Nausea and Vomiting of Pregnancy: Treatment and Outcome: Authors: Section Editor: Deputy Editor
Nausea and Vomiting of Pregnancy: Treatment and Outcome: Authors: Section Editor: Deputy Editor
Nausea and Vomiting of Pregnancy: Treatment and Outcome: Authors: Section Editor: Deputy Editor
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2023. | This topic last updated: Oct 21, 2022.
INTRODUCTION
Nausea with or without vomiting is common in early pregnancy. Severe vomiting resulting in
hypovolemia and weight loss is termed hyperemesis gravidarum and occurs infrequently.
Symptoms usually resolve by midpregnancy regardless of severity and need for therapy.
Management of patients with nausea and vomiting of pregnancy (NVP) depends upon
symptom severity, the impact of their symptoms on their health and quality of life, and the
safety of treatment for both them and their fetus. Treatment approaches vary widely and
include conservative measures (dietary/lifestyle changes), medication(s), and hospitalization for
parenteral fluids and therapies in patients with hypovolemia or hyperemesis gravidarum who
fail to respond to outpatient management. Enteral or parenteral nutrition may be required for
those with persistent weight loss despite these interventions, although this is rare.
The treatment and outcomes of NVP will be reviewed here. Our approach is generally consistent
with that of the American College of Obstetricians and Gynecologists [1]. The pathophysiology,
clinical features, and evaluation of this disorder are discussed separately. (See "Nausea and
vomiting of pregnancy: Clinical findings and evaluation".)
● Reduce symptoms and improve quality of life through dietary and lifestyle changes
followed by initiation of treatment with medications, if necessary.
Early intervention and treatment of patients with mild and moderate symptoms may prevent
progression to severe disease (eg, hyperemesis gravidarum [HG]) [1].
For patients whose primary symptom is nausea, the initial treatment approach involves
counseling about dietary and lifestyle changes, such as trigger avoidance. Ginger and/or
pyridoxine or the combination of doxylamine and pyridoxine are initial recommended therapies
if symptoms do not improve ( algorithm 1).
Dietary changes
Meals and snacks — Patients with nausea are advised to eat before, or as soon as, they feel
hungry to avoid an empty stomach, which can aggravate nausea [2]. A snack before getting out
of bed in the morning and snacks during the night may also be helpful (eg, crackers with
peanut butter or cheese taken prior to getting up for nighttime bathroom trips).
Meals and snacks should be eaten slowly and in small amounts every one to two hours to avoid
an overly full stomach, which can also aggravate nausea for some patients [3].
Patients should determine which foods they tolerate best and try to consume those foods.
Dietary manipulations that help some patients include eliminating coffee and spicy, odorous,
high-fat, acidic, or very sweet foods, and instead consuming snacks/meals that are protein-
dominant, salty, low-fat, bland, and/or dry (eg, nuts, pretzels, crackers, cereal, toast) [2-4].
Sucking on peppermint candies may reduce postprandial nausea [5].
https://www.uptodate.com/contents/6811/print 2/47
3/30/23, 12:35 AM 6811
However, high-quality evidence of the optimal dietary components to reduce nausea are sparse.
Although clinicians commonly recommend ingestion of frequent, small, carbohydrate-
predominant meals/snacks (eg, soda crackers or dry toast) based primarily on anecdotal
evidence passed down over a century [6], consumption of protein-predominant meals/snacks
may be more helpful and was associated with quantifiable decreases in nausea in one study [7].
Patients whose symptoms are related to delayed gastric emptying should improve with a diet
consisting of low-fat solids and liquids since these foods are more readily emptied by the
stomach. However, it is not known to what degree gastric emptying and dysfunction account
for symptoms in patients with NVP.
Fluids — Patients are advised to consume fluids at least 30 minutes before or after solid food
to minimize the effect of a full stomach [3]. Fluids are better tolerated if cold, clear, and
carbonated or sour (eg, ginger ale, lemonade, popsicles) and taken in small amounts; using a
straw or very small cup sometimes helps [8]. Some patients find aromatic liquids, such as
lemon, mint, or peppermint tea, more tolerable and helpful in reducing nausea.
Trigger avoidance — Along with dietary changes, avoidance of environmental triggers is a key
intervention for reducing NVP [4]. Examples of some triggers include stuffy rooms, odors (eg,
perfume, chemicals, food, smoke) [9], heat, humidity, noise, and visual or physical motion (eg,
flickering lights, driving) [10].
Lying down soon after eating and lying on the left side are additional potentially aggravating
factors because these actions may delay gastric emptying [3]. Quickly changing position and
not getting enough rest/sleep may also aggravate symptoms [11].
Cold solid foods are tolerated better than hot solid foods because they have less odor and
require less preparation time (ie, shorter exposure to the trigger if the patients is preparing
their own meal) [3].
Brushing teeth after a meal [5], spitting out saliva, and frequently rinsing the mouth can also be
helpful. Switching to a different toothpaste may help those for whom strongly flavored
toothpaste is a trigger.
Supplements containing iron should be avoided until symptoms resolve as iron causes gastric
irritation and can provoke nausea and vomiting [12]. Taking prenatal vitamins before bed with a
snack, instead of in the morning or on an empty stomach, may also be helpful [13]. Some
https://www.uptodate.com/contents/6811/print 3/47
3/30/23, 12:35 AM 6811
patients may find chewable prenatal vitamins more tolerable than tablets or capsules. If
prenatal vitamins are stopped, a supplement containing folic acid (400 to 800 mcg daily) is
recommended, especially throughout the first trimester, until prenatal vitamins are again
tolerated. (See "Preconception and prenatal folic acid supplementation".)
Ginger supplements — We suggest that patients with nausea try consuming ginger-containing
foods (eg, ginger lollipops, ginger tea, foods or drinks containing ginger root or syrup). We do
not prescribe powdered ginger because standard pharmacologic-grade ginger preparations are
not readily available [14]; however, if prescribed, a common dose is 1 to 1.5 g orally divided over
24 hours (eg, 250 mg ginger capsules orally four times a day); doses of 0.5 to 2.5 g orally over
24 hours have been used and appear to be safe [15]. In meta-analyses of randomized trials
(including over 1000 participants), ginger improved nausea compared with placebo but did not
significantly reduce vomiting [16,17].
Initial pharmacotherapy
Pyridoxine (vitamin B6) monotherapy — Pyridoxine can improve nausea, has a good safety
profile with minimal side effects, and is easy to obtain; therefore, we generally begin pyridoxine
as the initial treatment.
As a single agent, the recommended dose of pyridoxine is 10 to 25 mg orally every six to eight
hours with the maximum treatment dose suggested for pregnant individuals at 100 mg/day
[18]. In settings where a 10 mg tablet is unavailable (eg, United States, Canada), half of a 25 mg
pyridoxine tablet (ie, 12.5 mg) may be reasonably substituted with the understanding that the
medication may not be evenly distributed throughout the oral tablet. Sensory neuropathy has
been reported with chronic intake of pyridoxine at doses >500 mg/day [19,20], but cumulative
doses up to 500 mg/day appear to be safe for the patient [21]. Human data on fetal safety at
high doses are limited but reassuring. An observational study of 96 pregnant patients in the
first trimester with >50 mg/day pyridoxine intake (mean dose 132 mg/day, range 50 to 510
mg/day) and 96 control pregnancies found no association with major fetal malformations [22].
Pyridoxine 100 mg/kg was not teratogenic in animal studies [23].
Systematic reviews of randomized and/or controlled trials have reported that pyridoxine
(vitamin B6) improves mild to moderate nausea but does not significantly reduce vomiting [24-
26]. The mechanism for the therapeutic effect is unknown. Hypotheses include
prevention/treatment of vitamin B6 deficiency, intrinsic antinausea properties, and/or synergy
with the antinausea properties of antihistamines [27]. Although vitamin B6 levels decrease as
gestation advances, there is no proven correlation between maternal vitamin B6 levels and
incidence or severity of nausea [28].
https://www.uptodate.com/contents/6811/print 4/47
3/30/23, 12:35 AM 6811
The recommended prescription starts with two extended-release tablets (each tablet contains
doxylamine 10 mg and pyridoxine 10 mg) orally at bedtime [29,30]. The dose may be increased
to four tablets orally over the course of the day, as needed, for more severe nausea (two tablets
at bedtime and add one tablet midmorning and one tablet in midafternoon if needed). Thus, a
patient will take two to four tablets per day depending on the regimen that controls their
symptoms. A randomized placebo-controlled trial found that doxylamine succinate 10 mg and
pyridoxine 10 mg combination preparation administered in doses of two to four tablets daily
was not associated with an increased risk of any adverse event and was well tolerated by
patients with NVP [31].
The combination extended-release tablets may be costly. In the United States, doxylamine is
available in some over-the-counter sleeping pills (eg, Unisom Sleep Tabs) and as a prescription
antihistamine chewable tablet (eg, Aldex AN): One-half of the 25 mg over-the-counter tablet or
two chewable 5 mg tablets can be used off-label as an antiemetic. In addition, pyridoxine 25
mg, also available over-the-counter, can be taken three or four times per day along with 12.5
mg of doxylamine; the 10 mg dose of pyridoxine is not commercially available in the United
States. This is a reasonable, less expensive substitute for combination extended-release tablets.
The combination of doxylamine-pyridoxine was proven modestly effective for treatment of NVP
in a meta-analysis of placebo-controlled randomized trials [32] and appears to be more
effective than either therapy alone. It was the formulation for Bendectin, which was voluntarily
withdrawn from the market in 1983 due to lawsuits alleging teratogenicity, although scientific
evidence supports its safety [23,33,34] and efficacy [32,35-38]. A meta-analysis of controlled
studies on outcome of pregnancies exposed to Bendectin reported no increase in the incidence
of congenital anomalies [34].
Other interventions
Self-administered nerve stimulation therapy over the volar aspect of the wrist at the P6
acupressure point using a commercial device has shown mixed results, with some promise
in two randomized trials [44,45].
