100 Original article

Is there an association between Helicobacter pylori infection

and hyperemesis gravidarum among Egyptian women?
Ahmed Aboul Nasra, Ismail Aboulfoutouha, Adel Nadaa, Mariam A. Younanb,
Mohamed Saeda and Waleed El-Khayata

Departments of aObstetrics & Gynecology and Objectives

b
Clinical & Chemical Pathology, Faculty of Medicine,
Cairo University, Cairo, Egypt
Correspondence to Mariam A. Younan, Les
Laboratoires Servier (Scientific office-Gulf),
Suite#801, API World Tower, Sheikh Zayed Road,
Raafat Hosny, P.O. Box 1586, Dubai, UAE
Tel: + 009 715 5443 1610;
e-mail: babyverena@yahoo.com
Received 2 December 2011
Accepted 2 January 2012
Evidence Based Womens Health Journal
2012, 2:100103
To detect the association between Helicobacter pylori infection and hyperemesis
gravidarum among Egyptian women.
Participants and methods
Thirty pregnant women with hyperemesis gravidarum were recruited from the Cairo
University outpatient clinics and 30 healthy pregnant volunteers with no vomiting were
selected as controls. The age range in both the groups were between 18 and 39 years
and the gestational age ranged from 5 to 12 weeks. All participants were subjected to
full history taking, clinical examination, and ultrasound to exclude obstetric causes of
hyperemesis gravidarum. Routine and special laboratory investigations were
performed to test the serum for H. pylori seropositivity IgG using an enzyme-linked
immunosorbent assay.
Results
There was a highly significant difference in the H. pylori IgG antibody titer between the
cases (18.1100 U/ml) and the controls (0.962.7 U/ml) (Po0.01). The number of
cases found to be seropositive to H. pylori IgG (100%) was higher than the number of
the control individuals (86.67%), but the difference between both the groups was not
statistically significant (P = 0.37).
Conclusion
Our results showed that there might be an association between H. pylori infection and
hyperemesis gravidarum. We recommend that further studies be carried out to confirm
this finding with a larger number of participants and for a longer duration of time.

Keywords:
Helicobacter pylori, H. pylori IgG titer, hyperemesis gravidarum

Evid Based Women Health J 2:100103

& 2012 Evidence Based Womens Health Journal
2090-7265

European data indicating that more than 90% of women

Introduction
Nausea and vomiting during pregnancy, commonly known
as morning sickness, affect approximately 7080% of all
pregnant women in the first trimester. The typical onset
is between 4 and 8 weeks of gestation, with symptoms
continuing until 1618 weeks. It is generally a mild and
self-limiting condition. A small percentage of pregnant
women have a more profound course, with the most severe
form known as hyperemesis gravidarum. Vomiting, from an
evolutionary perspective, is an adaptation and not a disease,
as it correlates primarily to the period of organogenesis,
protecting against the exposure to teratogens, and is
associated with positive pregnancy outcomes [1]. The
symptoms force women to reduce their consumption of two
very common teratogens: cigarettes and alcohol [1].
with hyperemesis gravidarum have H. pylori infection [4].
The prevalence of H. pylori infection is strongly correlated
with low socioeconomic conditions and poor sanitation [5].
The frequency of H. pylori infection is higher in blacks
than in the white population [6]. The infection is
acquired by oral ingestion of the bacterium, and water
may be a vector of H. pylori by the fecooral route [5].
H. pylori is a microaerophilic helical-shaped Gram-
negative bacterium with 46 flagella [7]. It can transform
from a helical to a coccoid form, which contributes toward
its survival and the epidemiology of the bacterium [8].
The bacterium colonizes the superficial mucus gel layer
in the stomach and produces large amounts of ammonia,
which is toxic to the epithelial cells [9].

