Relation between Helicobacter Pylori Infection and Mild Pre-eclampsia

INTRODUCTION

Preeclampsia (PE) is a main contributor to motherly and embryonic morbidities and mortalities, as it affects from 2 to 8% of gestations. It is a multi-system condition and its complex pathophysiology still under study.¹ It is hypothesized that insufficient trophoblast invasions and poor spiral artery remodeling result in placental ischemia and oxidative-stress. This procedure indorses the releases of several intermediaries into the motherly circulations, causing elevated vaso-reactivity and generalized endothelial injury.²

The function of systematic inflammations is maintained by the fact that pre-eclampsia is accompanying with increased motherly circulating cytokines, particularly Tumor Necrosis Factor-a (TNF- a), Interleukin-6 (IL-6 a), Interleukin-10 (IL-10) and Interferon-y (IFN-y). There is rising indication that numerous infectious parameters are concerned in the pathogenesis of the disease, like

periodontal disorder, urogenital and parasitic infection.³

Helicobacter pylori is an infectious agent that was related to several complications throughout the gestation course, counting iron insufficiency anemia and hyper-emesis gravidarum. It is assessed to be existing in 46 percent of gestations.⁴ Cytotoxin associating gene-A (CagA) is a 120-145 kDa protein that was formerly related to the advance of gastric tumor.⁵

AntiCagA anti-bodies cross-reacts in vitro with placental p-actin, decreasing the intrusiveness of the cytotrophoblast. Exceeding 10 years ago, the same authors detected that antiCagA antibodies cross-reacts with antigens from ordinary to atherosclerotic blood vessel. The procedure includes vascular wall peptides and is supposed to cause activations of the inflammation cascades which was formerly concerned in the pathogenesis of pre-eclampsia. Although, experimental researches in this topic are still lost.⁶

In the previous 2 decades, the frequency of PE has increased in the Western Republics, perhaps because of an elevated prevalence of influencing parameters, like advanced motherly ages, chronic Hypertension (HPT), Diabetes Mellitus (DM), obese, and the growing usage of supported reproducing methods.⁷

In spite of this latter observations, numerous observational researchers have discovered H.pylori sero-positivity status with PE. But, up to the present time it still unidentified whether cases with H.pylori infections are at elevated of rising PE.¹

The aim of the current study was to illustrate the role of H.pylori infections in women with mild pre-eclampsia.

PATIENTS AND METHODS

This prospective cohort study enrolled a number of 100 women between 36^th  to full-term gestational weeks has been performed at obstetrics and gynecology dep, El-Hussein Hospital, Al-Azhar University, the interval between May 2020 to December 2020.

This study based on study carried out by Tersigni et al.⁷ Epi Info STATCALC was used to calculate the sample size by considering the following assumptions: - 95% two-sided confidence level, with a power of 80%. &a error of 5% odds ratio calculated= 1.115. The final maximum sample size taken from the Epi- Info output was 92. Thus, the sample size was increased to 100 cases to assume any drop out cases during follow up.

Written knowledgeable agreement was attained and the research was accepted by the Ethical Committee of Al-Azhar Faculty of Medicine.

Inclusion criteria: Gestational age between 36^th to full-term gestational weeks according to a reliable date for the last menstrual period and ultrasound evaluation, and mild pre-eclampsia. 

Exclusion criteria: Manifold gestations, embryonic irregularities, DM, chronic HPT, auto-immune diseases, early membrane ruptures, infections, systemic diseases as renal or hepatic disorders detected before gestation, and women in active labor.

All women were allocated into 2 groups: Group I: (Cases group): including 50 pregnant preeclamptic women with gestational age 36st weeks to full-term gestation, and Group II: (Control group): included 50 pregnant nonpreeclamptic women who are matched in age, and gestational age with the case group.

A PE diagnosing is performed if a BP of 140/90 mm-Hg was established by 2 measures done at 6 hours periods and in the existence of extra quantity of protein (100-300 mg/L) in a one day urine sample.

All patients were subjected to:

Complete history taking: Personal history. menstrual history, history Parity, present history: of chronic diseases and medication, past history of HTN, DM, family history of similar condition or diabetes, history of allergy to any medication, and surgical history of operation.

Examination:  General examination and abdominal, local clinical examination, and vaginal examination.