The available evidence on these measures is limited and studies have methodological
flaws. Although data do not prove benefit, these measures are unlikely to be harmful. If a
patient wants to try one or more of them, the provider should not discourage use.
● Most other alternative medicine approaches have not been studied rigorously for
efficacy or safety, and should be avoided for this reason. As an example, in 2009, the US
Food and Drug Administration notified health care professionals and pregnant or
breastfeeding individuals to avoid consuming Nzu, a traditional African remedy for
morning sickness, because of potential health risks from high levels of lead and arsenic, a
problem that has been reported by others [47]. Nzu may be sold under such names as
Calabash clay, Calabar stone, Mabele, Argile, or La Craie. In addition, there are no well-
designed trials demonstrating safety and efficacy of essential oils, although low-quality
studies have been published.
● Cannabis (also called marijuana) use during pregnancy has been increasing, and
pregnant individuals increasingly self-report using it to alleviate the symptoms of NVP
[48]. Although cannabis has been used to mitigate nausea and vomiting in nonpregnant
individuals, the American College of Obstetricians and Gynecologists and public health
authorities recommend advising pregnant individuals and those considering becoming
pregnant to avoid using it or other cannabinoids to treat their nausea as concerns exist
regarding fetal safety [49,50]. Individuals may not receive this information from cannabis
dispensary employees, who have been found to endorse its use in pregnant people [51].
Potential adverse effects of prenatal cannabis use are reviewed separately. (See
"Substance use during pregnancy: Overview of selected drugs", section on 'Cannabis
(marijuana)'.)
https://www.uptodate.com/contents/6811/print 6/47
3/30/23, 12:35 AM 6811
Initial approach — For patients whose primary symptom is vomiting but who are not
hypovolemic (no lassitude, postural dizziness, thirst, tachycardia, decreased urine volume and
frequency; able to keep down some fluids), laboratory test results (eg, BUN, electrolytes, acid-
base balance) are likely to be normal or near normal. A reasonable approach in these patients is
to discuss dietary changes and trigger avoidance, as well as use of doxylamine-pyridoxine
rather than pyridoxine alone. (See 'Management of nausea as the primary symptom' above and
"Nausea and vomiting of pregnancy: Clinical findings and evaluation", section on 'Laboratory
tests'.)
We also offer additional medications that are reported to be effective and have a good
maternal-fetal safety profile. If doxylamine-pyridoxine is ineffective, then other medications are
added in a stepwise progression because a combination of drugs may be effective
( algorithm 1) [54,55]. We typically continue a medication for a week to determine whether
nausea and vomiting are improving. If symptoms persist, then we add another class of
medication to the existing regimen; however, if the patient is experiencing side effects, we
substitute another medication in its place.
Patients who are vomiting most food and liquids require frequent, even daily, assessment of
their medical status and response to therapy. Ambulatory management may be appropriate for
patients with severe symptoms who have a strong preference to avoid admission, provided
intensive follow-up and daily treatment with intravenous fluid and injectable medication are
available, if needed [56]. Those who are becoming hypovolemic or have electrolyte
abnormalities or vital sign or neurologic changes are admitted for hour-to-hour evaluation and
more intensive therapy. (See 'Management of vomiting with hypovolemia' below.)
Historically, pregnant individuals have been excluded from most clinical drug trials. Thus, there
are only limited data on pregnant people to support the safety and efficacy of medications used
to treat nausea and vomiting. A number of reports have demonstrated that antiemetic therapy
is more effective than placebo and does not increase the incidence of congenital anomalies
[8,11,26,32,35,55,57]. However, there is little evidence from well-designed comparative trials
that show clear superiority of one medication over another. It is therefore recommended that
https://www.uptodate.com/contents/6811/print 7/47
3/30/23, 12:35 AM 6811
safety profiles, patient tolerance, and cost all be considered in the choice of
pharmacotherapeutic management [58].
Dimenhydrinate, meclizine, and diphenhydramine are the antihistamines that have been most
extensively studied for treatment of NVP. There are no data on use of the scopolamine patch for
NVP. Scopolamine should be avoided in patients with preeclampsia with severe features as
eclamptic seizures have been reported after parenteral administration [59].
The efficacy of antihistamines was illustrated in an analysis of pooled data from controlled trials
that found use of these agents significantly reduced pregnancy-related nausea and vomiting
(relative risk [RR] 0.34, 95% CI 0.27-0.43); however, these studies used a variety of
antihistamines and measured different outcomes [35].
The safety of antihistamines was affirmed in a meta-analysis that examined the association
between histamine 1 [H1] antihistamine use and major malformations [60]. This review of 37
controlled studies, including nearly 50,000 first-trimester exposures, found that the risk of
major malformations was similar in exposed and nonexposed pregnancies (cohort studies:
odds ratio [OR] 1.07, 95% CI 0.98-1.16; case-control studies: OR 1.05, 95% CI 0.90-1.23).
Common side effects of antihistamines include sedation, dry mouth, lightheadedness, and
constipation.
Meclizine — Meclizine is used primarily for managing motion sickness and vertigo. In the
United States, it is not the H1 antagonist chosen for treatment of NVP, but it is one of the
options used for this indication in some countries [66]. Meclizine can be given 25 mg orally
every four to six hours, as needed. Meclizine has caused cleft palate in rats but at exposures far
higher than those used therapeutically. Human data of an association between facial clefts and
meclizine have been mixed, but three large studies did not show an increased risk of
malformations [67-69].
Add a dopamine antagonist — Several types of dopamine receptor antagonists can be used
for the treatment of NVP. The three main classes are benzamides (metoclopramide),
phenothiazines (promethazine and prochlorperazine), and butyrophenones (droperidol).
Metoclopramide, promethazine, and prochlorperazine are discussed here; droperidol is
discussed below. (See 'Droperidol' below.)
The use of these medications is based on the observation that dopaminergic mechanisms are
involved in the regulation of gastrointestinal motility. In the stomach, dopamine receptor
agonists inhibit gastric motility, whereas dopamine receptor antagonists stimulate gastric
motility and emptying and thus have antiemetic effects. Blockade of dopamine 2 receptors also
appears to block emetic signaling.
https://www.uptodate.com/contents/6811/print 9/47
3/30/23, 12:35 AM 6811
Maternal side effects are a concern, especially with long-term use. Metoclopramide accounts
for almost one-third of all drug-induced movement disorders; however, in the randomized trial
discussed above, dystonia was more common with promethazine than metoclopramide (14/73
[19.2 percent] versus 4/70 [5.7 percent]) [71]. Older age, higher dose, and female sex are risk
factors for development of these side effects [76]. Tardive dyskinesia is rare in young patients.
More information on side effects is available separately. (See "Characteristics of antiemetic
drugs", section on 'Benzamides'.)
Early detection and discontinuation of the metoclopramide are important for the prevention of
permanent tardive dyskinesia. Use of metoclopramide with diphenhydramine or hydroxyzine
may mask a dystonic reaction. Tapering rather than abrupt discontinuation is unnecessary.
Upon discontinuation, metoclopramide-induced tardive dyskinesia (involuntary and repetitive
movements of the body) can be irreversible in some cases.
Metoclopramide can be effective in the setting of diabetic gastroparesis; however, the degree to
which delayed gastric emptying is involved in NVP independent of gastroparesis is unknown.
Domperidone is another promotility agent, but there is no information on its safety or efficacy
for treatment of NVP.
https://www.uptodate.com/contents/6811/print 10/47
3/30/23, 12:35 AM 6811
Fetal safety and maternal efficacy in relief of both nausea and vomiting have been reported in
most studies including large numbers of patients [35,71,78-81]. Disadvantages include
prominent sedation and risk of dystonic reactions. These risks are elevated under conditions of
prolonged use and high dosing. Use of promethazine appears to lower the seizure threshold,
which may be important in patients with seizure disorders or late in pregnancy in patients with
preeclampsia.
There are conflicting reports regarding a potential risk of neonatal respiratory depression
following the administration of promethazine during labor. Neonatal platelet aggregation also
may be impaired when it is given intrapartum, but this does not appear to increase the need for
intervention in the newborn. These observations are unlikely to be relevant for patients who
take promethazine in early pregnancy for nausea and vomiting.
Common mild side effects include drowsiness, dizziness, headaches, and urinary retention.
Some patients experience extrapyramidal symptoms, but this is uncommon. In a randomized
trial involving 84 male and female emergency department patients with uncomplicated nausea
and vomiting due to gastritis/gastroenteritis, prochlorperazine 10 mg intravenously relieved
symptoms of nausea and vomiting more quickly and completely than promethazine 25 mg
intravenously, with no difference in incidence of extrapyramidal effects [82].
The use of ondansetron in pregnancy is controversial. We individualize its use, weighing the
risks and benefits during pregnancy. We counsel pregnant patients regarding the available data
and the possible associated small risk of cardiovascular anomalies (see 'Ondansetron' below).
There are limited human data on the safety of granisetron, dolasetron, or other 5-HT3
antagonists in pregnancy; animal studies did not show adverse pregnancy effects.
Ondansetron
https://www.uptodate.com/contents/6811/print 11/47
3/30/23, 12:35 AM 6811
● Candidates – We believe, ideally, a combination of two oral agents should be tried and
found to be unsuccessful before initiating oral ondansetron in pregnancies less than 10
weeks of gestation. The American College of Obstetricians and Gynecologists
recommends discussing the available data (see below) with patients and weighing the
potential risks against the effectiveness of ondansetron in treating nausea and vomiting
on a case-by-case basis in patients less than 10 weeks of gestation whose symptoms are
refractory to the medications discussed above [1]. Some other organizations have
recommended avoidance in the first trimester or use as a second-line agent because of a
possible small increase in risk of oral clefts and possibly ventricular septal defects (see
below) [83,84].
NVP and hyperemesis gravidarum are common off-label uses of ondansetron. In a small
randomized trial, use of ondansetron resulted in clinically significant reductions in both
nausea and vomiting compared with the combination of doxylamine and pyridoxine [85].
In another randomized trial, it was more effective than metoclopramide for reduction of
vomiting but not nausea [86].
