WASHINGTON – A groundbreaking study published today in JAMA demonstrates significant inconsistencies with pediatric reference intervals, which are essential to high quality pediatric medical testing. Completed by AACC’s laboratory medicine experts, this study identifies some of the most pressing issues in this area, thereby paving the way for the medical community to develop more reliable pediatric reference intervals and vastly improve children’s medical care.

View the full study here.

To correctly interpret clinical test results for pediatric patients, physicians must evaluate results within the context of reference intervals—the range of normal test values appropriate for the age, stage of development, ethnicity, and gender of a child. However, the pediatric reference intervals in use today are highly inconsistent for a broad range of common clinical laboratory tests, a problem that puts children at risk for inappropriate or even harmful medical care. For example, imprecise reference intervals can lead to a physician missing that a child has a serious medical condition and failing to administer treatment in time. CDC has partnered with AACC and other key stakeholders to remedy this issue, but a detailed picture of the problems associated with pediatric reference intervals is needed to guide this initiative as it moves forward.

With this in mind, a team of AACC scientists led by Hubert W. Vesper, PhD—who is both an AACC member and director of clinical standardization programs at CDC—analyzed the reference intervals for several common and important pediatric tests. These reference intervals included those for free thyroxine, thyrotropin, ferritin, hemoglobin, and IGF-1, all of which are crucial for early identification and treatment of various disorders that impact pediatric cognitive and physical development; cystatin C, which is used to predict end-stage kidney disease in children; estradiol (a form of estrogen); and testosterone. The researchers examined the numerous reference intervals for each of these tests that are published in the scientific literature, as well as those developed and used by individual clinical labs.

From this, Vesper’s team found that many of these pediatric reference intervals are inappropriate for assessing a child’s health or monitoring treatment. The reference intervals for free thyroxine, thyrotropin, ferritin, cystatin C, estradiol, and testosterone were particularly inconsistent, especially during developmental stages where children undergo rapid biochemical changes. As just one example, some pediatric reference intervals for free thyroxine and thyrotropin fail to capture the surge in these two hormones that occurs in the first few days of life, which could lead to incorrect diagnoses of thyroid diseases in newborns. Inconsistencies such as this are due, in part, to the high variability in the age groups used to represent certain life stages during pediatric reference interval development—a finding that is essential to improving these reference intervals in the future.

“There is a need to correctly describe the biochemistry of child development, as well as to identify strategies to develop accurate and consistent pediatric reference intervals for improved pediatric care,” said Vesper. He also added that, “continued communication and collaboration between clinicians and their laboratory colleagues ensures appropriate clinical test interpretation and patient assessment and remains essential to effective implementation of common [pediatric reference intervals].”

About AACC

Dedicated to achieving better health through laboratory medicine, AACC brings together more than 70,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, AACC has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit www.myadlm.org.