Accurate pediatric reference intervals (PRIs) are vital for effectively interpreting children’s test results, yet there is considerable inconsistency in existing PRIs, putting children at risk for misdiagnosis and inappropriate treatment. On October 10, the Association for Diagnostics & Laboratory Medicine (ADLM), together with the Children’s Hospital Association and The Endocrine Society, hosted a congressional briefing where experts in laboratory medicine and pediatric health described the scope of the problem and the Centers for Disease Control and Prevention’s (CDC) plan for improving PRIs.
The briefing was moderated by Patricia Jones, PhD, DABCC, FADLM, who began by inviting Representative John Joyce (R-Pa.) to address the audience. Joyce is co-chair of the Children’s Health Care Caucus and has supported funding for pediatric research throughout his career. “Pediatric patients are not tiny adults,” Joyce said, emphasizing the need for PRIs that are distinct from adult reference intervals. “We have the responsibility to understand that and produce the high quality of care that kids deserve.”
Jones, who is the clinical director of the chemistry and metabolic disease labs at Children’s Medical Center of Dallas, described the current state of PRIs as a “hodgepodge.” Existing reference intervals for many diagnostic tests do not accurately reflect normal health conditions in children, who may not always be able to communicate their symptoms like adults. “In the pediatric realm, lab testing can be even more important than in the adult realm,” Jones said.
The consequences of using adult reference intervals in pediatric care were illustrated by John Fuqua, MD, professor of clinical pediatrics at Indiana University School of Medicine. He shared how an 8-day-old baby in his hospital was diagnosed with thyroid disease due to a high level of thyroid stimulating hormone (TSH) compared to an adult reference population. The baby subsequently began treatment for hypothyroidism, even though it is in fact normal for newborns to have higher amounts of TSH and the baby was healthy. Fuqua went on to explain that, while this might seem like an innocuous mistake, medication for hypothyroidism actually suppresses thyroid hormone in healthy newborns, effectively causing the condition it was intended to treat. This means that this child was now committed to taking medication until 3 years of age, when it would finally be safe to discontinue treatment. Needless procedures, medical complications, and costs, said Fuqua, can result from the absence of accurate PRIs.
Dennis Dietzen, PhD, DABCC, FADLM, medical director of laboratory services at St. Louis Children’s Hospital, outlined the challenges of constructing effective PRIs, without which he said, “you either miss a diagnosis, or give a diagnosis for something that’s not there.” One of the biggest challenges is that individual biomarkers vary according to a host of variables, including a person’s developmental stage, and children progress through developmental stages much more rapidly than adults. Dietzen added that receiving consent from the parents of healthy children for drawing large amounts of blood — necessary for building reference intervals — can be difficult. He emphasized that trust and open communication between doctors and patients must be established in this regard, rather than “running at patients with a consent form in one hand and a needle in the other.”
CDC projects it will need an additional $10 million from Congress to establish appropriate PRIs. Hubert Vesper, PhD, director of clinical standardization programs at CDC, explained that over the next 10 years, CDC plans to improve PRIs by leveraging its existing infrastructure, particularly the National Health and Nutrition Examination Survey (NHANES). “The plan that we have is to use NHANES to collect more data on children, and develop new laboratory methods for various biomarkers,” Vesper said.
ADLM is joined by more than 30 other groups, including the American Academy of Pediatrics, in supporting CDC’s approach to generating more accurate PRIs. “It will improve pediatric healthcare,” said Jones of CDC’s plan.