● Side effects – Headache, fatigue, constipation, and drowsiness are the most common
drug-related side effects. A stool softener and mild laxative can be helpful for patients
experiencing constipation. At least 10 patients have had signs or symptoms of myocardial
ischemia (most commonly during intravenous administration) that resolved with prompt
treatment and where a causal role of ondansetron could not be ruled out, prompting the
manufacturer to recommend patient monitoring during and after administration [88].
Ondansetron can cause QT prolongation, particularly in patients with underlying
arrhythmia risk factors, such as a personal or family history of long QT syndrome,
hypokalemia or hypomagnesemia, heart failure, administration of concomitant
medications that lead to QT prolongation, and use of multiple doses or intravenous
ondansetron. Electrocardiographic and electrolyte monitoring is recommended in these
https://www.uptodate.com/contents/6811/print 12/47
3/30/23, 12:35 AM 6811
patients [89]. More detailed information on side effects is available separately. (See
"Characteristics of antiemetic drugs", section on '5-HT3 receptor antagonists'.)
● Risk of congenital anomalies – Available data suggest that use of ondansetron in early
pregnancy is not associated with a high risk of congenital malformations, but a small
absolute increase in risk of cardiovascular malformations (especially septum defects) and
cleft palate may exist [90-93]. One review of available data through 2020 estimated that
the absolute increase in risk above baseline for orofacial defects may be only 0.03 percent,
and for ventricular septal defects it may be 0.3 percent [94].
A retrospective cohort study including over 1.8 million pregnancies among individuals
enrolled in Medicaid concluded that first-trimester oral ondansetron exposure was not
associated with an increased risk of cardiac malformations or congenital malformations
overall after adjustment for known confounders [90]. There was an increased risk of oral
clefts (RR 1.24, 95% CI 1.03-1.48), but the absolute risk difference was low (risk difference
2.7 per 10,000 births, 95% CI 0.2-5.2). This study, which included almost 90,000 first-
trimester ondansetron exposures, is the largest study of this issue and provides the most
reassuring data. The same authors repeated the analysis for intravenous exposures and
found that intravenously administered ondansetron was not associated with an increase
in the risk of oral clefts (RR 0.95, 95% CI 0.63-1.43), cardiac malformations, or congenital
malformations overall [95]. Although the point estimate was lower for intravenous
ondansetron compared with oral ondansetron, the 95% CI was wide and the upper limit
was similar to that for oral ondansetron; thus, the authors concluded that the observed
risks are not clearly different for intravenous versus oral ondansetron [96].
Meta-analyses have not found increased risks for major congenital malformations
associated with ondansetron use in pregnancy [97,98]. A meta-analysis that included the
studies discussed above was limited by inclusion of many other studies that did not adjust
for known confounders, as well as moderate to high risk of bias of all included studies
[97]. In this analysis, first-trimester exposure to ondansetron was associated with a trend
toward an increase in risk for oral clefts (OR 1.22, 95% CI 1.00-1.49) and ventricular septal
defects (OR 1.11, 95% CI 1.00-1.23), but not for major congenital malformations overall,
cardiac malformations overall, atrial septal defects, or cleft lip with or without cleft palate.
https://www.uptodate.com/contents/6811/print 13/47
3/30/23, 12:35 AM 6811
Human data on reproductive effects are sparse [100-102]. Adverse effects have not been
reported in animal reproduction studies. A study that compared the effects of two doses of
granisetron (3 ng/mL and 30 ng/mL) in primary cells isolated from human fetal organs did not
identify any toxicity [100]. A study of 100 granisetron-exposed pregnancies (88 with first-
trimester exposure) reported no increase in major or minor congenital anomalies compared
with unexposed pregnancies [101].
Side effects are similar to those for other 5-HT3 antagonists, such as ondansetron. (See
'Ondansetron' above and "Characteristics of antiemetic drugs", section on '5-HT3 receptor
antagonists'.)
Adjunctive therapy
Antacids containing aluminum or calcium are safe for pregnant patients and preferable to
those containing bismuth or bicarbonate, which may have adverse fetal/neonatal effects [104].
The largest experience with pharmacologic acid-suppressive therapy in pregnant patients has
been with the H2 receptor antagonists cimetidine and ranitidine, which appeared to have a
good maternal-fetal safety profile; however, in 2020, the US Food and Drug Administration
requested manufacturers withdraw all ranitidine products from the market immediately
because some ranitidine products contained the contaminant N-Nitrosodimethylamine (NDMA),
a probable human carcinogen. Cimetidine dosing ranges from 200 mg orally twice daily for
symptomatic relief of dyspepsia to up to 400 mg orally twice daily for gastroesophageal reflux
https://www.uptodate.com/contents/6811/print 14/47
3/30/23, 12:35 AM 6811
disease. In 2005, the European Network of Tetralogy Information Network Services reported
553 cases in which pregnant patients were exposed to H2 blockers, of whom 113 were exposed
to cimetidine [105]. Rates of malformations, low birth weight, and preterm birth were similar for
exposed and non-exposed fetuses. (See "Medical management of gastroesophageal reflux
disease in adults", section on 'Pregnancy and lactation'.)
There is less experience using proton pump inhibitors (eg, lansoprazole or esomeprazole 30 or
40 mg intravenously or orally every 24 hours) during pregnancy. Overall, they probably have a
good maternal-fetal safety profile [106,107]. However, use of alternative agents may be prudent
in patients with renal disease, as some studies have linked chronic use of proton pump
inhibitors with an increased risk of acute kidney injury and end stage renal disease [108].
Safety data for acid-reducing agents are reviewed in more detail separately. (See "Medical
management of gastroesophageal reflux disease in adults", section on 'Pregnancy and
lactation'.)
General approach — Patients with persistent nausea and vomiting should be evaluated by
their clinician and/or in the emergency department to assess their volume and metabolic
status, exclude other diagnoses that could account for their symptoms, and guide replacement
and pharmacologic therapy. (See "Nausea and vomiting of pregnancy: Clinical findings and
evaluation", section on 'Evaluation'.)
We instruct patients with NVP to report to the emergency department or labor and delivery unit
if they have symptoms of hypovolemia (eg, lassitude, postural dizziness, thirst, tachycardia,
decreased urine volume and frequency) or if they are unable to keep food/fluids down for more
than 12 hours. A trial of replacement fluid and intravenous antiemetic therapy before admission
is reasonable for patients with normal electrolyte levels and normal acid-base balance. Hospital
admission is appropriate for those with persistent symptoms after replacement fluid and
https://www.uptodate.com/contents/6811/print 15/47
3/30/23, 12:35 AM 6811
intravenous antiemetic therapy, as well as patients who present with abnormal electrolyte levels
and acid-base balance. The decision to admit versus discharge to home needs to be
individualized based on the patient's severity of disease, resources, and ability to access
outpatient resources (eg, home health care, infusion pump for administration of intravenous
ondansetron at home) and comply with recommendations.
These patients and their families/close contacts often need emotional support to help deal with
stress and anxiety about the maternal illness and its effect on the fetus, and the disruption to
their home- and work-related activities [110]. In some cases, psychiatric consultation and
psycho-social counseling can be helpful to teach the patient relaxation and coping techniques
and address underlying psychopathology, if present [111].
It should also be noted that a single episode of inpatient treatment is often not durable; in a
literature review, approximately 25 percent of patients who were admitted to the hospital for
treatment of hyperemesis required readmission for persistent or recurrent symptoms [112]. As
a result, prior to discharge, patients should be given a clear explanation of which medications
to take, how to take them, and how long to continue them. For patients with persistent
vomiting after inpatient therapy, it is important to exclude underlying diseases that can cause
hyperemesis. (See "Nausea and vomiting of pregnancy: Clinical findings and evaluation",
section on 'Differential diagnosis'.)
Replacement fluid therapy and nutrition — Most patients respond to intravenous hydration
and a short period of gut rest, followed by reintroduction of oral intake and pharmacologic
therapy.
Fluids and electrolytes — Hypovolemia occurs when fluid losses exceed fluid intake and is
often associated with electrolyte abnormalities, fatigue, dizziness, and weakness. We correct
hypovolemia with up to 2 L intravenous Ringer's lactate infused over three to five hours,
supplemented with appropriate electrolytes and vitamins.
After initial replacement fluid therapy with Ringer's lactate, we administer dextrose 5 percent in
0.45 percent saline with 20 mEq potassium chloride at 150 mL/hour to patients with normal
https://www.uptodate.com/contents/6811/print 16/47
3/30/23, 12:35 AM 6811
potassium levels (hypokalemia is discussed below). The infusion rate is adjusted to maintain a
urine output of at least 100 mL/hour.
The optimum replacement fluid regimen has not been studied. It is prudent to avoid use of
dextrose in the initial replacement fluid because of the theoretical concern of inducing
Wernicke's encephalopathy from dextrose infusion in a thiamine-deficient state [113]. We delay
dextrose infusion until after the patient has received thiamine in their initial replacement fluid
(see 'Vitamins and minerals' below). A single small randomized trial of intravenous replacement
fluid therapy with 5 percent dextrose-0.9 percent saline versus 0.9 percent saline solution in
patients hospitalized for hyperemesis gravidarum did not report significant differences in
important clinical outcomes (vomiting, resolution of electrolyte abnormalities, length of
hospitalization, duration of intravenous antiemetic), but nausea improved faster in the 5
percent dextrose group; all participants also received thiamine and an antiemetic intravenously
[114]. A limitation of this trial is that only 60 percent of the patients had severe disease (eg,
weight loss ≥5 percent body weight).
Most hypokalemic patients have a serum potassium concentration of 3.0 to 3.4 mEq/L. This
degree of potassium depletion usually produces no symptoms. Treatment is usually started
with 10 to 20 mEq of potassium given two to four times per day (20 to 80 mEq/day), depending
upon the severity of the hypokalemia. Potassium must be given more rapidly to patients with
hypokalemia that is severe (serum potassium less than 2.5 to 3.0 mEq/L) or symptomatic. A
saline rather than a dextrose solution should be used for initial therapy of hypokalemia since
the administration of dextrose stimulates the release of insulin which drives extracellular
potassium into the cells, which can lead to a transient 0.2 to 1.4 mEq/L reduction in the serum
potassium concentration, particularly if the solution contains only 20 mEq/L of potassium.
