{"paper_id":"337b2cac-91cb-4d57-9c51-6ed99625bf13","body_text":"Reliability of Echocardiographic Measurements in Infants Exposed to Zika Virus. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Reliability of Echocardiographic Measurements in Infants Exposed to Zika Virus. Dulce Helena Gonçalves Orofino , Sonia Regina Lambert Passos, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-38421/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Ecocardiography is currently the gold standard imaging method for the diagnosis of most congenital and acquired cardiopathies and for the evaluation of myocardial function and cardiac chamber size and overload. Ecocardiographic measures of left ventricular and right ventricular structure and function are used to define ventricular function and guide medical decisions.The objective of this study is to assess the reproducibility of echocardiographic cardiac chamber measurements in infants in utero exposed to Zika virus. Methods: Masked cross-sectional diagnostic study with two independent measurements of cardiac chamber dimensions using echocardiography. We studied 50 infants with in utero exposure to Zika virus ranging from 30 to 270 days old of the outpatient clinic of a national reference center for maternal and child health, Rio de Janeiro, Brazil.The analysis included the measurements of the aortic root, left atrium, end diastolic left ventricle, systolic left ventricule, left ventricular ejection fraction, ventricular end diastolic septal thickness, end diastolic thickness of the left ventricular posterior wall and right ventricule. Bland-Altman plots were used to explore differences. Agreement according to intraclass correlation coefficients (ICC) was interpreted as follows: excellent≥0.75, fair to good 0.4≤ICC<0.75, and poor with ICC<0.4. Results: All parameters had mean difference of diameters near to zero, excluding left ventricule ejection fraction. Ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall showed few unique mean values. Reproducibility was excellent for the aortic root and end diastolic left ventricule (ICC=0.86 and 0.91, respectively), fair/good to poor for other parameters and the left ventricule ejection fraction, ventricular end diastolic septal thickness and the end diastolic thickness of the left ventricular posterior wall showed the lowest reproducibility (ICC=0.46,0.37,0.53, respectively). Conclusions: The minor divergences did not affect the echocardiography results in our sample. However, caution is required to interpret results of measures with low reproducibility. Nuclear Medicine & Medical Imaging Reproducibility echocardiography cardiac chamber dimensions Zika virus Figures Figure 1 Figure 2 Background: Ecocardiography (ECHO) is currently the gold standard imaging method for the diagnosis of most congenital and acquired cardiopathies and for the evaluation of myocardial function and cardiac chamber size and overload. It is a non-invasive and safe test with rapid real-time acquisition of images at low cost and without contraindications. Ecocardiographic measures of left ventricular (LV) and right ventricular (RV) structure and function are used to define ventricular function and guide decisions to the need for indication of inotropic medications, to assess the hemodynamic repercussions of patent ductus arteriosus (PDA) in premature infants and the possible need for pharmacological or surgical closure, to assess the repercussions and indication of closure of pulmonary hyper-flow congenital cardiopathies like ventricular septal defect (VSD) and atrial septal defect (ASD), for pharmacological and surgical treatment of valvular regurgitations like mitral valve insufficiency (MVI) and aortic valve insufficiency (AVI), and to determine the most adequate surgical procedure in cases of complex congenital cardiopathies.[ 1 ] Despite the clinical and research importance placed on pediatric echocardiographic measurements, little has been published about the reliability of these measurements for which multiple raters independently measure the same sample when the true value is not known.[ 2 ] Studies from the 1970s and 1980s provided the normal parameters for cardiac cavitary dimensions until 2000,[ 3 , 4 ] when the results from a study in 2,036 children were published, redefining the normal ranges for parameters through the production of graphs that used body surface as a criterion and established mean values -/+ 2 standard deviations for each measurement.[ 5 ] As with any measurement, echocardiographic quantification is subject to error, so it is important to assess the degree of agreement between two observers. Intraclass correlation coefficient (ICC) estimates the fraction of the total variability of measurements due to inter-individual variations. Variation due to errors should include different components, depending on the study design.[ 6 ] The Bland-Altman plot is used to assess agreement between two quantitative measurements. The mean and standard deviation of the measurements are used to calculate the agreement’s statistical limits. Bland-Altman is a scatter plot in which the Y axis is the difference between the two paired measurements and the X axis is the mean of these measurements. The diameter of the points is directly proportional to the frequency of inter-examiner agreement.[ 7 , 8 ] In previous study, our search group demonstrated cardiac alterations associated with in utero exposure to Zika virus (ZIKV): 10% of patients presented major defects such as ASD, VSD, and PDA.[ 9 ] We study the reliability of cardiac chamber measurements using ECHO in a sample of patients from a cohort of infants in utero exposed to ZIKV followed by a Brazilian national reference center to maternal and child health. All the infants were referred for a clinical and echocardiographic evaluation. Methods: We performed a blinded cross-sectional diagnostic study with two independent measurements of cardiac dimensions using ECHO of infants born between November 2015 and January 2017 who were followed at our outpatient Pediatric Infectious Disease Clinic at the Fernandes Figueira Institute (IFF-FIOCRUZ). The infants who received echocardiograms were born either at IFF or other institutions with positive ZIKV maternal polymerase chain reaction (PCR) results during pregnancy or positive PCR results at birth. Our institution is a national research referral center for high risk pregnancies and high risk infants. For this reason, during the Zika epidemic we were the major referral center in Rio de Janeiro for cases of suspected maternal or infant ZIKV infection. The study was approved by the Institutional Review Board of the Brazilian National Institute of Infectious Diseases (INI-FIOCRUZ – CAAE 62728516.2.0000.5262). All parents or guardians provided written informed consent. All data analyzed were anonymized. The tests were performed by two of the three pediatric cardiologists at the Department of Pediatric Cardiology of IFF, using an Acuson X300 echocardiography system, blinded in relation to the previous tests.The doubles were chosen at random. All pediatric cardiologists are certified specialists in Pediatric Cardiology by the Brazilian Society of Cardiology and Brazilian Society of Pediatrics and have at least 15 years of practice in the specialty. No patient required sedation to undergo the tests, which were repeated by the respective examiners with a maximum interval of 15 days. The tests were performed during the normal patient flow in the Pediatric Cardiology Outpatient Department of IFF, and the cavitary measurements were taken. The cardiological evaluation took place between 30 and 270 days of life and included measurements of aortic root, left atrium, end-diastolic left ventricle, systolic left ventricle, right ventricle, left ventricular ejection fraction, ventricular end-diastolic septum thickness, and end diastolic thickness of the left ventricular posterior wall. Measurements were taken at the cross-sections defined in the echocardiography guidelines, namely the unidimensional mode of the parasternal longitudinal section of the long axis of the left ventricle at the level of the aortic valve leaflets to measure the aorta and left atrium, and for the others, the parasternal section of the short axis of the left ventricle at the level of the mitral valve leaflets.[ 1 ] The analysis was performed in Med Calc 17.9 and the free software R 3.5.1 [ 10 ]in the BlandAltmanLeh and nopaco packages. The median values expressed in centimeters with the respective interquartile ranges (IQR) were summarized in tables and compared with the normal values according to body surface wich does not change in 15 days.