[Infections in pregnancy]

Infections in pregnancy may complicate its course and harm the fetus or newborn after vertical transmission. Treatment of asymptomatic bacteriuria is mandatory in pregnant women given the high risk of secondary pyelonephritis. Intraamniotic infection usually arises by the ascending route and is associated with premature rupture of membranes. Vaginal infections promote preterm labour or premature rupture of membranes and may be transmitted to the child during labour. They must therefore be treated although they often cause little discomfort to the pregnant woman. Systemic infections due to viral, protozoal and bacterial pathogens may be transmitted transplacentally and cause embryopathies, fetopathies or neonatal infections. Depending on the responsible agent the negative impact on the course of pregnancy and on the fetus' or neonate's health can be prevented or reduced by prophylactic or therapeutic interventions.

Group B Streptococcus colonization in pregnancy: prevalence and prevention strategies of neonatal sepsis

Early onset neonatal sepsis due to Group B streptococci (GBS) is responsible for severe morbidity and mortality of newborns. While different preventive strategies to identify women at risk are being recommended, the optimal strategy depends on the incidence of GBS-sepsis and on the prevalence of anogenital GBS colonization. We therefore aimed to assess the Group B streptococci prevalence and its consequences on different prevention strategies. We analyzed 1316 pregnant women between March 2005 and September 2006 at our institution. The prevalence of GBS colonization was determined by selective cultures of anogenital smears. The presence of risk factors was analyzed. In addition, the direct costs of screening and intrapartum antibiotic prophylaxis were estimated for different preventive strategies. The prevalence of GBS colonization was 21%. Any maternal intrapartum risk factor was present in 37%. The direct costs of different prevention strategies have been estimated as follows: risk-based: 18,500 CHF/1000 live births, screening-based: 50,110 CHF/1000 live births, combined screening- and risk-based: 43,495/1000 live births. Strategies to prevent GBS-sepsis in newborn are necessary. With our colonization prevalence of 21%, and the intrapartum risk profile of women, the screening-based approach seems to be superior as compared to a risk-based approach.

Hyperaldosteronism in pregnancy

Aldosterone is a key regulator of electrolyte and water homeostasis and plays a central role in blood pressure regulation. Hormonal changes during pregnancy, among them increased progesterone and aldosterone production, lead to the required plasma volume expansion of the maternal body as an accommodation mechanism for fetus growth. This review discusses the regulation of aldosterone production by aldosterone synthase (CYP11B2); the impact on aldosterone secretion due to the presence of a chimeric gene originating from a crossover between CYP11B1 and CYP11B2 in glucocorticoid remediable aldosteronism (GRA) - the inherited form of hypertension; enhanced aldosterone production in aldosterone-producing adenoma (APA); and idiopathic hyperaldosteronism (IHA). Features of hyperaldosteronism are also found in patients with apparent mineralocorticoid excess (AME), in which glucocorticoids exacerbate activation of the mineralocorticoid receptor (MR) because of a defect in the 11beta-hydroxysteroid dehydrogenase type 2 enzyme. Regulation of aldosterone production and tissue-specific activation of the mineralocorticoid receptor are prerequisites for optimal control of body fluids and blood pressure during pregnancy and contribute largely to the wellbeing of the mother-to-be.

1.59 Reduced inflammatory potential of circulating gammadelta T cells in pregnancy induced improvement of Rheumatoid Arthritis