Sequential monitoring of the serum potassium is essential to determine the response. (See
"Clinical manifestations and treatment of hypokalemia in adults", section on 'Treatment'.)
Relief of symptoms is common within one to two days of replacement fluid therapy [8].
Relocation from the home environment, as well as replenishment of fluids and electrolytes, may
contribute to palliation of symptoms.
https://www.uptodate.com/contents/6811/print 17/47
3/30/23, 12:35 AM 6811
● Other vitamins – We administer a multivitamin (MVI) intravenously daily: MVI (10 mL) plus
0.6 mg folic acid (to bring the folic acid total to 1 mg) in one liter and vitamin B6 25 mg in
every liter. Intravenous MVI has 150 mcg of vitamin K. Additional vitamin K replacement is
not necessary unless clinically indicated to treat a coagulopathy.
Once serum magnesium levels are restored, we reassess the calcium level. If serum
calcium is still low, we administer 1 to 2 g calcium gluconate in 50 mL of 5 percent
dextrose solution over 10 to 20 minutes.
Diet — A diet that attempts to minimize nausea and vomiting can be resumed after a short
period of gut rest. We usually begin with a diet consisting of bananas, rice, applesauce, and
toast (BRAT diet) and then advance the diet as tolerated. Consistent protein intake is key in
helping prevent nausea. Additional dietary manipulations are described above. Referral to a
nutritionist may be helpful for those patients with underlying medical conditions, like diabetes,
or who would benefit from more education on the ideal diet to manage the symptoms of NVP.
(See 'Dietary changes' above.)
Patients who have not eaten for several days may develop edema when resuming feeding with
carbohydrates [120]. This results from the retention of sodium during fasting combined with
enhanced sodium resorption due to the actions of insulin once carbohydrates are reintroduced
[121]. No intervention is required; the edema will gradually resolve.
https://www.uptodate.com/contents/6811/print 18/47
3/30/23, 12:35 AM 6811
If symptoms recur, antiemetic medications are the same as those used to treat patients with
frequent vomiting without hypovolemia or other serious sequelae ( algorithm 1). Oral
medications are initiated in patients who can tolerate them. These oral medications can then be
used at home when the patient is discharged from the hospital. Rectally administered
medications are an alternative. (See 'Management of vomiting without hypovolemia' above.)
Ideally, a patient who has been admitted for treatment should be sent home when they have
been stabilized on a scheduled antiemetic. In addition, they should have a second agent that
has been effective for breakthrough symptoms. They should continue this prescribed regimen
for at least a week, at which time they can be reevaluated to see if medications can be tapered
or discontinued. The goal is to prevent relapse and an additional hospitalization. However,
discharge medications are often not prescribed. In a population-based study, 50 percent of
patients discharged from the hospital after treatment of NVP were not offered prescriptions for
antiemetics [122].
REFRACTORY SYMPTOMS
Additional laboratory evaluation in patients with refractory symptoms — Case reports and
small series have reported improvement in symptoms in patients with severe disease after
treatment of Helicobacter pylori [123]. Although these observations support the hypothesis of H.
pylori as an etiologic factor, confirmatory evidence from controlled trials is needed. The
American College of Obstetricians and Gynecologists suggests considering testing for H. pylori
infection in patients who are unresponsive to standard therapy [1]. It can also be considered in
patients whose symptoms have not subsided by 16 to 20 weeks of gestation. Indications for
diagnostic testing for H. pylori in the general population, appropriate choice of test, and
consideration of treatment of patients who test positive are reviewed separately. (See
"Indications and diagnostic tests for Helicobacter pylori infection in adults" and "Treatment
https://www.uptodate.com/contents/6811/print 19/47
3/30/23, 12:35 AM 6811
regimens for Helicobacter pylori in adults", section on 'Treatment during pregnancy and
lactation'.)
The mechanism of action is not well understood [124-127], and there is a paucity of evidence
that glucocorticoids are effective [26,35,128]. The largest placebo-controlled trial included 110
patients with severe hyperemesis and reported that patients who received glucocorticoid
therapy had a similar clinical course and need for rehospitalization as those given placebo
[129]. However, a systematic review that included three randomized clinical trials comparing
glucocorticoids with placebo or promethazine or metoclopramide found that patients with
severe nausea and vomiting may benefit with corticosteroids [57]. We have also observed
improvement in symptoms with glucocorticoid use in some patients with refractory severe
vomiting.
Glucocorticoid use has been associated with a slightly increased risk of oral clefts when
administered before 10 weeks of gestation; although this association remains controversial and
has not been confirmed in recent studies (see "Etiology, prenatal diagnosis, obstetric
management, and recurrence of cleft lip and/or palate", section on 'Environmental factors'),
ideally, use of glucocorticoids should be avoided in the first trimester [130-134]. If administered
after 10 weeks, the palate has formed and is not at risk for developing defects.
An effective dose is methylprednisolone (16 mg) intravenously every 8 hours for 48 to 72 hours
[124]. An alternative regimen is hydrocortisone 100 mg intravenously twice daily [57].
Glucocorticoids can be stopped abruptly if there is no response and tapered over two weeks in
patients who experience relief of symptoms. Glucocorticoid use may lead to hyperglycemia;
therefore, blood glucose levels should be monitored in patients with pregestational and
gestational diabetes.
After intravenous therapy, we use an oral prednisone taper regimen of 40 mg oral prednisone
per day for one day, followed by 20 mg per day for three days, followed by 10 mg per day for
three days, and then 5 mg per day for seven days. This regimen may be repeated up to three
times over a six-week period.
https://www.uptodate.com/contents/6811/print 20/47
3/30/23, 12:35 AM 6811
Droperidol — We rarely use droperidol to treat NVP because of maternal safety concerns,
although it is an effective antiemetic. In one study, patients with hyperemesis gravidarum
treated with droperidol-diphenhydramine had significantly shorter hospitalizations (3.1 versus
3.8 days), fewer days per pregnancy hospitalized for hyperemesis (3.5 versus 4.8 days), and
fewer readmissions with this diagnosis (15.0 versus 31.5 percent) than patients treated with
other parenteral therapies [135]. No congenital anomalies were reported in 108 pregnancies.
However, maternal side effects are a concern, especially with long-term use. Droperidol has
been associated with QT prolongation and/or torsades de pointes when used in doses higher
than those typically used for treatment of nausea and vomiting [136]. The US Food and Drug
Administration issued a boxed warning in 2001 [137], and the medication was removed from
the European market in March 2001.
Tube feeding and parenteral nutrition — Patients whose symptoms are refractory to all
pharmacologic and nonpharmacologic interventions should be supported with tube feeding or
parenteral nutrition (and intravenous fluids) for as long as necessary [138,139]. Nutritional
support during early pregnancy can reduce the frequency of late pregnancy morbidities
associated with hyperemesis gravidarum. We also administer pharmacologic interventions if
they provide some relief of nausea and vomiting.
Nutritional status and methods of alimentation (eg, tube feeding, parenteral nutrition) should
be assessed in conjunction with a nutritionist or nutrition service. The optimal timing for
initiating tube feeding or parenteral nutrition has not been established; the decision is based
upon clinical judgment.
In general, tube feeding or parenteral nutrition is begun in patients who cannot maintain their
weight because of vomiting and despite a trial of the interventions described above. Enteral
nutrition via gastric or duodenal intubation is preferable to the parenteral route and may
relieve nausea and vomiting [140]. In patients hospitalized for hyperemesis, routine initiation of
enteral tube feeding in addition to standard care (replacement fluid therapy, antiemetic
https://www.uptodate.com/contents/6811/print 21/47
3/30/23, 12:35 AM 6811
therapy) upon hospital admission did not appear to improve any maternal or newborn outcome
compared with standard care alone in a randomized trial [141]. In particular, nausea and
vomiting symptoms and duration of hospital stay were similar in both groups. Tube feeding was
supposed to be continued for at least seven days or until the patient was able to maintain an
oral intake of 1000 kcal/day; however, 53 percent went off protocol, primarily because the tube
was poorly tolerated. Although the trial has several limitations such as a high drop-out rate,
missing data, and outcomes based on survey of participants, it is the first randomized trial
examining the value of early enteral tube feeding. (See "Enteral feeding: Gastric versus post-
pyloric" and "Nutrition support in critically ill patients: Enteral nutrition".)
Adequate protein-caloric parenteral nutrition requires a central venous access device, which
may lead to catheter-related infection or thrombosis [142,143] (see "Nutrition support in
critically ill patients: Parenteral nutrition"). The American Gastroenterological Association has
published a technical review and position statement on parenteral nutrition [144,145].
SPECIAL POPULATIONS
Nausea and vomiting in patients with diabetes — Special care should be taken for patients
with preexisting diabetes and nausea and vomiting to avoid a hypoglycemic crisis, especially
after taking insulin. Such patients should have glucose tablets, juice, or other glucose-
containing liquids available to help increase blood glucose when needed and should be able to
adjust insulin dosing, as necessary. Clear instructions about how to appropriately self-adjust
insulin dosing based on food intake and when to seek additional medical care (eg,
hypoglycemia that does not resolve with oral glucose intake, intractable vomiting) are essential.
(See "Management of type 1 diabetes mellitus in children during illness, procedures, school, or
travel", section on 'Sick-day management'.)
We continue the medication regimen that has been effective until the patient has been
completely asymptomatic (no nausea or vomiting) for at least a week. At that time, we
discontinue the medications and see how they respond. If nausea and vomiting recurs, we
resume therapy. The majority of patients will have resolution of nausea and vomiting by 16 to
20 weeks of gestation and will be able to discontinue their medications. Rare patients require
therapy beyond 20 weeks.
Short-term outcomes
● Nausea and vomiting of pregnancy — Although the maternal course can be long and
tedious [149], NVP is typically not associated with adverse pregnancy outcomes in the
absence of severe malnutrition [150]. The frequency of congenital anomalies does not
appear to be increased among offspring of patients with NVP or hyperemesis [151,152].
