Review Article

iMedPub Journals Health Science Journal 2018

www.imedpub.com Vol.12 No.6:603
ISSN 1791-809X
DOI: 10.21767/1791-809X.1000603

Risk Factors of Hyperemesis Gravidarum: Review Article

Abanoub Gabra*
Department of Obstetrics and Gynecology, Assuit University, Egypt
*Corresponding author: Abanoub Gabra, Department of Obstetrics and Gynecology, Assuit University, Egypt, Tel: +18135399367; E-mail:

abanoub.gabra@med.au.edu.eg
Received date: 16 October 2018; Accepted date: 21 November 2018; Published date: 30 November 2018
Copyright: © 2018 Gabra A. This is an open-access article distributed under the terms of the creative commons attribution license, which
permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Citation: Gabra A. (2018) Risk Factors of Hyperemesis Gravidarum: Review Article. Health Sci J Vol.12.No.6:603.

Introduction
Abstract Nausea and vomiting is a common disease among pregnant
women. The spectrum of nausea and vomiting range from mild
Hyperemesis gravidarum (HG) is the most severe form of to severe disease which involves persistent and excessive
nausea and vomiting during pregnancy (NVP). It is vomiting [1]. The severe form of the disease is hyperemesis
diagnosed clinically by its typical clinical picture and gravidarum (HG) may cause significant maternal and fetal
exclusion of other causes of nausea and vomiting in the complications if not treated adequately [2].
pregnant woman. Nausea and vomiting are a common
experience affecting 50% to 90% of all women. It is the The term "morning sickness" is a miss-nomination, as this
most common indication for hospitalization during the condition often lasts throughout the day not only in the
first half of pregnancy. HG occurs in only about 0.5 to 2% morning [3]. Only 17% of women suffer nausea only in the
of cases but when it occurs, it may be associated with morning [4].
morbidity of both mother and fetus. There are many risk
factors related to HG, but we are still in need of adequate The International Statistical Classification of Disease and
clinical research methodology and design for reporting Related Health Problems, Tenth Revision, defines hyperemesis
these associations. In this article, we will discuss them gravidarum (HG) as persistent and excessive vomiting starting
and review epidemiological studies and statistics that before the end of the 22nd gestational week and further
support them. HG is found to be common in young aged subdivides it into mild and severe, the severe condition is
mothers. There is a debate between studies regarding complicated by metabolic disturbances such as carbohydrate
ethnicity as a risk factor. Low socio-economic level is depletion, dehydration or electrolyte imbalances [5].
found to be associated with HG. Dietary factors are
considered in Indians who are mostly vegan and Asians
The incidence of NVP reaches 91% which equals
who are mostly lactose intolerant. Deficiencies of trace approximately 4 million and 350,000 women who are affected
elements are associated with more progression of the every year in the United States and Canada respectively [2].
disease. Women affected by NVP are mostly nonsmoker. Although HG is a rare disease compared to NVP, it occurs in
Molar pregnancy, multiple pregnancies, fetus with Down 0.3% to 2% of all pregnancies [6]. It varies with ethnicity and
syndrome and primi-gravidity are common obstetric risk ranges between 3 and 20 per 1000 pregnancies [2,6]. This
factors. Studies theorize relation between varies may be due to different diagnostic criteria in addition to
hyperthyroidism and HG based on structural similarity ethnic variation in populations [7]. NVP is found more often in
between hCG and TSH but more studies are needed to Western countries and urban populations and is rare among
highlight this relation. Mood and anxiety disorders are African societies, Native Americans, Eskimos, and most Asian
associated with the disease but causal relation has not populations. A study from Canada of 367 women found that
been established yet. GERD, peptic ulcer disease and Asians and blacks were less likely to report symptoms of NVP
specifically H. pylori infection are among common risk than Caucasians. Socio-demographic factors did not explain
factors. Asthma is associated with prolonged duration of the racial/ethnic variation in disease prevalence, suggesting
hospitalization. Strong positive family history of HG in that genetic and/or cultural factors may contribute [2].
patients highlights genetic predisposition of this disease.
Its severity can be assessed using the Pregnancy Unique-
Keywords: Hyperemesis; Disease; Health Quantification of Emesis (PUQE) Score which has been
validated and has an intimate correlation with clinical
Abbreviations: NVP: Nausea and Vomiting in Pregnancy; diagnosis and severity of the case. The PUQE score includes
HG: Hyperemesis Gravidarum questions on the number of daily vomiting episodes, the
length of nausea per day in hours and the number of retching
episodes, with a minimum score of 3 and a maximum score of

