Article Access Statistics   Viewed  14404   Printed  344   Emailed  13   PDF Downloaded  1036   Comments  [Add]   Cited by others  18  

Click on image for details.



Year : 2012
 Volume
: 5  Issue : 2  Page
: 179184 

The use of Zscores in paediatric cardiology 

Henry Chubb, John M Simpson
Department of Congenital Heart Disease, Evelina Children's Hospital, Guy's and St Thomas' NHS Trust, London, United Kingdom
Click here for correspondence address and
email
Date of Web Publication  11Aug2012 




Abstract   
Zscores are a means of expressing the deviation of a given measurement from the size or age specific population mean. By taking account of growth or age, Zscores are an excellent means of charting serial measurements in paediatric cardiological practice. They can be applied to echocardiographic measurements, blood pressure and patient growth, and thus may assist in clinical decisionmaking. Keywords: Blood pressure, cardio Z, echocardiography, paediatric cardiology, Zscore
How to cite this article: Chubb H, Simpson JM. The use of Zscores in paediatric cardiology. Ann Pediatr Card 2012;5:17984 
What are ZScores?   
Measurements are an important part of clinical assessment in the practice of paediatric cardiology. At the most basic level this typically includes measurement of the child's weight, height and blood pressure at clinic visits. Echocardiographic assessment is integral to patient assessment in the majority of children and decisions with respect to surgery or catheter intervention are frequently based on echocardiographic findings. In adult practice, ultrasound measurements are often reported with respect to a single "normal range" but this approach is impossible in growing children because the normal range of measurements will be impacted by patient growth and / or patient age. Therefore, the interpretation of these measurements during childhood presents a unique challenge, in determining whether a given measurement is within the expected range. In addition, if a measurement deviates from normality it is necessary for the clinician to gauge the magnitude of such deviation.
An approach to the description of clinical and echocardiographic variables is to describe the measurement in terms of a Zscore. The Zscore describes how many standard deviations above or below a size or agespecific population mean a given measurement lies. This approach has major attractions in paediatric cardiology and is increasingly being adopted. As an example, the left ventricle will become larger in all children as they grow. However, if a patient with chronic aortic or mitral valve regurgitation is being followed through serial assessment then clearly it is an abnormal and inappropriate dilation of the left ventricle that must be excluded. The use of Zscores facilitates the detection of pathological increases in left ventricular dimensions, over and above that expected due to normal growth, by showing an increased Zscore over time.
ZScores versus Centiles   
Many paediatricians and paediatric cardiologists are familiar with centiles, particularly with regard to patient height and weight. The relationship between centiles and Zscores, for a normally distributed parameter, is shown in [Figure 1]; the use of either means of expression assumes a normal distribution of the data.  Figure 1: The relationship of Zscores and centiles, assuming Normal distribution of the parameter. Note that the centile remains virtually constant at values distant from the mean (typically over 3 standard deviations from the mean), whilst the Zscore continues to be sensitive to changes in measurements
Click here to view 
Derivation of Zscores   
A Zscore is defined as
where χ is the observed measurement, μ is the expected measurement (population mean) and σ is the standard deviation of the population. Thus, Zscores above the population mean have a positive value and those below the population mean have a negative value. The Zscore value conveys the magnitude of deviation from the mean. For example, where the mean size of the aortic valve is 20mm, with a defined standard deviation of 3 mm, the Zscore of an aortic valve with annulus 14 mm is:
Therefore, in order to calculate a Zscore one must define the mean for each body size point, and the corresponding standard deviation. These values have been derived in many separate studies, of varying sample sizes, [Table 1] and the word 'allometry' has been used since 1936 to describe the "relationship between changes in shape and overall size". ^{[1]} The determination of the 'bestfit' relationship relies upon finding the best mathematical fit for the data, and it has long been recognised that the correlation between size of body structure (e.g. heart valve) and surrogate marker of total body size (e.g. body surface area or weight) is rarely a simple linear one. ^{[2],[3],[4]} In other words, structures do not tend to obey the relationship (where y is the measured structure, x is the marker of total body size, a is the scaling coefficient and b is a constant).  Table 1: Key references with respect to important paediatric and fetal echocardiographic data