There is strong evidence that patients with nausea and vomiting in early pregnancy have a
lower rate of miscarriage than patients without these symptoms. In one meta-analysis,
the odds of pregnancy loss in patients with nausea and vomiting in the first 20 weeks of
pregnancy was odds ratio (OR) 0.36 (95% CI 0.2-0.42) [153]. The analysis did not correlate
outcome with respect to the severity of the disorder, most of the patients in the studies
had mild symptoms rather than hyperemesis, most data were collected retrospectively,
and patients with pregnancy losses before recognition of pregnancy were not included.
These limitations were addressed in a subsequent prospective study of 797 patients with a
history of one or two pregnancy losses in whom early pregnancy was identified by daily
periconceptional human chorionic gonadotrophin testing and nausea and vomiting were
recorded in preconception and pregnancy diaries [154]. In this population, nausea alone
was associated with a 50 percent reduction in clinical pregnancy loss (hazard ratio [HR]
0.50, 95% CI 0.32-0.80), and nausea with vomiting was associated with a 75 percent
reduction in clinical pregnancy loss (HR 0.25, 95% CI 0.12-0.51), after adjustment for
covariates (eg, age, smoking, number of prior losses and live births, karyotype).
Symptomatic patients had a similar reduction in peri-implantation pregnancy loss, which
was not statistically significant.
https://www.uptodate.com/contents/6811/print 23/47
3/30/23, 12:35 AM 6811
vomiting, as long as prepregnancy weight was in the normal range and there was "catch
up" weight gain later in pregnancy [155-157]. In contrast, patients with severe vomiting
who require multiple hospitalizations may not have "catch up" weight gain; an adverse
effect on birth weight is more likely in these pregnancies, and rarely the fetus is growth-
restricted [158-162]. Patients who have less than 7 kg weight gain are more likely to have
preterm birth/low birth weight/small for gestational age newborns [138,162,163]. When
studies of patients with hyperemesis gravidarum were pooled without regard to
prepregnancy weight or catch-up weight gain, the risks of preterm birth, low birth weight
(LBW), and birth of a small for gestational age (SGA) newborn were slightly but
significantly increased (preterm birth OR 1.32, 95% CI 1.04-1.68; LBW OR 1.42, 95% CI 1.27-
1.58; SGA OR 1.28, 95% CI 1.02-1.60; 17.9 versus 12.7 percent) [151].
The availability of parenteral and enteral nutrition has reduced maternal morbidity, and
mortality is virtually nonexistent in patients who are treated. If left untreated, there have
been reports of sequelae of micronutrient deficiency (eg, most commonly Wernicke
encephalopathy from deficiency of vitamin B1, possibly very rare bleeding diathesis or
embryopathy from vitamin K deficiency) and adverse effects of malnutrition
(immunosuppression, poor wound healing, muscle wasting) [118,158,164-168].
Esophageal tears (Mallory-Weiss), esophageal rupture, splenic avulsion, pneumothoraces,
pneumomediastinum, rhabdomyolysis, osmotic demyelination syndrome (formerly known
as central pontine myelinolysis), hepatic insufficiency, diaphragmatic tear, venous
thrombosis, and acute tubular necrosis are other rare complications in patients with
persistent severe vomiting [169-176]. An association between second-trimester
hyperemesis gravidarum and placental dysfunction (eg, preeclampsia, abruption, SGA)
was reported in a population-based cohort study [177]. It is unclear whether there is a
small increase in risk of perinatal death [151,178].
https://www.uptodate.com/contents/6811/print 24/47
3/30/23, 12:35 AM 6811
adjustment for clinically significant confounding factors [185]. These findings should be
confirmed in a prospective study. Prophylaxis for postoperative nausea and vomiting is
routinely administered before or during cesarean birth, but a specific approach for
patients with hyperemesis has not been studied. Patients with a history of hyperemesis
gravidarum may need higher doses of antiemetic prophylaxis (eg, ondansetron 8 mg
every 8 hours scheduled for 24 hours or metoclopramide 10 mg every 8 hours then as
needed to prevent nausea/vomiting). It is important to remind patients that loss of
appetite is the first sign of nausea/vomiting, and they should take the ondansetron before
it worsens. They need to stay ahead of nausea because it is easier to prevent than to
relieve after it occurs. (See "Anesthesia for cesarean delivery", section on 'Preventing
nausea and vomiting' and "Postoperative nausea and vomiting".)
Long-term outcomes
● Offspring – Although long-term follow-up data are limited, NVP and hyperemesis do not
appear to adversely affect cognitive development of offspring [186,187]. Hyperemesis has
been associated with reduced insulin sensitivity in prepubertal children [188], and poor in
utero nutrition has been associated with some cancers in adulthood [189]. Larger follow-
up studies are needed to determine whether NVP and/or hyperemesis gravidarum have
long-term effects on offspring. These studies need to use well-defined criteria for the
severity of the disease, and adjust for key maternal characteristics, such as prepregnancy
weight and weight gain during pregnancy. Metabolic and cardiovascular outcomes should
be evaluated since SGA birth has been linked to chronic disease in adult life [190]. A study
of offspring of individuals with early pregnancy weight loss >5 kg did not show an adverse
effect on glucose or lipid levels or body mass index at 5 to 6 years of age, but diastolic
blood pressure was 1.4 mmHg higher in this group [191]. Meta-analysis has not been
useful in defining the long-term risks because of few studies are available and they are
generally of low quality, with high heterogeneity and inconsistent findings [192].
PREVENTION
Ideally, all females of child-bearing age should be advised to take a daily multivitamin with folic
acid beginning at least one month prior to conception; this reduces the risk of congenital
anomalies, particularly neural tube defects, and may help to decrease the frequency and
severity of nausea and vomiting during pregnancy [200-202]. The positive effects of
multivitamins are likely due to the general optimization of nutritional status and metabolism.
(See "Preconception and prenatal folic acid supplementation".)
In addition, heartburn and acid reflux have been associated with increased severity of NVP,
which suggests that managing these disorders prior to pregnancy might prevent or reduce the
severity of symptoms [203]. (See "Medical management of gastroesophageal reflux disease in
adults", section on 'Pregnancy and lactation'.)
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Nausea and vomiting of
pregnancy".)
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.
https://www.uptodate.com/contents/6811/print 26/47
3/30/23, 12:35 AM 6811
Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Morning sickness (The Basics)" and "Patient
education: Taking over-the-counter medicines during pregnancy (The Basics)" and "Patient
education: Hyperemesis gravidarum (The Basics)")
● Beyond the Basics topic (see "Patient education: Nausea and vomiting of pregnancy
(Beyond the Basics)")
● Behavioral interventions – Patients with nausea and vomiting should try to become
aware of, and avoid, environmental triggers and foods which might provoke their
symptoms. (See 'Management of nausea as the primary symptom' above.)
• Acupuncture and acupressure – Acupuncture and acupressure have not been proven
to significantly reduce nausea and vomiting. However, given the absence of harm and
the strong placebo effect, some patients may benefit from a trial of acupressure wrist
bands. Patient preferences should guide therapy. (See 'Other interventions' above.)
• Trial of outpatient therapy – For patients with vomiting, hypovolemia, and normal
electrolyte levels and acid-base balance, a trial of replacement fluid and intravenous
antiemetic therapy in the emergency medicine department is reasonable.
• Pharmacotherapy
• Alimentation
- Oral – We suggest a short period of gut rest during volume replacement, followed
by reintroduction of oral intake with liquids and bland, low-fat foods. (See
'Replacement fluid therapy and nutrition' above and 'Dietary changes' above.)
- Enteral and parenteral – The optimal timing for initiating enteral or parenteral
nutrition has not been established; the decision is based upon clinical judgment. In
general, enteral nutrition is begun in patients who cannot maintain their weight
because of vomiting and despite a step-wise trial of pharmacologic interventions.
(See 'Tube feeding and parenteral nutrition' above.)
ACKNOWLEDGMENT
The UpToDate editorial staff acknowledges Susan Ramin, MD, and Jerrie S Refuerzo, MD, who
contributed to an earlier version of this topic review.
REFERENCES
1. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And
Vomiting Of Pregnancy. Obstet Gynecol 2018; 131:e15. Reaffirmed 2020.
2. Newman V, Fullerton JT, Anderson PO. Clinical advances in the management of severe
nausea and vomiting during pregnancy. J Obstet Gynecol Neonatal Nurs 1993; 22:483.
3. Bischoff SC, Renzer C. Nausea and nutrition. Auton Neurosci 2006; 129:22.
4. Erick M. No More Morning Sickness: A Survival Guide for Pregnant Women, Plume, New Yor
k 1993.
5. Koretz RL, Rotblatt M. Complementary and alternative medicine in gastroenterology: the
good, the bad, and the ugly. Clin Gastroenterol Hepatol 2004; 2:957.
6. Duncan JW, Harding VJ. A report on the effect of high carbohydrate feeding on the nausea
and vomiting of pregnancy. Can Med Assoc J 1918; 8:1057.
https://www.uptodate.com/contents/6811/print 29/47
3/30/23, 12:35 AM 6811
7. 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.
8. Association of Professors of Gynecology and Obstetrics. Nausea and vomiting of pregnanc
y. https://www.apgo.org/ (Accessed on December 05, 2016).
9. Heinrichs L. Linking olfaction with nausea and vomiting of pregnancy, recurrent abortion,
hyperemesis gravidarum, and migraine headache. Am J Obstet Gynecol 2002; 186:S215.
10. Erick M. Hyperolfaction and hyperemesis gravidarum: what is the relationship? Nutr Rev
1995; 53:289.
11. Arsenault MY, Lane CA, MacKinnon CJ, et al. The management of nausea and vomiting of
pregnancy. J Obstet Gynaecol Can 2002; 24:817.
12. Gill SK, Maltepe C, Koren G. The effectiveness of discontinuing iron-containing prenatal
multivitamins on reducing the severity of nausea and vomiting of pregnancy. J Obstet
Gynaecol 2009; 29:13.
