Acute maternal infection and risk of pre-eclampsia: a population-based case-control study.

BACKGROUND: Infection in pregnancy may be involved in the aetiology of pre-eclampsia. However, a clear association between acute maternal infection and pre-eclampsia has not been established. We assessed whether acute urinary tract infection, respiratory tract infection, and antibiotic drug prescriptions in pregnancy (a likely proxy for maternal infection) are associated with an increased risk of pre-eclampsia. METHODS AND FINDINGS: We used a matched nested case-control design and data from the UK General Practice Research Database to examine the association between maternal infection and pre-eclampsia. Primiparous women aged at least 13 years and registered with a participating practice between January 1987 and October 2007 were eligible for inclusion. We selected all cases of pre-eclampsia and a random sample of primiparous women without pre-eclampsia (controls). Cases (n=1533) were individually matched with up to ten controls (n=14236) on practice and year of delivery. We calculated odds ratios and 95% confidence intervals for pre-eclampsia comparing women exposed and unexposed to infection using multivariable conditional logistic regression. After adjusting for maternal age, pre-gestational hypertension, diabetes, renal disease and multifetal gestation, the odds of pre-eclampsia were increased in women prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14-1.44) and in women with urinary tract infection (adjusted odds ratio 1.22;1.03-1.45). We found no association with maternal respiratory tract infection (adjusted odds ratio 0.91;0.72-1.16). Further adjustment for maternal smoking and pre-pregnancy body mass index made no difference to our findings. CONCLUSIONS: Women who acquire a urinary infection during pregnancy, but not those who have a respiratory infection, are at an increased risk of pre-eclampsia. Maternal antibiotic prescriptions are also associated with an increased risk. Further research is required to elucidate the underlying mechanism of this association and to determine whether, among women who acquire infections in pregnancy, prompt treatment or prophylaxis against infection might reduce the risk of pre-eclampsia

Intrauterine Growth Restriction Is a Direct Consequence of Localized Maternal Uropathogenic Escherichia coli Cystitis

Despite the continually increasing rates of adverse perinatal outcomes across the globe, the molecular mechanisms that underlie adverse perinatal outcomes are not completely understood. Clinical studies report that 10% of pregnant women will experience a urinary tract infection (UTI) and there is an association of UTIs with adverse perinatal outcomes. We introduced bacterial cystitis into successfully outbred female mice at gestational day 14 to follow pregnancy outcomes and immunological responses to determine the mechanisms that underlie UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing localized cystitis displayed intrauterine growth restriction (20–80%) as early as 48 hours post-infection and throughout the remainder of normal gestation. Robust infiltration of cellular innate immune effectors was observed in the uteroplacental tissue following introduction of UTI despite absence of viable bacteria. The magnitude of serum proinflammatory cytokines is elevated in the maternal serum during UTI. This study demonstrates that a localized infection can dramatically impact the immunological status as well as the function of non-infected distal organs and tissues. This model can be used as a platform to determine the mechanism(s) by which proinflammatory changes occur between non-contiguous genitourinary organ

P2492The impact of diabetes mellitus newly diagnosed by glycated hemoglobin on outcomes in patients undergoing percutaneous coronary intervention - five years prospective follow up study

