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Aspirin for prevention of preeclampsia in women with historical risk factors: a systematic review.

OBJECTIVE To examine the effectiveness of aspirin in preventing perinatal death and preeclampsia in women with predisposing historical risk factors, such as previous history of preeclampsia, chronic hypertension, diabetes, and renal disease. DATA SOURCES: Searches were conducted in MEDLINE, EMBASE, Cochrane Library, National Research Register, SCISEARCH, and ISI Conference Proceedings without any language restriction, using the following medical subject headings and text words: “aspirin,” “antiplatelet*,” “salicyl*,” “acetylsalicyl*,” “platelet aggregation inhibitors,” “pre-eclamp*,” “preeclamp*,” and “hypertens*.” METHODS OF STUDY SELECTION: We included all randomized trials that evaluated the effectiveness of aspirin compared with placebo or no treatment in women with predisposing historical risk factors and reported clinically relevant perinatal or maternal outcomes. Study selection, quality appraisal, and data extractions were performed independently and in duplicate. TABULATION, INTEGRATION, AND RESULTS: We identified 14 relevant trials, including a total of 12,416 women. Meta-analysis showed a significant benefit of aspirin therapy in reducing perinatal death (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.64, 0.96) and preeclampsia (OR 0.86, 95% CI 0.76, 0.96). Aspirin was also associated with a reduction in rates of spontaneous preterm birth (OR 0.86, 95% CI 0.79, 0.94), and an increase of 215 g in mean birth weight (weighted mean difference 215, 95% CI 90, 341). There was no increase in the risk of placental abruption with aspirin (OR 0.98, 95% CI 0.79, 1.21). Funnel plot analysis indicated that publication and related biases were unlikely (Egger test, P = .84). CONCLUSION Aspirin reduces the risk of perinatal death and preeclampsia in women with historical risk factors. Given the importance of these outcomes and the safety and low cost of aspirin, aspirin therapy should be considered in women with historical risk factors.