BACKGROUND AND OBJECTIVES During pregnancy, gammadelta T cells expand at the fetomaternal interface where they induce a tolerogenic milieu. Patients with rheumatoid arthritis (RA) experience a spontaneous improvement of their disease during pregnancy and a postpartum aggravation. By contrast, pregnant patients with ankylosing spondylitis (AS) often experience persistent active disease. We hypothesised that the pregnancy related modulation of disease activity in RA patients versus AS patients is associated with numerical and functional changes of circulating gammadelta T cells. MATERIAL AND METHODS The frequency of surface markers and the intracellular cytokine profile of freshly isolated gammadelta T cells from RA (n = 54) and AS (n = 26) patients and healthy controls (n = 40) were analysed at each trimester during pregnancy and 6-8 weeks postpartum by flow cytometry. RESULTS Very discrete changes of Vdelta1 or Vdelta2 frequency were seen during pregnancy and postpartum in healthy controls and AS patients. In RA, however, the frequency of Vdelta2 cells decreased in the third trimester when disease activity was low. Low percentages of Vdelta 2 cells were also found in non-pregnant RA patients with active arthritis, yet only pregnant RA patients showed reduced percentages of Vdelta2 cells positive for the activation marker CD69 and the intracellular cytokine TNFalpha. Similarly, Vdelta1 + TNFalpha + cells were lower in pregnant RA patients compared to non-pregnant RA patients. The percentage of Vdelta2 + TNFalpha + cells, Vdelta2+ CD69+ and Vdelta1+ CD69+ cells correlated with disease activity in RA. As for the receptors which modulate cytotoxicity, RA patients showed a rise of the anti-cytotoxic receptor NKG2A on Vdelta1 cells in the 2(nd) trimester and a decrease postpartum. Since the pro-cytotoxic receptor NKG2D remained unchanged, the NKG2D/NKG2A ratio on Vdelta1 cells was reduced in RA patients during pregnancy. In AS patients, persistent disease activity during pregnancy was reflected by an increased frequency of Vdelta2+ CD69+ cells and an unchanged frequency of Vdelta2+ TNFalpha+ cells. In addition, pregnant AS patients showed an increased frequency of Vdelta1+CD161+ cells. CONCLUSIONS Disease amelioration of RA during pregnancy correlates with changes of cell activation, pro-inflammatory cytokines and anti-cytotoxic receptors of gammadelta T cells. By contrast, active disease during pregnancy as found in AS is associated with unchanged inflammatory responses of gammadelta T cells. Since gammadelta T cells remain unchanged in healthy pregnant controls, the modulation of gammadelta T cells in RA rather seems to be an effect of improved disease than of pregnancy itself.

Developing and Integrating the Management of Elder Abuse in Primary Practice: A Case Study Using A Web-Based CME Course Format

Introduction: As the population in the United States continues to age, more attention in primary practice settings is now devoted toward managing the care of the elderly. The occurrence of elder abuse is a growing problem. It is a condition many professionals in primary care may be ill prepared with the knowledge or resources to identify and manage. [See PDF for complete abstract]

Cost-effectiveness of universal prophylaxis in pregnancy with prior group B streptococci colonization.

OBJECTIVE: To estimate the costs and outcomes of rescreening for group B streptococci (GBS) compared to universal treatment of term women with history of GBS colonization in a previous pregnancy. STUDY DESIGN: A decision analysis model was used to compare costs and outcomes. Total cost included the costs of screening, intrapartum antibiotic prophylaxis (IAP), treatment for maternal anaphylaxis and death, evaluation of well infants whose mothers received IAP, and total costs for treatment of term neonatal early onset GBS sepsis. RESULTS: When compared to screening and treating, universal treatment results in more women treated per GBS case prevented (155 versus 67) and prevents more cases of early onset GBS (1732 versus 1700) and neonatal deaths (52 versus 51) at a lower cost per case prevented ($8,805 versus $12,710). CONCLUSION: Universal treatment of term pregnancies with a history of previous GBS colonization is more cost-effective than the strategy of screening and treating based on positive culture results.

The effect of body mass index on therapeutic response to bacterial vaginosis in pregnancy.