Click here to view 
Instead, a much better fit is generally shown by more complex polynomial equations (e.g. y=ax^{3} +bx^{2} +cx+d) or by a power law relationship (y=ax^{b} , where a is the scaling factor, and b the scaling exponent).
Once a best fit relationship is defined, a standard deviation and mean can be derived at each body size point. It is important to note that the standard deviation may vary with body size, a property termed 'heteroscedasticity'.
Which Patient Factors Should be Considered?   
The question of which patient factors should be used to reflect overall body size has been addressed in recent published guidelines. ^{[5]} For most measurements, the recommendation has been to calculate Zscores with respect to patient body surface area rather than height or weight alone. ^{[4]} Many formulas have been used to calculate body surface area including those of Boyd, Dubois and Dubois and Haycock, and it should be noted that there is considerable discrepancy in the values derived by each formula, particularly at low body size. Recent published guidance has recommended the use of the Haycock formula, ^{[6]} but there is a strong argument that for a valid comparison the same BSA formula should be used as in the original reference study which was used to compute the Zscores.
However, it should not be assumed that body surface area is always the favoured approach. For left ventricular mass, for example, patient height has been preferred. ^{[7],[8],[9]} Other factors, such as patient sex and race, may also be important for certain measurements. Echocardiographic measurements do not simply relate to measurement of the size of heart structures. Normal values of functional data such as blood pool Doppler and tissue Doppler data also change across the paediatric age range, and are heavily influenced by patient age ^{[10],[11]} and heart rate. ^{[11]}
Application of ZScores   
In order to optimise the relevance of the computed Zscore in the clinical situation, the methodology used for the measurement should match, as far as possible, that of the original investigators.
In order for body surface area to be computed, conventionally both height and weight are required, and our normal practice has been to record both whenever possible. However, from experience, weight is recorded more commonly than height, particularly in smaller babies and children. Weight only equations for the calculation of BSA, such as BSA = 0.1023 (weight ^{0.68} ), ^{[25]} are convenient but risk misappropriating the Zscore data. In addition, for some echocardiographic measurements there may be variability as to whether a measurement is made in systole or diastole or whether a leading edge to leading edge versus internal dimension method has been used.
One of the most useful applications of Zscores is in tracking allometric growth over time. The same Zscore algorithm should be used each time, and a note made of which reference data has been employed. Zscores may vary significantly between different authors [Figure 2]. If different Zscore references are used in the erroneous belief that these are interchangeable then an apparent change in Zscore may be produced in the absence of a true variation. In practice, an institution should decide which reference data is going to be used for which measurements and this should be used consistently during patient followup.  Figure 2: (a) demonstrates the relationship between mitral valve size in mm and the Zscore as derived by the three most commonly used algorithms. Values are calculated for a typical one year old male, weight 10kg, height 75 cm. The algorithms agree relatively closely around the mean (Z=0). (b) and (c). There is considerable discrepancy between the different algorithms, particularly at low Zscores. Δ1 and Δ2 demonstrate the difference in magnitude of the change in Zscore, with a 1mm variation in measurement, at low and high Zscores respectively
Click here to view 
An example where zscores can be very informative is in following progressive dilation of the aortic root in a patient with Marfan's syndrome. The diameter at the sinuses of Valsalva will increase as the child grows, but at times of rapid total body growth it can be difficult to detect disproportionate growth of a single structure. [Table 2] illustrates such a clinical scenario, where a child starts to grow rapidly at the age of 10 years. The aortic root grows even faster, and the significant increase in the Zscore of the sinuses of Valsalva demonstrates this succinctly and clearly, alerting the clinician.  Table 2: Increasing Zscore over time of the sinuses of Valsalva, suggesting pathological aortic root dilation