Hyperemesis gravidarum is most commonly defined as
persistent vomiting in pregnancy not attributed to specific
causes [2] and leads to weight loss, dehydration, acidosis
from starvation, alkalosis from loss of hydrochloric acid, and
hypokalemia [3]. Although it is a disease whose exact
cause has not yet been established, it is linked to the
presence of Helicobacter pylori infection as shown by
2090-7265 & 2012 Evidence Based Womens Health Journal
Some strains of the bacteria have a particular mechanism
by which they inject the inflammatory-inducing agent
peptidoglycan from their own cell wall directly into
epithelial stomach cells. This may play a role in allowing
certain strains to invade the host [9]. Other virulence
factors include the production of a toxin (Vac A) and a
cytotoxin-associated gene protein (Cag A), which is
DOI: 10.1097/01.EBX.0000415476.10289.d1

Copyright Evidence Based Women's Health Journal. Unauthorized reproduction of this article is prohibited.
 H. pylori infection and hyperemesis gravidarum Aboul Nasr et al. 101

controlled by genes located on the Cag pathogenicity solution and finally the stopping solution. The optical
island [10]. Strains with this DNA island are more likely signal generated, which is proportional to the amount of
to induce severe symptoms. The Cag A gene is a marker anti-Hp IgG antibodies present in the samples, was read
for this island [11]. using a microtitration plate reader set to a dual wave-
length measurement at 450 nm (620 nm). IgG was quan-
The infection in adults is usually chronic and may not
tified by means of a standard wave calibrated in units per
heal without specific therapy. There is a major con-
milliliter (U/ml) and the cutoff value was 5 U/ml.
troversy regarding the role of H. pylori infection in
hyperemesis gravidarum. Several reports have found a
Statistical methodology
significant association [4,1215], whereas others have not
The quantitative values were expressed as mean SD
established such an association [1618]. Serologic detec-
and were compared using the Student t-test for the two
tion of H. pylori in patients with hyperemesis gravidarum
groups. P value less than 0.05 was considered significant.
is a noninvasive technique with high sensitivity and
SPSS 12 (Statistical Package for Social Science, SPSS
specificity to predict a H. pylori infection [19]. The aim of
Inc., Chicago, Illinois, USA) was used for analyses.
our work was to detect the association between H. pylori
infection and hyperemesis gravidarum among Egyptian
women.
Results
The age of the pregnant women who presented with
hyperemesis gravidarum ranged between 18 and 38 years
Participants and methods
(26.2 5.2), and their gestational age ranged from 5 to 12
This is a casecontrol study that recruited 60 pregnant
weeks (8.59 1.98). In the control group, the women
women, 30 of whom presented with hyperemesis gravidar-
ranged in age between 18 and 39 years (26.38 4.9), and
um defined by severe nausea and vomiting intractable to
the gestational age ranged from 6 to 12 weeks (9.14 2.3).
any treatment, with weight loss [20], and the other 30
There was no significant difference in terms of age
women were healthy volunteers with no vomiting (con-
(P = 0.45), gestational age (P = 0.11), and parity (P =
sidered as controls). They were recruited during their visit
0.37) between both the groups (Table 1).
to the outpatient clinic of the Gynecology and Obstetrics
Unit of Kasr EL Aini Hospital. They were all recruited The H. pylori IgG antibody titer was higher in the
during the first trimester of their ongoing pregnancies and hyperemesis gravidarum group (46.86 28.60) compared
were medically free from any condition that may cause with the control group (24.97 17.81) and the difference
vomiting, for example cholecystitis, appendicitis, and was found to be highly significant (Po0.01). Among the
colitis. Women with a history of gastric disorders and also primigravida women, the H. pylori IgG antibody titer was
those with a twin pregnancy were excluded. higher in the hyperemesis gravidarum group (49.54
27.19) compared with the control group (24.71 15.44),
All participants provided informed consent for participat-
and the difference was statistically significant (P =
ing in this study and were subjected to the following
0.002). Also, among the multigravida women, the
protocol: full history taking, clinical examination, trans-
H. pylori IgG antibody titer was higher in the hyperemesis
abdominal or transvaginal pelvic sonography, routine
gravidarum group (44.81 27.19) compared with the
laboratory investigations, and a special laboratory inves-
control group (28.70 17.43), and the difference was also
tigation to test the serum for H. pylori IgG seropositivity
statistically significant (P = 0.022). Although the number
using an enzyme-linked immunosorbent assay. We then
of study participants found to be seropositive for H. pylori
compared the data collected from the two groups in terms
IgG (100%) was higher than that of the control individuals
of maternal age, gestational age, parity, H. pylori IgG
(86.67%), the difference between both the groups was not
antibody seropositivity, and titer.
statistically significant (P = 0.37) (Table 2).
Methods
Seven milliliters of venous blood was collected from each
patient and control individual by aseptic venipuncture and Discussion
divided as follows: 2 ml of venous blood for the routine Hyperemesis gravidarum may have negative effects on
laboratory investigations and 5 ml for the enzyme immu- maternal and fetal health [21,22]. H. pylori infection might
noassay (EIA) for qualitative and quantitative determina-
tion of H. pylori IgG in the serum (Biosewoom, Seoul,
Korea).
Table 1 Comparison between the patients and the control
group in the demographic and clinical data
Procedure
Patients Controls
For the EIA, the manufacturers instructions were Items (n = 30) (n = 30) P value
followed. In brief, a volume of 100 ml of the diluted
Maternal age (years) 26.24 5.22 26.38 4.9 0.451 (NS)
serum samples was added to each well. The bound anti-
Gestational age (weeks) 8.59 1.98 9.14 2.3 0.110 (NS)
HP IgG (if present) was detected by the addition of Parity
100 ml of the enzyme conjugate solution, followed by the Primigravida 12 (40%) 9 (30%) 0.372 (NS)
addition of 100 ml of each of the working substrate Multigravida 18 (60%) 21 (70%) 0.451 (NS)