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15. A score of <6 suggests mild HG, 7-12 is moderate HG and diet or high BMI diet also carries the risk of prolonged duration
13 or more is a severe disease [8]. of the disease [14,15]. On the other hand, a high intake of fish
and seafood and a high intake of allium vegetables have a
The PUQE score is also used to monitor treatment outcome
reduced risk of developing HG. Interestingly, The intake of one
during hospitalization on daily basis [8]. The score of PUQE is
to two glasses of water daily seemed also to be protective
found to be related to the quality of patient's life and her
against HG [21]. Deficiencies of trace elements and vitamins
willing to be pregnant again [9]. Moreover, a strong inverse
either due to diet or repeated vomiting have been considered
correlation between the scores of the PUQE questionnaire and
as possible etiologies of progression to hyperemesis
the self-reported food intake and weight gain [10].
gravidarum [12]. So recommendations about weight control
should be given to women with high or low BMI
Risk Factors preconceptionally [22].
There are many risk factors related to HG, but we are still in Smoking: It was found that women who vomit in pregnancy
need of adequate clinical research methodology and design in are less likely to be smoker [18] and this relation is considered
reporting these associations [11]. preexisting and it is not a response to either the pregnancy or
the vomiting [16]. It may be explained as smoking pregnant
Personal risk factors women also have lower levels of estrogen and there is a
relationship between high estrogen level and HG [16]. If NVP is
Age: Most studies agreed that hyperemesis gravidarum is an expression of a well-functioning placenta, the negative
more common among young aged mothers [12,13]. Moreover, relation with smoking may be because of a negative effect of
young age of pregnant women also carries a risk of prolonged maternal smoking on early placental development during
duration of the disease more than 27 gestational weeks embryogenesis [13].
[14,15]. The decreased risk of incidence of hyperemesis with
age may be explained by subsequent dealing with high Obstetric factors
estrogen levels by the production of sex hormones binding
globulin during subsequent menstrual cycles [16]. The incidence of HG is higher in multiple pregnancy [18],
molar disease and Down syndrome [24]. Nulliparous has
Socioeconomic factors: The low socioeconomic level is higher risk because of having higher serum [18] and urinary
considered as a risk factor to HG [14,15,17,18]. But socio- estrogen levels than multiparous women and those women in
demographic factors did not account for the racial/ethnic their first pregnancies have higher first-trimester estrogen
variation in prevalence of HG, but these variations among levels than in subsequent pregnancies [16]. The risk of
societies are due to other cultural, genetic and diet-related hyperemesis in the second pregnancy increased with
factors [2]. Low socio-economic living is also a major risk factor increasing time interval between pregnancies [25]. In multiple
for infection with H. pylori, that is why Infection with H. pylori pregnancies, it was found that the incidence of HG is higher in
should be kept in mind in cases of HG in pregnant women with male-male twins and male-female twins, all female twins have
lower socioeconomic status because crowded populations lower incidence which was unexpected because of higher
which are mostly characterized by poverty, have an increased maternal estrogen levels [18]. Although, it has been well
risk of transmission and higher prevalence rates of H. pylori established that patients with hyperemesis have altered sex
[17] because H. pylori is thought to spread between persons ratios and her fetus is mostly a female and maternal levels of
through the fecal-oral or oral-oral route and contaminated hormones associated with female fetus may play a role in the
water is a possible environmental reservoir [19]. It was pathogenesis of disease [18]. Also it was found that having
interested to find that women who worked outside home have singleton female fetus is associated with higher incidence of
lower risk of HG and NVP compared with housewives [13]. It hospitalization in HG [14,15,17,18].
was found that the biological relationship between partners
which are common in many societies especially in Africa and
the Middle East is not associated with an increased woman's Medical factors
risk of developing HG [20]. Hyperthyroidism: Diagnosis of thyroid disease and
Dietary factors: Researchers studied the diet of pregnant interpretation of thyroid function tests in women is complex in
women during the 12 months preconceptionally and they pregnancy as there are different ranges which vary from one
found that women with certain dietary habits are at risk of HG trimester to another because of structural and functional
in different populations e.g., Asian, Indian people [21]. Asian similarity between TSH and hCG [12]. Although autoimmune
women have an increased risk of HG due to being lactose thyroid disease has previously been considered the most
intolerant and have diets low or deficient in dairy products common cause of thyrotoxicosis in pregnancy [26], recent
[14,15]. Indian population who are more commonly to be studies indicate that increased production of hCG is the most
vegan, are more likely to have HG [14,15]. This data could be common cause of abnormal thyroid function tests at the first
used for the development of new strategies in the trimester of pregnancy [27]. And it was found that pregnant
management plan of HG [22]. women with past medical history hyperthyroidism are more
liable to HG at their pregnancy [18].
It is also found that pregnant with high fat intake is more
liable to HG [23] restrictive pre-conceptional diet like vegan

