Invited Review

Nutrition in Clinical Practice

Volume 0 Number 0
Hyperemesis Gravidarum xxxx 2018 1–16

C 2018 American Society for

Parenteral and Enteral Nutrition

DOI: 10.1002/ncp.10205
wileyonlinelibrary.com
Kerstin Austin, MD1 ; Kelley Wilson, MS, RDN, CNSC2 ; and Sumona Saha, MD, MS1

Abstract
Nausea and vomiting of pregnancy affect the majority of pregnancies, while the most severe version, hyperemesis gravidarum (HG),
affects a much smaller subset of women. Despite the prevalence of nausea and vomiting of pregnancy and the severe consequences
of HG, the pathophysiology of these conditions is not fully understood. Currently, it is thought that a combination of hormonal
factors accounts for their development. Multiple treatments have been described for nausea and vomiting of pregnancy and HG
with varying levels of success. In this paper we describe the epidemiology of nausea and vomiting of pregnancy and HG, the
recommended workup, their proposed etiologic factors, treatments, and their potential impact on mother and baby. (Nutr Clin
Pract. 2018;0:1–16)

Keywords
hyperemesis gravidarum; nausea; nutrtiional support; nutrition therapy; pregnancy; vomiting

Introduction to genetic or epigenetic factors, differences in incidence rates

Nausea and vomiting of pregnancy (NVP) are among
the most common gastrointestinal disorders of pregnancy,
affecting 70%–80% of pregnant women.1 Although most
cases of NVP resolve after the first trimester, ࣘ10% of
women have symptoms beyond 22 weeks.2 Women with
severe nausea and vomiting during pregnancy may have
hyperemesis gravidarum (HG), a condition associated with
fluid, electrolyte, and acid–base imbalance and nutrition
deficiency and weight loss.3 HG is commonly defined as
the occurrence of >3 episodes of vomiting per day with
associated ketonuria and weight loss of >3 kg or 5% of body
weight.4 Although NVP and HG exist on a continuum, they
are distinct conditions which are associated with different
outcomes for both mother and fetus. Thus, providers must
be able to differentiate HG from NVP and tailor treatment
to the severity of disease to improve maternal health and
quality of life and optimize newborn outcomes.
may also be due to the lack of uniformity in the diagnostic
criteria used to identify cases across studies.12
While NVP is 1 of the most common indications for hos-
pitalization throughout pregnancy, HG is the most common
cause of hospitalization in the first half of pregnancy, ac-
counting for >59,000 hospitalizations annually.13,14 Apart
from requiring hospitalization, HG leads to extra physician
visits and emergency room visits throughout pregnancy.15-17
Conservative estimates put the total economic burden posed
by NVP in 2012 to be >$1.7 billion annually in the United
States, with >$1 billion in direct costs.18 Indirect costs,
which include lost time from work and caregiver time and
which totaled >$700 million, were believed to be underesti-
mated as not all applicable costs could be included.
The burden of NVP and HG are not financial alone.
In addition to causing physical symptoms which will be
discussed later in this paper, they also negatively impact
emotional and psychosocial health. Affected women often

