Each year the American Association of Poison Control Centers (AAPCC) receives reports of more than 2 million toxic exposures, most from ingestions of household products, medications, and illicit substances. Remarkably, half occur in children younger than age 6 owing to their natural propensity to explore and put things in their mouths. In contrast, teenagers more commonly experience toxicities from intentional drug exposures. Regardless of cause, drug and toxin exposure is a leading cause of emergency department visits among children. With their rapidly changing physiologies, these young patients are quite susceptible to toxicity and pose unique concerns for clinicians and laboratorians.
Across the Spectrum of Exposures
Within the pediatric population, neonates and infants are particularly vulnerable, as they face short- and long-term consequences from fetal drug and alcohol exposure and also may experience iatrogenic exposures when their physiologies and organ systems are quite immature. Examples of the latter include benzyl alcohol from fluid preservatives, boric acid in diaper rash creams, hexachlorophene in contaminated talc powders, and skin cleansers containing iodine and isopropyl alcohol.
Luckily, as babies grow into early childhood, most of their drug exposures are from relatively non-toxic substances. However, even small ingestions of certain drugs and toxins pose the risk of significant injury or even death for these young children. Problematic medications include antimalarials, antidysrhythmics, antipsychotics, beta-blockers, calcium channel blockers, clonidine, hypoglycemic agents, iron, opioids, theophylline, and tricyclic antidepressants.
As children mature into adolescents, the risk from intentional toxic exposure rises. Rapid physiological changes and social stresses place teens and tweens in danger of self-injury and suicide attempts from drug overdoses and encourage risk-taking behaviors like experimenting with drugs in bizarre ways. In addition to traditional drugs of abuse such as cannabinoids, amphetamines, cocaine, and opiates, newer drugs such as synthetic marijuana, cathinones (bath salts), synthetic opioids, and 251-NBOMe are becoming popular among adolescents.
Laboratory Considerations
Labs analyzing toxicology-related samples from children and youth face some unique considerations. As with adult toxicology samples, immunoassays and chromatographic methods are appropriate for drug testing in children, with the same pros and cons. Immunoassays offer fast turnaround times and are available on automated chemistry analyzers but test for a limited number of drugs and are prone to interferences. In contrast, chromatographic methods are specific and screen simultaneously for hundreds of drugs but have hefty startup costs and need specially trained laboratorians.
Like in adult toxicology, urine is the most common sample type in young people, but urine collection from pediatric patients has particular challenges, including that they may need to be bagged or catheterized. Labs also may need to test very small sample volumes. In addition, children’s urine samples generally are dilute and are more likely to yield false-negative results. Furthermore, drugs of abuse cutoffs for both immunoassays and confirmatory methods are fairly high to keep false-positive rates low for their most common use, workplace drug testing. As an example, the usual cutoff for opiates—2,000 ng/mL—is very high for drug screening in children. A more appropriate pediatric drug screening cutoff is 300 ng/mL in order to increase drug detection rates. False-negative results may lead to a child’s continued drug exposure from drug-using caregivers. Blood may be the specimen of choice when ingestion is known and quantification of a particular drug and/or metabolite is needed.
Sample types unique to pediatric populations include meconium, neonatal hair, and placental tissue. Meconium—the most common specimen for detecting in utero drug exposure—is easy to collect and reveals the baby’s drug exposure during the last 5 months or so of gestation. However, meconium also has some analytical caveats. Sticky, heterogeneous, and gelatinous, meconium samples need to be thoroughly homogenized before analysis. Labs commonly use methanol or acetonitrile as extraction solvents. Direct analysis is one option, or labs might dry an organic solvent and suspend the residue in aqueous media such as phosphate-buffered saline. Since there are no Food and Drug Administration (FDA)-approved assays for meconium, labs also need to perform extensive method validation, particularly for immunoassays. Meconium’s color also leads to high false-positive rates.
Beyond analytical factors, meconium poses interpretation challenges due to poorly established cutoffs and the possibility of discordant baby-mother test results. If the mother has only recently abused drugs, her urine may yield positive results but the neonate’s meconium test may be negative. Alternatively, if the mother recently abstained, her urine screen may be negative, while the baby’s meconium may be positive. The newborn’s hair and placental tissue also reveal in utero drug exposure but like meconium, both are difficult to work with and there are no FDA-approved assays for their analysis.
Another unique aspect of pediatric toxicology testing is that labs have a definitive obligation to confirm drugs of abuse positive screening results, as the consequences of finding an illicit drug in a child may be huge, including having the child removed from his or her parents. Most clinical labs are not equipped to confirm screen-positive results, so they need to communicate clearly with clinicians not only any screen-positive or negative results but also the limitations of immunoassays. Of note, positive screening results could be true positives due to prescribed medications. For example, a teenager taking an amphetamine for attention deficit hyperactivity disorder will show a true amphetamine-positive result. Finally, labs should know that their test results might be used in a court of law or in child abuse/neglect investigations even if patient samples don’t follow chain-of-custody and are submitted for clinical management.
Uttam Garg, PhD, DABCC, FABFT, FACB, is director of the laboratory medicine division, and of clinical chemistry, toxicology, and biochemical genetics at Children’s Mercy Hospital and professor of pediatric pathology at the University of Missouri School of Medicine in Kansas City. +Email: [email protected]