Accuracy of FETAL ECHOCARDIOGRAPHY, A systematic review Authors: Abreu, Tânia; med05099@med.up.pt Afonso, Tânia med05100@med.up.pt; Cardoso, Tiago; med05104@med.up.pt Costa, Zoe Ferreira, Vítor (med05240@med.up.pt; (med05107@med.up.pt): Rito, Tiago; med05105@med.up.pt) Rodrigues, Sofia; med05098@med.up.pt Adviser: Cristina Santos; csantos@med.up.pt 1 Bastos, Teresa (med05102@med.up.pt); Santos, Telma (med05101@med.up.pt Class: 22 Abstract Introduction: The fetal echocardiography is the only way we can study fetal heart. It is of great importance since congenital heart diseases have been reported to occur in 8/1000 live births. Aim- Estimate the sensitivity and specificity of fetal echocardiography in detection of cardiac anomalies. Methods- It was made a Medline systematic review of studies about sensitivity and specificity of fetal echocardiography in detection of cardiac anomalies. There were three phases of revision of the articles by the abstracts: in the first and in the second, all the abstracts were read so that each article was read twice by two different revisers; in the third, only the articles in discordance were analysed by a third reviser. We extract true positive, true negatives, false positives and false negatives that were treated in Metadisc (pool sensitivity and specificity). Homogeneity test was performed. We also submitted these articles to some quality criteria to evaluate their relevance Results: We obtained 1696 articles, from which only 16 were included.. Our plot was very heterogeneous so we had to divide it in two groups with different sensitivity values: in the first one the value obtained was 0,92 and in the second one it was 0,46. The specificity was 1,00. Discussion: The lack of concordance among the sensitivity results could be explained by methodological differences (methods, population, quality and date). Differences among populations (high and low risk ) were the main causes to this heterogeneity. Conclusion: Echocardiography is a very useful and reliable tool in the evaluation of the fetal cardiovascular system, and has high sensitivity and specificity for congenital heart diseases in high risk populations. Key words: systematic review, fetal echocardiography, cardiac anomalies, sensitivity, specificity, true positives, true negatives, false positives, false negatives 2 Introduction Fetal Echocardiography is the only way we can study fetal heart. This technique requires the use of high-resolution ultrasound equipment with Mmode, pulsed and colour Doppler imaging capabilities [1]. Congenital heart disease has been reported to occur in 8/1000 live births. Prenatal diagnosis of congenital heart disease is crucial to optimal obstetric and neonatal care. In utero identification of congenital heart disease allows a variety of treatment options to be considered, including delivery at an appropriate facility, termination of pregnancy and in some cases in utero therapy. With this presentation, we intend to study the specificity and sensitivity of fetal echocardiography in detection of cardiac anomalies. Sensitivity and specificity are the most widely used statistics used to describe a diagnostic test. sensitivity is the probability of a positive test among patients with disease specificity is the probability of a negative test among patients without disease Clinicians don’t generally know whether or not the human fetus has a heart disease; that’s why they order the test in the first place. Thus, sensitivity and specificity do not give the information needed to interpret the test results, these parameters provide just an idea of how reliable the test results are. Anyway, no matter how high these values may be, there is always a small margin of error. Picture 1 : M-mode echocardiography [1] Picture 2: Pulsed Doppler echocardiography. [1] Picture 3: colour Doppler echocardiography [1] Picture 4: Power Doppler echocardiography [1]. 3 OBJECTIVE Our study was designed to collect all the information about the sensitivity and specificity of fetal echocardiography in detection of cardiac anomalies. This systematic review was made to show whether this diagnostic test is effective or not and what the scale of trust we can expect from it. Methods ARTICLE’S SEACH Pubmed and SCOPUS were the databases selected. a) In Pubmed our original query [2] selected was: #1 ( (((((("sensitivity and specificity"[All Fields] OR "sensitivity and specificity/standards"[All Fields]) OR "specificity"[All Fields]) OR"screening"[All Fields]) OR "false positive"[All Fields]) OR "false negative"[All Fields]) OR "accuracy"[All Fields]) OR ((("predictive value"[All Fields] OR "predictive value of tests"[All Fields]) OR "predictive value of tests/standards"[All Fields]) OR "predictive values"[All Fields]) OR "predictive values of tests"[All Fields]) ) #2 (("reference value"[All Fields] OR "reference values"[All Fields]) OR "reference values/standards"[All