Epidemiology and Burden of Disease
While NVP affects most pregnant women, HG affects a
much smaller subset of women. It is estimated that HG
affects 0.3%–3.6% of all pregnancies worldwide.5 Several
risk factors have been identified for the development of
NVP and HG. These include history of prior pregnancy
affected by HG, multiple gestations, female fetus, history of
psychiatric illness, high and low prepregnancy BMI, young
age, black or Asian ethnicity, and type I diabetes.6-9 Notably,
smoking has been associated with a decreased risk of HG.10
Variations exist in the reported incidence of NVP and HG
across different study populations.11 While this may be due
From the 1 Department of Gastroenterology and Hepatology,
University of Wisconsin School of Medicine and Public Health,
Madison, Wisconsin, USA; and the 2 Clinical Nutrition Services,
University of Wisconsin Hospital and Clinics, Madison, Wisconsin,
USA.
Conflicts of interest: None declared.
Financial disclosures: None declared.
This article originally appeared online on xxxx 0, 0000.
Corresponding Author:
Sumona Saha, MD, MS, Associate Professor of Medicine, University
of Wisconsin School of Medicine and Public Health, 1685 Highland
Avenue, Suite 4000, Madison, WI 53705-2281.
Email: ssaha@medicine.wisc.edu
2 Nutrition in Clinical Practice 0(0)
struggle with depression, anxiety, and post-traumatic stress
disorder secondary to HG.19,20 Women also report feelings
of isolation and not being appropriately managed because
NVP is perceived as a normal component of pregnancy by
much of the general population.21 Until the 1950s, HG was
a common cause of maternal death.22
Pathophysiology
The pathophysiology of HG remains an area of active
research. No single mechanism has been identified as being
the cause of NVP or HG. Several etiologies, however, have
been proposed as being potential contributing factors. It is
likely that a combination of these factors is responsible for
disease onset.
Psychologic Factors
Since the first century, underlying maternal psychiatric
disturbances have been purported to contribute to the de-
velopment of NVP and HG.23 It has also been long believed
that HG may be a psychosomatic illness or conversion
disorder.24 Today this is mainly of historic interest as there is
no substantial data to validate these hypotheses. Currently,
depression, anxiety, and other psychiatric disorders associ-
ated with HG are thought to be secondary to HG rather
than contributing factors.25,26
Hormonal Factors
Beta human chorionic gonadotropin (β-hCG). Serum con-
centrations of β-hCG and the symptoms of NVP peak
at the same time during early pregnancy. Furthermore,
rising hCG levels may affect areas of the brain involved
in nausea, either directly or by indirectly inducing a rise
in other hormones (eg, thyroid hormones, estradiol) which
affect nausea.27 Thus, it is widely believed that β-hCG is
implicated in the development of NVP and HG; however,
studies examining the relationship between β-hCG levels
and the presence or severity of NVP and HG have been
conflicting. Several studies have shown higher levels of
β-hCG in women with HG compared with unaffected
controls.3 Furthermore, several conditions associated with
a higher risk for HG are also characterized by higher
β-hCG levels, including multiple gestations, Down syn-
drome, carrying a female fetus, and molar pregnancy.28
The typical improvement in symptoms following the first
trimester, when β-hCG levels decline, also lends support
to this hypothesis. However, studies have not consistently
found women with HG to have elevated levels of β-hCG,29
and some conditions characterized by elevated β-hCG, such
as choriocarcinoma, are often not accompanied by nausea
and vomiting.30,31 As β-hCG concentrations increase by
number of days since implantation of the embryo, a recent
study evaluated β-hCG on a fixed day in early pregnancy in
women who conceived via in vitro fertilization to evaluate
for risk of developing HG based on β-hCG levels.32 It found
no significant association between maternal levels of β-hCG
and the development of HG or trend of increasing risk by
increasing β-hCG concentrations, suggesting that β-hCG
concentrations may not be linked to HG.
One possible explanation for the inconsistent findings of
elevated levels of β-hCG in women with HG is that only spe-
cific isoforms of β-hCG may cause HG. Different isoforms
have different half-lives and potency at the luteinizing hor-
mone (LH) and thyroid-stimulating hormone (TSH) recep-
tors. Those isoforms without the carboxyl-terminal segment
have a shorter half-life but more potent stimulation of the
LH and TSH receptors, while hyperglycosylated β-hCG has
a longer half-life and longer duration of action.33 Different
isoform patterns of β-hCG likely result from genetic and/or
epigenetic factors and may account for the variation in
incidence of HG among different ethnic groups.33,34
Progesterone. Like β-hCG, progesterone levels peak in the
first trimester when symptoms of NVP are typically at their
greatest and, thus, have been implicated in the endocrine
etiology for NVP and HG.30 Progesterone alone or in
combination with estrogen may decrease gastric smooth
muscle contractility and promote gastric dysrhythmias and
thereby elicit nausea and vomiting.35 Multiple studies eval-
uating the association between progesterone concentrations
and NVP/HG, however, have been negative.36-38 Thus, it
remains unclear what role, if any, progesterone plays in the
development of HG.
Estrogen. Maternal levels of estrogen have been evaluated
as a potential etiology of NVP as patients on exogenous
estrogen often experience nausea as a side effect.39-41 Es-
trogen decreases gastric emptying and prolongs overall
intestinal transit time, which may produce the symptoms
of NVP. However, studies evaluating gastric motility in
women with HG have shown faster rates of gastric emptying
compared with controls.42 Furthermore, as with studies
evaluating β-hCG and progesterone concentrations, studies
of estrogen levels among pregnant women with HG have
yielded inconsistent results. In a 2002 review of 17 studies,
only 5 showed a positive association between NVP and
estrogen levels.43 Additionally, estrogen levels peak in the
third trimester of pregnancy, a time by which HG symptoms
have typically improved, which further raises doubt about
the role of estrogen in HG development.3
Thyroid hormones. The thyroid gland is stimulated in the
first trimester of pregnancy, making gestational thyrotox-
icosis common during pregnancy. TSH and β-hCG are
glycoproteins which share the same α subunit.44 Therefore,
β-hCG can cross-react with the TSH receptor and stimulate
free thyroxine (T4) production and suppress serum TSH.
Austin et al
Gestational transient thyrotoxicosis (GTT) results from
inappropriate β-hCG secretion and is a common form of
hyperthyroidism in early pregnancy. A 2014 study found
that 45% of women admitted to the hospital with HG met
criteria for GTT.45 Previous studies have similarly reported
that 30%–60% of patients with HG have high free T4 and
low TSH levels.44,46-48 Despite these abnormalities, women
with HG are generally euthyroid,49,50 and almost all women
with HG normalize their TSH levels by 20 weeks gestation
without intervention.44
Hunger regulatory hormones. Leptin is a hormone that acts
as an afferent satiety signal to regulate body weight and has
recently been shown to be secreted by the placenta.51 Lower
levels of leptin were found in 1 study of 20 patients with
HG compared with 20 controls as were higher levels of
nesfatin-1, another hormone thought to regulate appetite
and weight.52 Of note, the leptin level results in this study
differ from what has previously been reported in the
literature53 ; thus, further studies are needed to determine
the role of hunger hormones in HG and whether they can
serve as a marker for disease severity.
Helicobacter pylori. Helicobacter pylori (H. pylori) is a
Gram-negative flagellate that colonizes up to half of
the world’s population with varying prevalence based
on location, socioeconomic status, and family history.54
The prevalence of H. pylori varies geographically among
pregnant women as well, with higher rates reported among
populations in Africa compared with Europe.55 The clinical
significance of H. pylori infection in women with HG in
pregnancy has been debated. A 2008 Norwegian study
found a 2-fold increase in the rates of H. pylori infection
in patients with HG compared with controls.56 This finding
has been replicated in 2 separate meta-analyses. Sandven
et al reported an odds ratio (OR) of 3.32 (95% confidence
interval [CI]: 2.25–4.90) among 25 case-control studies with
high heterogeneity across studies,57 while Ng et al found
a lower OR of 1.35 (95% CI: 1.12–1.54, P < .001) across
38 cross-sectional and case-control studies with decreased