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 102 Evidence Based Womens Health Journal
Table 2 Helicobacter pylori results in the patients and the
control group
Items Patients (n = 30) Controls (n = 30)
Helicobacter pylori IgG antibody titer
Range (U/ml) 18.1100 0.962.7 o0.01 (S)
Mean SD 46.86 28.60 24.97 17.81
H. pylori IgG antibody titer in primigravida
Range (U/ml) 18.1100 0.948.6 0.002 (S)
Mean SD 49.54 27.19 24.71 15.44
H. pylori IgG antibody titer in multigravida
Range (U/ml) 18.8100 3.862.7 0.022 (S)
Mean SD 44.81 27.19 28.70 17.43
H. pylori IgG seropositivity
Positive 30 (100%) 26 (86.67%)
Negative 0 (0%) 4 (13.3%)
S, statistically significant.
play a role in emesis gravidarum. H. pylori seropositivity
was found to be present in up to 60% of pregnant
women [4]. Chronic H. pylori infection has been found in
cases of persistent vomiting in pregnancy not responding
to supportive treatment [23,24].
In our study, we attempted to prove that there is an
association between the severity of the disease and the
level of IgG.
Our data showed that the age difference between the
hyperemesis gravidarum group and the control group was
not statistically significant (P = 0.45). These results are
in agreement with those reported by Salimi-Khayati
et al. [18]. However, Shirin et al. [25] found that the
women who had complaints of frequent vomiting in the
first trimester and were positive for H. pylori IgG were
significantly older than those who were negative for H.
pylori IgG.
We found that the percentages of primigravida and
multiparous women were 40 and 60%, respectively, in
the hyperemesis gravidarum group and 30 and 70%,
respectively, in the control group. The difference was not
statistically significant (P = 0.37). These data are in
agreement with those reported by Wu et al. [14]. How-
ever, Broussard and Richter [26] found that there was an
increased incidence of hyperemesis gravidarum in multi-
parity, whereas Salimi-Khayati et al. [18] and the
ACOG [27] found that there was an increased incidence
of hyperemesis gravidarum in primigravida.
Our results showed that the mean value of the IgG titers
in the hyperemesis gravidarum group (46.86 U/ml) were
significantly higher than that in the controls (24.97 U/
ml), with a P value less than 0.01. These results are in
agreement with those reported by several studies. Kocak
et al. [28] found that the mean value of H. pylori IgG
antibody titers was 73.8 U/ml in the hyperemesis
gravidarum group and 25.8 U/ml (Po0.01) in the control
group . Jamal and colleagues found that the mean value of
the IgG antibody titers in the emesis group was 25 U/ml
compared with 10.5 U/ml in the control group (Po0.05).
Frigo and colleagues found that the mean value of the H.
pylori IgG antibody titers was 74.2 U/ml in the hyperem-
esis gravidarum group and 24.3 U/ml (Po0.01), in the
control group; they also suggested that this association
between H. pylori infection and hyperemesis gravidarum
Copyright Evidence Based Women's Health Journal. Unauthorized reproduction of this article is prohibited.
is because of the increased accumulation of fluids and the
displacement of both intracellular and extracellular
P value volumes in the early phase of pregnancy as a result of
the increased steroid hormone, which in turn results in a
change in the pH in the gastrointestinal tract. This
alteration in acidity could lead to the activation of latent
H. pylori infection [12,20]. Other explanations for this
association are the impaired defensive mechanisms
against H. pylori as pregnancy is associated with changes
in both humoral and cell-mediated immunity [29]. The
tendency of H. pylori to cause nausea and vomiting is
0.372 (NS) aggravated by abnormal gastric emptying, reduced
0.321 (NS) gastrointestinal motility, and hypersensitivity to gastric
