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ORIGINAL ARTICLE
Year : 2016  |  Volume : 29  |  Issue : 3  |  Page : 705-709

Relationship between Helicobacter pylori infection and pre-eclampsia complicated by intrauterine growth restriction


1 Obstetrics and Gynecology Department, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
2 Obstetrics and Gynecology Department, Alagouza Police Authority Hospital, Cairo, Egypt

Date of Web Publication23-Jan-2017

Correspondence Address:
Mostafa M Hussain
Obstetrics and Gynecology Department, Alagouza Police Authority Hospital, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.198786

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  Abstract 

Objectives
The objective of this study was to evaluate the association of Helicobacter pylori stool antigen (HPSA) with pre-eclampsia (PE) complicated by intrauterine growth restriction (IUGR).
Background
PE is a severe hypertensive pregnancy-related disorder that affects 5-8% of women worldwide, thus representing the main cause of fetomaternal mortality and morbidity; it is often associated with fetal growth restriction (IUGR), which is defined as failure of the fetus to achieve its genetically determined growth potential.
Materials and methods
This is a prospective study for 100 pregnant women divided into two groups: 50 pregnant women with a diagnosis of PE with IUGR and 50 women with uneventful pregnancies (control); maternal stool samples were collected from all patients between 34 and 38 weeks of gestation, and HPSA was measured using monoclonal antibody test, which is an immunochromatographic assay that uses antibody-coated colloidal gold.
Results
A significantly higher percentage of women who were positive for HPSA were found among PE cases complicated by IUGR (76%) compared with uneventful pregnancies (32%) (P < 0.001).
Conclusion
HPSA has a direct role in the etiopathogenesis of PE complicated by IUGR.

Keywords: Helicobacter pylori stool antigen, intrauterine growth restriction, pre-eclampsia


How to cite this article:
Shabana AA, Sanad ZF, Alkelany OA, El Khouly NI, Hussain MM. Relationship between Helicobacter pylori infection and pre-eclampsia complicated by intrauterine growth restriction. Menoufia Med J 2016;29:705-9

How to cite this URL:
Shabana AA, Sanad ZF, Alkelany OA, El Khouly NI, Hussain MM. Relationship between Helicobacter pylori infection and pre-eclampsia complicated by intrauterine growth restriction. Menoufia Med J [serial online] 2016 [cited 2020 Apr 2];29:705-9. Available from: http://www.mmj.eg.net/text.asp?2016/29/3/705/198786


  Introduction Top


Pre-eclampsia (PE), a nonconvulsive form of pregnancy-induced hypertension, accounts for a significant proportion of maternal and fetal morbidity and mortality [1] .

PE is characterized by excessive maternal inflammatory response, with high circulating levels of proinflammatory cytokines and endothelial injury [2],[3] . Despite being an object of intense investigation, the etiopathogenetic mechanisms of PE are still poorly understood. Several lines of evidence suggest that subclinical infections could play a role in the onset of PE [4],[5] .

Helicobacter pylori is a Gram-negative spiral-shaped bacterium. Usually acquired in infancy, this bacterium induces chronic gastric inflammation persisting for the life of its host [6] .

It has been demonstrated that this pathogen enhances platelet activation and thrombus formation [7],[8] , thus inducing endothelial inflammation. Therefore, H. pylori could directly cause or intensify the generalized inflammation and endothelial dysfunction typical of PE [9] . Furthermore, it was recently observed that H. pylori seropositive PE subjects are characterized by a more severe inflammatory status [10] .

Intrauterine growth restriction (IUGR) is an important clinical problem, being the most important cause of perinatal morbidity and mortality second only to prematurity. IUGR affects ∼7-15% of pregnancies. The prevalence is estimated to be ∼8% in the general population. It has been reported that 52% of unexplained stillbirths are associated with IUGR, which is also the cause of 10% perinatal mortality. Furthermore, up to 72% of unexplained fetal deaths are associated with small for gestational age below the 10 th percentile [11] .


  Materials and methods Top


This study is a prospective observational study that was conducted at Obstetrics and Gynecology Department, Alagouza Police Authority Hospital on a total of 100 pregnant women who were recruited from the inward section from February 2011 to December 2014; the study was approved by our hospital ethics committee and a written consent was obtained from each female patient.