heterogeneity across studies.58
In small case reports using different antibiotic regimens,
treatment of H. pylori improved symptoms.54,59 One of the
complicating factors in the literature regarding H. pylori
and HG is the mode of testing. Many studies use serum
immunoglobulin G (IgG) antibodies as a marker of in-
fection. Positivity for IgG antibodies directed at H. pylori
is not a direct marker for active infection. Thus, it is not
clear whether any infection with H. pylori (past and cleared
or current) increases the risk for HG or what role active
or cleared infection might play. At present, H. pylori is
considered to be 1 of several factors which predispose a
woman to developing HG.
3
Gastric Transit
During pregnancy, progesterone and estrogen rise and lead
to abnormal gastrointestinal transit.60 A normal stomach
at baseline contracts at a rate of 3 cycles/min (cpm) sec-
ondary to a rhythmic electric depolarization called the
slow wave. Abnormalities in the basal rhythm of the slow
wave have been associated with nausea and vomiting. Koch
et al evaluated gastric myoelectric activity in pregnant
women with and without nausea. Gastric dysrhythmias
were demonstrated in all nauseated women, while normal
3-cpm patterns were seen in all of the women with minimal
to no nausea.61 Furthermore, high levels of progesterone
and estrogen increase gastric dysrhythmias (both brady and
tachygastria) as shown by administration of these hormones
to nonpregnant women.35 However, other studies of gastric
transit have not found abnormalities in women with HG
compared with controls. Maes et al evaluated gastric empty-
ing using gastric emptying studies in nonpregnant women,
women with HG, and pregnant women without HG. They
found that women with HG did not have higher rates of de-
layed gastric emptying compared with the other groups, sug-
gesting that HG is not due to increased gastric transit time.42
Lower Esophageal Sphincter Resting Pressure
The esophagus during pregnancy has been shown to have
lower resting lower esophageal sphincter (LES) pressure
and reduced percentage of transmitted contractions.62 De-
creased LES resting pressure due to the effects of estrogen
and progesterone on the smooth muscle of the esophagus
may be a major contributor to the high prevalence of gas-
troesophageal reflux disease (GERD) during pregnancy.63-65
Increasing abdominal girth has also been proposed to de-
crease LES pressure. However, studies evaluating LES pres-
sure in patients with ascites before and after diuresis have
found LES pressure significantly decreases after diuresis and
loss of abdominal girth,66 which calls into question whether
the mechanical effects of the growing uterus impacts LES
pressure or whether the changes seen in pregnancy are
explained solely by hormonal factors.
Although decreased LES pressure is most likely to pro-
duce heartburn, GERD can also produce atypical symp-
toms including nausea and vomiting.67 Furthermore, use
of acid-reducing medications has been shown to reduce the
severity of NVP.68
With regard to choice of acid-suppressing medication,
antacids can be used in pregnancy, but they are weak acid
suppressants, and patients who take them should be mon-
itored for side effects, which include decreased absorption
of supplemental iron, milk-alkali syndrome for calcium-
based antacids, seizures and arrest of labor for magnesium-
based antacids, and metabolic alkalosis and fluid overload
in the mother and fetus with sodium bicarbonate.69-71 Both
4 Nutrition in Clinical Practice 0(0)
histamine 2 receptor blockers and proton pump inhibitors
can be taken in pregnancy.72 Meta-analyses of both classes
of drugs have shown no increased risk for adverse outcomes
to the fetus when used during pregnancy.73,74
Genetics
Family history of NVP, specifically history of NVP in
mother or sister, has been noted to be a risk factor for
NVP for several decades.75 A 1992 study of twins found
that the rate of NVP was twice as high in monozygotic
twins compared with dizygotic controls.76 More recently,
Fejzo et al examined the familial component of HG and
the potential role of maternal genetic susceptibility in the
development of NVP and HG. In a survey of >1200 patients
with HG, 28% of woman reported their mother had been
affected with severe NVP or HG as well. Additionally, 9% of
participants reported having 2 affected family members.77
A subsequent study by this group identified 2 potential
candidate genes, GDF15 and IGFBP7, both of which have
roles in early pregnancy which may be implicated in HG.78
Clinical Features
Although often termed “morning sickness,” NVP typically
persists throughout the day and is limited to the morning
in <2% of women.2 It begins within 4 weeks after the last
menstrual period in most patients.79 Symptoms usually peak
between 10–16 weeks gestation and usually resolve after
20 weeks, with only a minority of women continuing to have
symptoms beyond 22 weeks.2
In addition to severe nausea and vomiting, 60% of
women with HG experience excess salivation.80 Patients
may also complain of gastroesophageal symptoms, such as
retrosternal discomfort and heartburn.
On physical exam, women with HG may demonstrate
evidence of dehydration and orthostasis. Most women with
NVP, in comparison, have normal vital signs and a benign
physical exam. A careful abdominal exam, however, should
be done to rule out peritonitis and other intra-abdominal
causes of nausea and vomiting. Women with suspected
HG should be evaluated for muscle wasting and weak-
ness, peripheral neuropathies due to vitamin B6 and B12
deficiencies, and mental status changes. Recently the term
“altered sensorium gestosis” has been coined to describe the
cognitive malfunction which can be seen in women with HG
due to nausea, dehydration, malnutrition/starvation, and
electrolyte abnormalities as well as sleep deprivation.81
Diagnostic and Laboratory Tests
Once pregnancy had been established by a positive preg-
nancy test, no specific laboratory studies are needed for the
diagnosis of NVP. A white blood cell count, liver function
tests, and fasting serum glucose and TSH screening, how-
ever, may be helpful in excluding other causes of nausea and
vomiting, such as infection, diabetes, and thyroiditis.
Radiographic imaging is generally not needed; however, a
pelvic ultrasound can be considered to document pregnancy
and evaluate for conditions which increase the risk for NVP,
such as multiple gestation. Upper endoscopy can be consid-
ered to rule out gastritis and peptic ulcer disease (PUD).
For women with suspected HG, laboratory studies
should be obtained to determine its severity and help with
management. Common abnormalities include increased
serum blood urea nitrogen, creatinine, and hematocrit due
to volume depletion and hemoconcentration. Urinalysis
may reveal ketonuria and increased urine specific gravity.
Electrolyte disturbances, such as hyponatremia and hy-
pokalemia, may also be found. Furthermore, electrolyte
analysis may also show hypochloremic metabolic alkalosis
or metabolic acidosis with severe volume contraction.82
Preserum albumin levels may be low, reflecting poor protein
nutrition status in the mother and possibly predicting lower
fetal birth weights.83 Vitamin and mineral deficiencies such
as vitamin B1 (thiamin), iron, calcium, and folate are also
possible.84
Liver function tests are abnormal in ࣘ50% of hospital-
ized patients with HG.85 Mild hyperbilirubinemia (bilirubin
<4 mg/dL) and/or a rise in alkaline phosphatase to twice
the upper limit of normal may be seen.86 A moderate
transaminitis is the most common liver test abnormal-
ity with alanine aminotransferase levels generally greater
than aspartate aminotransferase levels. The transaminase
elevation is usually 2–3 times the upper limit of normal;
however, a significant transaminitis with levels >1000 U/mL
have also been reported.87 The abnormal liver tests resolve
promptly upon resolution of the vomiting. While the eti-
ology for the elevated liver function tests is not entirely
clear, hypovolemia, malnutrition, and lactic acidosis are all
likely contributory. Hyperbilirubinemia may also be due to
impaired secretion of bilirubin.88
Serum amylase and lipase elevation are seen in 10%–15%
of women.83 The amylase elevation is thought to be due
to excessive salivary gland production of amylase due to
prolonged vomiting.3
TSH levels may be low in NVP and HG. In the majority
of cases this is not clinically relevant as patients are
euthyroid.
Differential Diagnosis
The differential diagnosis for NVP includes GERD, PUD,
small-bowel obstruction, acute cholecystitis, cholelithia-
sis, pancreatitis, as well as appendicitis, gastroenteritis,
nephrolithiasis, pyelonephritis, and hepatitis.85 The onset of
nausea >8 weeks after the last menstrual period is atypical
for NVP and should prompt investigation for other causes.80
Austin et al 5

