Humoral immunity in late-onset Pre-eclampsia and linkage with angiogenic and inflammatory markers.

PROBLEM: Pre-eclampsia (PE) is a leading cause of maternal and foetal morbidity worldwide. Given the implication of immune mechanisms, we compared markers of humoral immunity in PE and their relationship to circulating markers of inflammation, angiogenic factors, and renal function. METHOD OF STUDY: Serum samples from 88 previously healthy women admitted to hospital with PE and 107 healthy pregnant controls at term were analysed for serum immunoglobulins (Ig), including IgG subclasses and free light chain (sFLC) levels, beta-2 microglobulin (B2-M), high-sensitivity C-reactive protein (HS-CRP), albumin, complement proteins (C3 & C4), creatinine, cystatin-C and the ratio of soluble fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF). RESULTS: Compared to the controls, women with PE had significantly reduced renal function, serum IgG (subclass 1 & 3), albumin, and C4 levels, whilst concentrations of total sFLC, HS-CRP, B2-M, and sFLT-1:PlGF were raised. On multivariable analysis, sFLT-1:PlGF ratio (P < 0.001), sFLC (P < 0.001) and IgG1 (P < 0.024) were found to be independently associated with PE, after accounting for renal function, patient age, BMI, ethnicity, and parity. B2-M and sFLT-1:PlGF had comparable diagnostic association with PE (P = 0.184), and correlated strongly with each other (ρ = 0.588, P < 0.001) as well as with renal function and adverse clinical outcome. CONCLUSION: We describe for the first time that PE is independently associated with activation of the humoral immune system independent of deranged kidney function and angiogenic markers. The role of B2-M as a potential predictive marker of PE remains to be determined.

A review of the methodological features of systematic reviews in fetal medicine.

Systematic reviews of fetal medicine can serve as a tool for translation of research findings from a few expert centres to a wider healthcare specialty. The extent to which reviews of fetal medicine research are systematic and unbiased is not known. In this review of systematic reviews in fetal medicine, we have searched without language restrictions, Medline, Embase, DARE (Database of Abstracts of Reviews of Effectiveness), Cochrane Library (from database inception to 2005) and bibliographies of known reviews, and contacted experts to identify potentially relevant citations of literature for reviews of fetal medicine studies. The selected reviews were assessed for information on framing of questions, literature search and methods of review. The search yielded 659 citations of which 84 reviews met the inclusion criteria. Most of the reviews were in the field of fetal pathology (49/84, 59%). A majority of reviews (58/84, 69%) specified the question to be answered but only half (44/84, 52%) addressed a focussed question. Although 57/84 (68%) reviews had a detailed search description, only 32/84 (38%) searched without language restriction. 45/84 (54%) searched in multiple databases and 27/84 (32%) assessed for the risk of missing studies. There was no difference in quality between reviews of fetal pathology, screening for aneuploidy, fetal growth and fetal therapy, except with respect to specifying the question (p<0.03), search without language restriction (p<0.004), assessment of risk of missing studies (p<0.006) and study quality assessment (p<0.002) where reviews of fetal growth performed better than other domains. Our study reflects the paucity of good quality reviews in fetal medicine research. Existing reviews tend to be poor in reporting methodological features. Particularly, not enough attention is paid to assessment of validity of included studies and means to improving reliability of results through appropriate use of meta-analysis. There is a need for conducting further reviews and for rigour when reviewing fetal medicine research.

The accuracy of various tests for bacterial vaginosis in predicting preterm birth: a systematic review.