13. Einarson A, Maltepe C, Boskovic R, Koren G. Treatment of nausea and vomiting in
pregnancy: an updated algorithm. Can Fam Physician 2007; 53:2109.
14. Schwertner HA, Rios DC, Pascoe JE. Variation in concentration and labeling of ginger root
dietary supplements. Obstet Gynecol 2006; 107:1337.
15. Crichton M, Davidson AR, Innerarity C, et al. Orally consumed ginger and human health: an
umbrella review. Am J Clin Nutr 2022; 115:1511.
16. Viljoen E, Visser J, Koen N, Musekiwa A. A systematic review and meta-analysis of the effect
and safety of ginger in the treatment of pregnancy-associated nausea and vomiting. Nutr J
2014; 13:20.
17. Hu Y, Amoah AN, Zhang H, et al. Effect of ginger in the treatment of nausea and vomiting
compared with vitamin B6 and placebo during pregnancy: a meta-analysis. J Matern Fetal
Neonatal Med 2022; 35:187.
18. National Institutes for Health office of dietary supplements. Vitamin B6 fact sheet for healt
h professionals https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/ (Accessed
on October 12, 2022).
19. Bender DA. Non-nutritional uses of vitamin B6. Br J Nutr 1999; 81:7.
20. Gdynia HJ, Müller T, Sperfeld AD, et al. Severe sensorimotor neuropathy after intake of
highest dosages of vitamin B6. Neuromuscul Disord 2008; 18:156.
21. Cohen M, Bendich A. Safety of pyridoxine--a review of human and animal studies. Toxicol
Lett 1986; 34:129.
https://www.uptodate.com/contents/6811/print 30/47
3/30/23, 12:35 AM 6811
22. Shrim A, Boskovic R, Maltepe C, et al. Pregnancy outcome following use of large doses of
vitamin B6 in the first trimester. J Obstet Gynaecol 2006; 26:749.
23. Brent RL. Bendectin: review of the medical literature of a comprehensively studied human
nonteratogen and the most prevalent tortogen-litigen. Reprod Toxicol 1995; 9:337.
24. Niebyl JR, Goodwin TM. Overview of nausea and vomiting of pregnancy with an emphasis
on vitamins and ginger. Am J Obstet Gynecol 2002; 186:S253.
25. Koren G, Maltepe C. Pre-emptive therapy for severe nausea and vomiting of pregnancy and
hyperemesis gravidarum. J Obstet Gynaecol 2004; 24:530.
26. Boelig RC, Barton SJ, Saccone G, et al. Interventions for treating hyperemesis gravidarum.
Cochrane Database Syst Rev 2016; :CD010607.
27. Reeve BK, Cook DJ, Babineau D, et al. Prophylactic Diclectin reduces the incidence of
postoperative vomiting. Can J Anaesth 2005; 52:55.
28. Schuster K, Bailey LB, Dimperio D, Mahan CS. Morning sickness and vitamin B6 status of
pregnant women. Hum Nutr Clin Nutr 1985; 39:75.
29. Koren G, Hankins GD, Clark S, et al. Effectiveness of doxylamine-pyridoxine for morning
sickness. Am J Obstet Gynecol 2016; 214:664.
30. Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and
pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial.
Am J Obstet Gynecol 2010; 203:571.e1.
31. Koren G, Clark S, Hankins GD, et al. Maternal safety of the delayed-release doxylamine and
pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo
controlled trial. BMC Pregnancy Childbirth 2015; 15:59.
32. Matthews A, Haas DM, O'Mathúna DP, Dowswell T. Interventions for nausea and vomiting
in early pregnancy. Cochrane Database Syst Rev 2015; :CD007575.
33. Neutel CI, Johansen HL. Measuring drug effectiveness by default: the case of Bendectin.
Can J Public Health 1995; 86:66.
34. McKeigue PM, Lamm SH, Linn S, Kutcher JS. Bendectin and birth defects: I. A meta-analysis
of the epidemiologic studies. Teratology 1994; 50:27.
35. Magee LA, Mazzotta P, Koren G. Evidence-based view of safety and effectiveness of
pharmacologic therapy for nausea and vomiting of pregnancy (NVP). Am J Obstet Gynecol
2002; 186:S256.
36. GEIGER CJ, FAHRENBACH DM, HEALEY FJ. Bendectin in the treatment of nausea and
vomiting in pregnancy. Obstet Gynecol 1959; 14:688.
https://www.uptodate.com/contents/6811/print 31/47
3/30/23, 12:35 AM 6811
https://www.uptodate.com/contents/6811/print 32/47
3/30/23, 12:35 AM 6811
55. Badell ML, Ramin SM, Smith JA. Treatment options for nausea and vomiting during
pregnancy. Pharmacotherapy 2006; 26:1273.
56. Mitchell-Jones N, Farren JA, Tobias A, et al. Ambulatory versus inpatient management of
severe nausea and vomiting of pregnancy: a randomised control trial with patient
preference arm. BMJ Open 2017; 7:e017566.
57. McParlin C, O'Donnell A, Robson SC, et al. Treatments for Hyperemesis Gravidarum and
Nausea and Vomiting in Pregnancy: A Systematic Review. JAMA 2016; 316:1392.
58. Boelig RC, Barton SJ, Saccone G, et al. Interventions for treating hyperemesis gravidarum: a
Cochrane systematic review and meta-analysis. J Matern Fetal Neonatal Med 2018; 31:2492.
https://www.uptodate.com/contents/6811/print 33/47
3/30/23, 12:35 AM 6811
75. Sun L, Xi Y, Wen X, Zou W. Use of metoclopramide in the first trimester and risk of major
congenital malformations: A systematic review and meta-analysis. PLoS One 2021;
16:e0257584.
76. Pasricha PJ, Pehlivanov N, Sugumar A, Jankovic J. Drug Insight: from disturbed motility to
disordered movement--a review of the clinical benefits and medicolegal risks of
metoclopramide. Nat Clin Pract Gastroenterol Hepatol 2006; 3:138.
77. Buttino L Jr, Coleman SK, Bergauer NK, et al. Home subcutaneous metoclopramide therapy
for hyperemesis gravidarum. J Perinatol 2000; 20:359.
78. Kallen B. Hyperemesis gravidarum during pregnancy and delivery: A registry study. In: Nau
sea and Vomiting of Pregnancy: State of the Art 2000, Koren G, Bishai R (Eds), Motherisk, To
ronto 2000. p.36.
79. Braude D, Crandall C. Ondansetron versus promethazine to treat acute undifferentiated
nausea in the emergency department: a randomized, double-blind, noninferiority trial.
Acad Emerg Med 2008; 15:209.
80. Hansen C, Desrosiers TA, Wisniewski K, et al. Use of antihistamine medications during early
pregnancy and selected birth defects: The National Birth Defects Prevention Study, 1997-
2011. Birth Defects Res 2020; 112:1234.
https://www.uptodate.com/contents/6811/print 34/47
3/30/23, 12:35 AM 6811
81. Bártfai Z, Kocsis J, Puhó EH, Czeizel AE. A population-based case-control teratologic study of
promethazine use during pregnancy. Reprod Toxicol 2008; 25:276.
82. Ernst AA, Weiss SJ, Park S, et al. Prochlorperazine versus promethazine for uncomplicated
nausea and vomiting in the emergency department: a randomized, double-blind clinical
trial. Ann Emerg Med 2000; 36:89.
83. European Medicines Agency's (EMA's) pharmacovigilance risk assessment committee (PRA
C) https://www.ema.europa.eu/en/documents/prac-recommendation/prac-recommendatio
ns-signals-adopted-8-11-july-2019-prac-meeting_en.pdf (Accessed on February 20, 2020).
84. UK Teratology Information Service (UKTIS), in collaboration with the European Network of T
eratology Information Services (ENTIS) http://www.uktis.org/docs/Ondansetron%20UKTIS%
20Response%20Statement.pdf (Accessed on February 20, 2020).
85. Oliveira LG, Capp SM, You WB, et al. Ondansetron compared with doxylamine and
pyridoxine for treatment of nausea in pregnancy: a randomized controlled trial. Obstet
Gynecol 2014; 124:735.
86. Kashifard M, Basirat Z, Kashifard M, et al. Ondansetrone or metoclopromide? Which is
more effective in severe nausea and vomiting of pregnancy? A randomized trial double-
blind study. Clin Exp Obstet Gynecol 2013; 40:127.
87. Klauser CK, Fox NS, Istwan N, et al. Treatment of severe nausea and vomiting of pregnancy
with subcutaneous medications. Am J Perinatol 2011; 28:715.
88. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020103s035_020605s019_020
781s019lbl.pdf (Accessed on November 03, 2021).
89. Freedman SB, Uleryk E, Rumantir M, Finkelstein Y. Ondansetron and the risk of cardiac
arrhythmias: a systematic review and postmarketing analysis. Ann Emerg Med 2014; 64:19.
90. Huybrechts KF, Hernández-Díaz S, Straub L, et al. Association of Maternal First-Trimester
Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring. JAMA 2018;
320:2429.
91. Parker SE, Van Bennekom C, Anderka M, et al. Ondansetron for Treatment of Nausea and
Vomiting of Pregnancy and the Risk of Specific Birth Defects. Obstet Gynecol 2018; 132:385.
92. Danielsson B, Wikner BN, Källén B. Use of ondansetron during pregnancy and congenital
malformations in the infant. Reprod Toxicol 2014; 50:134.
93. Zambelli-Weiner A, Via C, Yuen M, et al. First trimester ondansetron exposure and risk of
structural birth defects. Reprod Toxicol 2019; 83:14.
94. Andrade C. Major Congenital Malformation Risk After First Trimester Gestational Exposure
to Oral or Intravenous Ondansetron. J Clin Psychiatry 2020; 81.
https://www.uptodate.com/contents/6811/print 35/47
3/30/23, 12:35 AM 6811
96. Huybrechts KF, Hernandez-Diaz S, Bateman BT. Ondansetron Use in Pregnancy and
Congenital Malformations-Reply. JAMA 2020; 323:2097.