Table 1. Pharmacologic Treatments for NVP and HG.

Treatment Dose Possible Side Effects Contraindications References

Ginger 250 mg, ࣘ4 times daily Heartburn None 87–90

Vitamin B6 10–25 mg, 3–4 times daily Numbness, paresthesia, None 96, 97
(Pyridoxine) unsteady gait
Antihistamine/B6 10–12.5 mg doxylamine + Fatigue, epigastric pain, None 101–103
combination 10 mg B6, ࣘ4 times constipation, impaired
daily coordination, paresthesia
Metoclopramide 10 mg, ࣘ4 times daily Fatigue, anxiety, headache, Hypertension, seizure 107, 110,
dizziness, depression, disorder, Parkinson’s 116–118
galactorrhea, disease, history of
extrapyramidal symptoms, tardive dyskinesia,
dystonia depression
Phenothiazine 10–25 mg, ࣘ3 times daily Tissue damage, seizures, Respiratory depression, 110,
derivatives respiratory depression, seizure disorder 112–115
(Promethazine, hallucinations, sedation,
Compazine, extrapyramidal symptoms,
Thorazine) dry mouth
Ondansetron ࣘ24 mg/d in 3–4 divided Headache, constipation, Congenital long QT 119–125
doses urinary retention, dizziness, interval
possible increased risk for
birth defects
Corticosteroids Hydrocortisone 100 mg Possible increased risk for Corticosteroids 128–136
twice daily IV, oral clefts
converted to
prednisone 40 mg and
taper to lowest effective
dose
Clonidine 5 mg patch Hypotension, headache, Recent myocardial 137
sedation, contact infarction,
dermatitis, dizziness, depression,
constipation hemodynamic
instability, renal
impairment
Gabapentin 300–900 mg, ࣘ3 times Fatigue, depression with Renal impairment, 140
daily abrupt withdrawal depression

HG, hyperemesis gravidarum; NVP, nausea and vomiting of pregnancy.