Click here to view 
Limitations of ZScores   
Zscores have major advantages for the presentation of paediatric echocardiographic and physiological data. However, Zscores remain an imperfect approximation and there are some important drawbacks which merit discussion. The first, and most important, factor to bear in mind is that the mean and standard deviation at each body size point are only estimation and may vary widely between investigators [Figure 2].
Secondly, to have statistical confidence in both the mean and the more extreme Zscores an extremely large sample size is required, particularly in the assessment of patients across a wide range of sizes. The change in variance across body size (heteroscedasticity) means that it is important to include sufficient numbers of patients at extremes of body size. The inappropriate averaging of variance would tend to underestimate Zscores values for the smallest children, and overestimate Zscore values for the larger subjects.
Thirdly, the use of Zscores may amplify errors in measurements. A degree of intra and interobserver variability in measurements is unavoidable, but Zscores can amplify only minimal changes in absolute measurement [Figure 2]b, particularly at negative Zscores. The exact nature of any amplification effect depends upon the algorithm used to derive the Zscore, and some do not exhibit such a phenomenon.
Finally, it is important that the user does not accept published data uncritically. If there is a wide standard deviation for example in smaller patients, then a value of zero can appear to lie within 2 standard deviations of the mean. For instance, a complete absence of movement on tissue Doppler at some positions, in the under one year age group, may yield a Zscore of >2. ^{[10]}
How to Calculate ZScores in Practice   
For the clinician, it is impractical to trawl through multiple paper reference sources in a clinic setting. It is important, though, that there is the ability to calculate Zscores when required and there are some commercially available echocardiography archive packages that facilitate this. Though convenient, these integrated packages are often limited to a single set of reference data and have not extended to the incorporation of functional data such as blood pool or tissue Doppler. Fetal echocardiographic data is available on some archive solutions and not others.
Some institutions do not have image archiving systems installed and so webbased calculators have evolved. Probably the best known of these is at www.parameterz.com, where the user can input the relevant data for online calculation of Zscores based on published reference data. Our own unit has recently released the "Cardio Z" App which can be installed on an iPhone/ipad platform and does not depend on an Internet connection. This permits user configuration of the preferred reference source for multiple fetal and paediatric echocardiographic measurements. The user has the option to change the body surface area formula, but the default position is to use that of the original reference. Diagrams detail the exact measurement methodology used by each paper, in order to facilitate valid comparisons with the reference data. Functional data, such as pulsed wave and tissue Doppler with derived functional indices, can also be entered. Supplementary information such as Zscores for growth and blood pressure, and normal electrocardiographic data can also be analysed. A screenshot of the App is shown in [Figure 3].  Figure 3: Main menu screenshot of the Cardio Z app showing the variables for which Zscores can be calculated. The user can configure the reference data to be used and the formula to be used to calculate body surface area. The data can be stored as a ".pdf" document for emailing or storage
Click here to view 
Conclusions   
The use of Zscores represents a helpful way of presenting patient specific information in paediatric cardiology. Users need to have an awareness of how such scores are calculated and their limitations. Purposedesigned software is making access to Zscore information far easier than it was possible in the past.
Declarations   
HC and JMS are the joint authors of Cardio Z, an App developed for iPhone and available for purchase. Profits from the App are used to maintain future development and are donated to the Evelina Children's Hospital Appeal.
References   
1.  Huxley JS, Teissier G. Terminology of Relative Growth. Nature 1936;137:7801. 
2.  McMahon T. Size and shape in biology. Science 1973;179:12014. [PUBMED] 
3.  Neilan TG, Pradhan AD, King ME, Weyman AE. Derivation of a sizeindependent variable for scaling of cardiac dimensions in a normal pediatric population. Eur J Echocardiogr 2009;10:505. [PUBMED] 