[ 5 ] Due to rejection of the normality of measurements according to the boxplot and Shapiro-Wilk test, the measurements were also compared between the two observers using the Wilcoxon non-parametric test. Intraclass correlation coefficients (ICC) were calculated (measures of unique consistency and means), with the respective 95% confidence intervals (95% CI). Interpretation of ICC values was as follows: excellent reliability when ≥ 0.75, fair to good with 0.4 ≤ ICC < 0.75, and poor when ICC < 0.4.[ 6 ] Bland-Altman plots were produced to explore the distribution of each ECHO measurement considering the size of the differences between the two independent evaluations, using as the reference the mean of the differences and limits determined by two standard deviations below and above the mean. Each point’s size is determined by the value’s frequency. Few unique observations and concentration of points in certain mean values can lead to bad overall agreement parameters, as for example ICC. Results: We performed two echocardiograms with maximum interval of 15 days in 50 infants of the 120 patients who were brought by their parents or guardians to the pediatric clinic for a cardiac consult and performance of an echocardiogram because of the in utero exposure to ZIKV. No infant had a diagnosis of congenital cardiopathy with hemodynamic repercussions. The mean age of the 50 infants was 111 days (95% CI = 94.7-127.3), with body surface varying from 0.2 to 0.3 m 2 ; 60% were girls, and 86% were term infants. Table 1 showed the medians calculated for the measurements performed by observers 1 and 2. The medians for the measurements were mostly identical. All the median measurements were within normal ranges. Table 1 Dimensions (in centimeters) of two independent echocardiographic measurements in 50 infants (medians and interquartile ranges) with in utero exposure to ZIKV, and respective normal values. Appraiser 1 Appraiser 2 Normal values Parameter (Diameter) Body surface 0.25 m 2 0.30 m 2 Median (IQ*) Mean Median (IQ*) Mean p value † Mean Mean (95%CI) (95%CI) (95%CI ‡ ) (95%CI ‡ ) Aortic root (cm) 1.10 (1.00-1.20) 1.09 (1.04–1.14) 1.10 (1.00-1.20) 1.11 (1.06–1.16) 0.401 1.04 (0.80–1.28) 1.13 (0.9–1.36) Left atrium(cm) 1.40 (1.20–1.60) 1.40 (1.32–1.47) 1.40 (1.30–1.60) 1.42 (1.35–1.49) 0.688 1.40 (1.05–1.75) 1.53 (1.15–1.91) End-diastolic left ventricule (cm) 2.10 (1.90–2.40) 2.10 (1.99–2.21) 2.10 (1.90–2.40) 2.10 (2.00-2.20) 0.694 2.0 (1.64–2.36) 2.29 (1.8–2.58) Systolic left ventricule (cm) 1.20 (1.00-1.30) 1.18 (1.11–1.25) 1.30 (1.10–1.40) 1.25 (1.19–1.32) 0.052 1.32 (1.02– 1.62) 1.48 (1.08–1.88) Ventricular end-diastolic septal thickness (cm) 0.40 (0.30–0.40) 0.38 (0.36–0.41) 0.40 (0.30–0.40) 0.38 (0.36–0.41) 0.596 0.38 (0.24–0.52) 0.39 (0.25–0.53) End-diastolic thickness of the left ventricular posterior wall (cm) 0.40 (0.30–0.40) 0.37 (0.34–0.39) 0.40 (0.30–0.40) 0.35 (0.33–0.38) 0.260 0.36 (0.26–0.46) 0.41 (0.28–0.54) Right ventricule (cm) 0.90 (0.73-1.00) 0.89 (0.84–0.95) 0.90 (0.80–0.90) 0.87 (0.83–0.91) 0.381 0.87 (0.42–1.32) 0.87 (0.42–1.32) Left ventricule ejection fraction (%) 76.5 (69.0-82.8) 75.7 (73.2–78.2) 69.5 (66.0-74.8) 70.4 (68.3–72.5) 0.003 > 55 > 55 *Interquartile ranges; † Wilcoxon test (p value < 0,05); ‡ Confidence interval. Table 2 showed ICC for the measurements performed by observers 1 and 2. Table 2 Reliabiltiy of target parameters in two independent echocardiographic measurements, expressed as intraclass correlation coefficients (ICC) and respective 95% confidence intervals in 50 infants with in utero exposure to ZIKV. Parameter (diameter in cm) Single Interpretation ICC 95% CI Aortic root 0.75 0.60 0.85 Excellent Left atrium 0.43 0.17 0.63 Fair / Good End-diastolic left ventricule 0.83 0.72 0.90 Excellent Systolic left ventricule 0.44 0.19 0.64 Fair / Good Ventricular end-diastolic septal thickness 0.23 -0.049 0.48 Poor End-diastolic-thickness of the left ventricular posterior wall 0.36 0.09 0.58 Poor Right ventricule 0.40 0.14 0.61 Fair / Good Left ventricule ejection fraction 0.19 -0.04 0.09 Poor Diameters of aortic root and end-diastolic left ventricle had low differences between two observers, with mean difference near to zero and mean values varied up to 0.5 cm (Fig. 1). Medians of aortic root and end-diastolic left ventricle (1.1 cm and 2.1 cm) did not show differences between two evaluations (p > 0.05, Table 1 ). Also, it was observed excellent agreement for these two measurements (Table 2 ). The Bland Altman plot of diameter of systolic left ventricle showed low differences between two observers, with mean difference near to zero and mean values varied up to 0.6 cm (Fig. 1). Medians of systolic left ventricle (1.2 and 1.1 cm) did not show differences between two measurements (p > 0.05, Table 1 ). The agreement was considered good (Table 2 ). Although the mean difference in diameter of ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall are near to zero, few unique mean values were observed (Fig. 1). Medians of ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall (0.4 and 0.4 cm) did not show differences between two observers (p > 0.05, Table 1 ). These measurements were the lowest structures when compared with others (Table 1 ). The agreement was considered poor (Table 2 ). Other measurement with low agreement between observers was left ventricle ejection fraction (Table 2 ). The medians were higher 7 percentage points when compared by the two observers (p < 0.05, Table 1 ). Discussion: This is one of the first studies on the reliabiltiy of echocardiographic parameters in infants. The most reliable parameters were the diameters of aortic root and end-diastolic left ventricle, while the other parameters varied from good/fair to bad, especially those with smaller dimensions, namely ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall. However, the disagreements occurred in approximately 0.5% of patients. The small divergences did not affect the echocardiographic test reports, which could be explained by the fact that differences of 1 mm altered the reliability of two measures but did not exceed the normal range for the cavitary measurements assessed in this study. Since the system calculates left ventricle ejection fraction as the ratio between end-diastolic left ventricle and systolic left ventricle, it was mainly affected by the discrepancies in the measurements of the systolic left ventricle. Medical consensuses and guidelines use clinical and complementary test criteria to orient diagnosis and treatment decisions. This involves assessing the parameters’ diagnostic accuracy by measuring the sensitivity and specificity, with reliability as a prerequisite for accuracy.[ 10 ] Echocardiography is an easy test to perform, and its use as a parameter to guide clinical or surgical approaches requires good reliability of measurements obtained by different observers. However, there is little information in the literature on the reliability of the parameters obtained with echocardiography and that are used in cardiology guidelines to indicate closure of the ductus arteriosus, VSD, and ASD or valvuloplasty in cases of valvular insufficiencies such as rheumatic mitral and aortic valve insufficiencies. Geelhoed et al found good reliability for echocardiographic measurements of left heart structures in 28 healthy children with median age of 7.5 years.[ 12 ] Another study assessing reliability of left ventricular systolic function of 59 potential pediatric heart donnors with less than 18 years reported that ICC between measurements done by local hospitals and by trained pediatric cardiologist at a pediatric heart center was 0,59 (fair to good) and in this study, 20% of echocardiograms with LV dysfunction by local measurements turned out to have normal function when measured in the central laboratory.[ 13 ] Lipshultz et al compared measurements of LV dimension and wall thickness obtained on 735 children of HIV-mothers at 10 clinical sites and concluded that they differed so much that a central echocardiographic facility is needed to provided consistent and reliable data for research studies and clinically meaningful results.[ 14 ]None of these studies evaluated infants. The low reliability of a test limits the generalization of approaches and recommendations in guidelines and consensus.[ 15 , 16 ] As an example, the score proposed by McNamara and Sehgal for closure of the PDA in premature infants included clinical criteria and echocardiographic measurements. Among the measurements tested, those with the highest predictive value for indication of closure of a hemodynamically significant PDA were the size of aortic root and left atrium, but they were also the parameters with the lowest inter-examiner reliability.