated with tissue damage); oral, rectal, or intramuscular administration is safer; can be compounded as transdermal gel

Therapies for refractory nausea and vomiting

Droperidol

1.25 to 2.5 mg intramuscularly or intravenously

Torsades de pointes, prolonged QT interval

Methylprednisolone

16 mg every eight hours for three days, then taper over two weeks

Increased risk of cleft lip if used before 10 weeks' gestation; data on effectiveness are mixed; may be given orally or intravenously

Prochlorperazine

5 to 10 mg every six hours

Sedation, extrapyramidal symptoms, hypotension

Available as buccal tablet

Scopolamine

1-mg patch behind ear every three days

Drowsiness, dry mouth, urinary retention

May cause limb and trunk deformities if used in first trimester

Trimethobenzamide (Tigan)

300 mg every six to eight hours

Sedation, anticholinergic effects

Table 3.

Pharmacologic Treatments for Nausea and Vomiting of Pregnancy

AgentDosageAdverse effectsNotes

Primary therapies

Vitamin B6

10 to 25 mg every eight hours

Paresthesias, headache, fatigue

First-line therapy

Doxylamine (Unisom SleepTabs)

12.5 to 25 mg every eight hours

Drowsiness

May use lower dose in the morning and at midday, and larger dose at night

Secondary therapies

Dimenhydrinate

50 to 100 mg every four to six hours

Drowsiness, dizziness, headache, fatigue

Diphenhydramine (Benadryl)

25 to 50 mg every eight hours

Drowsiness, dizziness, headache, fatigue

Hydroxyzine (Vistaril)

50 mg every four to six hours

Drowsiness, dizziness, headache, fatigue

Meclizine (Antivert)

25 mg every six hours

Drowsiness, dizziness, headache, fatigue

Metoclopramide (Reglan)

10 mg every six hours

Tardive dyskinesia

Avoid high dosages or treatment for longer than 12 weeks

Ondansetron (Zofran)

4 to 8 mg every six hours

Headache, diarrhea, constipation, fatigue

Available as oral disintegrating tablet

Promethazine

12.5 to 25 mg every four to six hours

Sedation, extrapyramidal symptoms

Avoid intravenous administration (associated with tissue damage); oral, rectal, or intramuscular administration is safer; can be compounded as transdermal gel

Therapies for refractory nausea and vomiting

Droperidol

1.25 to 2.5 mg intramuscularly or intravenously

Torsades de pointes, prolonged QT interval

Methylprednisolone

16 mg every eight hours for three days, then taper over two weeks

Increased risk of cleft lip if used before 10 weeks' gestation; data on effectiveness are mixed; may be given orally or intravenously

Prochlorperazine

5 to 10 mg every six hours

Sedation, extrapyramidal symptoms, hypotension

Available as buccal tablet

Scopolamine

1-mg patch behind ear every three days

Drowsiness, dry mouth, urinary retention

May cause limb and trunk deformities if used in first trimester

Trimethobenzamide (Tigan)

300 mg every six to eight hours

Sedation, anticholinergic effects

Antiemetics. Chlorpromazine and prochlorperazine have been shown to reduce symptoms of nausea and vomiting of pregnancy and of hyperemesis gravidarum.36 Buccal administration of prochlorperazine is associated with less sedation than oral administration.37 Promethazine is commonly used, but is sedating. It is available as a rectal suppository and can be compounded as a topical agent that is applied to the wrist. Its safety in the first trimester has been established.38

Small studies have shown comparable effectiveness between ondansetron (Zofran) and promethazine in treating nausea and vomiting, although patients receiving ondansetron had less sedation.39 Ondansetron is significantly more expensive than promethazine. The use of ondansetron in pregnancy has not been shown to increase the risk of miscarriage, major malformations, or low birth weight.40

Antihistamines and Anticholinergics. Antihistamines decrease stimulation of the vomiting center by affecting the vestibular system.11 Diphenhydramine (Benadryl), meclizine (Antivert), and dimenhydrinate have been shown to be safe and more effective than placebo in reducing the symptoms of nausea and vomiting of pregnancy.36 Although scopolamine is likely effective, its use in the first trimester is not recommended because of the potential for limb and trunk defects.41

