CLN Daily
An overlooked but consequential problem in pediatric medicine is gaining renewed attention: Children are often evaluated using laboratory reference intervals that were not designed for them. In today’s session, “Pediatric reference intervals: Progress, challenges, and future perspectives,” four expert speakers will discuss the current and future direction of pediatric reference intervals and prospects for future improvement. The presenters include Khosrow Adeli, PhD, DABCC, FADLM, FCACB; Kwaku Baryeh, PhD, DABCC; Dennis Dietzen, PhD, DABCC, FADLM; and Kelly Doyle, PhD, DABCC, FADLM.
Baryeh, the session moderator, captured the core issue with this statement: “Children are not small adults, and neither are their lab results.” When clinicians interpret a child’s laboratory result against an adult reference interval, the result can be misinterpreted, leading to unnecessary follow‑up testing, missed abnormalities, or compromised care. The good news is that new scientific tools and growing policy momentum are converging to help close this long‑standing gap.
At the center of the discussion are three intertwined challenges: establishing high‑quality pediatric reference intervals, harmonizing them across laboratories, and building the national infrastructure needed to sustain them.
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Historically, the first challenge--generating reliable reference intervals--has been the most difficult. Recruiting healthy children for blood draws is ethically complex, logistically challenging, and expensive.
Adeli will discuss what a direct approach looks like, pointing to the CALIPER program — which seeks to develop a global benchmark for direct pediatric reference interval programs. CALIPER has enrolled more than 15,000 healthy children and produced reference intervals for over 200 tests across multiple testing platforms.
Doyle will describe her work applying indirect statistical methods to large retrospective datasets. By utilizing “big data,” such efforts can yield age‑stratified reference intervals at a fraction of the cost of direct programs.
Yet even where strong reference intervals exist, the field faces a second obstacle: harmonization. Reference intervals often differ across institutions, instruments, and demographics, limiting their clinical utility. Without greater consistency, even high-quality data may fail to translate into better care. This is especially true for neonates and premature infants, who remain among the most underserved populations in laboratory medicine.
The third challenge is infrastructure and policy. Dietzen will highlight why the United States needs sustained federal support to advance more consistent, evidence-based pediatric reference intervals. ADLM has urged Congress to fund CDC work in this area, and recent appropriations activity shows growing momentum for a coordinated national approach. Such work could give clinicians and laboratories a more unified foundation for interpreting pediatric test results across care settings.
The motivation behind this work is simple: the consequences of using the wrong reference interval may not be immediately obvious, but they can ripple across the healthcare system.
From neonatal intensive care units (NICUs) to endocrinology clinics, laboratory testing drives a large share of clinical decisions. Many clinicians may not know which tests have robust pediatric reference intervals and which still rely on adult data. Because children’s physiology changes dramatically from birth through adolescence, using the wrong reference interval is not a minor technical issue; it is a systemic vulnerability.
The speakers will cover real-life examples that illustrate both the problem and the promise of pediatric testing. G6PD deficiency, a genetic condition that affects roughly 400 million people worldwide, has long lacked pediatric reference intervals. Using tens of thousands of routine test results, Doyle and her colleagues established reliable age‑stratified intervals without prospective recruitment. Meanwhile, CALIPER’s direct‑reference interval studies — which are freely available through an app and website — have become an international benchmark.
The field is at an inflection point. Advances in machine learning, large‑scale biobanking, and statistical modeling have made once daunting problems increasingly solvable. At the same time, national advocacy efforts are gaining momentum. As this scientific session suggests, the scientific and policy stars are aligning. The question now is whether the clinical community and policymakers will seize the moment.
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