Treatment used across multiple specialties including oncology, anes-

Goal of Treatment
The goal of therapy in HG is to improve symptoms in the
mother while minimizing risks to both mother and fetus.
As is true for other conditions experienced in pregnancy,
there are limited data from randomized controlled trials
given the ethical considerations of studying novel therapies
in pregnant women. To help quantify symptom severity and
improvement after intervention, validated scoring systems
are used in many treatment studies. The Pregnancy Unique
Quantification of Emesis (PUQE)-24 assesses symptoms
of nausea, vomiting, and retching during a 24-hour pe-
riod, while the Hyperemesis Impact of Symptoms ques-
tionnaire was designed to holistically assess the impact
of HG by quantifying both physical and psychosocial
symptoms.89,90 Furthermore, visual analog scales have been
thesia, and emergency medicine to determine the efficacy
of antiemetic therapy and are employed in several HG
treatment studies.91-93
Treatments can be divided into 3 categories: first-line,
second-line, and third-line, with severity of symptoms and
response to prior therapies guiding decision-making on
treatment. Pharmacologic treatments for NVP and HG are
summarized in Table 1.
First-Line Treatments
Ginger. The use of ginger as an aid for nausea can be
traced to ancient China and has been documented in Greek,
Roman, Indian, Mediterranean, and Arabic civilizations.94
The precise mechanism by which ginger produces antiemetic
effects is unknown. In vitro studies suggest that gingerol, the
6 Nutrition in Clinical Practice 0(0)
active constituent of fresh ginger, has antagonistic effects on
serotonergic 5-hydroxytryptamine Type 3 (5-HT3) 5-HT3
and cholinergic receptors.95,96 Additionally, ginger helps
stimulate GI tract motility and increase bile and gastric acid
secretion.94,97 Ginger has been found to improve mild to
moderate nausea and vomiting across several studies and
meta-analyses.94,98,99
Ginger has repeatedly shown superiority over placebo
in studies of NVP. In a double-blind, placebo-controlled,
randomized crossover trial of 30 women in which the
women received 250 mg ginger vs placebo 4 times daily for
4 days, followed by a 2-day washout period, and then a
return to therapy with the alternate treatment from what
they initially received, 70% of women reported a preference
for ginger.100 Vutyavanich et al performed a similar study
comparing ginger to placebo and reported an improvement
in both nausea and vomiting in 67 women with NVP.101
A recent meta-analysis of 12 randomized controlled
trials by Viljoen et al involving 1278 women further supports
the use of ginger to help improve symptoms of NVP
compared with placebo.102 Notably, the subjective feeling
of nausea showed the greatest improvement after treatment
with ginger across studies, while improvement in vomiting
approached but did not reach significance.
The safety of ginger in pregnancy has been evaluated
in relation to risk for congenital abnormalities, pregnancy
complications, and pregnancy outcomes. A randomized
controlled trial of 291 women found no difference in birth
weight and length or head circumference in mothers taking
ginger during pregnancy compared with those taking vita-
min B6.103 Furthermore, the Viljoen et al study found no
significant difference in the risk of spontaneous abortion be-
tween women who had taken ginger compared with placebo
or risk for the side effects of heartburn or drowsiness.102
Acupressure and acupuncture. Acupressure is a form of
complementary medicine which involves applying physical
pressure to specific areas of the body to activate the small
myelin nerves of the muscle, and then pass stimulation to
higher nerve centers, including the spinal cord and brain.
Stimulation of the median nerve at the Pericardium 6
(known as P6 or Neiguan) acupuncture point by placing
pressure on the ventral aspect of the wrist has been the
focus of numerous studies of NVP. A study by Bayreuther
et al evaluated P6 compared with sham acupressure in the
treatment of early NVP. Although only 16 participants
completed the study, two-thirds reported more relief with
P6 stimulation than sham.104 A larger study of 60 patients
showed similar results with improvement in nausea but
not vomiting when comparing P6 acupressure to a sham
acupressure site.105 A systematic review of 26 trials includ-
ing >3000 patients found an improvement in nausea and
vomiting caused by a variety of conditions (chemotherapy,
postoperative sickness, and pregnancy) compared with
sham acupressure.106 Emerging data on Kidney21, a tradi-
tional Chinese point on the upper abdomen, 6 cm above the
umbilicus and 5 cm lateral to the anterior midline, suggest
that acupressure to this area may improve NVP as well.107
Acupuncture has also been evaluated for the treatment
of NVP. One study by Smith et al compared acupuncture
(traditional acupuncture and P6 acupuncture) with sham
acupuncture and no acupuncture. They found that by the
third week, patients receiving traditional and P6 treatments
had less nausea compared with the other 2 groups. However,
there was no difference in vomiting.108
Given the low risk associated with acupressure and
acupuncture, a trial of either is reasonable in women with
mild to moderate NVP, either alone or in combination with
other treatments.
Second-Line Treatments
Vitamin B6 (pyridoxine) and vitamin B6 with doxylamine.
Randomized controlled trials have shown that vitamin B6
(pyridoxine) taken at doses of 10–25 mg every 8 hours
reduces symptoms among women with NVP. A 1991 study
showed that women with severe symptoms benefited after
taking 25 mg orally every 8 hours for 72 hours, while
those with mild to moderate symptoms did not show sig-
nificant improvement.109 A subsequent study also showed
an improvement in nausea scores with doses of 30 mg
daily compared with placebo. Of note, episodes of vomiting
improved but did not reach clinical significance.110
Although there are data to support its use alone, vitamin
B6 has also been used in conjunction with doxylamine.
Combination pills comprised of vitamin B6 and doxylamine
have been available throughout the world for decades; how-
ever, in the United States, the combination pill, Bendectin
(Merell Dow, Laval, Quebec, Canada) was removed from
the market in 1983 due to concerns for teratogenicity.111
These concerns were ultimately determined to be unjustified
after 2 large meta-analyses studies including >200,000
women showed no difference in risk for birth defects infants
among those who were born to mothers who had taken or
had not taken Bendectin.112,113 In 2013, the FDA approved
the return of a combination formulation of vitamin B6
and doxylamine for NVP, and in 2016, an extended release
version, Diclegis (Duchesney, Bryn Mawr, PA), became
available for women with NVP not responding to dietary
and lifestyle changes.114,115 Notably, women can also obtain
the components of these combination pills over the counter
and take 10 mg of vitamin B6 and 12.5 mg of Unisom
(Chattem Inc, Chattanooga, TN) individually.
Diclegis is recommended by many to be first-line in the
treatment of NVP given its favorable safety profile and
efficacy across multiple studies.116 The American College of
Obstetricians and Gynecologists recommends with Level A
evidence the use of vitamin B6 alone or in combination with
Austin et al
doxylamine as first-line pharmacotherapy for treatment of
NVP.114 This combination, however, has not been studied
in HG.
Antihistamines. Antihistamines are thought to reduce nau-
sea and vomiting by indirectly affecting the vestibular sys-
tem and decreasing stimulation of the vomiting center.117 In
addition, inhibition of muscarinic receptors may also pro-
duce antiemetic effects. Although no randomized trials have
evaluated their efficacy in NVP, first-generation and second-
generation histamine blockers have long been used, and
many studies have found them to be effective.118 A recent
systematic review of 37 studies found no increased risk for
spontaneous abortions, prematurity, still birth, or low birth
rate in woman taking antihistamines for a wide array of
reasons, including seasonal allergies, asthma, and NVP.119
Dopamine antagonists. Peripheral and central-acting
dopamine antagonists are commonly used for the treatment
of nausea and vomiting in the general population. These
medications include metoclopramide (Reglan, Baxter
Healthcare Corporation, Deerfield, IL) and several
phenothiazine derivatives: promethazine (Phenergan,
Baxter Healthcare Corporation, Deerfield, IL), and
prochloroperazine (Compazine, multiple manufacturers).
Metoclopramide is thought to improve nausea and vomiting
by antagonizing D2 receptors in the chemoreceptor trigger
zone within the central nervous system and at higher doses
by antagonizing 5-HT3 receptors. Promethazine derivatives
work as D2 antagonists and have antihistamine activity by
blocking H1 receptors.120,121
A double-blind, randomized, controlled trial of intra-
venous (IV) promethazine compared with metoclopramide
showed similar efficacy for reducing nausea and vomiting
between the 2 drugs, but a better side-effect profile for