Promotility Agents. Metoclopramide (Reglan) is often used alone and in combination with other agents, such as vitamin B6, for the treatment of nausea and vomiting of pregnancy. As a promotility agent, it increases gastric transit and lowers esophageal sphincter pressure. It is as effective as promethazine, but has fewer adverse effects.42 Metoclopramide in combination with vitamin B6 is more effective than prochlorperazine or promethazine, although all three therapies improve symptoms.43 Because metoclopramide is associated with tardive dyskinesia, the U.S. Food and Drug Administration has issued a boxed warning. The risk of this rare complication increases with total dosage and duration of treatment; therefore, it should not be used for longer than 12 weeks.

Corticosteroids. A study involving 40 women found that methylprednisolone is superior to promethazine in reducing symptoms of nausea and vomiting in patients with hyperemesis gravidarum.44 However, a meta-analysis of four studies found that the use of glucocorticoids before 10 weeks' gestation is associated with a three- to fourfold increased risk of cleft lip.45 Therefore, glucocorticoids should be used only after 10 weeks' gestation.

Intravenous Fluids. Fluid replacement is safe and effective in restoring volume and electrolytes in women who have hyperemesis gravidarum and are unable to tolerate oral intake. Lactated Ringer solution or normal saline is acceptable. Because of the risk of Wernicke encephalopathy, intravenous thiamine should be added if dextrose-containing fluids are administered, if vomiting has lasted longer than three weeks, or if fluid replacement lasts longer than three days.46

Enteral and Parenteral Nutrition. Patients who have refractory nausea and vomiting may require hospitalization. In these patients, enteral tube feeding in addition to routine intravenous fluids may be helpful. If patients do not respond to this therapy, parenteral nutrition may be necessary.47 Administration of parenteral nutrition is associated with significant risk during pregnancy, including a 25% risk of line sepsis, as well as steatohepatitis if lipid emulsion is used.48 Therefore, it should be reserved for extreme cases that have been refractory to enteral nutrition.

Acid-Reducing Medications. Recent data indicate that pregnant women who have acid reflux have more severe nausea and vomiting.49 Histamine H2 antagonists and proton pump inhibitors are safe and effective for use in pregnant women, and may improve nausea and vomiting.

OVERALL APPROACH TO TREATMENT

Nausea and vomiting of pregnancy is a common and sometimes challenging problem, and hyperemesis gravidarum may be associated with adverse perinatal outcomes. Both conditions may significantly affect the quality of life and psychological well-being of the mother. A variety of safe and effective therapeutic options are available, and a multimodal approach to treatment is helpful. The treatment algorithm presented in Figure 1 is closely aligned with treatment recommendations from the American College of Obstetricians and Gynecologists.34

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Evaluation of Nausea and Vomiting During Pregnancy

Figure 1.

Treatment algorithm for nausea and vomiting of pregnancy.

Evaluation of Nausea and Vomiting During Pregnancy


Figure 1.

Treatment algorithm for nausea and vomiting of pregnancy.

Data Sources: A PubMed search was completed using the key terms nausea and vomiting, pregnancy, and hyperemesis gravidarum. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Clinical Evidence, the Cochrane database, and Essential Evidence Plus were also searched. Search date: January 15, 2012, and January 24, 2014.

The Author

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HOWARD ERNEST HERRELL, MD, is clerkship director in the Department of Obstetrics and Gynecology at East Tennessee State University in Johnson City....

Author disclosure: No relevant financial affiliations.

Address correspondence to Howard Ernest Herrell, MD, East Tennessee State University, 325 N. State of Franklin Rd., Johnson City, TN 37604 (e-mail: herrellh@etsu.edu). Reprints are not available from the author.