Laboratory investigation: CBC: Hb (%), RBCs, WBCs, platelet count. S. ALT. AST. sCr. S.prolactine.  Coagulation profiles (pro-thrombin time [PT], activated partial thromboplastin time [aPTT], and fibrinogen. Serum lactate dehydrogenase level (LDH). Urinary albumin creatinine ratio (uACr). Urine: albumin assessment by dipstick. Plasma Thrombomodulin (TM) was assessed with ELISA. Serological tests were performed for detection of anit-H. Pylori IgG using ELISA serology kits with sensitivity and specificity of 85% and79%. Anti-H. pylori IgG remain for along time eve after treatment thus current infection was confirmed by Urea breath test (UBT), a highly accurate and reproducible test with near 95% sensitivity and specificity, was used for confirmation of current H. pylori infection by the urease activity of H. pylori. the 13C- labeled urea was ingested by the patient to be hydrolyzed into labeled CO2 in stomach, then the labeled CO2 absorbed in the blood and exhaled by breathing in which labeled CO2 was measured.

Statistical Analysis:

Data analyzed via SPSS-20 (IBM, USA). Quantitative variables have been introduced as mean and SD. Qualitative variables have been introduced as numbers and percentages. For comparison between parametric quantitative variables of 2 groups, Student t testing has been utilized.  Qualitative variables comparison has been performed via chi-square (X2) testing or Fisher’s exact testing when frequencies were less than 5. Pearson correlation coefficients have been utilized to evaluate the associations among 2 variables with normal distribution. When a variable wasn’t of normally distribution, At P< 0.05 the results had statistical significance

RESULTS

  BMI: Body mass index. SBP: systolic blood pressure. DBP: Diastolic blood pressure.

Table 1: Demographic and clinical parameters among the study groups.

There was no significant difference between the 2 groups regarding Age or parity (P=0.081, 0.455). there was significant difference between the 2 groups regarding BMI, SBP and DBP which were increased in the preceramic group (P-Value=0.032, 0.000 and 0.000) (Table 1).

Hb: Hemoglobin. TLC: Total lymphocyte count. PLT: Platelet count. ALT: Alanine transaminase AST: Aspartate aminotransferase. RBS: Random blood sugar. LDH: Lactate dehydrogenase. UACR: Urine Albumin-to-Creatinine ratio. TM: Tumor marker.

Table 2: Laboratory results between the study groups.

There was significant difference regarding ALT, AST, LDH, creatinine, proteinuria, UACR and TM which were increased in preeclamptic group (P-Value=0.000, 0.000, 0.007, 0.001, 0.000, 0.000 and 0.000 respectively). There was there was significant difference regarding Hb which was decreased in the preeclamptic group (P-Value=0.042) and there was non-significant difference regarding TLC, RBS and Urea between the 2 groups. (Table 2).

Table 3: Anti H.pylori antibodies between the two studied groups

There was significant difference regarding anti H. pylori Ab as 34 (68%) cases of the preeclamptic cases were positive compared to 23 (46%) cases from the normotensive group. There were 16 (32%) negative cases of the preeclamptic cases compared to to 27 (54%) cases from the normotensive group (P-Value = 0.026). (Table 3).

Table 4: Demographic data distribution according to anti H.pylori antibodies in pre-eclampsia group

A nonsignificant change was found among the study groups regarding Age, BMI and parity. The mean age in cases with positive Anti H.pylori antibodies was 27.46± 4.27 years compared to 26.3 ± 4.62 years (P-Value=0.387). the mean BMI in cases with positive Anti H.pylori antibodies was 26.84 ± 3.45 kg/m2 compared to 25.72 ± 3.14 kg/m2 (P-Value=0.277). the mean parity in cases with positive Anti H.pylori antibodies was 1.29 ± 1.05 compared to 1.11 ± 0.964 (P-Value= 0.557)  (Table 4).

GA: Gestational age.

Table 5: Neonatal outcomes between the studied groups

A significant change was found among the study groups as regard birth weight only with P-Value= 0.019. there was non-significant change in GA, Apgar score at 1 min and Apgar score at 5 min as P-Value= 0.315, 0.163 and 0.419 respectively. (Table 5).

Table 6: Correlation between H. pylori and severity of preeclampsia.

A significant difference was found among the study groups regarding preeclampsia severity. There was increase in the severity of preeclampsia in correlation to the positivity of anti H. pylori antibodies observed in 19 (86.4%) cases compared to 15 (53.6%) cases with mild preeclampsia and positive anti H. pylori antibodies. The number of cases with severe preeclampsia decreased in patients with negative antibodies. (P-Value= 0.014).