Maternal stool samples were collected before delivery from 50 pregnant women with a diagnosis of PE with IUGR, and from 50 women with uneventful pregnancies. The diagnosis of PE was based on the definition of American College of Obstetricians and Gynecologists [12] :

  • Systolic blood pressure greater than 140 mmHg or a rise of at least 30 mmHg
  • Diastolic blood pressure greater than 90 mmHg or a rise of at least 15 mmHg (manifested on two occasions at least 6 h apart)
  • Proteinuria of 300 mg or greater in 24-h urine collection in the absence of a urinary infection or protein concentration of 1 g/l (on two occasions of at least 6 h apart).


Severe features of PE according to American College of Obstetricians and Gynecologists (any of these findings) are as follows [13] :

  • Hypertension: systolic greater than 160 or diastolic greater than 110 on two occasions at least 4 h apart while the patient is on bed rest (unless antihypertensive therapy is initiated before this time)
  • Thrombocytopenia (platelet count <100 000)
  • Impaired liver function (elevated blood levels of liver transaminases to twice the normal concentration), severe persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnoses, or both
  • New development of renal insufficiency (elevated serum creatinine greater than 1.1 mg/dl, or doubling of serum creatinine in the absence of other renal disease)
  • Pulmonary edema
  • New-onset cerebral or visual disturbances.


The fetus is considered to have IUGR when the ultrasound fetal measurements, particularly the abdominal circumference or serial weight measurements, are below what is considered normal for that age and gestation [14] . This is below the 10 th centile when compared with the normal growth and gestational age by ultrasound measurements [15] .

The exclusion criteria were as follows:

  • Women with multiple pregnancies
  • Fetal congenital malformations that could be detected by ultrasound
  • Morbid obesity (BMI>40)
  • Subjects suffering from autoimmune diseases
  • Endocrine disorder
  • Ischemic heart diseases
  • Chronic liver and chronic renal disease.


For all cases and controls, we collected the following data: maternal age at delivery, BMI (kg/m 2 ), gestational age at birth, birth weight, parity, blood pressure, urinary protein.

Stool samples from each patient were collected into clean cups and stored at −30°C until analysis. All samples were tested for H. pylori stool antigen (HPSA) by using the monoclonal antibody test, which is an immunochromatographic assay that uses antibody-coated colloidal gold to detect the presence of H. pylori antigen in stool specimens by commercially available precheck rapid test assay kits; these kits were purchased from Prechek Bio Inc.,  which is one of the major manufacturers of immunochromatographic in-vitro diagnostic products with manufacturing base located in China and marketing office located in USA.

Data  collected were tabulated and analyzed by SPSS (Statistical Package for the Social Science software) statistical package version 16 on an IBM-compatible computer (SPSS version 16; SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean and SD (X+SD) and analyzed by applying Student's t-test for comparison of two groups of normally distributed variables. Qualitative data were expressed as number and percentage [n (%)] and analyzed by applying χ2 -test. All these tests were used as tests of significance at P value less than 0.05 [16] .


  Results Top


The baseline characteristics of the participants are shown in [Table 1]. There was no significant difference between the healthy pregnant (control) and PE with IUGR group regarding their age, with a median of 27.06 ± 1.41 and 27.74 ± 2.54 years, respectively (P = 0.101), and BMI, which was 28.70 ± 1.09 and 28.41 ± 1.17 kg/m 2 respectively (P = 0.198).
Table 1 Demographic data of the studied groups as regards certain chosen parameters


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In the PE/IUGR group, there were significantly more HPSA-positive subjects (76%) than in normal pregnant women (32%) (P < 0.001), as seen in [Table 2] and [Figure 1].
Table 2 The  Helicobacter pylori Scientific Name Search ntigen test results in the studied groups


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Figure 1: Number and percent distribution of the studied groups regarding the Helicobacter pylori stool antigen (HPSA) test results.

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At delivery, there was a significantly shorter median duration of pregnancy (35.60 ± 1.12, 38.02 ± 0.97 weeks, P < 0.001) and lower neonatal weight (1923.40 ± 157.17, 3500.40 ± 129.07 g, P < 0.001) in the PE/IUGR group compared with the normal healthy group; this is because of the IUGR that complicates PE and also termination of the pregnancy remote from term because of severe PE.