REFERENCES

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1. Louik C, Hernandez-Diaz S, Werler MM, Mitchell AA. Nausea and vomiting in pregnancy: maternal characteristics and risk factors. Paediatr Perinat Epidemiol. 2006;20(4):270–278....

2. 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(4):931–937.

3. Black FO. Maternal susceptibility to nausea and vomiting of pregnancy: is the vestibular system involved? Am J Obstet Gynecol. 2002;186(5 suppl Understanding):S204–S209.

4. Heinrichs L. Linking olfaction with nausea and vomiting of pregnancy, recurrent abortion, hyperemesis gravidarum, and migraine headache. Am J Obstet Gynecol. 2002;186(5 suppl Understanding):S215–S219.

5. Källén B, Lundberg G, Aberg A. Relationship between vitamin use, smoking, and nausea and vomiting of pregnancy. Acta Obstet Gynecol Scand. 2003;82(10):916–920.

6. Niebyl JR. Clinical practice. Nausea and vomiting in pregnancy [published correction appears in N Engl J Med. 2010;363(21):2078]. N Engl J Med. 2010;363(16):1544–1550.

7. Golberg D, Szilagyi A, Graves L. Hyperemesis gravidarum and Helicobacter pylori infection: a systematic review. Obstet Gynecol. 2007;110(3):695–703.

8. Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol. 1998;41(3):597–605.

9. Broussard CN, Richter JE. Nausea and vomiting of pregnancy. Gastroenterol Clin North Am. 1998;27(1):123–151.

10. Schiff MA, Reed SD, Daling JR. The sex ratio of pregnancies complicated by hospitalisation for hyperemesis gravidarum. BJOG. 2004;111(1):27–30.

11. Lee NM, Saha S. Nausea and vomiting of pregnancy. Gastroenterol Clin North Am. 2011;40(2):309–334vii.

12. Davis M. Nausea and vomiting of pregnancy: an evidence-based review. J Perinat Neonatal Nurs. 2004;18(4):312–328.

13. Gadsby R, Barnie-Adshead AM, Jagger C. A prospective study of nausea and vomiting during pregnancy [published correction appears in Br J Gen Pract. 1993;43(373):325]. Br J Gen Pract. 1993;43(371):245–248.

14. Weigel RM, Weigel MM. Nausea and vomiting of early pregnancy and pregnancy outcome. A meta-analytical review. Br J Obstet Gynaecol. 1989;96(11):1312–1318.

15. Tierson FD, Olsen CL, Hook EB. Nausea and vomiting of pregnancy and association with pregnancy outcome [published correction appears in Am J Obstet Gynecol. 1989;160(2):518–519]. Am J Obstet Gynecol. 1986;155(5):1017–1022.

16. Deuchar N. Nausea and vomiting in pregnancy: a review of the problem with particular regard to psychological and social aspects. Br J Obstet Gynaecol. 1995;102(1):6–8.

17. Kuçscu NK, Koyuncu F. Hyperemesis gravidarum: current concepts and management. Postgrad Med J. 2002;78(916):76–79.

18. Zhang J, Cai WW. Severe vomiting during pregnancy: antenatal correlates and fetal outcomes. Epidemiology. 1991;2(6):454–457.

19. 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(4 pt 1):G855–G861.

20. Simpson SW, Goodwin TM, Robins SB, et al. Psychological factors and hyperemesis gravidarum. J Womens Health Gend Based Med. 2001;10(5):471–477.

21. Locock L, Alexander J, Rozmovits L. Women's responses to nausea and vomiting in pregnancy. Midwifery. 2008;24(2):143–152.

22. Puangsricharern A, Mahasukhon S. Effectiveness of auricular acupressure in the treatment of nausea and vomiting in early pregnancy. J Med Assoc Thai. 2008;91(11):1633–1638.

23. Matthews A, Dowswell T, Haas DM, Doyle M, O'Mathúna DP. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2010;(9):CD007575.

24. Smith C, Crowther C, Beilby J. Acupuncture to treat nausea and vomiting in early pregnancy: a randomized controlled trial. Birth. 2002;29(1):1–9.