[ 15 ] In our study, the size of aortic root showed excellent reliability, while reliability of left atrium was fair. This suggests that the use of this score or any other to indicate closure of PDA may be compromised by the difficulty in reproducing these measurements by different observers and in distinct settings. Schwarz et al. (2016) studied the reliability of echocardiographic parameters for the diagnosis of PDA in low birth weight premature infants and found bad reliability for the size of aortic root and left atrium, while the reliability was somewhat better for other parameters (short axis of the ductus arteriosus, resistance index of the celiac artery and anterior cerebral artery, among others)but some of these parameters were not assessed in our study.[ 17 ] Alterations in the Bland-Altmann plot may occur due to the limited number of unique observations and the concentration of points at given mean values, which can lead to low overall agreement indices (e.g., ICC). ICC also considers normal data and is affected by the data’s deviation from normality and variability, as is the Bland-Altman plot. Due to the non-normality of four of the parameters studied in the current sample (systolic left ventricle, ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall and right ventricle), caution is recommended when interpreting the plots, as well as the reliability results (ICC). This study has limitations. The sample size is small but was similar to or larger than other studies on this topic in the literature and the observers have high and homogeneous level of training. Conclusions: Although we found variable reliability for all the cardiac measurements, the minor divergences did not affect the echocardiography results in our sample. However, caution is required to interpret results of measures with low reliability (ventricular end-diastolic septal thickness, end-diastolic-thickness of the left ventricular posterior wall and left ventricle ejection fraction). List Of Abreviations: ECHO:Echocardiography LV: Left ventricle RV: Right ventricle PDA: Patente ductus arteriosus VSD: Ventricular septal defect ASD: Atrial septal defect MVI: Mitral valve insufficiency AVI: Aortic valve insufficiency IQR: Interquartile ranges ICC: Intraclass correlation coefficient PCR: Polymerase chain reaction Declarations Ethics approval and consent to participate: The study was approved by the Institutional Review Board of the Brazilian National Institute of Infectious Diseases (INI-FIOCRUZ – CAAE 62728516.2.0000.5262). All parents or guardians of minors included in this study provided written informed consent. Consent for publication : Not applicable. Data availability : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests : The authors declare that they have no competing interests\" in this section. Funding : This study was supported by MCTI and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq,Brasília) Grant 440846/2016-1 and Coordenacão de Aperfeiçoamento de Pessoal de Nível Superior (CAPES,Brasília) Grant 88881130793/2016-01. Sonia R.L.Passos had grants from CNPq 310765 /2016-1 and by Universidade Estácio de Sá Produtividade em Pesquisa, RJ. Thiago M Ramos had a scholarship by ITI A CNPq,Brasília Processo: 180767/2017-8 ; Letícia M.L. e Silva had a scholarship by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES,Brasília) Grant 88887130789/2016-00. The funders had no role in study design, data collection and analysis , decision to publish, or preparation of the manuscript. Authors' contributions : All authors contribute to the conception of the study.DHGO,SRLP,RVCO,TMR,LMLS and RO conducted the analysis and wrote the first draft. DHGO, CVBF and MFMPL performed the exams and provided critical editorial input. All authors read and approved the final manuscript. Acknowledgements: SRLP was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants Nº 440846/2016-1 and 310765/2016-1, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), grant Nº 88881130793/2016-01, and by Universidade Estácio de Sá - Produtividade em Pesquisa. LMLS was supported by CAPES grant Nº 88887.162025/2017-00. RO and TMR had a scholarship ITI-A from CNPq. References 1 Grau CRPC, Kozak MF, Guerra VC. Ecocardiografia. In: Croti UA, Mattos SS, Pinto Jr VC, Aiello VD, Moreira VM. Cardiologia e Cirurgia Cardiovascular Pediátrica. 2 a ed. São Paulo:Roca 2012: 119-40. 2 Fleiss, JL. The design and analysis of clinical experiments. New York, NY: John Wiley and Sons; 1986. 3 Epstein ML, Goldberg SJ, Allen HD, Konecke L, Wood J. Great vessel, cardiac chamber, and wall growth patterns in normal children. Circulation 1076Jun;51(6):1124-9. 4 Henry WL, Gardin JM, Ware JH.Echocardiographic measurements in normal subjects from infancy to old age. Circulation 1980Nov;62(5):1054-61. 5 Kampmann C, Wiethoff C, Wenzel A, et al. Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe. Heart 2000;83(6):667-672. doi:10.1136/heart.83.6.667. 6 Shrout PE, Fleiss JL. Intraclass Correlations: Uses in Assessing Rater Reliability. Psychological Bulletin 1979;86(2):420-428 7 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1(8476):307–10. doi: 10.1016/S0140-6736(86)90837- 8 Giavarina D. Understanding Bland Altman analysis. Biochemia Medica 2015;25(2):141-151. doi:10.11613/BM.2015.015. 9 Orofino DHG, Passos SRL, de Oliveira RVC, Farias CVB, Leite MdFMP, Pone SM, et al. (2018) Cardiac findings in infants with in utero exposure to Zika virus- a cross sectional study . PLoS Negl Trop Dis. 2018Mar 26;12(3): e0006362. doi: 10.1371/journal.pntd.0006362. eCollection 2018 Mar 10 R Core Team (2015). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/. 11 Bossuyt PMM, Reitsma JB, Bruns DE, et al. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Clin Chem . 2003;49(1):7-18. 12 Geelhoed MJ, Snijders SP, Kleyburg-Linkers VE, Steegers EA, van Osch-Gevers L, Jaddoe VW. Reliability of echocardiographic measurements of left cardiac structures in healthy children. Cardiol Young 2009 Sep;19(5):494-500. doi: 10.1017/S1047951109990862. Epub 2009 Aug 20. 13 Chen S, Selamet Tierney ES, Khush KK, Nguyen J, Goldstein BA, May LJ, Hollander SA, Kaufman BD, Rosenthal DN. Reliability of echocardiographic measurements of left ventricular systolic function in potential pediatric heart transplant donors. J Heart Lung Transp 2015Jan;34(1):100-6. doi: 10.1016/j.healun.2014.08.019. Epub 2014 Aug 28. 14 Lipshultz SE, Easley KA, Orav EJ, Kaplan S, Starc TJ, Bricker JT, Lai WW, Moodie DS, Sopko G, Schluchter MD, Colan SD. Reliability of Multicenter Pediatric Echocardiographic Measurements of Left Ventricular Structure and Function: The Prospective P 2 C 2 HIV Study. Circulation. 2001 Jul 17;104(3):310-6. 15 McNamara PJ, Sehgal A. Towards rational management of the patent ductus arteriosus: the need for disease staging. Arch Dis Child Fetal Neonatal Edition 2007;92(6): F424–7. doi: 10.1136/adc.2007.118117. 16 Iyer P, Evans N. Re-evaluation of left atrium to aortic root ratio as a marker of patent ductus arteriosus. Arch Dis Fetal Neonatal Ed 1994;70:f112-7. 17 Schwarz C E, Preusche A, Baden W Poets C F,Franz A R.Repeatability of echocardiographic parameters to evaluate the hemodynamic relevance of patent ductus arteriosus in preterm infants: a prospective observational study. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-38421\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research article\",\"associatedPublications\":[],\"authors\":[{\"id\":2390179,\"identity\":\"6c6feb33-23d1-41b3-b047-b4a403c63d34\",\"order_by\":0,\"name\":\" Dulce Helena Gonçalves Orofino \",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYDCCA8wNYJq9GUh8YGBIgEkkYFUO1sII0cJzmIGBcQZpWg4wMDDzEKOF70Zi44cPFffkeNh5Dz62bbPL42dvYPzwMYchz7wBuxbJG4nNkjPOFBvzMPMlG+e2JRdL9hxglpy5jaFY5gB2LQY3EtuYedsSEvcz85hJ57YxJ264kcDGzLuNIXEGDoeBtfwFaukBabFsqydSCyNMC2PbYcJaJM88bJbsOZMA9AuPsWHPueOJM3sONgP9IlEsgSvEjicf/PCjIkGOh/+M4YMfZdWJ/ezNBz983GaTh0sLKmBkA5MNQII4DUDwh1iFo2AUjIJRMJIAAGVHWa3JAsk+AAAAAElFTkSuQmCC\",\"orcid\":\"https://orcid.org/0000-0002-0953-1831\",\"institution\":\"Instituto Fernandes Figueira\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Dulce\",\"middleName\":\"Helena Gonçalves\",\"lastName\":\"Orofino\",\"suffix\":\"\"},{\"id\":2390180,\"identity\":\"773edaae-8957-4721-9102-5195fbe71c9a\",\"order_by\":1,\"name\":\"Sonia Regina Lambert Passos\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Fundacao Oswaldo Cruz\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Sonia\",\"middleName\":\"Regina Lambert\",\"lastName\":\"Passos\",\"suffix\":\"\"},{\"id\":2390181,\"identity\":\"bdd1d0a6-b3e6-4bed-a4e5-112830e1973d\",\"order_by\":2,\"name\":\"Maria de Fatima Moreira Pereira Leite\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Instituto Fernandes Figueira\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Maria\",\"middleName\":\"de Fatima Moreira Pereira\",\"lastName\":\"Leite\",\"suffix\":\"\"},{\"id\":2390182,\"identity\":\"c6b4e0c9-a80f-4811-b239-d67dc3a0f1f4\",\"order_by\":3,\"name\":\"Carla Verona Barreto Farias\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Instituto Fernandes