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Pre-eclampsia is associated with Helicobacter pylori
seropositivity in Italy
Antonio Ponzetto
a
, Simona Cardaropoli
b
, Ettore Piccoli
b
, Alessandro Rolfo
b
,
Luisa Gennero
a
, Darja Kanduc
c
and Tullia Todros
b
Objectives Pre-eclampsia (PE) is characterized by an
excess of inflammation and endothelial dysfunction.
Helicobacter pylori (H. pylori) causes chronic inflammatory
changes and endothelial damage. We investigated the
prevalence of seropositivity for IgG against H. pylori and
cytotoxin-associated antigen A (CagA) in PE patients and
the presence of H. pylori DNA in their placentas.
Methods We tested 47 pregnant women with PE and 47
with uneventful pregnancies for serum antibodies against
H. pylori (enzyme immunoassays) and CagA protein
(immunoblot assays). In 20 of them (10 normal and 10 PE)
we assessed the presence, in the placenta, of H. pylori DNA
by means of nested polymerase chain reaction (PCR). The
odds ratios (OR) and 95% confidence intervals (CI),
adjusted for parity, were calculated using logistic regression
analysis to assess the risk of PE associated with H. pylori
infection.
Results Helicobacter pylori seropositivity frequency was
higher in mothers with PE (51.1%) compared to women with
uneventful pregnancy (31.9%) (OR, 2.668; 95% CI, 1.084–
6.566; P U 0.033). The difference was even greater for CagA
seropositivity (80.9 and 14.9%, respectively) (OR, 26.035;
95% CI, 8.193–82.729; P < 0.001). All placentas were
negative for H. pylori DNA.
Conclusions Helicobacter pylori, and especially strains
carrying the CagA gene, may contribute to the inflammatory
mechanisms involved in the pathogenesis of PE. J Hypertens
24:2445–2449 Q 2006 Lippincott Williams & Wilkins.
Journal of Hypertension 2006, 24:2445–2449
Keywords: CagA protein, Helicobacter pylori, pre-eclampsia
a
Department of Internal Medicine,
b
Department of Obstetrics and Gynecology,
University of Turin and
c
Department of Biochemistry and Molecular Biology,
University of Bari, Italy
Correspondence and requests for reprints to Simona Cardaropoli, Department of
Obstetrics and Gynecology, University of Turin, via Ventimiglia 3, 10126 Torino,
Italy
Tel: +39 011 3134436; fax: +39 011 3134450;
e-mail: simona.cardaropoli@unito.it
Sponsorship: A.P. was supported by grants from the Ministry of University,
University of Turin, Regione Piemonte and the Stola Auto group. S.C. was
supported by grants from Compagnia di San Paolo, Turin, Italy.
Received 2 March 2006 Revised 22 June 2006
Accepted 28 July 2006
See editorial commentary on page 2353
Introduction
Pre-eclampsia (PE) is a hypertensive and coagulative
disorder affecting 2–7% of all pregnancies and remains
one of the major causes of maternal and fetal mortality
and morbidity. Maternal mortality attributable to PE has
been reduced in developed countries; however, perinatal
mortality, perinatal and long-term morbidity, and neuro-
logical sequelae resulting from fetal growth restriction
and/or preterm delivery are still unresolved [1]. More-
over, it has been shown that PE mothers are at increased
risk for ischaemic heart disease and death from cardio-
vascular causes later in life [2,3].
The disappointing therapeutic results for child well-
being reflect the fact that the aetiology and pathogenesis
of PE are largely unknown. The most likely hypothesis is
that a generalized endothelial dysfunction is the first step
in the development of PE [4]. It has been proposed that
in PE, the normal inflammatory response of pregnancy,
involving intravascular leucocytes and the clotting sys-
tem, is exaggerated [5].
There is mounting evidence that certain infectious
agents can induce endothelial inflammation and injury;
the bacterium Helicobacter pylori (H. pylori) is one of these
agents [6]. Helicobacter pylori is the aetiological cause of
the large majority of peptic ulcer diseases, gastric cancer,
and gastric MALT lymphoma [7]. Moreover, it has been
demonstrated that this pathogen enhances platelet acti-
vation and therefore thrombus formation [6,8]. The par-
tial or complete vascular obstruction in H. pylori-infected
individuals may lead to acute myocardial infarction [9] or
ischaemic stroke [10]. It has been demonstrated that
some H. pylori strains express genes (VacA, CagA, IceA,
etc.) conferring specific biological properties – proinflam-
matory, cytotoxic, vacuolating – which could enhance the
in vivo pathogenicity of H. pylori. The strains carrying the
cytotoxin-associated antigen A (CagA) gene are among
the most virulent and associated with increased inflam-
mation [11].
Original article 2445
Part of this work was presented in abstract form at the First SGI International
Summit ‘Preterm Birth’ (10–12 November 2005, Siena, Italy).
0263-6352 ß 2006 Lippincott Williams & Wilkins