metoclopramide.122 Concerns regarding the safety of phe-
nothiazines in pregnancy were raised following a study from
1977 which found a higher rate of congenital malformations
in infants born to mothers who had taken phenothiazines
in the first trimester compared with those who had not123 ;
however, more recent data have been reassuring.124,125 Ad-
ditionally, there is conflicting data regarding the safety of
promethazine, with an increased incidence of hip dysplasia
reported in 1 study, while another found no teratogenic
effects.126,127
There have been no studies showing any increased
risk for major congenital malformations, low birth weight
(LBW), preterm delivery, or perinatal death with the use
of metoclopramide.128-130 The drug does, however, carry
an FDA-issued black box warning due to the risks of
tardive dyskinesia with high cumulative doses. It is gener-
ally recommended to keep the duration of treatment with
metoclopramide to <12 weeks.
7
5-HT3 receptor antagonists (serotonin antagonists).
Serotonin antagonists prevent nausea and vomiting by
acting peripherally on the vagus nerve and centrally by
blocking chemoreceptors in the area postrema of the
brain. Randomized controlled trials support the use of on-
dansetron (Zofran, Novartis, Research Triangle Park, NC),
with improvement in symptoms across all levels of severity
among women with NVP. A head-to-head randomized
trial favored the use of ondansetron over metoclopramide
for HG with significant improvements in vomiting and
some, albeit less so, improvement in nausea during a
14-day period.131 A subsequent randomized controlled trial
showed similar levels of symptom improvement in women
treated with ondansetron compared with metoclopramide,
but a better side-effect profile with ondansetron.132 More
recently, a 2014 double-blind randomized clinical trial
of 30 patients compared ondansetron with vitamin B6–
doxylamine and found an overall improvement in symptoms
for both groups, but a statistically greater improvement
in both nausea and vomiting in the ondansetron
group.133
With regard to safety in pregnancy, a prospective, com-
parative observational study published in 2004 did not
show significant differences between the rates of live births,
miscarriages, stillbirths, therapeutic abortions, gestational
age, or risk of major malformations among infants of
mothers who had taken ondansetron, other antiemetics,
other prescription medications, or who had not taken any
medications during pregnancy.134 A 2012 study found an
increase rate of cleft palate in infants born to mothers using
ondansetron.135 More recent data, including a nationwide
historic cohort study in Denmark over a 7-year period
which included >600,000 pregnancies, found no increase in
adverse fetal events, including preterm birth or small for
gestational age (SGA).136 Conversely, a similar, yet larger
Danish study of >1,500,000 pregnancies found an increased
risk for cardiovascular birth defects (specifically cardiac
septum defects) with an OR of 1.62 (95% CI: 1.04–2.14) but
no increased risk when all major adverse birth defects were
pooled: OR 1.11 (95% CI: 0.81–1.53).137
The practice of continuous infusion of antiemetics and
use of high doses of 5-HT3 antagonists have been evaluated
in oncology as a possible means for better symptom control
following chemotherapy. Based on available data, it has been
recommended by expert panels that doses of ondansetron
above the current FDA recommended maximum of 32 mg/d
should not be used to treat patients with nausea secondary
to chemotherapy.138 Furthermore, they have stated that
there is no benefit with continuous subcutaneous infusions
compared with intermittent dosing. In the NVP population,
a study by Klauser et al, which compared the treatment
effects of subcutaneous ondansetron with those of subcuta-
neous metoclopramide via a microinfusion pump in women
with a PUQE score >12, found a similar improvement in
8 Nutrition in Clinical Practice 0(0)
symptoms between the 2 groups, but a higher rate of side
effects with metoclopramide.139
Third-Line Treatments
Corticosteroids. Corticosteroids are frequently coadmin-
istered with 5-HT3 antagonists to treat chemotherapy-
induced nausea and vomiting.138 With regard to HG, several
small, randomized, controlled trials evaluating the use of
corticosteroids vs placebo or promethazine in patients have
been published. Two such studies comparing corticosteroids
with promethazine found no improvement in symptoms
of nausea or episodes of vomiting.140,141 A third study of
40 women with HG admitted to the intensive care unit
compared hydrocortisone with metoclopramide and found
that the patients treated with corticosteroids had a greater
reduction in vomiting within 3 days of treatment.142 Other
studies comparing corticosteroids with placebo or meto-
clopramide have shown no benefit in terms of symptoms
or length of hospital stay.143 Furthermore, no differences
have been shown for need for rehospitalization or emergency
room visits when corticosteroids were added to promet-
hazine and metoclopramide in women who failed outpatient
HG therapy in the first half of pregnancy.144
Studies dating back to the 1950s have reported an
increased risk for orofacial clefts in rodents exposed to
corticosteroids in utero.145 In humans, data for malforma-
tions with first trimester corticosteroid exposure have been
mixed. One study by Carmichael et al published data from
a population-based case-control study and found an unad-
justed OR of 1.7 (95% CI: 1.1–2.6) for cleft lip ± cleft palate
for infants born to mothers with reported prepregnancy or
early pregnancy corticosteroid use.146 Others, however, have
found no increased risk for orofacial cleft, suggesting that
if clinically indicated, corticosteroids can be used during
pregnancy.147,148
Transdermal clonidine. Recently, the use of transdermal
clonidine has been evaluated in a small, double-blind,
placebo-controlled trial of women with HG refractory to
standard antiemetic treatment. Results of this trial of 12
patients found an improvement in both PUQE scores and
visual analog scale scores as well as decreased need for
rescue antiemetic therapy with transdermal clonidine use.149
Side effects included decrease in resting blood pressure, and
no adverse fetal outcomes or birth defects were reported.
Larger studies are needed to further evaluate the efficacy of
this drug for HG.
Gabapentin. The mechanism of action for gabapentin as
an antiemetic is unclear; however, studies have shown it to
be beneficial for reducing nausea and vomiting.150 Studies
in patients with refractory chemotherapy-induced nausea
and vomiting showed a 67% improvement in symptoms.151
Guttuso et al performed an open-label pilot study to eval-
Table 2. Estimated Energy Requirement (EER) for
Pregnancy.
EERpg = EER prepg + additional energy expended during
pg + energy deposition
where:
First trimester = EER prepg + 0
Second trimester = EER prepg + 340
Third trimester = EER prepg + 452
Prepregnancy EER for age 19 and older = 354 − (6.91 ×
age[years]) + PA × (9.36 × weight [kg] + 726 × height [m])
where PA is the physical activity coefficient
PA = 1.0 for sedentary
PA = 1.12 for low active
PA = 1.27 for active
PA = 1.45 for very active
PA, physical activity; pg, pregnancy; prepg, prepregnancy.
Source: Kaiser LL, Campbell CG. Practice Paper of the Academy of
Nutrition and Dietetics: Nutrition and Lifestyle for a Healthy
Pregnancy Outcome. J Acad Nutr Diet. 2014;114(9):1447.
uate the safety and effectiveness of gabapentin in women
with HG. Seven patients were included, all of whom had
significant improvements in symptoms by 12–14 days. Main
side effects noted included dizziness and sleepiness, and 2
congenital defects were noted.152 Larger, controlled trials
are currently underway to further assess effectiveness and
safety of gabapentin in HG.
Nutrition
The nutrition consequences of HG are many, including
dehydration, electrolyte disturbance, ketonuria, nutrient
deficiency, and weight loss.153,154 Nutrient provision to a
fetus relies solely on the nutrition status of the mother, and
substantial evidence links maternal malnutrition with an
increased risk of negative fetal outcomes, including LBW
and intrauterine growth restriction.155 Therefore, nutrition
therapy deserves attention and is an essential component of
the care plan for the patient with HG.
Nutrient Requirements
Additional calories are needed during pregnancy to support
the growth of the fetus, placenta, amniotic fluid, and
maternal tissue deposition. Total daily calorie needs for
each trimester are approximated using Estimated Energy
Requirement (EER) formulas for pregnancy (Table 2). With
the exception of multiple gestations, calorie needs generally
do not increase beyond those of prepregnancy requirements
until the second and third trimesters.156 It is estimated
that 340 and 452 additional kcal/d are needed during the
second and third trimester, respectively, for healthy preg-
nant women 19 years and older.156 The EER formulas are
typically not used for overweight, obese, or multiple gesta-
tion pregnancies. The Academy of Nutrition and Dietetics
Nutrition Care Manual recommends 24 kcal/kg pregravid
Austin et al 9