25. Knight B, Mudge C, Openshaw S, White A, Hart A. Effect of acupuncture on nausea of pregnancy: a randomized, controlled trial. Obstet Gynecol. 2001;97(2):184–188.

26. Keating A, Chez RA. Ginger syrup as an antiemetic in early pregnancy. Altern Ther Health Med. 2002;8(5):89–91.

27. Ozgoli G, Goli M, Simbar M. Effects of ginger capsules on pregnancy, nausea, and vomiting. J Altern Complement Med. 2009;15(3):243–246.

28. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai. 2007;90(1):15–20.

29. Sripramote M, Lekhyananda N. A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy. J Med Assoc Thai. 2003;86(9):846–853.

30. Ensiyeh J, Sakineh MA. Comparing ginger and vitamin B6 for the treatment of nausea and vomiting in pregnancy: a randomised controlled trial. Midwifery. 2009;25(6):649–653.

31. Smith C, Crowther C, Willson K, Hotham N, McMillian V. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol. 2004;103(4):639–645.

32. 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(1):33–36.

33. Vutyavanich T, Wongtra-ngan S, Ruangsri R. Pyridoxine for nausea and vomiting of pregnancy. Am J Obstet Gynecol. 1995;173(3 pt 1):881–884.

34. American College of Obstetrics and Gynecology. ACOG practice bulletin: nausea and vomiting of pregnancy. Obstet Gynecol. 2004;103(4):803–814.

35. McKeigue PM, Lamm SH, Linn S, Kutcher JS. Bendectin and birth defects: I. A meta-analysis of the epidemiologic studies. Teratology. 1994;50(1):27–37.

36. Leathem AM. Safety and efficacy of antiemetics used to treat nausea and vomiting in pregnancy. Clin Pharm. 1986;5(8):660–668.

37. Singh S, Sharma DR, Chaudhary A. Evaluation of prochlorperazine buccal tablets (Bukatel) and metoclopramide oral tablets in the treatment of acute emesis. J Indian Med Assoc. 1999;97(8):346–347.

38. Witter FR, King TM, Blake DA. The effects of chronic gastrointestinal medication on the fetus and neonate. Obstet Gynecol. 1981;58(5 suppl):79S–84S.

39. Sullivan CA, Johnson CA, Roach H, Martin RW, Stewart DK, Morrison JC. A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol. 1996;174(5):1565–1568.

40. 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(9):940–943.

41. Yu JF, Yang YS, Wang WY, Xiong GX, Chen MS. Mutagenicity and teratogenicity of chlorpromazine and scopolamine. Chin Med J (Engl). 1988;101(5):339–345.

42. Tan PC, Khine PP, Vallikkannu N, Omar SZ. Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2010;115(5):975–981.

43. Bsat FA, Hoffman DE, Seubert DE. Comparison of three outpatient regimens in the management of nausea and vomiting in pregnancy. J Perinatol. 2003;23(7):531–535.

44. Safari HR, Fassett MJ, Souter IC, Alsulyman OM, Goodwin TM. The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double-blind, controlled study. Am J Obstet Gynecol. 1998;179(4):921–924.

45. 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(6):385–392.

46. Bottomley C, Bourne T. Management strategies for hyperemesis. Best Pract Res Clin Obstet Gynaecol. 2009;23(4):549–564.

47. Hsu JJ, Clark-Glena R, Nelson DK, Kim CH. Nasogastric enteral feeding in the management of hyperemesis gravidarum. Obstet Gynecol. 1996;88(3):343–346.

48. Folk JJ, Leslie-Brown HF, Nosovitch JT, Silverman RK, Aubry RH. Hyperemesis gravidarum: outcomes and complications with and without total parenteral nutrition. J Reprod Med. 2004;49(7):497–502.

49. Gill SK, Maltepe C, Mastali K, Koren G. The effect of acid-reducing pharmacotherapy on the severity of nausea and vomiting of pregnancy. Obstet Gynecol Int. 2009;2009:585269.



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