OBJECTIVE: To determine the accuracy with which various types of tests for bacterial vaginosis predict spontaneous preterm birth in pregnant women. DATA SOURCES: Studies were identified without language restrictions through nine different databases, and manual searching of bibliographies of known primary and review articles. STUDY SELECTION AND DATA EXTRACTION: There are four different bacterial vaginosis testing methods: Gram staining tests using either Nugent's or Spiegel's criteria, and gas liquid chromatography are laboratory based, and the fourth method uses clinical (Amsel's) criteria to diagnose bacterial vaginosis. Two reviewers independently selected studies and extracted data on their characteristics, quality and accuracy. Accuracy data were used to form 2 x 2 contingency tables of the bacterial vaginosis test results with spontaneous preterm birth as the reference standard. DATA SYNTHESIS: Data on asymptomatic women and women with symptoms of threatened preterm labour were analysed separately. Data were pooled to produce summary estimates of likelihood ratios for positive (LR+) and negative (LR-) test results for the various types of tests. RESULTS: There were 18 primary articles, involving altogether 17,868 women. There was unexplained heterogeneity in the meta-analyses of the accuracy results, which requires caution in their interpretation. Meta-analyses of studies testing asymptomatic women in the second trimester showed that clinical criteria had a LR+ of 0.98 (95% confidence interval 0.59 to 1.6) and a LR- of 1.00 (0.93 to 1.1), Gram staining (Nugent's criteria) had a LR+ of 1.6 (1.4 to 1.9) and a LR- of 0.9 (0.8 to 0.9), and Gram staining (Spiegel's criteria) had a LR+ of 2.4 (1.4 to 4.9) and a LR- of 0.81 (0.64 to 1.0). Among symptomatic women, Gram staining (Spiegel's criteria) had a LR+ of 1.3 (1.0 to 1.6) and LR- of 0.9 (0.7 to 1.0). CONCLUSION: There was a lack of difference in the accuracy of the various bacterial vaginosis tests for predicting preterm birth in both asymptomatic and symptomatic women of threatened preterm labour.

Effectiveness of nifedipine versus atosiban for tocolysis in preterm labour: a meta-analysis with an indirect comparison of randomised trials.

OBJECTIVE: To explore the effectiveness of nifedipine compared with atosiban for tocolysis in preterm labour. DESIGN: A systematic review of randomised controlled trials with meta-analysis using adjusted indirect comparison. POPULATION: Six hundred and seventy-nine women recruited in nine randomised trials evaluating the effectiveness of nifedipine versus beta-agonists, and 852 women recruited in four trials of atosiban versus beta-agonists. There were no trials comparing nifedipine directly with atosiban. METHODS: We performed meta-analysis with a technique involving an adjusted indirect comparison between nifedipine and atosiban using beta-agonists as the common comparator. This approach preserves the benefit accrued by randomisation in the original comparisons. MAIN OUTCOME MEASURES: Reduction in neonatal respiratory distress syndrome and delay in delivery by 48 hours. RESULTS: Nifedipine tocolysis was associated with a significant reduction in respiratory distress syndrome compared with atosiban (OR 0.55, 95% CI 0.32-0.97). It also increased the number of women whose delivery was delayed by 48 hours (OR 1.20, 95% CI 0.73-1.95), although this result was not statistically significant. CONCLUSIONS: When indirectly compared with atosiban, nifedipine tocolysis is more effective. In the absence of a direct comparison, our analysis provides a way to explore the potential benefits of nifedipine versus atosiban.

Oxytocin antagonists for tocolysis in preterm labour -- a systematic review.

BACKGROUND: Oxytocin antagonists have been shown to inhibit uterine contractions and delay preterm delivery. Our objective was to examine the clinical effectiveness and safety of oxytocin antagonists for tocolysis in preterm labour. MATERIAL/METHODS: We searched MEDLINE, EMBASE, the Cochrane Controlled Trials Register and Science Citation Index using the following Medical Subject Headings and textwords: oxytocin (antagonists and inhibitors), atosiban, antocin, oxytocin antagonists, oxytocin receptor antagonists and oxytocin inhibitors. All randomised controlled trials that compared effectiveness and safety of atosiban with a placebo or another tocolytic in women with threatened or actual preterm labour were included. The primary outcome measure was the proportion of women undelivered by 48 hours from the commencement of treatment. RESULTS: Six articles met the inclusion criteria - two compared atosiban to placebo and four atosiban to a beta-agonist. Meta-analysis showed a significant increase in the proportion of women undelivered by 48 hours in women receiving atosiban compared to placebo (RR 1.13, 95%CI 1.02, 1.26). When compared with beta-agonists, atosiban increased the proportion of women undelivered by 48 hours, but this trend did not reach statistical significance (RR 1.07, 95%CI 0.98, 1.17). Side effect profile was substantially better for atosiban compared to beta-agonists. CONCLUSIONS: Oxytocin antagonists appear to be effective and safe for tocolysis in preterm labour.