Abstract Background Following percutaneous coronary interventions (PCI), both short and long terms ischemic outcomes are worse in patients with Diabetes Mellitus (DM) compared to those without DM. Methods We prospectively enrolled consecutive patients undergoing PCI. Glycated Hemoglobin (HbA1c) levels were assessed during the index hospitalization and newly diagnosed DM was defined as HbA1c≥6.5% in the absence of the previous diagnosis. The primary outcome was Major Adverse Cerebro and Cardiovascular Events (MACCE) defined as death, stroke, PCI or acute myocardial infarction at five years. Results Diabetes was previously diagnosed in 391 (34%) patients (DM group), 221 (19%) had newly diagnosed DM based on the HbA1c level and 539 (47%) did not have diabetes (Non-DM). In DM group HbA1c was 7.80±1.36% as compared with 7.62±1.30% in patients with newly diagnosed DM (p&lt;0.001). These patients were younger (62.0±11.3 years) compared to DM (67.9±10.4 years) and non-DM (63.7±13.0) patients, p&lt;0.001. five years MACCE rates were 37.8%, 65.5% and 42.5% in the non-DM, newly diagnosed DM and DM groups, respectively (p&lt;0.001). Multivariate analysis showed that compared to non-DM, the adjusted two year hazard ratios for MACCE were 1.83 (p&lt;0.001), 1.47 (p=0.01) and 0.52 (p=0.01) respectively in patients with known DM, newly diagnosed DM, and patients with newly diagnosis DM who had DM treatment started after PCI. Conclusion Newly diagnosed DM based on peri-procedural HbA1c is common and associated with increased short and long term risk for adverse outcomes. Our results show that the diagnosis and early treatment of diabetes in patients undergoing PCI should be included into the routine practice. </jats:sec

The association of tissue doppler E/e' ratio with poor survival is modified by gender and is attenuated with advanced age

Abstract Introduction Contemporary guidelines recommend a universal cutoff of 14 for the ratio between early mitral flow wave and early diastolic mitral annulus velocity measured by tissue doppler (E/e' ratio). While age-dependent normal E/e' values have been suggested, outcome data is lacking. Purpose We sought to evaluate the modification effect of age and gender on the prognostic value of the E/e' ratio. Methods Consecutive patients who underwent echocardiographic evaluation between 2009 and 2021 (N=104,315) in a single tertiary cardiovascular center. Patients with left or right ventricular dysfunction, any significant valvular disease, structural heart disease or evidence of pulmonary hypertension were excluded. Cancer and mortality data were available for all subjects from national registries. Patients with a metastatic malignancy at baseline or during follow up were excluded. Cox regression models were applied. Results Overall, 44,541 patients were included in the final analysis. Mean age was 55±17, 59% were male and 63% of the exams were performed in an outpatient setting. An elevated E/e' ratio above 14 was documented in 2,598 (7%) patients. During a median follow-up of 5.7 (IQR 2.8–9.1) years, 5,015 (11.3%) patients died. Kaplan Meier survival analysis demonstrated that the cumulative probability of death at 6 years was 23.4% (21.6–25.3) among patients with elevated E/e' ratio compared with 9.7% (9.3–10.0) among patients with E/e'&amp;lt;14 (p Log rank &amp;lt;0.001). This difference was less significant as age progressed (figure 1). Multivariate cox-regression model yielded consistent results such that an elevated E/e' ratio was associated with 2.66-fold increased risk of death during follow up (95% CI 2.44–2.89, p&amp;lt;0.001), and there was a decline in the increased risk and significant as age advanced in both genders (figure 2). Interaction analysis was significant for both gender and age such the association of elevated E/e' ratio with poor survival was more significant among men compared with women and among young vs. older subjects. Among women, elevated E/e' was associated with 2.4-fold increased risk of death versus 2.7-fold increased risk among men. Similarly, the hazard ratio for death associated with elevated E/e' was 2.29 (95% CI 1.74–3.02), 1.8 (95% CI 1.5–2.1), 1.13 (95% CI 0.97–1.31) and 1.07 (95% CI 0.92–1.25) for the age groups of &amp;lt;60, 60–70, 70–80 and &amp;gt;80, respectively. In a sensitivity analysis, similar findings were seen in when excluding patients with mild hypertrophy (maximal wall thickness &amp;gt;12mm) and without any mitral annulus calcification. Conclusion In apparently normal hearts, an elevated E/e' ratio is independently associated with increased mortality. This association is more pronounced among men and is attenuated with increased age. This study supports the need for gender-specific and age-specified outcome data with respect to measures of diastolic dysfunction. Funding Acknowledgement Type of funding sources: None. Survival by age and gender groupsE/e' &amp;gt;14 and mortality by age and gender </jats:sec