Fields]) #3 ((((((((((("roc"[All Fields] OR "roc analyses"[All Fields]) OR "roc analysis"[All Fields]) OR "roc and"[All Fields]) OR "roc area"[All Fields]) OR "roc auc"[All Fields]) OR "roc characteristics"[All Fields]) OR "roc curve"[All Fields]) OR "roc curve method"[All Fields]) OR "roc curves"[All Fields]) OR "roc estimated"[All Fields]) OR "roc evaluation"[All Fields]) ((((( #1 OR #2) OR #3) OR "likelihoodratio"[All Fields]) AND notpubref [sb]) AND "human"[MeSH Terms]) This query must provide all studies of sensitivity and specificity existent in Pubmed. So, to adequate it with our subject we had to include some key words and exclude “notpubref” (because of technical problems): AND ("echocardiography" OR echocardiography[MeSH Terms]) AND (Heart Defects, Congenital[MeSH Terms] OR "cardiac anomalies") Furthermore, we limited the cases studied to humans and to articles published until August 1st 2005. As a result, 1044 articles were found. Initially we obtained 1042 articles. Then, when we repeated the Pubmed search two another articles were added to our study. b) next, we applied a similar query in SCOPUS to obtain more articles. First, we had to adapt the query used in Pubmed to the SCOPUS software. So, we made the following changes: substitute All Fields and Mesh Terms for ALL. The result was: 4 (((((((((((ALL("sensitivity and specificity") OR ALL("sensitivity and specificity/standards")) OR ALL("specificity")) OR ALL("screening")) OR ALL("false positive")) OR ALL("false negative")) OR ALL("accuracy")) OR (((ALL("predictive value") OR ALL("predictive value of tests")) OR ALL("predictive value of tests/standards")) OR ALL("predictive values")) OR ALL("predictive values of tests"))) OR (ALL("reference value") OR ALL("reference values") OR ALL("reference values/standards"))) OR ((((((((((((ALL("roc") OR ALL("roc analyses")) OR ALL("roc analysis")) OR ALL("roc and")) OR ALL("roc area")) OR ALL("roc auc")) OR ALL("roc characteristics")) OR ALL("roc curve")) OR ALL("roc curve method")) OR ALL("roc curves")) OR ALL("roc estimated")) OR ALL("roc evaluation")))) AND (("echocardiography" OR ALL("echocardiography")) AND ALL(congenital heart defects) OR ALL("cardiac anomalies"))) We obtained 1370 articles. Next, we submitted these articles to the following limits: First, we added to the query AND ( EXCLUDE(PUBYEAR,2006) ) because our Pubmed query did not include articles published in 2006. The number reduced to 1342 articles; Second, we added AND (EXCLUDE(SUBJAREA, "VETE")) to restrict our search to humans. 1331 articles obtained. Finally, we added AND ALL(Fetus OR Fetuses OR fetal OR neonatal OR prenatal OR antenatal OR perinatal OR embryonic OR pregnancy OR pregnant OR pregnancies OR obstetric OR gestation OR utero OR feto OR fetos OR pré-natal OR gravidez OR grávida OR gestação OR útero) to include exclusively fethus in our study; As a result we obtained 810 articles. As we can see, 1954 articles were found. To remove repeated articles from the search we work with EndNote. The EndNote is a software which associates bibliographic resources. We made used of this to separate the articles existing in SCOPUS which are different from that obtained in Pubmed. We obtained 158 articles in common, which we excluded. Articles in Pubmed Articles in SCOPUS 1044 + 810 1854 Repeated articles - 158 1696 articles Tab refering the total articles obtained 5 ABSTRACT’S ANALYSIS In a first analyse we divided the articles with all students. Each one read 116 abstracts and selected those which follow our inclusion/exclusion criteria: To be applied to humans, fethus, in particular; Refer the echocardiography as the only diagnostic test used; Cardiac anomalies as the subject in study; Articles with their abstracts available; Sensitivity and specificity studies; Language: english and portuguese; A second reviewer analysed the abstracts and we compared the results between them. When there were no concordance, a third reviewer read these abstracts and came to a decision. We used SPSS as a statistic program which allowed an easier calculation of frequencies of two variables in study. As we can see in picture 5, we calculated the number of articles included: the result is 157 (from Pubmed) + 91 (from SCOPUS) 248 articles. As we obtained the articles of interest we search their full text, using the following strategy, attending that if the article were not available we selected other sources, according to that order: first, search in Pubmed; second, faculty’s library; third, contacting the autor (s) by e-mail. QUALITY CRITERIA To evaluate how relevant these articles are we needed to submit them to some quality criteria. With this purpose, we selected the STARD checklist [3]. In fact, this consists of twenty-five items which we have to select how many conditions does the articles fulfils. According to this checklist, the more items satisfied by the articles, the