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling

OBJECTIVES To identify combinations of tests and treatments to predict and prevent spontaneous preterm birth. DATA SOURCES Searches were run on the following databases up to September 2005 inclusive: MEDLINE, EMBASE, DARE, the Cochrane Library (CENTRAL and Cochrane Pregnancy and Childbirth Group trials register) and MEDION. We also contacted experts including the Cochrane Pregnancy and Childbirth Group and checked reference lists of review articles and papers that were eligible for inclusion. REVIEW METHODS Two series of systematic reviews were performed: (1) accuracy of tests for the prediction of spontaneous preterm birth in asymptomatic women in early pregnancy and in women symptomatic with threatened preterm labour in later pregnancy; (2) effectiveness of interventions with potential to reduce cases of spontaneous preterm birth in asymptomatic women in early pregnancy and to reduce spontaneous preterm birth or improve neonatal outcome in women with a viable pregnancy symptomatic of threatened preterm labour. For the health economic evaluation, a model-based analysis incorporated the combined effect of tests and treatments and their cost-effectiveness. RESULTS Of the 22 tests reviewed for accuracy, the quality of studies and accuracy of tests was generally poor. Only a few tests had LR+ > 5. In asymptomatic women these were ultrasonographic cervical length measurement and cervicovaginal prolactin and fetal fibronectin screening for predicting spontaneous preterm birth before 34 weeks. In this group, tests with LR- < 0.2 were detection of uterine contraction by home uterine monitoring and amniotic fluid C-reactive protein (CRP) measurement. In symptomatic women with threatened preterm labour, tests with LR+ > 5 were absence of fetal breathing movements, cervical length and funnelling, amniotic fluid interleukin-6 (IL-6), serum CRP for predicting birth within 2-7 days of testing, and matrix metalloprotease-9, amniotic fluid IL-6, cervicovaginal fetal fibronectin and cervicovaginal human chorionic gonadotrophin (hCG) for predicting birth before 34 or 37 weeks. In this group, tests with LR- < 0.2 included measurement of cervicovaginal IL-8, cervicovaginal hCG, cervical length measurement, absence of fetal breathing movement, amniotic fluid IL-6 and serum CRP, for predicting birth within 2-7 days of testing, and cervicovaginal fetal fibronectin and amniotic fluid IL-6 for predicting birth before 34 or 37 weeks. The overall quality of the trials included in the 40 interventional topics reviewed for effectiveness was also poor. Antibiotic treatment was generally not beneficial but when used to treat bacterial vaginosis in women with intermediate flora it significantly reduced the incidence of spontaneous preterm birth. Smoking cessation programmes, progesterone, periodontal therapy and fish oil appeared promising as preventative interventions in asymptomatic women. Non-steroidal anti-inflammatory agents were the most effective tocolytic agent for reducing spontaneous preterm birth and prolonging pregnancy in symptomatic women. Antenatal corticosteroids had a beneficial effect on the incidence of respiratory distress syndrome and the risk of intraventricular haemorrhage (28-34 weeks), but the effects of repeat courses were unclear. For asymptomatic women, costs ranged from 1.08 pounds for vitamin C to 1219 pounds for cervical cerclage, whereas costs for symptomatic women were more significant and varied little, ranging from 1645 pounds for nitric oxide donors to 2555 pounds for terbutaline; this was because the cost of hospitalisation was included. The best estimate of additional average cost associated with a case of spontaneous preterm birth was approximately 15,688 pounds for up to 34 weeks and 12,104 pounds for up to 37 weeks. Among symptomatic women there was insufficient evidence to draw firm conclusions for preventing birth at 34 weeks. Hydration given to women testing positive for amniotic fluid IL-6 was the most cost-effective test-treatment combination. Indomethacin given to all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among symptomatic women. For a symptomatic woman, the most cost-effective test-treatment combination for postponing delivery by at least 48 h was the cervical length (15 mm) measurement test with treatment with indomethacin for all those testing positive. This combination was also the most cost-effective option for postponing delivery by at least 7 days. Antibiotic treatment for asymptomatic bacteriuria of all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among asymptomatic women but this does not take into account the potential side effects of antibiotics or issues such as increased resistance. CONCLUSIONS For primary prevention, an effective, affordable and safe intervention applied to all mothers without preceding testing is likely to be the most cost-effective approach in asymptomatic women in early pregnancy. For secondary prevention among women at risk of preterm labour in later pregnancy, a management strategy based on the results of testing is likely to be more cost-effective. Implementation of a treat-all strategy with simple interventions, such as fish oils, would be premature for asymptomatic women. Universal provision of high-quality ultrasound machines in labour wards is more strongly indicated for predicting spontaneous preterm birth among symptomatic women than direct management, although staffing issues and the feasibility and acceptability to mothers and health providers of such strategies need to be explored. Further research should include investigations of low-cost and effective tests and treatments to reduce and delay spontaneous preterm birth and reduce the risk of perinatal mortality arising from preterm birth.

Reporting of measures of accuracy in systematic reviews of diagnostic literature.

BackgroundThere are a variety of ways in which accuracy of clinical tests can be summarised in systematic reviews. Variation in reporting of summary measures has only been assessed in a small survey restricted to meta-analyses of screening studies found in a single database. Therefore, we performed this study to assess the measures of accuracy used for reporting results of primary studies as well as their meta-analysis in systematic reviews of test accuracy studies.MethodsRelevant reviews on test accuracy were selected from the Database of Abstracts of Reviews of Effectiveness (1994–2000), which electronically searches seven bibliographic databases and manually searches key resources. The structured abstracts of these reviews were screened and information on accuracy measures was extracted from the full texts of 90 relevant reviews, 60 of which used meta-analysis.ResultsSensitivity or specificity was used for reporting the results of primary studies in 65/90 (72%) reviews, predictive values in 26/90 (28%), and likelihood ratios in 20/90 (22%). For meta-analysis, pooled sensitivity or specificity was used in 35/60 (58%) reviews, pooled predictive values in 11/60 (18%), pooled likelihood ratios in 13/60 (22%), and pooled diagnostic odds ratio in 5/60 (8%). Summary ROC was used in 44/60 (73%) of the meta-analyses. There were no significant differences in measures of test accuracy among reviews published earlier (1994–97) and those published later (1998–2000).ConclusionsThere is considerable variation in ways of reporting and summarising results of test accuracy studies in systematic reviews. There is a need for consensus about the best ways of reporting results of test accuracy studies in reviews.