Figueira\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Carla\",\"middleName\":\"Verona Barreto\",\"lastName\":\"Farias\",\"suffix\":\"\"},{\"id\":2390183,\"identity\":\"b875b26c-7371-4d35-b1b6-e5d6acce8843\",\"order_by\":4,\"name\":\"Thiago Moreira Ramos\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Universidade Estacio de Sa - Campus Reboucas-Rio Comprido\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Thiago\",\"middleName\":\"Moreira\",\"lastName\":\"Ramos\",\"suffix\":\"\"},{\"id\":2390184,\"identity\":\"db78bb75-1518-438c-9a1e-6600a001cd4a\",\"order_by\":5,\"name\":\"Leticia Machado Lima e Silva\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Universidade Estacio de Sa\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Leticia\",\"middleName\":\"Machado Lima e\",\"lastName\":\"Silva\",\"suffix\":\"\"},{\"id\":2390185,\"identity\":\"60888c22-c9b0-4f19-a77b-e24a1e623d08\",\"order_by\":6,\"name\":\"Raffaela Andrade Oliva\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Universidade Estacio de Sa - Campus Reboucas-Rio Comprido\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Raffaela\",\"middleName\":\"Andrade\",\"lastName\":\"Oliva\",\"suffix\":\"\"},{\"id\":2390186,\"identity\":\"6e1b8213-0543-439e-858d-bdc4767622b5\",\"order_by\":7,\"name\":\"Raquel de Vasconcellos Carvalhaes Oliveira\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Fundacao Oswaldo Cruz\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Raquel\",\"middleName\":\"de Vasconcellos Carvalhaes\",\"lastName\":\"Oliveira\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2020-06-29 08:27:01\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-38421/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-38421/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":2457307,\"identity\":\"921c5779-2b12-4cf0-988c-b8cd57c4cca7\",\"added_by\":\"auto\",\"created_at\":\"2020-09-17 16:05:59\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":146569,\"visible\":true,\"origin\":\"\",\"legend\":\"Bland-Altman plots of measurements of aorta and left ventricule in diastole diameter in 50 infants with in utero exposure to ZIKV. Rio de Janeiro, Brazil, 2018. \\nBland-Altman plot of ECHO measurements with excellent agreement by two pediatric cardiologists. Brazil, 2018. \\nNote:AO=aortic root, EDLV=end-diastolic left ventricule, SD=standard Deviation, CE1=cardiological evaluation 1 and CE2=cardiological evaluation 2. Excellent agreement (Mean difference between CEs near to zero and low differences). \\n\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-38421/v1/1.png\"},{\"id\":2457308,\"identity\":\"0fa087ce-8e22-476e-bb34-25e41b6e7540\",\"added_by\":\"auto\",\"created_at\":\"2020-09-17 16:05:59\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":587377,\"visible\":true,\"origin\":\"\",\"legend\":\"Bland-Altman plots of measurements of LVS, IVS, LVPW, LVEJ, RV and LA in 50 infants with in utero exposure to ZIKV. Rio de Janeiro, Brazil, 2018.\\nBland-Altman plot of ECHO measurements with good to poor agreement by two pediatric cardiologists. Brazil, 2018. \\nNote: SLV= systolic left ventricule, EDVS= end diastolic ventricular septum, EDPW= end-diastolic-thickness of the left ventricular posterior wall, LVEF=left ventricular ejection fraction, RV=right ventricule, LA= left atrium, CE1= cardiological evaluation 1, CE2= cardiological evaluation 2, SD=standard deviation. LA: Good agreement (Mean difference between CEs near to zero). EDPW and EDVS: Poor agreement (Mean difference between CEs near to zero with few unique values). SLV and RV: Fair to good agreement (Mean difference between CEs near to zero but with some differences higher than 0.4 mm) and LVEF: Poor agreement (High variability of differences between the two CEs). \\n\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-38421/v1/2.png\"},{\"id\":13594781,\"identity\":\"9d2be841-bf98-4c2b-9f0f-78d6bcd2422e\",\"added_by\":\"auto\",\"created_at\":\"2021-09-17 05:21:48\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":851640,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-38421/v1/16cded5c-fa44-4af0-abde-17862c66b9c7.pdf\"}],\"financialInterests\":\"\",\"formattedTitle\":\"\\u003cp\\u003eReliability of Echocardiographic Measurements in Infants Exposed to Zika Virus.\\u003c/p\\u003e\",\"fulltext\":[{\"header\":\"Background:\",\"content\":\" \\u003cp\\u003eEcocardiography (ECHO) is currently the gold standard imaging method for the diagnosis of most congenital and acquired cardiopathies and for the evaluation of myocardial function and cardiac chamber size and overload. It is a non-invasive and safe test with rapid real-time acquisition of images at low cost and without contraindications. Ecocardiographic measures of left ventricular (LV) and right ventricular (RV) structure and function are used to define ventricular function and guide decisions to the need for indication of inotropic medications, to assess the hemodynamic repercussions of patent ductus arteriosus (PDA) in premature infants and the possible need for pharmacological or surgical closure, to assess the repercussions and indication of closure of pulmonary hyper-flow congenital cardiopathies like ventricular septal defect (VSD) and atrial septal defect (ASD), for pharmacological and surgical treatment of valvular regurgitations like mitral valve insufficiency (MVI) and aortic valve insufficiency (AVI), and to determine the most adequate surgical procedure in cases of complex congenital cardiopathies.[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e] Despite the clinical and research importance placed on pediatric echocardiographic measurements, little has been published about the reliability of these measurements for which multiple raters independently measure the same sample when the true value is not known.[\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]\\u003c/p\\u003e \\u003cp\\u003eStudies from the 1970s and 1980s provided the normal parameters for cardiac cavitary dimensions until 2000,[\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e] when the results from a study in 2,036 children were published, redefining the normal ranges for parameters through the production of graphs that used body surface as a criterion and established mean values -/+ 2 standard deviations for each measurement.[\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]\\u003c/p\\u003e \\u003cp\\u003eAs with any measurement, echocardiographic quantification is subject to error, so it is important to assess the degree of agreement between two observers. Intraclass correlation coefficient (ICC) estimates the fraction of the total variability of measurements due to inter-individual variations. Variation due to errors should include different components, depending on the study design.[\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e] The Bland-Altman plot is used to assess agreement between two quantitative measurements. The mean and standard deviation of the measurements are used to calculate the agreement\\u0026rsquo;s statistical limits. Bland-Altman is a scatter plot in which the Y axis is the difference between the two paired measurements and the X axis is the mean of these measurements. The diameter of the points is directly proportional to the frequency of inter-examiner agreement.[\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]\\u003c/p\\u003e \\u003cp\\u003eIn previous study, our search group demonstrated cardiac alterations associated with in utero exposure to Zika virus (ZIKV): 10% of patients presented major defects such as ASD, VSD, and PDA.[\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]\\u003c/p\\u003e \\u003cp\\u003eWe study the reliability of cardiac chamber measurements using ECHO in a sample of patients from a cohort of infants \\u003cem\\u003ein utero\\u003c/em\\u003e exposed to ZIKV followed by a Brazilian national reference center to maternal and child health. All the infants were referred for a clinical and echocardiographic evaluation.\\u003c/p\\u003e \"},{\"header\":\"Methods:\",\"content\":\" \\u003cp\\u003eWe performed a blinded cross-sectional diagnostic study with two independent measurements of cardiac dimensions using ECHO of infants born between November 2015 and January 2017 who were followed at our outpatient Pediatric Infectious Disease Clinic at the Fernandes Figueira Institute (IFF-FIOCRUZ). The infants who received echocardiograms were born either at IFF or other institutions with positive ZIKV maternal polymerase chain reaction (PCR) results during pregnancy or positive PCR results at birth. Our institution is a national research referral center for high risk pregnancies and high risk infants. For this reason, during the Zika epidemic we were the major referral center in Rio de Janeiro for cases of suspected maternal or infant ZIKV infection.