Insights into the Role of Helicobacter pylori Infection in Preeclampsia: From the Bench to the Bedside

Abstract

Preeclampsia (PE) is defined as a hypertensive and coagulative disorder affecting about 2–8% of all pregnancies and is one of the main causes of maternal and fetal morbidity and mortality. Despite the great amount of studies run in this field, little is known about the precise pathogenic mechanisms behind PE. While endothelial and trophoblast dysfunctions, exaggerated inflammatory response, and hypercoagulative state have been shown to play a key role in the occurrence of PE, the primary trigger is still unknown. One of the hypotheses is that some infectious agents may represent a trigger for PE onset. Consistently, higher seroprevalence of Helicobacter pylori (HP) infection, a Gram-negative bacterium with a specific tropism for human gastric mucosa, has been shown in women with PE. Even tighter association has been found between PE and infection with cytotoxin-associated gene-A (CagA)-positive strains of HP. Recent in vitro studies have shown that anti-CagA antibodies cross-react with human trophoblast cells and determine a functional impairment in terms of cell invasiveness, thus, providing the first pathogenic model of HP infection-mediated placental damage. Since in the early process of implantation and placental development, trophoblast invasion of maternal decidua is a crucial step, the proposed autoimmune mechanism induced by HP infection, negatively interfering with the fetal side of the early developing placenta, may represent a mechanism explaining the higher seropositivity for HP infection among PE women. However, the contribution of HP infection to the pathogenesis of PE or to the worsening of its clinical presentation need to be further investigated as well as the possible impact of pre-pregnancy screening and eradication of HP infection on the incidence of the syndrome.

Helicobacter pylori and Perinatal Pathologies: Pathogen Transmission During Childbirth?

“…Recent in vitro-studies have proved that anti-CagA antibodies show a cross reaction with human trophoblastic cells and they determine a functional impairment in terms of cells invasiveness; therefore, the first model of placental damage mediated by a pathogen infection is introduced. However, H. pylori infection contribution to PE pathogenesis or to the aggravation of its clinical presentation needs further study as well as the potential impact that H. pylori infection might have on the pre-conception stage and the effect of infection eradication in the syndrome incidence [13]. Therefore, these observations provide a possible explanation for the autoimmune pathogenic mechanism induced by H. pylori infection which negatively interferes with the development of placentation.…”

“…In spite of the large amount of studies on the subject, little is known about its pathogenic mechanisms; one of the possible hypotheses is that some infectious agents might be a trigger for PE start [13].…”

“…PE is defined as the hypertension specifically induced by pregnancy; it is a hypertensive and clotting type of disorder that affects approximately 2-8% of all pregnancies and it is one of the major causes of maternal and fetal morbidity and mortality [13]. It is characterized by an excessive maternal inflammatory response with high circulating levels of pro-inflammatory cytokines and endothelial injury.…”

“…Hyperemesis gravidarum [8][9][10][11][12] Preeclampsia [13][14][15]23] Iron-deficiency Anemia [16][17][18][19] Intrauterine growth Restriction [20][21][22]27] Spontaneous abortion [24][25][26] and inflammatory damage over the gastric epithelium resulting in gastrointestinal disturbance such as hyperemesis gravidarum. H. pylori sequesters essential micronutrients from the host organism such as Iron (Fe) and it causes iron deficiency anemia.…”

Proteinuria as the Most Relevant Parameter Affecting Fetuin-A Levels in Preeclampsia

“…Preeclampsia (PE) is generally defined as new hypertension and substantial proteinuria at or after the second half of gestation (1). It is a dangerous complication of pregnancy that affects 5-10% of pregnant women and leads to increased mortality of fetus and mothers (2).…”