Our objective was to determine the effect of body mass index (BMI) on response to bacterial vaginosis (BV) treatment. A secondary analysis was conducted of two multicenter trials of therapy for BV and TRICHOMONAS VAGINALIS. Gravida were screened for BV between 8 and 22 weeks and randomized between 16 and 23 weeks to metronidazole or placebo. Of 1497 gravida with asymptomatic BV and preconceptional BMI, 738 were randomized to metronidazole; BMI was divided into categories: < 25, 25 to 29.9, and > or = 30. Rates of BV persistence at follow-up were compared using the Mantel-Haenszel chi square. Multiple logistic regression was used to evaluate the effect of BMI on BV persistence at follow-up, adjusting for potential confounders. No association was identified between BMI and BV rate at follow-up ( P = 0.21). BMI was associated with maternal age, smoking, marital status, and black race. Compared with women with BMI of < 25, adjusted odds ratio (OR) of BV at follow-up were BMI 25 to 29.9: OR, 0.66, 95% CI 0.43 to 1.02; BMI > or = 30: OR, 0.83, 95% CI 0.54 to 1.26. We concluded that the persistence of BV after treatment was not related to BMI.

The effect of body mass index on therapeutic response to bacterial vaginosis in pregnancy.

Our objective was to determine the effect of body mass index (BMI) on response to bacterial vaginosis (BV) treatment. A secondary analysis was conducted of two multicenter trials of therapy for BV and TRICHOMONAS VAGINALIS. Gravida were screened for BV between 8 and 22 weeks and randomized between 16 and 23 weeks to metronidazole or placebo. Of 1497 gravida with asymptomatic BV and preconceptional BMI, 738 were randomized to metronidazole; BMI was divided into categories: < 25, 25 to 29.9, and > or = 30. Rates of BV persistence at follow-up were compared using the Mantel-Haenszel chi square. Multiple logistic regression was used to evaluate the effect of BMI on BV persistence at follow-up, adjusting for potential confounders. No association was identified between BMI and BV rate at follow-up ( P = 0.21). BMI was associated with maternal age, smoking, marital status, and black race. Compared with women with BMI of < 25, adjusted odds ratio (OR) of BV at follow-up were BMI 25 to 29.9: OR, 0.66, 95% CI 0.43 to 1.02; BMI > or = 30: OR, 0.83, 95% CI 0.54 to 1.26. We concluded that the persistence of BV after treatment was not related to BMI.

Treatment for outpatients with comorbid schizophrenia and substance use disorders: a review

Aims: This review provides evidence of which interventions need to be part of effective outpatient integrated treatment for patients with comorbid schizophrenia and substance use disorders. Methods: A total of 14 randomized controlled trials were included. Effect sizes are provided to assess the magnitude of the treatments’ efficacy. Results: Despite the studies’ heterogeneity, we can conclude that certain programs (e.g., Behavioral Treatment for Substance Abuse in Schizophrenia) and specific interventions (e.g., motivational interviewing, family interventions) seem to be effective. Moreover, programs integrating multiple interventions are more likely to be positively related to better outcomes than single interventions. Finally, the lack of difference between effect sizes of assertive community treatment compared to case management suggests that a lower caseload is not necessary for positive treatment outcomes. Conclusion: Integrated treatment seems advantageous, although effect sizes are mostly modest. More homogeneous and qualitative sound studies are needed.

Normotensive blood pressure in pregnancy – the role of salt and aldosterone

A successful pregnancy requires an accommodating environment. Salt and water availability are critical for plasma volume expansion. Any changes in sodium intake would alter aldosterone, a hormone previously described beneficial in pregnancy. To date, it remains ambiguous whether high aldosterone or high salt intake is preferable. We hypothesized that increased aldosterone is a rescue mechanism and appropriate salt availability is equally effective in maintaining a normotensive blood pressure (BP) phenotype in pregnancy. We compared normotensive pregnant women (n=31) throughout pregnancy with young healthy female individuals (n=31–62) and performed salt sensitivity testing within the first trimester. Suppression of urinary tetrahydro-aldosterone levels by salt intake as measured by gas chromatography–mass spectrometry and urinary sodium excretion corrected for creatinine, respectively, was shifted toward a higher salt intake in pregnancy (P<0.0001). In pregnancy, neither high urinary tetrahydro-aldosterone nor sodium excretion was correlated with higher BP. In contrast, in nonpregnant women, systolic BP rose with aldosterone (P<0.05). Testing the impact of salt on BP, we performed salt sensitivity testing in a final cohort of 19 pregnant and 24 nonpregnant women. On salt loading, 24-hour mean arterial pressure rose by 3.6±1.5 and dropped by –2.8±1.5 mm Hg favoring pregnant women (P<0.01; χ2=6.04; P<0.02). Our data suggest first that salt responsiveness of aldosterone is alleviated in conditions of pregnancy without causing aldosterone-induced hypertension. Second, salt seems to aid in BP lowering in pregnancy for reasons incompletely elucidated, yet involving renin suppression and potentially placental sensing mechanisms. Further research should identify susceptible individuals and clarify effector mechanisms.

