I read with interest the article by Mawad et al. titled “A Review and Critique of the Statistical Methods Used to Generate Reference Values in Pediatric Echocardiography,” recently published in JASE , which highlights my group’s previous observations pertaining to the limitations of current pediatric nomograms. There continues to be a need for more robust and accurate pediatric nomograms, with ongoing efforts to establish these at this time. Valid nomograms are needed to reduce errors in pediatric echocardiographic quantification.

However, it is important to remember the complex interactions among all the variables that can affect “what is normal” in a pediatric population. In neonates and infants, for example, there are rapid changes in physiology with increasing body size that significantly affect echocardiographic measurements. The transition from placental circulation to neonatal circulation involves abrupt changes in lung volume and compliance as well as loading conditions for the right and left heart. In addition, neonates and infants (including sleeping babies) exhibit exaggerated variations in heart rate and blood pressure, with corresponding effects on cardiac output and loading conditions.

These variations may introduce an unpredictable bias in echocardiographic measurements, may occur at variable times for each subject, and may be influenced by heterogeneous external conditions. Accounting for these variables in mathematical models can be complicated, and they are often ignored, so clinicians must be aware that these limitations can result in significant discrepancies during pediatric echocardiographic quantification. The use of Z scores is quite helpful during pediatric quantification, but one should not focus solely on quantitative data without also considering the clinical context.

In summary, current nomograms for echocardiographic quantification in children are limited, with multiple sources of error. Standardized methodologies for the performance and normalization of measurements can reduce some of the biases, but they will not easily eliminate all the confounding issues related to defining “what is normal” in a pediatric population. In particular, the rapid variations in loading conditions, heart rate, and blood pressure that occur during the first few weeks of life are important and can create significant limitations with the establishment of new and more reliable nomograms for neonates.

At present, the enthusiasm for novel methodologies must be embraced with acknowledgment of the limitations of echocardiography within the context of variable clinical scenarios.