Therapeutic challenges. Prenatal and paediatric safety considerations.

Developmental changes make the fetus and child uniquely susceptible to drug toxicities which do not occur in mature individuals. Passive exposure to maternally administered drugs during fetal life introduces the potential risk of morphological or behavioural teratogenesis. Although animal studies are useful in identifying potential teratogens, they are poor predictors of human teratogenesis. Most drugs are excreted into breast milk in insufficient quantity to cause adverse effects in the nursing infant. However, there are several exceptions. Therefore, it is important to document the extent to which a drug appears in breast milk and is absorbed by the nursing infant prior to its use by the mother. Plasticity of growing tissues and changes in body composition, the rate of drug metabolism, drug metabolic pathways and elimination rates during growth and development may alter susceptibility to unique drug toxicities. This requires that drug safety and efficacy be established in children at different ages. Ethical and technical constraints inherent in drug studies in children introduce increased effort and cost. However, there is a moral imperative for academicians, government agencies and the pharmaceutical industry to work together to ensure that drugs intended for use in children are adequately tested in children.