Helicobacter Pylori and the Severity of Preeclampsia

DISCUSSION

Preeclampsia affects 8% of all pregnancies. Eclampsia is a serious complication that can happen before, during, or after delivery and is linked to an increased risk of maternal mortality ¹⁰.

Preeclampsia is a multisystem condition with a complicated pathophysiology that is still being studied. Placental ischaemia and oxidative stress are hypothesized to be caused by insufficient trophoblast invasion as well as poor spiral artery remodeling. This mechanism stimulates the release of a variety of mediators into the maternal circulation, resulting in improved vasoreactivity and endothelial damage in general. The fact that preeclampsia is linked to increased maternal circulation cytokines, particularly TNF-α, IL-6a, IL-10, and IFN-γ, lends support to the function of systematic inflammation. Numerous infectious factors, including periodontal disease, urogenital infections, as well as parasitic infections, have been linked to the syndrome's pathogenesis ⁷.

Helicobacter pylori represents an infection agent connected to a variety of pregnancy complications, which include iron-deficient anemia and hyperemesis gravidarum. It's predicted that it's found in 46% of pregnancies. CagA (cytotoxin-associated gene A) is a 120-145 kDa protein which has previously been connected to gastric cancer development. ⁵.

According toFranceschi et al.¹¹, anti-CagA antibodies cross-react with placental β-actin, in vitro, lowering the cytotrophoblast's invasiveness.

In spite of this latter result, various observational studies have looked into the link between H. pylori seropositivity and preeclampsia. Nevertheless, there is no experimental research in this field yet. As a result, it's unclear if H. pylori-infected women are more likely to have preeclampsia. Therefore, the present research has been undertaken to detect the severity of pre-eclampsia by serological examination of helicobacter pylori.

This case-control study included 100 pregnant women from the Obstetrics and Gynecology Departments of Al-Azhar Hospital and Mansoura International Hospital, who were separated into two groups:

Group A (control group): 50 healthy normal pregnant women.

Group B (case group): 50 cases diagnosed with pre-eclampsia.

All participants underwent the taking of history, a complete general examination, an obstetric examination and laboratory investigations (including complete urine analysis, blood hemoglobin, platelet count, serum creatinine, and liver enzymes). Obstetric ultrasound was done to confirm the gestational age and exclude the presence of low-lying placenta or fetal anomalies. The identification of anti-H. pylori IgG allowed for a serological diagnosis of H. pylori infection.

Our study found no statistically significant differences in mean age between the groups tested. But there was a statistically significant increase in both SBP and DBP among preeclampsia group compared to no preeclampsia group. In agreement with Di Simone et al. ⁽⁶⁾ also analyzed the relationship between Hp infection and anti-CagA antibody positivity and the severity of PE clinical presentation. They found no significant difference in terms of age.

Regarding degree of proteinuria, 30% of the studied cases had 1, 36% had 2 and 34% had 3. Also, researches as Di Simone et al.  ⁶ also observed high levels of proteinuria in PE (P<.001).

In our study, the preeclampsia group had a statistically significant increase in creatinine when compared to the non-preeclampsia group. No differences were found among the two groups in the other laboratory parameters. According to Di Simone et al.^{6 ,}preeclamptic women had a significantly lower platelet count (P<.001).

Regarding delivery data, there was a statistically significant decrease in mean GA and NVD among preeclampsia group compared to no preeclampsia group. Also, our results show the sameDi Simone et al.⁶ where he found lower GA at birth (P<.001) and lower neonatal birth weight (P<.001), as well as a greater frequency of SGA babies (P<.001) in preeclamptic women compared to controls.

Regarding helicobacter pylori titre, there has been a statistically significant rise in H. pylori in the preeclampsia group versus the no preeclampsia group. Also, Di Simone et al. ^6, observed that preeclamptic women (57.0%) had a greater seroprevalence of Hp infection than healthy pregnant women (33.3%) (P<.001). When seropositivity for CagA-positive Hp strains was examined (45.2% of women had PE versus 13.7% of controls; P<.001) the difference became even clearer.

Our study agrees with the previous study reported by Shiadeh et al.⁷   assessed the potential relationship between H. pylori infection and pre-eclampsia (PE) and found that women infected with H. pylori are more prone to develop PE than non-infected women. Furthermore, infection with Cag A positive H. pylori strains may significantly raise the chance of PE in pregnant women.

According to our findings, there had been a statistically significant increase in the frequency of IUGR, maternal ICU admission, and neonatal ICU admission among the preeclampsia group versus the non-preeclampsia group .researchers like Shabana et al.¹²   evaluated the relationship between H. pylori stool antigen (HPSA) and preeclampsia (PE) worsened by IUGR. They concluded that 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; they demonstrated a direct role for HPSA called catalase, which is a specific antigen in the feces of H. pylori-infected humans in the etiopathogenesis of PE with IUGR.

In the current study, there were statistically significant positive relationships between HP positivity and elevations in SBP/DBP as well as the degree of proteinuria among the pre-eclampsia group.

Moreover, there was a statistically significant increase in incidence of IUGR and maternal ICU admission among pre-eclampsia cases who tested positive to HP infection, compared to those who tested negative.

Our study had the same result as Di Simone et al.⁶ showed that clinical characteristics of PE patients were associated with Hp infection or anti-CagA antibody. There have been no differences in gestational age at beginning, disease severity, umbilical artery Doppler velocimetry, growth of the fetus or maternal proteinuria levels, uric acid, platelets, or antithrombin III between participants with and without Hp infection and anti-CagA antibody. The abnormalities of uterine arteries by Doppler velocimetry (P<.001) represented as higher resistance index (RI) mean value (P<.001) were observed to have a statistically significant connection with Hp infection and positivity for anti-CagA antibody. They showed a link between Hp infection and PE, as well as anomalous uterine artery Doppler velocimetry, implying that Hp infection has a role in compromising placental development and promoting the chance of developing PE.in agreement with Bellos et al.⁸ found that the existence of IUGR in preeclamptic pregnancies was significantly related to a higher incidence of H. pylori IgG antibodies, supporting the theory that H. pylori infection doubles the chance of having preeclampsia.

Anti-H. Pylori IgG serology testing is a non-invasive diagnostic approach that is unaffected by H. pylori infection-suppressing medicines like proton pump inhibitors and antibiotics. However, because false positive findings might happen following effective eradication therapy, its reliability differs greatly between studies. The HPSA assay is a very effective assay that can accurately differentiate between active and previous infections ¹³ . The findings of our study suggest a possible role of H. pylori infection in preeclampsia development.

Increased oxidative stress is linked to H. pylori infection, as it stimulates the production of reactive oxygen species and the depletion of antioxidant molecules like NO and glutathione. CagA-producing strains can also promote the release of numerous cytokines, resulting in long-lasting inflammatory responses. It's also possible that molecular mimicry across H. pylori antigens and components of the host causes a variety of extra gastric symptoms through an autoimmune mechanism ^{14 .}

In vitro investigations show that anti-cagA antibodies cross-react with placental tissue, resulting in decreased trophoblast invasion, which supports the pathophysiological connection between H. pylori infection and preeclampsia. Such a mechanism may result in inadequate placentation, which can accelerate the progression of preeclampsia ¹¹ .

CONCLUSION

According to our results, pregnant women who have H. pylori infection are at a higher risk of having preeclampsia. If HP eradication proves to be effective in minimizing the occurrence of PE, screening for HP infection might be expanded to the general population of childbearing age women.