Blood pressure was significantly higher in cases than in controls, with a systolic blood pressure of 165.80 ± 5.74 and 105.20 ± 5.79, respectively (P < 0.001), and diastolic blood pressure of 115.40 ± 7.61 and 74.40 ± 6.74, respectively (P < 0.001).


  Discussion Top


PE is a multisystem disorder that complicates 3-8% of pregnancies in Western countries and constitutes a major source of morbidity and mortality worldwide [17],[18] .

H. pylori is a Gram negative bacterium responsible for the large majority of peptic ulcers, gastric cancer, and gastric-mucosa-associated lymphoid tissue lymphoma; it has been shown that this pathogen enhances platelet activation and thrombus formation, thus inducing endothelial inflammation and injury. Therefore, H. pylori could directly cause or intensify the generalized inflammation and endothelial dysfunction typical of PE [19] .

HSPA  positivity was significantly higher among women with PE complicated with IUGR; of the 50 women with PE complicated with IUGR, 38 (76%) were HPSA-positive and 16 (32%) of the 50 women with normal uneventful pregnancy were HPSA-positive (P < 0.001).

The results in this study are relatively consistent with the study by Ponzetto et al. [9] , in which a total of 94 patients were tested in Italy (47 women with PE and 47 with normal pregnancies) for serum antibodies against H. pylori by enzyme immunoassays and CagA protein by immunoblot assays and found that H. pylori seropositivity frequency was higher in mothers with PE (51.1%) compared with women with normal pregnancy (31.9%) [odds ratio (OR) = 2.668; 95% confidence interval (CI) = 1.084-6.566; P = 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). They found that the association was stronger in cases of CagA-positive strains; the latter are more virulent, and therefore they are more likely to elicit the generalized inflammation and subsequent vascular damage typical of PE [18] .

The study results were also consistent with that of Cardaropoli et al. [19] , which was conducted on 111 pregnant women after dividing them into two groups: one group was the control and comprised 49 uneventful pregnancies and the other group comprised 62 women having pathological pregnancies complicated by fetal growth restriction (IUGR-only, n = 13), PE (PE-only, n = 17), or both (PE-IUGR, n = 32); it was found that H. pylori seropositivity was significantly more frequent in PE women with or without FGR (85.7%) (P < 0.001; OR = 9.22, 95% CI = 2.83-30.04), whereas it did not differ between IUGR-only (46.2%) and controls (42.9%). Further subdivision of the PE group showed a higher prevalence of seropositive subjects among PE-IUGR cases (93.8%) (P < 0.001; OR = 35.56, 95% CI = 5.22-242.43) compared with controls, whereas in the PE-only group the percentage of H. pylori-seropositive women was higher, but not statistically significant (70.6%), relative to controls.

This study focussed on the relationship of H. pylori infection with PE/IUGR by detecting the presence of the HPSA in the feces of human subjects; this was one of the strength points in this study, as it was different from previous studies that used the seropositivity for the antibodies of H. pylori.

Although specific combinations of different antibiotics are effective in eradicating H. pylori, antibiotic-resistant strains are already emerging, thus decreasing the efficacy of existing therapies. Pharmacogenomics-based treatments seem to increase the cure rates, and new therapeutic approaches targeting H. pylori virulence factors are required [20] .

In the case of pregnancy-related diseases, it would be preferable to prevent the exacerbated inflammation typical of PE, thus avoiding pharmacologic therapies during pregnancy. Recently, several clinical trials and animal studies have focused on generating H. pylori recombinant vaccines [21],[22] .


  Conclusion Top


The  HPSA test can detect an active gastrointestinal colonization and is more appropriate for the diagnosis and also for the follow-up of patients with H. pylori; the results demonstrated a direct role for HPSA called catalase, which is a specific antigen in the feces of humans infected with H. pylori in the etiopathogenesis of PE with IUGR, as previously seen in this study. More and further trials and studies are needed in this  area. Bigger scales and larger groups would be beneficial for such studies. Further studies are required to identify specific H. pylori-related therapeutic targets.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]


This article has been cited by
1 Helicobacter pylori infection increases the risk of developing preeclampsia: A meta-analysis of observational studies
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International Journal of Clinical Practice. 2018; : e13064
[Pubmed] | [DOI]



 

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