97. Picot C, Berard A, Grenet G, et al. Risk of malformation after ondansetron in pregnancy: An
updated systematic review and meta-analysis. Birth Defects Res 2020; 112:996.
98. Dormuth CR, Winquist B, Fisher A, et al. Comparison of Pregnancy Outcomes of Patients
Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational,
Population-Based Cohort. JAMA Netw Open 2021; 4:e215329.
99. Caritis S, Zhao Y, Chen HJ, Venkataramanan R. Pharmacodynamics of transdermal
granisetron in women with nausea and vomiting of pregnancy. Am J Obstet Gynecol 2016;
215:93.e1.
100. Smith JA, Julius JM, Gaikwad A, et al. Evaluating the potential effect on fetal tissue after
exposure to granisetron during pregnancy. Reprod Toxicol 2015; 53:92.
101. Shapira M, Avrahami I, Mazaki-Tovi S, et al. The safety of early pregnancy exposure to
granisetron. Eur J Obstet Gynecol Reprod Biol 2020; 245:35.
102. Le TN, Adler MT, Ouillette H, et al. Observational Case Series Evaluation of the Granisetron
Transdermal Patch System (Sancuso) for the Management of Nausea/Vomiting of
Pregnancy. Am J Perinatol 2017; 34:851.
103. 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.
104. Mahadevan U. Gastrointestinal medications in pregnancy. Best Pract Res Clin Gastroenterol
2007; 21:849.
105. Garbis H, Elefant E, Diav-Citrin O, et al. Pregnancy outcome after exposure to ranitidine and
other H2-blockers. A collaborative study of the European Network of Teratology
Information Services. Reprod Toxicol 2005; 19:453.
106. Tincello DG, Johnstone MJ. Treatment of hyperemesis gravidarum with the 5-HT3
antagonist ondansetron (Zofran). Postgrad Med J 1996; 72:688.
107. Sullivan CA, Johnson CA, Roach H, et al. A pilot study of intravenous ondansetron for
hyperemesis gravidarum. Am J Obstet Gynecol 1996; 174:1565.
108. Toth-Manikowski S, Grams ME. Proton Pump Inhibitors and Kidney Disease - GI Upset for
the Nephrologist? Kidney Int Rep 2017; 2:297.
110. 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; 102:6.
111. Lub-Moss MM, Eurelings-Bontekoe EH. Clinical experience with patients suffering from
hyperemesis gravidarum (severe nausea and vomiting during pregnancy): thoughts about
subtyping of patients, treatment and counseling models. Patient Educ Couns 1997; 31:65.
112. Gadsby R, Barnie-Adshead AM. CLINICAL INFORMATION ABOUT NAUSEA AND VOMITING O
F PREGNANCY ITS RELATION TO VARIOUS ASPECTS OF WOMEN‟S PERSONAL AND OBSTETR
IC HISTORIES AND OTHER SIGNIFICANT FACTORS RELATED TO NAUSEA AND VOMITING OF
PREGNANCY OR HYPEREMESIS GRAVIDARUM. A LITERATURE REVIEW. Available at https://w
ww.pregnancysicknesssupport.org.uk/documents/NVP-lit-review.pdf. .
113. Jarvis S, Nelson-Piercy C. Management of nausea and vomiting in pregnancy. BMJ 2011;
342:d3606.
114. Tan PC, Norazilah MJ, Omar SZ. Dextrose saline compared with normal saline rehydration
of hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol 2013; 121:291.
115. Majumdar S, Dada B. Refeeding syndrome: a serious and potentially life-threatening
complication of severe hyperemesis gravidarum. J Obstet Gynaecol 2010; 30:416.
116. Mayer KH, McGill AL. Second-Trimester Fetal Loss in a Patient With Hyperemesis
Gravidarum Complicated by Refeeding Syndrome. Obstet Gynecol 2019; 133:1167.
117. Kondo T, Nakamura M, Kawashima J, et al. Hyperemesis gravidarum followed by refeeding
syndrome causes electrolyte abnormalities induced rhabdomyolysis and diabetes
insipidus. Endocr J 2019; 66:253.
118. Chiossi G, Neri I, Cavazzuti M, et al. Hyperemesis gravidarum complicated by Wernicke
encephalopathy: background, case report, and review of the literature. Obstet Gynecol
Surv 2006; 61:255.
119. Giugale LE, Young OM, Streitman DC. Iatrogenic Wernicke encephalopathy in a patient with
severe hyperemesis gravidarum. Obstet Gynecol 2015; 125:1150.
120. Veverbrants E, Arky RA. Effects of fasting and refeeding. I. Studies on sodium, potassium
and water excretion on a constant electrolyte and fluid intake. J Clin Endocrinol Metab
1969; 29:55.
121. DeFronzo RA, Cooke CR, Andres R, et al. The effect of insulin on renal handling of sodium,
potassium, calcium, and phosphate in man. J Clin Invest 1975; 55:845.
122. Fiaschi L, Nelson-Piercy C, Deb S, et al. Clinical management of nausea and vomiting in
pregnancy and hyperemesis gravidarum across primary and secondary care: a population-
based study. BJOG 2019; 126:1201.
https://www.uptodate.com/contents/6811/print 37/47
3/30/23, 12:35 AM 6811
123. Mansour GM, Nashaat EH. Role of Helicobacter pylori in the pathogenesis of hyperemesis
gravidarum. Arch Gynecol Obstet 2011; 284:843.
124. Safari HR, Alsulyman OM, Gherman RB, Goodwin TM. Experience with oral
methylprednisolone in the treatment of refractory hyperemesis gravidarum. Am J Obstet
Gynecol 1998; 178:1054.
125. Taylor R. Successful management of hyperemesis gravidarum using steroid therapy. QJM
1996; 89:103.
129. Yost NP, McIntire DD, Wians FH Jr, et al. A randomized, placebo-controlled trial of
corticosteroids for hyperemesis due to pregnancy. Obstet Gynecol 2003; 102:1250.
130. Shepard TH, Brent RL, Friedman JM, et al. Update on new developments in the study of
human teratogens. Teratology 2002; 65:153.
131. Carmichael SL, Shaw GM. Maternal corticosteroid use and risk of selected congenital
anomalies. Am J Med Genet 1999; 86:242.
132. 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.
133. Rodríguez-Pinilla E, Martínez-Frías ML. Corticosteroids during pregnancy and oral clefts: a
case-control study. Teratology 1998; 58:2.
134. Pradat P, Robert-Gnansia E, Di Tanna GL, et al. First trimester exposure to corticosteroids
and oral clefts. Birth Defects Res A Clin Mol Teratol 2003; 67:968.
135. Nageotte MP, Briggs GG, Towers CV, Asrat T. Droperidol and diphenhydramine in the
management of hyperemesis gravidarum. Am J Obstet Gynecol 1996; 174:1801.
136. Jackson CW, Sheehan AH, Reddan JG. Evidence-based review of the black-box warning for
droperidol. Am J Health Syst Pharm 2007; 64:1174.
137. US Food and Drug Administration. Inapsine (droperidol) Dear Healthcare Professional Lette
r Dec 2001. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuma
nMedicalProducts/ucm173778.htm (Accessed on June 24, 2011).
https://www.uptodate.com/contents/6811/print 38/47
3/30/23, 12:35 AM 6811
138. Stokke G, Gjelsvik BL, Flaatten KT, et al. Hyperemesis gravidarum, nutritional treatment by
nasogastric tube feeding: a 10-year retrospective cohort study. Acta Obstet Gynecol Scand
2015; 94:359.
139. Peled Y, Melamed N, Hiersch L, et al. The impact of total parenteral nutrition support on
pregnancy outcome in women with hyperemesis gravidarum. J Matern Fetal Neonatal Med
2014; 27:1146.
140. Hsu JJ, Clark-Glena R, Nelson DK, Kim CH. Nasogastric enteral feeding in the management
of hyperemesis gravidarum. Obstet Gynecol 1996; 88:343.
141. Grooten IJ, Koot MH, van der Post JA, et al. Early enteral tube feeding in optimizing
treatment of hyperemesis gravidarum: the Maternal and Offspring outcomes after
Treatment of HyperEmesis by Refeeding (MOTHER) randomized controlled trial. Am J Clin
Nutr 2017; 106:812.
142. Holmgren C, Aagaard-Tillery KM, Silver RM, et al. Hyperemesis in pregnancy: an evaluation
of treatment strategies with maternal and neonatal outcomes. Am J Obstet Gynecol 2008;
198:56.e1.
143. Cape AV, Mogensen KM, Robinson MK, Carusi DA. Peripherally inserted central catheter
(PICC) complications during pregnancy. JPEN J Parenter Enteral Nutr 2014; 38:595.
144. Koretz RL, Lipman TO, Klein S, American Gastroenterological Association. AGA technical
review on parenteral nutrition. Gastroenterology 2001; 121:970.
145. American Gastroenterological Association. American Gastroenterological Association
medical position statement: parenteral nutrition. Gastroenterology 2001; 121:966.
146. Fiaschi L, Nelson-Piercy C, Gibson J, et al. Adverse Maternal and Birth Outcomes in Women
Admitted to Hospital for Hyperemesis Gravidarum: a Population-Based Cohort Study.
Paediatr Perinat Epidemiol 2018; 32:40.
147. Virkus RA, Løkkegaard E, Lidegaard Ø, et al. Risk factors for venous thromboembolism in
1.3 million pregnancies: a nationwide prospective cohort. PLoS One 2014; 9:e96495.
148. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium. Gr
een-top Guideline No. 37a April 2015 https://www.rcog.org.uk/globalassets/documents/gui
delines/gtg-37a.pdf (Accessed on May 28, 2019).
149. Tan PC, Jacob R, Quek KF, Omar SZ. Indicators of prolonged hospital stay in hyperemesis
gravidarum. Int J Gynaecol Obstet 2006; 93:246.