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In fact, decreased thyroid stimulating hormone has been especially in primigravida. Patients complain that their health
found in HG patients with normal levels of free T3 and free T4 care providers can not realize how ill they are. They may be
[1]. So it is thought that there may be a condition known as depressed just as any patient experiencing disabling disease
transient hyperthyroidism of hyperemesis gravidarum (THHG) can so our role as a physician is to normalize the patient's
[12], which is a self-limiting hyperthyroidism co-exist with HG. sense of anxiety because of the disease and counsel about any
Diagnosis of THHG is based on the following criteria: negative thoughts about her condition or her fetus [31].
Abnormal thyroid function tests coexist with hyperemesis GIT disorders: There is a correlation between hormonal
gravidarum. level changes in pregnancy especially high progesterone level
and relaxation of the upper esophageal sphincter and other
No past history of hyperthyroidism
GIT sphincters; this may have a role in pathogenesis dyspepsia
Absence of physical examination findings that indicate of pregnancy [12]. Pregnant women with past medical history
hyperthyroidism of peptic ulcer and GERD are more susceptible to
hospitalization due to HG [18]. Recently, Helicobacter pylori
Negative thyroid antibodies panel [24].
infection has been implicated as a possible cause of HG. In a
It has been suggested that the high incidence of transient prospective study, Helicobacter serum IgG concentrations in
hyperthyroidism in HG patients is caused by high levels of patients with HG were compared with those in asymptomatic
circulating hCG and hypersensitivity of thyroid hormone pregnant women of the same gestational week. Positive IgG
receptors for hCG or the presence of a certain type of hCG that concentrations were found in 95/105 hyperemesis patients
is more effective in stimulating the thyroid gland. During peak compared with 60/129 control patients. The authors conclude
hCG levels in normal pregnancy, serum TSH levels decrease that there is an association between infection with H. pylori
and free T3 and T4 levels are significantly elevated at this time and HG [1]. This was also confirmed by El Younis et al. [32]
induced by hCG which mimics TSH in stimulating the thyroid who treated two pregnant with HG by erythromycin; all the
gland. That’s why hCG has a role in causing hyperthyroidism symptoms resolved via this treatment.
and this is supported by thyroid hyper-stimulation in cases of
A question that needs to be answered is whether an
molar and multiple pregnancies, diseases that are associated
increased incidence of nausea and vomiting may lead to the
with higher hCG levels [24].
elevated levels of H. pylori found in these pregnant patients
Indeed, classes of hypersensitive TSH receptors have been due to loss of acid and creation of basic environment favors H.
observed in certain cases with gestational hyperthyroidism pylori’s growth [1]. Another possible explanation is that a
and HG. Those patients who suffered from recurrent HG displacement of intracellular and extracellular volume occurs
during pregnancies with hCG levels within the normal range in early pregnancy as a result of the increase in steroid
were found to have a mutation in the extracellular domain of hormones, and these results in a change of pH which could
the TSH receptor that made it over responsive to normal favor H. pylori infection [17]. Although an association between
serum hCG levels [28]. hyperemesis gravidarum and H pylori infection is suggested,
the considerable heterogeneity among studies cause
As women with hyperthyroidism uncommonly complain of
limitations of these studies [19]. Moreover, we need specific
vomiting, it may be unlikely that thyrotoxicosis or abnormal
guidelines for diagnosis and treatment of H pylori during
thyroid functions are the main cause of hyperemesis
pregnancy have not been established yet [19].
gravidarum [12]. Evidence supports a relationship between
hCG levels and THHG, but the exact role in HG is still in need to Respiratory disorder and allergies: Pregnant women with
be studied. Whether hCG level can participate in the triggering past medical history of asthma and other respiratory disorders
of vomiting or vomiting is a parallel coexistence of were found to be more liable to hospitalization due to HG [18].
hypersecretion of hCG. In addition, hyperthyroidism is more Besides, Past history of allergy has been associated with
prevalent but not only occurs in those patients, and many prolonged duration of the disease [14,15]. Autoimmune
other HG patients do not suffer from hyperthyroidism [24]. theory for HG and its response to steroid in certain refractory
cases may support this association [14,15].
Mental health problems: Pregnant women with past
medical history of depression, anxiety or any mood disorder Genetic factors: One of the theories that try to explain the
are more liable to HG at their pregnancy [18]. Moreover, stress etiology of hyperemesis gravidarum is the presence of a
and marital conflicts have been associated with increased risk genetic role. A 2008 study by Fejzo et al. in California, USA
of HG [1]. A significantly high incidence of depression and included 1,224 patients with hyperemesis gravidarum and
anxiety occur in women with HG especially with prolonged showed the significance of positive family history in the
duration of the disease which makes it difficult to explain the development of the disease. In this study, 28% of patients
causal relation between HG and mental health problems [29]. were found to have a family history of hyperemesis gravidarum
in their mothers, 19% reported a sibling with hyperemesis
Providers should immediately manage women with HG by
gravidarum and 9% of the patients reported at least 2
including the psychological care and support [30]. Moreover,
biological relatives with this disease. Interestingly among the
managing women with HG requires the health care providers
most refractory cases, those requiring total parenteral
to understand that patients' quality of life is severely disturbed
nutrition (TPN) or nasogastric feeding, the percentage of
while they are supposed to be happy for having a new baby,
patients with affected sisters was 25% [7].
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