Rapid tests for group B Streptococcus colonization in laboring women : A systematic review

OBJECTIVES. We set out to determine the accuracy and rapidity of various intrapartum group B Streptococcus (GBS) colonization tests. STUDY DESIGN. We performed a systematic review of test-accuracy studies, which were identified without language restriction from Medline and Cochrane databases; bibliographies of known primary and review articles; and contact with authors, experts, and manufacturers. Studies were selected if they tested pregnant women intrapartum for GBS colonization and confirmed by “gold-standard” laboratory cultures. Two reviewers independently selected studies and extracted data on their characteristics, quality, and results. Accuracy data were used to form 2 × 2 contingency tables. Heterogeneity was assessed, and LRs for positive and negative test results were pooled in subgroups of studies of various tests. RESULTS. There were 29 test-accuracy studies in 15691 women, evaluating 6 different tests: polymerase chain reaction (PCR), optical immunoassay (OIA), DNA hybridization, enzyme immunoassay, latex agglutination, and Islam starch medium tests. The methodologic quality of the studies was generally poor. The most accurate was the real-time PCR test, but it was less rapid than OIA test. Real-time PCR took 40 minutes to complete, whereas the OIA took 30 minutes. CONCLUSIONS. Real-time PCR and OIA are candidates for rapid near patient intrapartum GBS testing to determine the need for antibiotic prophylaxis to prevent neonatal GBS disease. Before implementation in practice, a robust technology assessment of their accuracy, acceptability, and cost-effectiveness is required.

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.

Electronic searching of the literature for systematic reviews of screening and diagnostic tests for preterm birth.

BACKGROUND Published systematic reviews on prediction of preterm birth have tended to focus on a limited number of tests and their search strategies have often been relatively simple. Evaluation of all available tests in a systemic review will require a broad search strategy. AIM To describe a case study of electronic searching for a systematic review of accuracy studies evaluating all tests for predicting preterm birth. METHODS The search strategy, developed to capture literatures concerning all the tests en-masse consisted of formulation of an appropriate combination of search terms, pilot searches to refine the search term combination, selection of relevant databases, and citation retrieval from the refined searches for selection of potentially relevant papers. Electronic searches were carried out on general bibliographic databases (Biosis, Embase, Medline, Pascal and Scisearch), specialised databases (Database of Abstracts of Reviews of Effectiveness, Medion, National Research Register, Cochrane Controlled Trial Register and Cochrane Database of Systematic Reviews). RESULTS A total of 30076 citations were identified. Of these 8855 (29%) citations were duplications either within a database or across databases. Of the remaining 21221 citations, 3333 were considered potentially relevant to the review after assessment by two reviewers. These citations covered 19 different tests for predicting preterm birth. CONCLUSIONS This case study suggests that with use of a concerted effort to organise and manage the electronic searching it is feasible to undertake broad searches for systematic reviews with multiple questions.

Prediction of spontaneous preterm birth: no good test for predicting a spontaneous preterm birth.

Purpose of review Spontaneous preterm birth complicates 3–11% of pregnancies and is a major cause of neonatal mortality and morbidity worldwide. If accurate tests can be identified, a potentially effective screening strategy with an adjunct preventive therapy may be trialled to reduce the rate of spontaneous preterm birth or effective measures be deployed at an early stage of a suspected spontaneous preterm labour before the onset of cervical changes to ameliorate prematurity complications. Recent findings There are many tests predicting spontaneous preterm births, published in the literature individually or in a systematic review. The information has not been collated about all candidate tests simultaneously in a systematic review incorporating a framework on how these tests may be evaluated, modelled with an intervention to provide a number needed to treat and test to inform decision-making. Summary There were 319 studies evaluating 22 tests. There are many promising tests, for example, history of previous spontaneous preterm birth, cervicovaginal swabs for markers such as fibronectin or HCG, cervical ultrasound, serum CRP and amniotic fluid interleukins for predicting spontaneous preterm birth, but none have exceptional accuracy and the quality of studies was generally poor. Some tests were able to achieve high LR+, but at the expense of LR−, that is, tests good for ruling in disease were poor for ruling out disease and vice versa.