Table 3. Micronutrients of Concern in Pregnancy. Table 4. Recommended Weight Gain in Pregnancy Based on
Prepregnancy BMI.
Nutrient Recommended Daily Allowance
Total Weight Gain Range (lbs)
Calcium 1000 mg/d ages 19 and older
Iron 27 mg/d BMI Category Single Gestation Twins
Folate 600 mcg/d
Vitamin D 600 IU/d Underweight (<18.5) 28–40
Thiamin 1.4 mg/d Normal weight (18.5–24.9) 25–35 37–54
Niacin 18 mg/d Overweight (>25.0–29.9) 15–25 31–50
Riboflavin 1.4 mg/d Obese (>30.0) 11–20 25–42

Source: Kaiser LL, Campbell CG. Practice Paper of the Academy of BMI, body mass index.
Nutrition and Dietetics: Nutrition and Lifestyle for a Healthy Source: Kaiser LL, Campbell CG. Practice Paper of the Academy of
Pregnancy Outcome. J Acad Nutr Diet. 2014;114(9):1447. Nutrition and Dietetics: Nutrition and Lifestyle for a Healthy
Pregnancy Outcome. J Acad Nutr Diet. 2014;114(9):1447.

weight for pregnant women with >120% desirable weight.156

For multiple gestation pregnancies, energy needs are based
upon pregravid weight, with 40–45 kcal/kg/d for normal
BMI, 42–50 kcal/kg/d for underweight, and 30–35 kcal/kg/d
for overweight.157
Nutrient prescriptions should always be individualized
and may need adjusting in the case of HG where uninten-
tional weight loss and inadequate dietary intake are com-
monplace. Thus, there is no standard higher energy require-
ment for women with NVP or HG. A dietitian can perform
a nutrition-focused physical exam, evaluating for fat loss,
muscle wasting, edema, and micronutrient deficiency, which
supports an effective nutrition care plan. In addition, the Figure 1. Common anti-nausea diet recommendations.
Interactive Dietary Reference Intake for Health Profession-
als is a free online tool that calculates prepregnancy BMI,
EER, and recommended nutrient intakes.158 Recommended Weight
dietary allowances of macronutrients in pregnancy may
Persistent vomiting results in poor appetite and inadequate
provide a starting point for calculating estimated needs for
calorie intake to meet needs. Consequently, women with
HG, which have yet to be established.159
HG struggle to meet pregnancy weight goals, and by most
It is standard recommendation for pregnant women
HG definitions, have lost at least 5% of prepregnancy
to consume a daily prenatal multivitamin with minerals.
weight. Because maternal weight change influences infant
Taking one may reduce the incidence and severity of NVP
health outcome, weight should be routinely monitored.
when used for at least 1 month prior to conception.114
Fluid status and prepregnancy weight should be taken into
Women with HG are at risk for micronutrient deficiency
consideration during weight assessments. Serum sodium
secondary to poor dietary intake and abnormal electrolyte
and plasma osmolality should be used to assess fluid status,
losses.153 In a controlled study of 40 pregnant women,
along with physical examination. Table 4 summarizes rec-
those with HG were found to have mean intakes of most
ommended pregnancy weight gain based on prepregnancy
nutrients that were <50% of the recommended dietary
BMI.
allowances, although all participants had healthy babies.154
If a standard prenatal multivitamin is not tolerated,
Oral Diet
a preparation without iron may be better tolerated,160
especially when taken at bedtime. If an oral multivitamin If nausea and vomiting are controlled and an oral diet is
fails, folic acid becomes the micronutrient of priority due to possible, nutrition counseling should be implemented by a
the link between folic-acid deficiency and fetal neural-tube dietitian. While there is limited scientific evidence to support
defects, and can be taken singularly.161 The RDA for a particular diet in the treatment of HG, the use of dietary
folic acid in pregnant women ࣙ19 years is 600 μg/d.156 modification to treat HG is well accepted.162
Micronutrients at risk for deficiency during pregnancy and Dietary recommendations for HG are similar to those
their recommended intakes are found in Table 3. For women for nausea and include the consumption of small, frequent
with HG requiring IV rehydration, a multivitamin should meals that are high in protein, bland in flavor, and low in
be given intravenously and additional folic acid if needed.114 odor (Figure 1).114,163,164 Small, frequent meals can help
10
prevent hypoglycemia and gastric overdistention.165 A
phone interview study exploring dietary choices in a pop-
ulation of women with severe NVP revealed a preference
towards small, frequent meals.166 Jednak et al assessed
the contribution of meal macronutrient composition to
symptoms of nausea and vomiting in 14 pregnant patients
using electrogastrography to measure gastric dysrhythmic
activity.167 In this crossover study, nausea and gastric dys-
rhythmic activity decreased with protein-rich meals when
compared with equicaloric carbohydrate and fat-rich meals
(P < .05). This was further supported by a descriptive inves-
tigational study that showed pregnant women with severe
nausea and vomiting reported protein-rich foods were the
most therapeutic food type to improve symptoms.168
Women with HG should be encouraged to eat any
pregnancy-safe food or beverage they can tolerate. If hospi-
talization is required to manage HG, the diet order should
be regular as tolerated. A focus on adequate calories vs
macronutrient distribution is advised. A dietitian should
elicit the patient’s food choices to identify types of foods
preferred and tolerated, which will help drive further dietary
suggestion. Books which provide insightful direction on
navigating various food characteristics and being adaptable
to changes in food tolerance from 1 day to the next are
available, and they are excellent resources for patients and
providers.169,170
Ginger
Ginger has been shown to decrease rates of nausea and
vomiting in pregnant women, and has not been associated
with adverse pregnancy events.171 It can be taken in various
forms, including fresh and in candies, teas, capsules, and
syrups. The dose of ginger found to be effective in a
crossover study of women with HG was 1 g/d.100 Further
information about ginger can be found in the section
discussing first-line treatments.
IV Fluids
Patients with HG who cannot tolerate oral liquids or
are clinically dehydrated should be treated with IV fluid
therapy.114 This not only improves their fluid status, but also
the symptoms of nausea and vomiting. The most suitable
composition of IV fluids, however, is controversial. Only 1
controlled trial has evaluated the effects of different fluid
types in women with HG.172 In this study, the effect of 5%
dextrose normal saline was compared with normal saline
(NS) in terms of resolution of ketonuria and overall sense
of well-being. After 24 hours of infusion, no significant
differences were found between the 2 groups regarding
these parameters. Eighty-nine percent of the NS group
experienced resolution of ketonuria at the 24-hour mark,
leading the authors to conclude that NS is an effective route
of rehydration.
Nutrition in Clinical Practice 0(0)
Oral Nutrion
Nasogastric Tube Percutatneous Endoscopic
Gastrostomy
Nasojejunal Tube Percutaneous
Endoscopic Gastrojejunostomy
Parenteral Nutrion
Figure 2. Algorithm for preference of route of nutrition
support in hyperemesis gravidarum.
Source: Mueller C, Ed. The A.S.P.E.N. Nutrition Support
Core Curriculum, 2nd Edition. American Society for
Parenteral Nutrition, 2012.
Thiamin deficiency is associated with HG from a com-
bination of excess vomiting, poor dietary intake, and in-
creased glucose demands as shown in 60% of pregnant
women with HG.154 Wernicke’s encephalopathy may de-
velop when dextrose-based solutions are given prior to thi-
amin repletion.173,174 Thiamin deficiency can occur within
2–3 weeks of persistent vomiting,175,176 prompting timely
replacement. Laboratory assessment of thiamin status is