\\u003c/p\\u003e \\u003cp\\u003eThe study was approved by the Institutional Review Board of the Brazilian National Institute of Infectious Diseases (INI-FIOCRUZ \\u0026ndash; CAAE 62728516.2.0000.5262). All parents or guardians provided written informed consent. All data analyzed were anonymized. The tests were performed by two of the three pediatric cardiologists at the Department of Pediatric Cardiology of IFF, using an Acuson X300 echocardiography system, blinded in relation to the previous tests.The doubles were chosen at random. All pediatric cardiologists are certified specialists in Pediatric Cardiology by the Brazilian Society of Cardiology and Brazilian Society of Pediatrics and have at least 15\\u0026nbsp;years of practice in the specialty. No patient required sedation to undergo the tests, which were repeated by the respective examiners with a maximum interval of 15\\u0026nbsp;days. The tests were performed during the normal patient flow in the Pediatric Cardiology Outpatient Department of IFF, and the cavitary measurements were taken. The cardiological evaluation took place between 30 and 270\\u0026nbsp;days of life and included measurements of aortic root, left atrium, end-diastolic left ventricle, systolic left ventricle, right ventricle, left ventricular ejection fraction, ventricular end-diastolic septum thickness, and end diastolic thickness of the left ventricular posterior wall. Measurements were taken at the cross-sections defined in the echocardiography guidelines, namely the unidimensional mode of the parasternal longitudinal section of the long axis of the left ventricle at the level of the aortic valve leaflets to measure the aorta and left atrium, and for the others, the parasternal section of the short axis of the left ventricle at the level of the mitral valve leaflets.[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]\\u003c/p\\u003e \\u003cp\\u003eThe analysis was performed in Med Calc 17.9 and the free software R 3.5.1 [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]in the BlandAltmanLeh and nopaco packages. The median values expressed in centimeters with the respective interquartile ranges (IQR) were summarized in tables and compared with the normal values according to body surface wich does not change in 15 days.[\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e] Due to rejection of the normality of measurements according to the boxplot and Shapiro-Wilk test, the measurements were also compared between the two observers using the Wilcoxon non-parametric test. Intraclass correlation coefficients (ICC) were calculated (measures of unique consistency and means), with the respective 95% confidence intervals (95% CI). Interpretation of ICC values was as follows: excellent reliability when \\u0026ge;\\u0026thinsp;0.75, fair to good with 0.4\\u0026thinsp;\\u0026le;\\u0026thinsp;ICC\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.75, and poor when ICC\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.4.[\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e] Bland-Altman plots were produced to explore the distribution of each ECHO measurement considering the size of the differences between the two independent evaluations, using as the reference the mean of the differences and limits determined by two standard deviations below and above the mean. Each point\\u0026rsquo;s size is determined by the value\\u0026rsquo;s frequency. Few unique observations and concentration of points in certain mean values can lead to bad overall agreement parameters, as for example ICC.\\u003c/p\\u003e \"},{\"header\":\"Results:\",\"content\":\" \\u003cp\\u003eWe performed two echocardiograms with maximum interval of 15 days in 50 infants of the 120 patients who were brought by their parents or guardians to the pediatric clinic for a cardiac consult and performance of an echocardiogram because of the \\u003cem\\u003ein utero\\u003c/em\\u003e exposure to ZIKV. No infant had a diagnosis of congenital cardiopathy with hemodynamic repercussions. The mean age of the 50 infants was 111 days (95% CI\\u0026thinsp;=\\u0026thinsp;94.7-127.3), with body surface varying from 0.2 to 0.3\\u0026nbsp;m\\u003csup\\u003e2\\u003c/sup\\u003e; 60% were girls, and 86% were term infants.\\u003c/p\\u003e \\u003cp\\u003eTable\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e showed the medians calculated for the measurements performed by observers 1 and 2.\\u003c/p\\u003e \\u003cp\\u003eThe medians for the measurements were mostly identical. All the median measurements were within normal ranges.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eDimensions (in centimeters) of two independent echocardiographic measurements in 50 infants (medians and interquartile ranges) with \\u003cem\\u003ein utero\\u003c/em\\u003e exposure to ZIKV, and respective normal values.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"8\\\"\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003eAppraiser 1\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e \\u003cp\\u003eAppraiser 2\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c8\\\" namest=\\\"c7\\\"\\u003e \\u003cp\\u003eNormal values\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eParameter (Diameter)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c8\\\" namest=\\\"c7\\\"\\u003e \\u003cp\\u003eBody surface\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.25\\u0026nbsp;m\\u003csup\\u003e2\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.30\\u0026nbsp;m\\u003csup\\u003e2\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eMedian (IQ*)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eMean\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eMedian\\u003c/p\\u003e \\u003cp\\u003e(IQ*)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eMean\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003ep value\\u0026nbsp;\\u003csup\\u003e\\u0026dagger;\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eMean\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003eMean\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(95%CI)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e(95%CI)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e(95%CI\\u0026nbsp;\\u003csup\\u003e\\u0026Dagger;\\u003c/sup\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e(95%CI \\u003csup\\u003e\\u0026Dagger;\\u003c/sup\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAortic root (cm)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.10\\u003c/p\\u003e \\u003cp\\u003e(1.00-1.20)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.09\\u003c/p\\u003e \\u003cp\\u003e(1.04\\u0026ndash;1.14)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.10\\u003c/p\\u003e \\u003cp\\u003e(1.00-1.20)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.11\\u003c/p\\u003e \\u003cp\\u003e(1.06\\u0026ndash;1.16)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.401\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1.04 (0.80\\u0026ndash;1.28)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e1.13 (0.9\\u0026ndash;1.36)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLeft atrium(cm)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.40\\u003c/p\\u003e \\u003cp\\u003e(1.20\\u0026ndash;1.60)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.40\\u003c/p\\u003e \\u003cp\\u003e(1.32\\u0026ndash;1.47)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.40\\u003c/p\\u003e \\u003cp\\u003e(1.30\\u0026ndash;1.60)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.42\\u003c/p\\u003e \\u003cp\\u003e(1.35\\u0026ndash;1.49)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.688\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1.40 (1.05\\u0026ndash;1.75)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e1.53 (1.15\\u0026ndash;1.91)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEnd-diastolic left ventricule (cm)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2.10\\u003c/p\\u003e \\u003cp\\u003e(1.90\\u0026ndash;2.40)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.10\\u003c/p\\u003e \\u003cp\\u003e(1.99\\u0026ndash;2.21)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2.10\\u003c/p\\u003e \\u003cp\\u003e(1.90\\u0026ndash;2.40)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2.10\\u003c/p\\u003e \\u003cp\\u003e(2.00-2.20)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.694\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e2.0 (1.64\\u0026ndash;2.36)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e2.29 (1.8\\u0026ndash;2.58)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSystolic left ventricule (cm)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.20\\u003c/p\\u003e \\u003cp\\u003e(1.00-1.30)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.18\\u003c/p\\u003e \\u003cp\\u003e(1.11\\u0026ndash;1.25)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.30\\u003c/p\\u003e \\u003cp\\u003e(1.10\\u0026ndash;1.40)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.25\\u003c/p\\u003e \\u003cp\\u003e(1.19\\u0026ndash;1.32)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.052\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1.32 (1.02\\u0026ndash; 1.62)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e1.48 (1.08\\u0026ndash;1.88)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eVentricular end-diastolic septal thickness (cm)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.40\\u003c/p\\u003e \\u003cp\\u003e(0.30\\u0026ndash;0.40)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.38\\u003c/p\\u003e \\u003cp\\u003e(0.36\\u0026ndash;0.41)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.40\\u003c/p\\u003e \\u003cp\\u003e(0.30\\u0026ndash;0.40)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.38\\u003c/p\\u003e \\u003cp\\u003e(0.36\\u0026ndash;0.41)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.596\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.38 (0.24\\u0026ndash;0.52)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.39 (0.25\\u0026ndash;0.53)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEnd-diastolic thickness of the left ventricular posterior wall (cm)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.40\\u003c/p\\u003e \\u003cp\\u003e(0.30\\u0026ndash;0.40)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.37\\u003c/p\\u003e \\u003cp\\u003e(0.34\\u0026ndash;0.39)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.40\\u003c/p\\u003e \\u003cp\\u003e(0.30\\u0026ndash;0.40)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.35\\u003c/p\\u003e \\u003cp\\u003e(0.33\\u0026ndash;0.38)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.260\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.36 (0.26\\u0026ndash;0.46)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.41 (0.28\\u0026ndash;0.54)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRight ventricule (cm)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.90\\u003c/p\\u003e \\u003cp\\u003e(0.73-1.00)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.89\\u003c/p\\u003e \\u003cp\\u003e(0.84\\u0026ndash;0.95)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.90\\u003c/p\\u003e \\u003cp\\u003e(0.80\\u0026ndash;0.90)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.87\\u003c/p\\u003e \\u003cp\\u003e(0.83\\u0026ndash;0.91)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.381\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.87 (0.42\\u0026ndash;1.32)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.87 (0.42\\u0026ndash;1.32)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLeft ventricule ejection fraction (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e76.5\\u003c/p\\u003e \\u003cp\\u003e(69.0-82.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e75.7\\u003c/p\\u003e \\u003cp\\u003e(73.2\\u0026ndash;78.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e69.5\\u003c/p\\u003e \\u003cp\\u003e(66.0-74.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e70.4\\u003c/p\\u003e \\u003cp\\u003e(68.3\\u0026ndash;72.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.003\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e\\u0026gt;\\u0026thinsp;55\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e\\u0026gt;\\u0026thinsp;55\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"8\\\"\\u003e*Interquartile ranges; \\u0026dagger; Wilcoxon test (p value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0,05); \\u0026Dagger; Confidence interval.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eTable\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e showed ICC for the measurements performed by observers 1 and 2.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eReliabiltiy of target parameters in two independent echocardiographic measurements, expressed as intraclass correlation coefficients (ICC) and respective 95% confidence intervals in 50 infants with \\u003cem\\u003ein utero\\u003c/em\\u003e exposure to ZIKV.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"7\\\"\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eParameter (diameter in cm)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003eSingle\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"3\\\" nameend=\\\"c7\\\" namest=\\\"c5\\\"\\u003e \\u003cp\\u003eInterpretation\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eICC\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e95% CI\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAortic root\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.75\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.60 0.85\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eExcellent\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLeft atrium\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.43\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.17 0.63\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eFair / Good\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEnd-diastolic left ventricule\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.83\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.72 0.90\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eExcellent\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSystolic left ventricule\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.44\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.19 0.64\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eFair / Good\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eVentricular end-diastolic septal thickness\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.23\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e-0.049 0.48\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003ePoor\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEnd-diastolic-thickness of the left ventricular posterior wall\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.36\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.09 0.58\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003ePoor\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRight ventricule\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.40\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.14 0.61\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eFair /\\u003c/p\\u003e \\u003cp\\u003eGood\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLeft ventricule ejection fraction\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.19\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e-0.04 0.09\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003ePoor\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eDiameters of aortic root and end-diastolic left ventricle had low differences between two observers, with mean difference near to zero and mean values varied up to 0.5\\u0026nbsp;cm (Fig.\\u0026nbsp;1). Medians of aortic root and end-diastolic left ventricle (1.1\\u0026nbsp;cm and 2.1\\u0026nbsp;cm) did not show differences between two evaluations (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05, Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Also, it was observed excellent agreement for these two measurements (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eThe Bland Altman plot of diameter of systolic left ventricle showed low differences between two observers, with mean difference near to zero and mean values varied up to 0.6\\u0026nbsp;cm (Fig.\\u0026nbsp;1). Medians of systolic left ventricle (1.2 and 1.1\\u0026nbsp;cm) did not show differences between two measurements (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05, Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). The agreement was considered good (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eAlthough the mean difference in diameter of ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall are near to zero, few unique mean values were observed (Fig.\\u0026nbsp;1). Medians of ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall (0.4 and 0.4\\u0026nbsp;cm) did not show differences between two observers (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05, Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). These measurements were the lowest structures when compared with others (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). The agreement was considered poor (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). Other measurement with low agreement between observers was left ventricle ejection fraction (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). The medians were higher 7 percentage points when compared by the two observers (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05, Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e \"},{\"header\":\"Discussion:\",\"content\":\" \\u003cp\\u003eThis is one of the first studies on the reliabiltiy of echocardiographic parameters in infants. The most reliable parameters were the diameters of aortic root and end-diastolic left ventricle, while the other parameters varied from good/fair to bad, especially those with smaller dimensions, namely ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall. However, the disagreements occurred in approximately 0.5% of patients.