more powerful is the test designed. We adopted the following strategy: a) in a first approach the articles were analysed by one reviewer; b) subsequently, we are going to analyse the others for the first time, and then, submit all to a second reviser, in order to eliminate the more errors we can. Moreover, the concordance between the two reviewers will be analysed, too. The results of this evaluation will be expressed in a SPSS table and in a excel graph. DESCRIPTIVE STATISTICS Metadisc was the adopted software to treat the information extracted from the full article. This included the number of: a)True positives; b)True negatives; c)False positives; and d)False negatives cases; With these results introduced, the software designs a forest plot. By analysing this graphics we are able to get some conclusions about the grade of sensitivity and specificity of fetal echocardiography in detection of cardiac anomalies. The plot obtained now is just a first interpretation of the final results. HOMOGENEITY VS HETEROGEINITY Finally, we intend to study the homogeneity/heterogeneity of all our results. This is important because we need to know whether the variance found is or is not the result of the variability of the sample. 6 So, we need to: a) evaluate the heterogeneity’s degree; b) find and explore the causes of this problem; c) adapt these results with the interpretation of the problem in study. This fact will be analysed with a Chi-square test. This will permit us to evaluate the heterogeneity by calculating the p value, with a significance level of 5%. If the p value obtained > 0.05, our results are relatively homogenous; whereas if the p value < 0.05, the heterogeneity are statistically relevant. FINAL EVALUATION With the forest plot and the degree of heterogeneity we are able to associate this information to understand the results obtained. This means that, if the situation justifies, we will proceed to a subgroups analyses, giving more relevance to the results with more quality. In addition to divide into subgroups, we can change the scale or designing a meta-regression. FLOWCHART 1 We designed a flowchart reflecting the methods used in our project. FLOWCHART 2 Results 7 SENSITIVITY AND SPECIFICITY RESULTS A forest plot of sensitivity and specificity were designed with Metadisc: Graph 1 - Articles with high sensitivity Graph 2 – Articles with low sensitivity 8 Graph 3 – Specificity Discussion QUALITY CRITERIA ANALYSES The table 1 illustrates a great variance of quality among the articles found. The quality mean – 15,8 (out of 25) – reveal that these articles have a reasonable classification in terms of quality. DATA ANALYSES Analysing the sensitivity of the studies included, we noticed that there was a great heterogeneity among them. One group had a low sensitivity value and the other had a high one. The aspects considered to explain the different sensitivities were: methods, population, quality and date. In high risk population studies, the sensitivity values tend to be high. On the contrary, in low risk population studies, the sensitivity was lower. 9 We also noticed that studies that used extensive echocardiography had a higher sensitivity and studies that used a common four-chamber view had lower sensitivity values. The extended echocardiography comprised the four-chamber view, and visualisation on the left ventricular outflow tract, the right ventricular outflow tract and the main pulmonary artery and its branches [4] All the articles had a very high specificity value. Conclusion Nowadays, we use the four-chamber view in low risk population, and extended echocardiography in high risk population. However, we have to consider that most neonates with congenital heart disease are born in women without any previous known risk factors. So, since four-chamber view is less expensive, needs less human resources and in high risk population the sensitivity tends to be higher with both techniques [4], we are able to conclude that the four-chamber view may be enough to detect cardiac anomalies in high risk population. The four-chamber view appears to be ineffective in low risk population as a screening method. So, if any, the screening technique to be used should be the extensive echocardiography. In the future, it would be useful to investigate how different the cost can be. As specificity values seem to be all alike, we can assume that fetal echocardiography has a great specificity, almost 100%. References [1] Julia A. Drose, “Fetal Echography”, W.B. Saunders Company Lindsey Allan, Lisa K Hornberger, Gurleen Sharland, “Text Book of fetal cardiology”, GMM [2] “Conducting systematic reviews of diagnostic studies: didactic guidelines” – http://www.biomedcentral.com/1471-2288/2/9. [3] “Towards complete and Accurate Reporting of Studies of diagnostic Accuracy: The STARD Initiative” – Patrick M. Bossuyt et al; available on http/www.annals.org. 10