not necessary if diagnosis of Wernicke’s encephalopathy is
suspected. Several treatment regimens have been described,
ranging from IV thiamin 100–500 mg/d for various amounts
of time, and oral supplementation is a recommended follow-
up measure.173,177,178
Repletion of potassium, magnesium, and phosphorus
guided by standard lab monitoring should also be given
careful attention while rehydrating the patient with HG.179
Enteral and Parenteral Nutrition
Nutrition support should be initiated in women with HG
who continue to lose weight and are unresponsive to phar-
macologic and nonpharmacologic treatments. The decision
to start enteral nutrition (EN) or parenteral nutrition (PN)
must be individualized and take into account the patient’s
gestational age, comorbidities, and preferences as well as
institutional resources and expertise. Figure 2 provides a
proposed pathway regarding nutrition support in HG.180
Randomized trials comparing EN with PN in women with
HG refractory to medical therapy are lacking. In general,
EN is preferred given the increased health risks with PN
during pregnancy, but it should not be given until dehy-
dration and electrolyte abnormalities are corrected. EN is
more cost-effective and less intensive than PN in both the
Austin et al
hospital and home setting. Nasogastric or nasoenteric tubes
are preferred for an anticipated duration of 4–6 weeks,
whereas longer-term needs require gastrostomy or jejunos-
tomy placement. While gastric feedings hold a higher risk of
aspiration, exposure to radiation occurs when the feeding
tube is placed past the pylorus, and tube dislodgement
is common. There are no studies comparing gastric feed-
ings with intestinal feedings or polymeric formulas with
elemental formulas in the treatment of HG. Antiemetics
can be coadministered with nutrition support to minimize
symptoms, risk of aspiration, and tube dislodgement.
Several studies have investigated the effect of EN in this
population. The first randomized controlled trial to evaluate
EN on birth outcomes in HG was performed by Grooten
et al. In this multicenter study, 115 women with HG were
randomly assigned to either standard care (IV rehydration,
antiemetics, and vitamins) or standard care plus enteral
feedings for at least 7 days.181 There were no significant
differences in maternal weight gain, birth weight, nausea
and vomiting, or quality of life between the groups. Notably
>half of the women were unable to follow the alimentation
protocol due to discomfort or failed insertion of the feeding
tube.
Other small case reports and observational studies have
demonstrated that some women with HG tolerate EN via
gastric and intestinal routes and have experienced improved
nausea and vomiting within a few days.182-185 In a retro-
spective study, 107 women with severe HG experienced
reversal of significant weight loss after a median of 5 days
on nasogastric tube feedings. When compared with women
with less severe HG given either IV fluids or PN, there were
no differences in total pregnancy weight gain or pregnancy
outcomes, including gestational length and birth weight.186
PN in HG should be reserved for those unable to main-
tain weight who failed EN or have contraindications. The
concern is primarily due to a higher rate of catheter-related
complications among pregnant women.187 A retrospective
study including 94 women with HG found neither EN nor
PN to be superior in achieving healthy birth outcomes
compared with those receiving IV medications only. Addi-
tionally, 64% of the participants with a peripherally inserted
central catheter (PICC) line suffered complications, such as
bacteremia, thrombosis, and pulmonary embolus, though
it should be noted that only 5 of the 33 women with a
PICC were receiving PN.188 Other studies regarding the use
of PICCs during pregnancy have also shown high rates
of complications.189 In selected patients, however, PN may
be the appropriate next step once metabolic instability is
corrected and good tolerance has been documented.190
Outcomes
NVP is associated with a favorable outcome for the fetus.
In a prospective study of 16,398 women, no difference was
11
found in congenital abnormalities between those with and
without NVP.191 A meta-analysis of 11 studies found a
decreased risk of miscarriage (common OR: 0.36; 95% CI:
0.32–0.42), and no consistent associations with perinatal
mortality192 in women with NVP. Moreover, women with-
out NVP have been found to deliver earlier compared with
women with NVP.193 NVP, however, causes substantial psy-
chosocial morbidity in the mother. NVP impairs employ-
ment, performance of household duties, and parenting.194 It
is also associated with feelings of depression, consideration
of termination of pregnancy, and impaired relationships
with partners.
HG, in comparison, is associated with both
adverse maternal and fetal outcomes. In a study of
>150,000 singleton pregnancies, women with HG had
increased rates of low pregnancy weight gain (<7 kg),
LBW babies, SGA babies, preterm birth, and poor
5-minute Apgar scores.195
Common maternal complications include weight loss,
dehydration, micronutrient deficiency, and muscle weak-
ness. More severe, albeit rare, complications include
Mallory-Weiss tears, esophageal rupture, Wernicke’s en-
cephalopathy with or without Korsakoff’s psychosis, cen-
tral pontine myelinolysis due to rapid correction of
severe hyponatremia, retinal hemorrhage, spontaneous
pneumomediastinum,196 and vasospasm of the cerebral
arteries.197 HG may also lead to psychologic problems and
result in termination of an otherwise wanted pregnancy and
decreased likelihood to attempt a repeat pregnancy.198
Some studies have found no increased risk for adverse
fetal outcomes in women with HG.199 However, many have
found an association between HG and fetal growth retarda-
tion, preeclampsia, and SGA.200 In a retrospective study of
3068 women, HG was associated with earlier delivery and
lower birth weight.201 Similarly, Dodds et al found higher
rates of LBW, preterm birth, and fetal death in women with
HG who gained <7 kg overall during pregnancy.195
Various congenital malformations have been observed
more in women with HG.201 These include Down syndrome,
hip dysplasia, undescended testes, skeletal malformations,
central nervous system defects, and skin abnormalities.202
Fetal coagulopathy and chondrodysplasia have been re-
ported from vitamin K deficiency203 with third trimester
fetal intracranial hemorrhage.204
Conclusion
NVP exists on a continuum with HG. While NVP is com-
mon during pregnancy and is mild to moderate in severity,
HG, in comparison, is rare and associated with severe symp-
toms and numerous potential complications for mother and
fetus. The pathophysiology of NVP and HG are still under
investigation, and it is hoped that with better understanding
of its etiology, more safe and effective treatments will
12
become available. For now, however, providers who care for
pregnant women should be familiar with the dietary modifi-
cations, pharmacologic treatments, and EN and PN options
which are available for calorie support and hydration so that
patients can be receive the optimal treatment for their level
of disease. This, in turn, should positively impact maternal
quality of life and fetal/newborn outcomes.
Statement of Authorship
K. Austin, K. Wilson, and S. Saha equally contributed to the
conception and design of the work; K. Austin, K. Wilson,
and S. Saha contributed to the acquisition and analysis of
the data; K. Austin, K. Wilson, and S. Saha contributed to
the interpretation of the data; and K. Austin, K. Wilson,
and S. Saha drafted the manuscript. S. Saha critically revised
the manuscript. All authors agree to be fully accountable for
ensuring the integrity and accuracy of the work, and read
and approved the final manuscript.
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