Accuracy of cervico-vaginal fetal fibronectin test in predicting the risk of spontaneous preterm birth—a systematic review

We studied the accuracy with which the cervico-vaginal fetal fibronectin test predicts spontaneous preterm birth in asymptomatic and symptomatic pregnant women. This was a systematic quantitative review of test accuracy studies. Two reviewers selected and extracted data on study characteristics, quality and accuracy independently. Accuracy data were used to form 2 × 2 contingency tables with spontaneous preterm birth before 34 and 37 weeks’ gestation and birth within 7–10 days of testing (only for symptomatic pregnant women) as reference standards. Data were pooled to produce summary receiver operating characteristic (ROC) curves and summary likelihood ratios for positive (LR+) and negative (LR−) test results. There were 64 primary articles consisting of 28 accuracy studies in asymptomatic women and 40 accuracy studies in symptomatic women, including a total of 22 390 women. Among asymptomatic women, the best summary LR+ was 4.01 (95% confidence interval 2.93–5.49) for predicting birth before 34 weeks’ gestation, with corresponding summary LR− of 0.78 (0.72–0.84). Among symptomatic women, the best summary LR+ was 5.42 (4.36–6.74) for predicting birth within 7–10 days of testing, with corresponding summary LR− of 0.25 (0.20–0.31).

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

To determine the accuracy with which various types of tests for bacterial vaginosis (BV) predict spontaneous preterm birth in pregnant women, studies were identified, without language restrictions, through nine different databases and manual searching of bibliographies of known primary and review articles. There are four different BV testing methods: Gram-staining test using either Nugents or Spiegels criteria, gas liquid chromatography and clinical criteria. Two reviewers selected studies independently and extracted data on their characteristics, quality and accuracy with spontaneous preterm birth as the reference standard. 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. There were 18 primary articles, involving a total of 17 868 women. Meta-analysis of studies testing asymptomatic women in the second trimester showed that clinical criteria had an LR+ of 5.14 (95% confidence interval 4.44–6.15) and an LR− of 0.48 (0.42–0.55), Gram-staining (Nugents criteria) had an LR+ of 1.64 (1.44–1.87) and an LR− of 0.88 (0.84–0.92), and Gram-staining (Spiegels criteria) had an LR+ of 2.44 (1.36–4.98) and an LR− of 0.81 (0.64 to 1.01). Among symptomatic women, Gram-staining (Spiegels criteria) had an LR+ of 1.29 (1.03–1.62) and an LR− of 0.85 (0.73–1.00).

Accuracy of cervical transvaginal ultrasonography in predicting preterm birth: a systematic review

To determine the accuracy with which transvaginal cervical ultrasonography predicts spontaneous preterm birth, studies were identified, without language restrictions, through nine different databases (1966–2002) and manual searching of bibliographies of known primary and review articles. Studies were selected if they undertook transvaginal ultrasonographic cervical length measurement among a population of pregnant women antenatally and had known gestation at delivery. Data were extracted for studies’ characteristics, quality and accuracy results for < 32, < 34 and < 37 weeks’ gestation outcome as the reference standards. Data were stratified according to singletons or twins, gestational age at testing, cervical length thresholds and the various reference standards. Data were pooled to produce summary estimates of likelihood ratios (LRs). Forty-six primary articles included a total of 31 577 women, consisting of 33 studies in asymptomatic and 13 studies in symptomatic women. There was a wide variation among studies with respect to gestational age at testing, definition of threshold for abnormality and definition of reference standard. The most commonly reported subgroup was testing of asymptomatic women at 20–24 weeks’ gestation using a threshold of 25 mm with spontaneous preterm birth before 34 weeks’ gestation as the reference standard. The summary LR+ for this group was 4.44 (95% confidence interval (CI) 3.23–6.08), with corresponding LR− of 0.68 (95% CI 0.49–0.94).