What is toxic in infants and children?

Abstract

Postmortem toxicology in adults is a problem area: what then in infants and children? When an infant or a young child dies, drugs are seldom found to be the cause of death. But is this because we are not looking for an adequate panel of substances, or is it because we are not able to interpret our findings? Sudden infant death syndrome is a diagnosis of exclusion, and a toxicological examination is therefore mandatory in order to rule out poisoning/drug intoxication as a cause of death [1]. From previous studies it seems that positive drug findings are detected in as many as 25 % of all sudden unexpected deaths in infancy [2–4], but what do these findings mean; what do we actually know about toxic and lethal drug concentrations in infants and children; and are infants and children pharmacologically different from adults? These questions need to be answered in order to able to interpret the concentrations of drugs and poisons that are detected in postmortem blood samples collected from infant and early childhood deaths. First of all, what do we know about drug concentration levels in the pediatric population? There are very few previous publications on toxicological findings among pediatric deaths [5, 6], and often such publications to not include drug concentration levels. Because of a large number of different drugs, and the low number of drugs detected in this population, the gathering of data from a large number of deaths will be necessary to gain sufficient experience with pediatric drug concentration levels. A pediatric toxicology registry, based upon case submission, was established in the USA in 1985 through the National Association of Medical Examiners [7]. The registry’s purpose was to address questions such as: what drugs and poisons are most often observed among diseased children, what concentrations can be considered therapeutic, nonlethal or lethal, and how does growth and development pertain to drug concentrations in children. However, only a few studies have been published on the data from the registry [8]. Some publications on individual drugs and case reports exist, but all in all, little information is available on drug concentrations from pediatric deaths. Children are, however, commonly exposed to different drugs and poisons, as observed through toxicological surveillance in different countries [9, 10]. However, most childhood drug exposures are survived, and many do not require hospitalization [10]. Even if a child is hospitalized, toxicological screening is often not performed, with patients being treated symptomatically or on the suspicion of the drug ingested [11]. If drug testing has in fact been performed, this is often based on drug identification in urine alone, and not on drug quantification in serum/blood [12]. Many publications on pediatric drug exposures therefore do not include concentration levels of drugs of possible interest that could have offered helpful information regarding toxic levels in infants and children. Therapeutic monitoring of drugs used in the pediatric population is likewise seldom performed [13]. Therefore, it may be concluded that information on therapeutic, toxic and lethal drug concentration levels among infants and children is scarce and limited. The question then becomes, is the data collected from adults of any relevance or use in regards to children? In many regards infants and young children are not small adults [14]. Several factors can influence the metabolism of drugs in this population, such as physiological factors, the M. Arnestad (&) Division of Forensic Medicine and Drug Abuse Research, Department of Toxicological and Pharmacological Assessment, The Norwegian Institute of Public Health, PO Box 4404, Nydalen, 0403 Oslo, Norway e-mail: marianne.arnestad@fhi.no