or duodenal distention in pregnancy [25]. This was also
reported by Murakami et al. [30], who demonstrated that
eradication of H. pylori accelerated gastric emptying and
postprandial gastric sensation. In contrast, Parente
et al. [31] and Rhee et al. [32] did not find these effects.
We subdivided our study group into primigravid and
multigravid groups to assess the effect of parity on the
prevalence of H. pylori infection. We found that the mean
value of the IgG antibody titers of the hyperemesis
gravidarum group (49.54 U/ml) was higher than that of
the controls (24.71 U/ml) in the primipara group, with a
highly significant statistical difference (P = 0.002). A
similar result was obtained in the multipara group; the
mean value of the IgG antibody titers of the hyperemesis
gravidarum group was 44.8, whereas that of the control
group was 28.7, with a significant statistical difference
(P = 0.022).
Our study results showed 100% seropositivity in the
hyperemesis gravidarum group compared with 86.67% in
the control group, but the difference was not statistically
significant (P = 0.37). The high frequency of seropositivity
among the participants of our study could be because of the
fact that they were all from a low socioeconomic class,
which is a major risk factor for H. pylori infection. Also, the
antibody titer against H. pylori may be elevated for several
months after successful eradication and this may increase
the false-positive rates [25]. In addition, it is well known
that H. pylori infection is one of the most common
infections, which may reach up to 90% in the developing
countries, and the majority of the infected patients remain
asymptomatic [33]. These results are in accordance with
the results of previous studies reporting an H. pylori sero-
positive rate of more than 85% in patients with emesis
gravidarum [12,16,18,28,34]. However, Nakajima et al. [35],
Erdem et al. [16], and Salimi-Khayati et al. [18] found no
correlation between the severity of symptoms and H. pylori
seropositivity in the emesis gravidarum group, which may
either indicate the existence of other underlying mechan-
isms, apart from the presence of H. pylori infection, for the
exacerbation of hyperemesis gravidarum, or the complex
nature of the H. pylori infection-related symptoms.
Our results are in agreement with a recent meta-analysis
carried out by Sandven et al. [36], in which it was reported
that infection with H. pylori is associated with an
increased risk of hyperemesis gravidarum. Also, Mansour
and Nashaat determined the role of H. pylori infection in
 H. pylori infection and hyperemesis gravidarum Aboul Nasr et al. 103
the pathogenesis of hyperemesis gravidarum among 80
patients of a hyperemesis gravidarum group A and another
80 normal pregnant women as a control group B. They
found that 71 patients in group A and 24 patients in group
B were positive for H. pylori [37]. Mansour and Nashaat
[37] concluded that screening for H. pylori should be
performed in cases of hyperemesis gravidarum.
Our study has two main limitations, one of which is the
small sample size, and the other is that we did not
measure the level of the H. pylori IgM antibody, which is a
more specific marker for recently acquired infection.
Finally, our results suggest that there might be an
association between H. pylori infection and hyperemesis
gravidarum. We recommend that further studies be
carried out to confirm this finding with a larger number
of participants and for a longer duration of time.
Acknowledgements
The authors would like to thank the staff of each of the Obstetrics &
Gynecology and the Clinical & Chemical Pathology Departments who
shared in this research work.
Conflicts of interest
There are no conflicts of interest.
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