Pre-eclampsia associated with Helicobacter pylori seropositivity

Pre-eclampsia, defined as newly diagnosed hypertension with quantified proteinuria at or after 20 weeks of pregnancy and its resolution after delivery, remains the most important cause of maternal and perinatal mortality in developed countries [1]. Although the precise aetiology of this clinical condition remains an enigma, multiple risk factors have been identified. Recently, Milne et al. [2] proposed evidence-based risk factors for clinical assessment to allow early referral and planned follow-up. In a systematic review by Duckitt and Harrington [3], a history of pre-eclampsia and the presence of antiphospholipid antibodies were strong risk factors for developing pre-eclampsia but other risk factors were also relevant, including pre-existing diabetes mellitus, pre-pregnancy obesity, nulliparity, family history of pre-eclampsia, twin pregnancy, maternal age ≥ 40 years and systolic blood pressure ≥ 130 mmHg. In this issue of the journal, Ponzetto et al. [4] explored the possibility of a relationship between Helicobacter pylori infection and the risk of developing pre-eclampsia. The background of their study is based on the fact that this microbial agent is not only an aetiological cause of some upper gastrointestinal disorders, such as peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma, but may also be responsible for enhanced platelet activation and thrombus formation, leading to established cardiovascular disease via an inflammatory mechanism. In this cross-sectional study, serology for H. pylori was tested in a group of 47 women who fulfilled the criteria for the diagnosis of pre-eclampsia and a group of women who had uneventful pregnancy. The authors showed that 51% of women with pre-eclampsia were seropositive for H. pylori compared to 31.9% of women with uneventful pregnancy [odds ratio (OR) = 2.668; P = 0.003]. However, a more sensitive marker for H. pylori exposure, CagA, determined by immunoblot test, demonstrated 80.9% of pre-eclamptic women to be seropositive compared to 14.9% of women with uncomplicated pregnancy (OR = 26.035; P < 0.001). This small study therefore provides initial evidence of a potential relationship between H. pylori infection and pre-eclampsia in a cohort of Italian pregnant women. What are we to make of the present findings? First, the study by Ponzetto et al. [4] will stimulate further studies on the relationship between sub-clinical infections and pre-eclampsia, potentially adding extra insight on the aetiology and pathogenesis of this clinical condition. Trongstad et al. [5] have already questioned whether pre-eclampsia is partly an infective disorder. Other studies also support this theory, suggesting a high incidence of infection of the urinary tract and asymptomatic bacteriuria in pregnant women with pre-eclampsia compared to normal pregnant women [6–8]. However, cross-sectional studies cannot exclude the possibility that higher infection rates, rather than being a cause, might merely be a consequence of developing pre-eclampsia (i.e. reverse causality). Prospective studies linking infection rates in early pregnancy to subsequent outcome would be more convincing, but again not conclusive due to potential for confounding. Nevertheless, other studies have suggested that early treatment of asymptomatic infections may lead to the improvement of pregnancy outcome [9], whereas eradication of H. pylori has been shown to lead to a clearance of antiphospholipid antibodies, providing a potential mechanism of direct relevance to pre-eclampsia [10]. To prove a causal link between H. pylori chronic infection and pre-eclampsia requires clinical trials designed to test whether early identification and treatment of H. pylori infection lessens risk for pre-eclampsia. However, such a trial would require large numbers and represent a considerable undertaking. It should also be noted that the considerable early interest in the relationship between infection and coronary heart disease has not matured, with recent randomized trial results suggesting no vascular end-point benefit of antibiotic treatment in patients with coronary heart disease [11]. At present, obstetricians screen for problems in pregnancy that have a lower incidence than pre-eclampsia, such as Rh iso-immunization, Down's syndrome and syphilis. Therefore, should this area of interest progress, with supportive prospective studies followed by subsequent supportive and adequately powered intervention trials, a simple blood test to screen for the presence of H. pylori could be included as part of the assessment of pregnant women at booking. Clearly, a substantial amount of additional work is needed to reach this point.