\\u003c/p\\u003e \\u003cp\\u003eThe small divergences did not affect the echocardiographic test reports, which could be explained by the fact that differences of 1\\u0026nbsp;mm altered the reliability of two measures but did not exceed the normal range for the cavitary measurements assessed in this study.\\u003c/p\\u003e \\u003cp\\u003eSince the system calculates left ventricle ejection fraction as the ratio between end-diastolic left ventricle and systolic left ventricle, it was mainly affected by the discrepancies in the measurements of the systolic left ventricle.\\u003c/p\\u003e \\u003cp\\u003eMedical consensuses and guidelines use clinical and complementary test criteria to orient diagnosis and treatment decisions. This involves assessing the parameters\\u0026rsquo; diagnostic accuracy by measuring the sensitivity and specificity, with reliability as a prerequisite for accuracy.[\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]\\u003c/p\\u003e \\u003cp\\u003eEchocardiography is an easy test to perform, and its use as a parameter to guide clinical or surgical approaches requires good reliability of measurements obtained by different observers. However, there is little information in the literature on the reliability of the parameters obtained with echocardiography and that are used in cardiology guidelines to indicate closure of the ductus arteriosus, VSD, and ASD or valvuloplasty in cases of valvular insufficiencies such as rheumatic mitral and aortic valve insufficiencies.\\u003c/p\\u003e \\u003cp\\u003eGeelhoed et al found good reliability for echocardiographic measurements of left heart structures in 28 healthy children with median age of 7.5\\u0026nbsp;years.[\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e] Another study assessing reliability of left ventricular systolic function of 59 potential pediatric heart donnors with less than 18\\u0026nbsp;years reported that ICC between measurements done by local hospitals and by trained pediatric cardiologist at a pediatric heart center was 0,59 (fair to good) and in this study, 20% of echocardiograms with LV dysfunction by local measurements turned out to have normal function when measured in the central laboratory.[\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e] Lipshultz et al compared measurements of LV dimension and wall thickness obtained on 735 children of HIV-mothers at 10 clinical sites and concluded that they differed so much that a central echocardiographic facility is needed to provided consistent and reliable data for research studies and clinically meaningful results.[\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]None of these studies evaluated infants.\\u003c/p\\u003e \\u003cp\\u003eThe low reliability of a test limits the generalization of approaches and recommendations in guidelines and consensus.[\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e] As an example, the score proposed by McNamara and Sehgal for closure of the PDA in premature infants included clinical criteria and echocardiographic measurements. Among the measurements tested, those with the highest predictive value for indication of closure of a hemodynamically significant PDA were the size of aortic root and left atrium, but they were also the parameters with the lowest inter-examiner reliability.[\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e] In our study, the size of aortic root showed excellent reliability, while reliability of left atrium was fair. This suggests that the use of this score or any other to indicate closure of PDA may be compromised by the difficulty in reproducing these measurements by different observers and in distinct settings. Schwarz et al. (2016) studied the reliability of echocardiographic parameters for the diagnosis of PDA in low birth weight premature infants and found bad reliability for the size of aortic root and left atrium, while the reliability was somewhat better for other parameters (short axis of the ductus arteriosus, resistance index of the celiac artery and anterior cerebral artery, among others)but some of these parameters were not assessed in our study.[\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]\\u003c/p\\u003e \\u003cp\\u003eAlterations in the Bland-Altmann plot may occur due to the limited number of unique observations and the concentration of points at given mean values, which can lead to low overall agreement indices (e.g., ICC). ICC also considers normal data and is affected by the data\\u0026rsquo;s deviation from normality and variability, as is the Bland-Altman plot. Due to the non-normality of four of the parameters studied in the current sample (systolic left ventricle, ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall and right ventricle), caution is recommended when interpreting the plots, as well as the reliability results (ICC).\\u003c/p\\u003e \\u003cp\\u003eThis study has limitations. The sample size is small but was similar to or larger than other studies on this topic in the literature and the observers have high and homogeneous level of training.\\u003c/p\\u003e \"},{\"header\":\"Conclusions:\",\"content\":\"\\u003cp\\u003eAlthough we found variable reliability for all the cardiac measurements, the minor divergences did not affect the echocardiography results in our sample. However, caution is required to interpret results of measures with low reliability (ventricular end-diastolic septal thickness, end-diastolic-thickness of the left ventricular posterior wall and left ventricle ejection fraction).\\u003c/p\\u003e \"},{\"header\":\"List Of Abreviations:\",\"content\":\" \\u003cp\\u003eECHO:Echocardiography\\u003c/p\\u003e \\u003cp\\u003eLV: Left ventricle\\u003c/p\\u003e \\u003cp\\u003eRV: Right ventricle\\u003c/p\\u003e \\u003cp\\u003ePDA: Patente ductus arteriosus\\u003c/p\\u003e \\u003cp\\u003eVSD: Ventricular septal defect\\u003c/p\\u003e \\u003cp\\u003eASD: Atrial septal defect\\u003c/p\\u003e \\u003cp\\u003eMVI: Mitral valve insufficiency\\u003c/p\\u003e \\u003cp\\u003eAVI: Aortic valve insufficiency\\u003c/p\\u003e \\u003cp\\u003eIQR: Interquartile ranges\\u003c/p\\u003e \\u003cp\\u003eICC: Intraclass correlation coefficient\\u003c/p\\u003e \\u003cp\\u003ePCR: Polymerase chain reaction\\u003c/p\\u003e \"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate:\\u003c/strong\\u003e The study was approved by the Institutional Review Board of the Brazilian National Institute of Infectious Diseases (INI-FIOCRUZ \\u0026ndash; CAAE 62728516.2.0000.5262). All parents or guardians of minors included in this study provided written informed consent.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e: Not applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData availability\\u003c/strong\\u003e: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e: The authors declare that they have no competing interests\\\" in this section.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e: This study was supported by MCTI and Conselho Nacional de Desenvolvimento Cient\\u0026iacute;fico e Tecnol\\u0026oacute;gico (CNPq,Bras\\u0026iacute;lia) Grant 440846/2016-1 and Coordenac\\u0026atilde;o de Aperfei\\u0026ccedil;oamento de Pessoal de N\\u0026iacute;vel Superior (CAPES,Bras\\u0026iacute;lia) Grant 88881130793/2016-01. Sonia R.L.Passos had grants from CNPq 310765 /2016-1 and by Universidade Est\\u0026aacute;cio de S\\u0026aacute; Produtividade em Pesquisa, RJ. Thiago M Ramos had a scholarship by ITI A CNPq,Bras\\u0026iacute;lia Processo: 180767/2017-8 ; Let\\u0026iacute;cia M.L. e Silva had a scholarship by Coordena\\u0026ccedil;\\u0026atilde;o de Aperfei\\u0026ccedil;oamento de Pessoal de N\\u0026iacute;vel Superior (CAPES,Bras\\u0026iacute;lia) Grant 88887130789/2016-00. The funders had no role in study design, data collection and analysis , decision to publish, or preparation of the manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors' contributions\\u003c/strong\\u003e: All authors contribute to the conception of the study.DHGO,SRLP,RVCO,TMR,LMLS and RO conducted the analysis and wrote the first draft. DHGO, CVBF and MFMPL performed the exams and provided critical editorial input. All authors read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements:\\u003c/strong\\u003e SRLP was supported by Conselho Nacional de Desenvolvimento Cient\\u0026iacute;fico e Tecnol\\u0026oacute;gico (CNPq), grants N\\u0026ordm; 440846/2016-1 and 310765/2016-1, by Coordena\\u0026ccedil;\\u0026atilde;o de Aperfei\\u0026ccedil;oamento de Pessoal de N\\u0026iacute;vel Superior (CAPES), grant N\\u0026ordm; 88881130793/2016-01, and by Universidade Est\\u0026aacute;cio de S\\u0026aacute; - Produtividade em Pesquisa. LMLS was supported by CAPES grant N\\u0026ordm; 88887.162025/2017-00. RO and TMR had a scholarship ITI-A from CNPq.