150. Agmon N, Sade S, Pariente G, et al. Hyperemesis gravidarum and adverse pregnancy
outcomes. Arch Gynecol Obstet 2019; 300:347.
https://www.uptodate.com/contents/6811/print 39/47
3/30/23, 12:35 AM 6811
151. Veenendaal MV, van Abeelen AF, Painter RC, et al. Consequences of hyperemesis
gravidarum for offspring: a systematic review and meta-analysis. BJOG 2011; 118:1302.
152. Schrager NL, Parker SE, Werler MM, for the National Birth Defects Prevention Study. The
association of nausea and vomiting of pregnancy, its treatments, and select birth defects:
Findings from the National Birth Defect Prevention Study. Birth Defects Res 2023; 115:275.
153. Weigel RM, Weigel MM. Nausea and vomiting of early pregnancy and pregnancy outcome.
A meta-analytical review. Br J Obstet Gynaecol 1989; 96:1312.
154. Hinkle SN, Mumford SL, Grantz KL, et al. Association of Nausea and Vomiting During
Pregnancy With Pregnancy Loss: A Secondary Analysis of a Randomized Clinical Trial. JAMA
Intern Med 2016; 176:1621.
155. Hallak M, Tsalamandris K, Dombrowski MP, et al. Hyperemesis gravidarum. Effects on fetal
outcome. J Reprod Med 1996; 41:871.
156. Tsang IS, Katz VL, Wells SD. Maternal and fetal outcomes in hyperemesis gravidarum. Int J
Gynaecol Obstet 1996; 55:231.
157. Flaxman SM, Sherman PW. Morning sickness: a mechanism for protecting mother and
embryo. Q Rev Biol 2000; 75:113.
158. Paauw JD, Bierling S, Cook CR, Davis AT. Hyperemesis gravidarum and fetal outcome. JPEN J
Parenter Enteral Nutr 2005; 29:93.
159. Källén B. Hyperemesis during pregnancy and delivery outcome: a registry study. Eur J
Obstet Gynecol Reprod Biol 1987; 26:291.
160. Bailit JL. Hyperemesis gravidarium: Epidemiologic findings from a large cohort. Am J Obstet
Gynecol 2005; 193:811.
161. 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.
162. Dodds L, Fell DB, Joseph KS, et al. Outcomes of pregnancies complicated by hyperemesis
gravidarum. Obstet Gynecol 2006; 107:285.
163. Ismail SK, Kenny L. Review on hyperemesis gravidarum. Best Pract Res Clin Gastroenterol
2007; 21:755.
164. Togay-Işikay C, Yiğit A, Mutluer N. Wernicke's encephalopathy due to hyperemesis
gravidarum: an under-recognised condition. Aust N Z J Obstet Gynaecol 2001; 41:453.
165. Spruill SC, Kuller JA. Hyperemesis gravidarum complicated by Wernicke's encephalopathy.
Obstet Gynecol 2002; 99:875.
https://www.uptodate.com/contents/6811/print 40/47
3/30/23, 12:35 AM 6811
https://www.uptodate.com/contents/6811/print 41/47
3/30/23, 12:35 AM 6811
181. O'Brien B, Naber S. Nausea and vomiting during pregnancy: effects on the quality of
women's lives. Birth 1992; 19:138.
182. Attard CL, Kohli MA, Coleman S, et al. The burden of illness of severe nausea and vomiting
of pregnancy in the United States. Am J Obstet Gynecol 2002; 186:S220.
183. Iliadis SI, Axfors C, Johansson S, et al. Women with prolonged nausea in pregnancy have
increased risk for depressive symptoms postpartum. Sci Rep 2018; 8:15796.
184. Poursharif B, Korst LM, Macgibbon KW, et al. Elective pregnancy termination in a large
cohort of women with hyperemesis gravidarum. Contraception 2007; 76:451.
185. Jacobs NF, Veronese LR, Okano S, et al. The incidence of postoperative nausea and
vomiting after caesarean section in patients with hyperemesis gravidarum: a retrospective
cohort study. Int J Obstet Anesth 2020; 44:81.
186. Nulman I, Rovet J, Barrera M, et al. Long-term neurodevelopment of children exposed to
maternal nausea and vomiting of pregnancy and diclectin. J Pediatr 2009; 155:45.
187. Roberts CJ. Developmental and neurological sequelae of the common complications of
pregnancy and birth. Br J Prev Soc Med 1970; 24:33.
188. Ayyavoo A, Derraik JG, Hofman PL, et al. Severe hyperemesis gravidarum is associated with
reduced insulin sensitivity in the offspring in childhood. J Clin Endocrinol Metab 2013;
98:3263.
189. Vandraas KF, Vikanes ÅV, Støer NC, et al. Hyperemesis gravidarum and risk of cancer in
offspring, a Scandinavian registry-based nested case-control study. BMC Cancer 2015;
15:398.
190. Barker DJ, Eriksson JG, Forsén T, Osmond C. Fetal origins of adult disease: strength of
effects and biological basis. Int J Epidemiol 2002; 31:1235.
191. Grooten IJ, Painter RC, Pontesilli M, et al. Weight loss in pregnancy and cardiometabolic
profile in childhood: findings from a longitudinal birth cohort. BJOG 2015; 122:1664.
192. Nijsten K, Jansen LAW, Limpens J, et al. Long-term health outcomes of children born
to mothers with hyperemesis gravidarum: a systematic review and meta-analysis. Am J
Obstet Gynecol 2022; 227:414.
193. Vandraas KF, Grjibovski AM, Støer NC, et al. Hyperemesis gravidarum and maternal cancer
risk, a Scandinavian nested case-control study. Int J Cancer 2015; 137:1209.
194. Fossum S, Vikanes ÅV, Naess Ø, et al. Hyperemesis gravidarum and long-term mortality: a
population-based cohort study. BJOG 2017; 124:1080.
195. Trogstad LI, Stoltenberg C, Magnus P, et al. Recurrence risk in hyperemesis gravidarum.
BJOG 2005; 112:1641.
https://www.uptodate.com/contents/6811/print 42/47
3/30/23, 12:35 AM 6811
196. Fejzo MS, Macgibbon KW, Romero R, et al. Recurrence risk of hyperemesis gravidarum. J
Midwifery Womens Health 2011; 56:132.
197. Gadsby R, Barnie-Adshead AM, Jagger C. Pregnancy nausea related to women's obstetric
and personal histories. Gynecol Obstet Invest 1997; 43:108.
198. Nurmi M, Rautava P, Gissler M, et al. Recurrence patterns of hyperemesis gravidarum. Am J
Obstet Gynecol 2018; 219:469.e1.
199. Nijsten K, Dean C, van der Minnen LM, et al. Recurrence, postponing pregnancy, and
termination rates after hyperemesis gravidarum: Follow up of the MOTHER study. Acta
Obstet Gynecol Scand 2021; 100:1636.
200. Czeizel AE, Dudas I, Fritz G, et al. The effect of periconceptional multivitamin-mineral
supplementation on vertigo, nausea and vomiting in the first trimester of pregnancy. Arch
Gynecol Obstet 1992; 251:181.
201. Källén B, Lundberg G, Aberg A. Relationship between vitamin use, smoking, and nausea
and vomiting of pregnancy. Acta Obstet Gynecol Scand 2003; 82:916.
202. 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;
22:106.
203. Gill SK, Maltepe C, Koren G. The effect of heartburn and acid reflux on the severity of
nausea and vomiting of pregnancy. Can J Gastroenterol 2009; 23:270.
Topic 6811 Version 142.0
https://www.uptodate.com/contents/6811/print 43/47
3/30/23, 12:35 AM 6811
GRAPHICS
Patients with mild symptoms may benefit from acupuncture, acupressure, or hypnosis. Women with heartb
reducing medications as adjunctive therapy anytime during the course of illness. Antacids containing alumin
the preferred H2 blocker. There is less experience using proton pump inhibitors (eg, lansoprazole or esome
https://www.uptodate.com/contents/6811/print 44/47
3/30/23, 12:35 AM 6811
* Eat small amounts of food every one to two hours to avoid an empty or full stomach. It can be helpful to e
very sweet foods, and substitute protein-dominant, salty, low-fat, bland, and/or dry foods. Fluids should be c
after solid food to minimize the effect of a full stomach. Fluids are better tolerated if cold, clear, and carbona
¶ Examples of some triggers include stuffy rooms, odors, heat, humidity, noise, visual or physical motion, an
supplements).
◊ We generally treat refractory cases with a short course of glucocorticoids but may begin with chlorproma
whom the side effects of glucocorticoids may be more serious.
§ We usually begin with a diet consisting of bananas, rice, applesauce, and toast (BRAT diet) and then advan
women with nausea and vomiting of pregnancy.
https://www.uptodate.com/contents/6811/print 45/47
3/30/23, 12:35 AM 6811
P6 acupressure point
https://www.uptodate.com/contents/6811/print 46/47
3/30/23, 12:35 AM 6811
Contributor Disclosures
Judith A Smith, PharmD, BCOP, CPHQ, FCCP, FHOPA, FISOPP Consultant/Advisory Boards:
VieCure[Contract Senior Clinical Pharmacist and Research Scientist role to help with oncology clinical
content development]. All of the relevant financial relationships listed have been mitigated. Karin A Fox,
MD, MEd Grant/Research/Clinical Trial Support: National Institute of Child Health and Human
Development [Placenta accreta]. Speaker's Bureau: Contemporary Forums [High-risk obstetrics
conference]; Society for Maternal-Fetal Medicine [Critical care in obstetrics course]; Symposia Medicus
[High-risk obstetrics conference]. Other Financial Interest: Pan-American Society for the Placenta Accreta
Spectrum [Placenta accreta]. All of the relevant financial relationships listed have been
mitigated. Shannon M Clark, MD, MMS No relevant financial relationship(s) with ineligible companies to
disclose. Charles J Lockwood, MD, MHCM No relevant financial relationship(s) with ineligible companies
to disclose. Vanessa A Barss, MD, FACOG No relevant financial relationship(s) with ineligible companies to
disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
https://www.uptodate.com/contents/6811/print 47/47