4.  Sluysmans T, Colan SD. Theoretical and empirical derivation of cardiovascular allometric relationships in children. J Appl Physiol 2005;99:44557. [PUBMED] 
5.  Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK, et al. Recommendations for quantification methods during the performance of a pediatric echocardiogram: A report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr 2010;23:46595; quiz 5767. [PUBMED] 
6.  Haycock GB, Schwartz GJ, Wisotsky DH. Geometric method for measuring body surface area: A heightweight formula validated in infants, children, and adults. J Pediatr 1978;93:626. [PUBMED] 
7.  de Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de Divitiis O, et al. Left ventricular mass and body size in normotensive children and adults: Assessment of allometric relations and impact of overweight. J Am Coll Cardiol 1992;20:125160. [PUBMED] 
8.  Khoury PR, Mitsnefes M, Daniels SR, Kimball TR. Agespecific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr 2009;22:70914. 
9.  Foster BJ, Mackie AS, Mitsnefes M, Ali H, Mamber S, Colan SD. A novel method of expressing left ventricular mass relative to body size in children. Circulation 2008;117:276975. [PUBMED] 
10.  Eidem BW, McMahon CJ, Cohen RR, Wu J, Finkelshteyn I, Kovalchin JP, et al. Impact of cardiac growth on Doppler tissue imaging velocities: A study in healthy children. J Am Soc Echocardiogr 2004;17:21221. [PUBMED] 
11.  Cui W, Roberson DA, Chen Z, Madronero LF, Cuneo BF. Systolic and diastolic time intervals measured from Doppler tissue imaging: Normal values and Zscore tables, and effects of age, heart rate, and body surface area. J Am Soc Echocardiogr 2008;21:36170. [PUBMED] 
12.  Pettersen MD, Du W, Skeens ME, Humes RA. Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: An echocardiographic study. J Am Soc Echocardiogr 2008;21:92234. [PUBMED] 
13.  Zilberman MV, Khoury PR, Kimball RT. Twodimensional echocardiographic valve measurements in healthy children: Genderspecific differences. Pediatr Cardiol 2005;26:35660. [PUBMED] 
14.  Daubeney PE, Blackstone EH, Weintraub RG, Slavik Z, Scanlon J, Webber SA. Relationship of the dimension of cardiac structures to body size: an echocardiographic study in normal infants and children. Cardiol Young 1999;9:40210. [PUBMED] 
15.  Kampmann C, Wiethoff CM, Wenzel A, Stolz G, Betancor M, Wippermann CF, et al. Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe. Heart 2000;83:66772. [PUBMED] 
16.  Warren AE, Boyd ML, O'Connell C, Dodds L. Dilatation of the ascending aorta in paediatric patients with bicuspid aortic valve: Frequency, rate of progression and risk factors. Heart 2006;92:1496500. [PUBMED] 
17.  Gautier M, Detaint D, Fermanian C, Aegerter P, Delorme G, Arnoult F, et al. Nomograms for aortic root diameters in children using twodimensional echocardiography. Am J Cardiol 2010;105:88894. [PUBMED] 
18.  Dallaire F, Dahdah N. New Equations and a Critical Appraisal of Coronary Artery Z Scores in Healthy Children. J Am Soc Echocardiogr 2011;24:6074. [PUBMED] 
19.  McCrindle BW, Li JS, Minich LLA, Colan SD, Atz AM, Takahashi M, et al. Coronary artery involvement in children with Kawasaki disease: risk factors from analysis of serial normalized measurements. Circulation 2007;116:1749. 
20.  Olivieri L, Arling B, Friberg M, Sable C. Coronary artery Z score regression equations and calculators derived from a large heterogeneous population of children undergoing echocardiography. J Am Soc Echocardiogr 2009;22:15964. [PUBMED] 
21.  Schneider C, McCrindle B, Carvalho JS, Hornberger LK, McCarthy KP, Daubeney PE. Development of Zscores for fetal cardiac dimensions from echocardiography. Ultrasound Obstet Gynecol 2005;26:599605. 
22.  Pasquini L, Mellander M, Seale A, Matsui H, Roughton M, Ho SY, et al. Zscores of the fetal aortic isthmus and duct: An aid to assessing arch hypoplasia. Ultrasound Obstet Gynecol 2007;29:62833. [PUBMED] 
23.  Koestenberger M, Ravekes W, Everett AD, Stueger HP, Heinzl B, Gamillscheg A, et al. Right ventricular function in infants, children and adolescents: Reference values of the tricuspid annular plane systolic excursion (TAPSE) in 640 healthy patients and calculation of z score values. J Am Soc Echocardiogr 2009;22:7159. [PUBMED] 
24.  National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114(2 Suppl 4 ^{th} Report):55576. 
25.  Bailey BJ, Briars GL. Estimating the surface area of the human body. Stat Med 1996;15:132532. [PUBMED] 
Correspondence Address: John M Simpson Evelina Children's Hospital, Guy's and St Thomas' Hospital NHS Trust, London United Kingdom
Source of Support: None, Conflict of Interest: HC and JMS are the joint authors of Cardio Z, an App developed for iPhone and available for purchase. Profits from the App are used to maintain future development and are donated to the Evelina Children’s Hospital Appeal.  Check 
DOI: 10.4103/09742069.99622
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2] 