Screening, Identification and Preliminary Investigation of Target Transporters in Pregnancy Pathologies

Screening, Identification and Preliminary Investigation of Target Transporters in Pregnancy Pathologies. INTRODUCTION: Pre-eclampsia (PE), intrauterine growth restriction (IUGR) and gestational diabetes mellitus (GDM) are major sources of clinical morbidity and mortality in pregnant women worldwide. The mechanisms underlying these gestational diseases are complex and not yet fully understood, but one factor contributing to their development is impaired maternal-fetal nutrient transport. Therefore, we aimed to identify candidate membrane transporters involved in transplacental nutrient transfer associated with PE/IUGR or GDM. METHODS: Using in silico strategies, we analysed various gene expression data sets generated on different platforms focusing on solute carriers, ABC transporters and TRP channels in order to identify transporters that are differently expressed between patients and gestational age-matched controls. These bioinformatic analyses were combined with literature data to define a catalogue of target transporters that could be involved in the development of PE/IUGR or GDM. Transporters of interest were then analysed for gene expression using qRT-PCR in placental tissues of patients and controls. For validating the results on protein and functional level, we started to establish an in vitro assay using freshly isolated primary cytotrophoblast cells polarized on the Transwell® system. RESULTS: Using bioinformatics approaches, we initially identified 37 target membrane proteins which were mainly associated with the transport of amino acids, vitamins, and trace elements. At the current state of analysis, the amino acid transporters SLC7A7, SLC38A2, SLC38A5, and the thiamine transporter SLC19A3 showed significant differences in placental mRNA expression between controls and patients affected by PE and/or IUGR. Subsequent gene expression analysis in our in-house GDM placental tissue bank is still ongoing. CONCLUSIONS: Based on our in silico analyses, literature data and first follow-up in vitro validations, we were able to define potentially interesting candidate transporters implicated in PE/IUGR or GDM. To date, additional newly defined candidate targets are being analysed on mRNA level in PE/IUGR and GDM. Subsequent analyses on protein and functional level will reveal whether these targets could be of diagnostic or therapeutical interest in these pregnancy pathologies.

Hypertension in pregnancy

PURPOSE OF REVIEW Hypertension in pregnancy contributes substantially to perinatal mortality and morbidity of both the mother and her child. High blood pressure is mainly responsible for this adverse outcome, in particular when associated with preeclampsia. Although preeclampsia is nowadays a well-known clinical-obstetrical entity, and screening for this complication has been part of routine care during pregnancy for nearly 100 years, its cause is still enigmatic. RECENT FINDINGS Profound changes of the demographic development of our society, the worldwide rising prevalence of obesity and metabolic disorders, and progress in reproductive medicine will inevitably modify the prevalence of many medical problems in pregnancy. Complications such as gestational diabetes mellitus, chronic hypertension, and preeclampsia will rise and an interdisciplinary approach is necessary to handle these women during pregnancy and also after delivery. Indeed, it is now well established that these women and their offspring born large or small-for-gestational age are at increased risk for severe cardiovascular and metabolic complications later in life. SUMMARY Knowledge of the pregnancy course is not only important for an obstetrician but also increasingly inevitable for the general practitioner. Recognition, classification, and adequate management of hypertensive pregnancy disorders and associated complications may considerably reduce perinatal death and morbidity.