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003cp\\u003e1 Grau CRPC, Kozak MF, Guerra VC. Ecocardiografia. In: Croti UA, Mattos SS, Pinto Jr VC, Aiello VD, Moreira VM. Cardiologia e Cirurgia Cardiovascular Pedi\\u0026aacute;trica. 2 a ed. S\\u0026atilde;o Paulo:Roca 2012: 119-40.\\u003c/p\\u003e\\n\\u003cp\\u003e2 Fleiss, JL. The design and analysis of clinical experiments. New York, NY: John Wiley and Sons; 1986.\\u003c/p\\u003e\\n\\u003cp\\u003e3 Epstein ML,\\u0026nbsp;Goldberg SJ,\\u0026nbsp;Allen HD,\\u0026nbsp;Konecke L,\\u0026nbsp;Wood J. Great vessel, cardiac chamber, and wall growth patterns in normal children. \\u003cem\\u003eCirculation\\u003c/em\\u003e 1076Jun;51(6):1124-9.\\u003c/p\\u003e\\n\\u003cp\\u003e4 Henry WL,\\u0026nbsp;Gardin JM, Ware JH.Echocardiographic measurements in normal subjects from infancy to old age.\\u003cem\\u003eCirculation\\u003c/em\\u003e 1980Nov;62(5):1054-61.\\u003c/p\\u003e\\n\\u003cp\\u003e5 Kampmann C, Wiethoff C, Wenzel A, et al. Normal values of M mode echocardiographic measurements of more than 2000\\u0026nbsp;healthy infants and children in central Europe.\\u0026nbsp;\\u003cem\\u003eHeart \\u003c/em\\u003e2000;83(6):667-672. doi:10.1136/heart.83.6.667.\\u003c/p\\u003e\\n\\u003cp\\u003e6 Shrout PE, Fleiss JL. Intraclass Correlations: Uses in Assessing Rater Reliability. \\u003cem\\u003ePsychological Bulletin\\u003c/em\\u003e 1979;86(2):420-428\\u003c/p\\u003e\\n\\u003cp\\u003e7 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement.\\u0026nbsp;\\u003cem\\u003eLancet\\u003c/em\\u003e\\u0026nbsp;1986;1(8476):307\\u0026ndash;10. doi: 10.1016/S0140-6736(86)90837-\\u003c/p\\u003e\\n\\u003cp\\u003e8 Giavarina D. Understanding Bland Altman analysis. \\u003cem\\u003eBiochemia Medica\\u003c/em\\u003e 2015;25(2):141-151. doi:10.11613/BM.2015.015.\\u003c/p\\u003e\\n\\u003cp\\u003e9 Orofino DHG, Passos SRL, de Oliveira RVC, Farias CVB, Leite MdFMP, Pone SM, et al. (2018) Cardiac findings in infants with \\u003cem\\u003ein utero\\u003c/em\\u003e exposure to Zika virus- a cross sectional study\\u003cem\\u003e. \\u003c/em\\u003e\\u003cem\\u003ePLoS Negl Trop Dis.\\u003c/em\\u003e\\u0026nbsp;2018Mar 26;12(3): e0006362. doi: 10.1371/journal.pntd.0006362. eCollection 2018 Mar\\u003c/p\\u003e\\n\\u003cp\\u003e10 R Core Team (2015). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/.\\u003c/p\\u003e\\n\\u003cp\\u003e11 Bossuyt PMM, Reitsma JB, Bruns DE, et al. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. \\u003cem\\u003eClin Chem\\u003c/em\\u003e. 2003;49(1):7-18.\\u003c/p\\u003e\\n\\u003cp\\u003e12 Geelhoed MJ,\\u0026nbsp;Snijders SP,\\u0026nbsp;Kleyburg-Linkers VE,\\u0026nbsp;Steegers EA,\\u0026nbsp;van Osch-Gevers L,\\u0026nbsp;Jaddoe VW. Reliability\\u0026nbsp;of echocardiographic\\u0026nbsp;measurements\\u0026nbsp;of left cardiac structures in healthy children. \\u003cem\\u003eCardiol Young\\u003c/em\\u003e 2009 Sep;19(5):494-500. doi: 10.1017/S1047951109990862. Epub 2009 Aug 20.\\u003c/p\\u003e\\n\\u003cp\\u003e13 Chen S,\\u0026nbsp;Selamet Tierney ES,\\u0026nbsp;Khush KK,\\u0026nbsp;Nguyen J,\\u0026nbsp;Goldstein BA,\\u0026nbsp;May LJ,\\u0026nbsp;Hollander SA,\\u0026nbsp;Kaufman BD,\\u0026nbsp;Rosenthal DN. Reliability of echocardiographic measurements of left ventricular systolic function in potential pediatric heart transplant donors.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eJ Heart Lung Transp\\u003c/em\\u003e\\u0026nbsp;2015Jan;34(1):100-6. doi: 10.1016/j.healun.2014.08.019. Epub 2014 Aug 28.\\u003c/p\\u003e\\n\\u003cp\\u003e14 Lipshultz SE,\\u0026nbsp;Easley KA,\\u0026nbsp;Orav EJ,\\u0026nbsp;Kaplan S,\\u0026nbsp;Starc TJ,\\u0026nbsp;Bricker JT,\\u0026nbsp;Lai WW,\\u0026nbsp;Moodie DS,\\u0026nbsp;Sopko G,\\u0026nbsp;Schluchter MD,\\u0026nbsp;Colan SD. Reliability of Multicenter Pediatric Echocardiographic Measurements of Left Ventricular Structure and Function: The Prospective P\\u003csup\\u003e2\\u003c/sup\\u003eC\\u003csup\\u003e2\\u003c/sup\\u003e\\u0026nbsp;HIV Study. \\u003cem\\u003eCirculation.\\u003c/em\\u003e\\u0026nbsp;2001 Jul 17;104(3):310-6.\\u003c/p\\u003e\\n\\u003cp\\u003e15 McNamara PJ, Sehgal A. Towards rational management of the patent ductus arteriosus: the need for disease staging.\\u0026nbsp;\\u003cem\\u003eArch Dis Child Fetal Neonatal Edition\\u003c/em\\u003e\\u0026nbsp;2007;92(6): F424\\u0026ndash;7. doi: 10.1136/adc.2007.118117.\\u003c/p\\u003e\\n\\u003cp\\u003e16 Iyer P, Evans N. Re-evaluation of left atrium to aortic root ratio as a marker of patent ductus arteriosus.\\u003cem\\u003eArch Dis Fetal Neonatal Ed\\u003c/em\\u003e 1994;70:f112-7.\\u003c/p\\u003e\\n\\u003cp\\u003e17 Schwarz C E, Preusche A, Baden W Poets C F,Franz A R.Repeatability of echocardiographic parameters to evaluate the hemodynamic relevance of patent ductus arteriosus in preterm infants: a prospective observational study. \\u003cem\\u003eBMC Pediatrics\\u003c/em\\u003e 2016; 16: 18.\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Reproducibility,echocardiography, cardiac chamber dimensions, Zika virus\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-38421/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-38421/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground:\\u003c/strong\\u003e Ecocardiography\\u0026nbsp;is currently the gold standard imaging method for the diagnosis of most congenital and acquired cardiopathies and for the evaluation of myocardial function and cardiac chamber size and overload. Ecocardiographic measures of left ventricular and right ventricular structure and function are used to define ventricular function and guide medical decisions.The objective of this study is to assess the reproducibility of echocardiographic cardiac chamber measurements\\u0026nbsp;in infants in utero exposed to Zika virus. \\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eMethods:\\u003c/strong\\u003e Masked cross-sectional diagnostic study with two independent measurements of cardiac chamber dimensions using echocardiography.\\u0026nbsp;We studied 50 infants with in utero exposure to Zika virus ranging from 30 to 270 days old of the outpatient clinic of a national reference center for maternal and child health, Rio de Janeiro, Brazil.The analysis included the measurements of the aortic root, left atrium, end diastolic left ventricle, systolic left ventricule, left ventricular ejection fraction, ventricular end diastolic septal thickness, end diastolic thickness of the left ventricular posterior wall and right ventricule. Bland-Altman plots were used to explore differences. Agreement according to intraclass correlation coefficients (ICC) was interpreted as follows: excellent≥0.75, fair to good 0.4≤ICC\\u0026lt;0.75, and poor with ICC\\u0026lt;0.4. \\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u003c/strong\\u003e All parameters had mean difference of diameters near to zero, excluding left ventricule ejection fraction. Ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall showed few unique mean values. Reproducibility was excellent for the aortic root and end diastolic left ventricule (ICC=0.86 and 0.91, respectively), fair/good to poor for other parameters and the left ventricule ejection fraction, ventricular end diastolic septal thickness and the end diastolic thickness of the left ventricular posterior wall\\u0026nbsp;showed the lowest reproducibility (ICC=0.46,0.37,0.53, respectively). \\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eConclusions:\\u003c/strong\\u003e The minor divergences did not affect the echocardiography results in our sample. However, caution is required to interpret results of measures with low reproducibility.\\u0026nbsp;\\u003c/p\\u003e\",\"manuscriptTitle\":\"Reliability of Echocardiographic Measurements in Infants Exposed to Zika Virus.\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2020-09-17 16:05:57\",\"doi\":\"10.21203/rs.3.rs-38421/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"3334d5dd-5913-4576-9dca-e8c4330339ce\",\"owner\":[],\"postedDate\":\"September 17th, 2020\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[{\"id\":540831,\"name\":\"Nuclear Medicine \\u0026 Medical Imaging\"}],\"tags\":[],\"updatedAt\":\"2020-11-10T13:39:25+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2020-09-17 16:05:57\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-38421\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-38421\",\"identity\":\"rs-38421\",\"version\":[\"v1\"]},\"buildId\":\"7rjqhiLT3MXkJMwkYKINL\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}