This article has been cited by  1 
Subclinical Alterations of Cardiac Mechanics Present Early in the Course of Pediatric Type 1 Diabetes Mellitus: A Prospective Blinded Speckle Tracking Stress Echocardiography Study 

 Kai O. Hensel,Franziska Grimmer,Markus Roskopf,Andreas C. Jenke,Stefan Wirth,Andreas Heusch   Journal of Diabetes Research. 2016; 2016: 1   [Pubmed]  [DOI]   2 
Cardiopulmonary Function, Exercise Capacity, and Echocardiography Finding of Pediatric Patients With Kawasaki Disease 

 ShengHui Tuan,MinHui Li,MiaoJu Hsu,YunJeng Tsai,YinHan Chen,TinYun Liao,KoLong Lin   Medicine. 2016; 95(2): e2444   [Pubmed]  [DOI]   3 
Canine fetal echocardiography: correlations for the analysis of cardiac dimensions 

 Amália Turner Giannico,Elaine Mayumi Ueno Gil,Daniela Aparecida Ayres Garcia,Marlos Gonçalves Sousa,Tilde Rodrigues Froes   Veterinary Research Communications. 2016; 40(1): 11   [Pubmed]  [DOI]   4 
Proposal for a revised definition of dilated cardiomyopathy, hypokinetic nondilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases 

 Yigal M. Pinto,Perry M. Elliott,Eloisa Arbustini,Yehuda Adler,Aris Anastasakis,Michael Böhm,Denis Duboc,Juan Gimeno,Pascal de Groote,Massimo Imazio,Stephane Heymans,Karin Klingel,Michel Komajda,Giuseppe Limongelli,Ales Linhart,Jens Mogensen,James Moon,Petronella G. Pieper,Petar M. Seferovic,Stephan Schueler,Jose L. Zamorano,Alida L.P. Caforio,Philippe Charron   European Heart Journal. 2016; : ehv727   [Pubmed]  [DOI]   5 
Vesicoureteral refux detection in children: a comparison of the midlinetoorifice distance measurement by ultrasound and voiding urosonography 

 Nina Battelino,Damjana Kljucevšek,Mojca Tomažic,Tanja Kersnik Levart   Pediatric Nephrology. 2016;   [Pubmed]  [DOI]   6 
Predictors of LongTerm Outcome in Children with Hypertrophic Cardiomyopathy 

 Lidia Ziólkowska,Anna TurskaKmiec,Joanna Petryka,Wanda Kawalec   Pediatric Cardiology. 2015;   [Pubmed]  [DOI]   7 
Clinical relevance of echocardiogram in patients with cerebral palsy undergoing posterior spinal fusion 

 Sabina DiCindio,Lynda Arai,Michael McCulloch,Kesavan Sadacharam,Suken A. Shah,Peter Gabos,Kirk Dabney,Mary C. Theroux,Andrew Davidson   Pediatric Anesthesia. 2015; 25(8): 840   [Pubmed]  [DOI]   8 
Fetal aortic valve stenosis: a critique of case selection criteria for fetal intervention 

 Lindsey E. Hunter,Henry Chubb,Owen Miller,Gurleen Sharland,John M. Simpson   Prenatal Diagnosis. 2015; 35(12): 1176   [Pubmed]  [DOI]   9 
Assessment of the carotid artery intimamedia complex through ultrasonography and the relationship with Pathobiological Determinants of Atherosclerosis in Youth 

 Thacira D. A. Ramos,Tatianne M. E. Dantas,Mônica O. S. Simões,Danielle F. Carvalho,Carla C. M. Medeiros   Cardiology in the Young. 2015; : 1   [Pubmed]  [DOI]   10 
Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 7: Aortic Diseases, Including Marfan Syndrome 

 Alan C. Braverman,Kevin M. Harris,Richard J. Kovacs,Barry J. Maron   Journal of the American College of Cardiology. 2015; 66(21): 2398   [Pubmed]  [DOI]   11 
The influence of realtime blood glucose levels on left ventricular myocardial strain and strain rate in pediatric patients with type 1 diabetes mellitus  a speckle tracking echocardiography study 

 Kai O. Hensel,Franziska Grimmer,Andreas C. Jenke,Stefan Wirth,Andreas Heusch   BMC Cardiovascular Disorders. 2015; 15(1)   [Pubmed]  [DOI]   12 
Bedeutung von ZScores bei angeborenen Herzfehlern 

 H.G. Kehl,D. Kiski,A. Orth,C. Jux,E. Malec,K. Januszewska   Zeitschrift für Herz,Thorax und Gefäßchirurgie. 2014;   [Pubmed]  [DOI]   13 
Evaluación ecocardiográfica de prótesis valvulares en población pediátrica 

 Iván F. Quintero,Raúl D. Santos,Claudia Guerrero,Walter Mosquera,Jaiber Gutiérrez,Jairo Sánchez,Juan G. Echeverri   Revista Colombiana de Cardiología. 2014; 21(1): 60   [Pubmed]  [DOI]   14 
Authorsæ Reply 

 Martijn G. Slieker,Matthias W. Freund   Journal of the American Society of Echocardiography. 2014; 27(4): 451   [Pubmed]  [DOI]   15 
Prenatal screening for structural congenital heart disease 

 Lindsey E. Hunter,John M. Simpson   Nature Reviews Cardiology. 2014;   [Pubmed]  [DOI]   16 
Quantification of Error in the Calculation of Z Scores in Neonates 

 Henry Chubb,John M. Simpson   Journal of the American Society of Echocardiography. 2014; 27(4): 449   [Pubmed]  [DOI]   17 
Technical performance score as Predictor for post discharge reintervention in valve sparing tetralogy of Fallot repair 

 Meena Nathan,Audrey C Marshall,Jason Kerstein,Hua Liu,Francis FynnThompson,Christopher W Baird,John E Mayer,Frank A Pigula,Pedro J del Nido,Sitaram Emani   Seminars in Thoracic and Cardiovascular Surgery. 2014;   [Pubmed]  [DOI]   18 
Fetal cardiac disease and fetal lung volume: anin uteroMRI investigation 

 Elisabeth Mlczoch,Lisa Schmidt,Maximilian Schmid,Gregor Kasprian,Sophie Frantal,Vanessa BergerKulemann,Daniela Prayer,Ina MichelBehnke,Ulrike SalzerMuhar   Prenatal Diagnosis. 2014; : n/a   [Pubmed]  [DOI]  






