Issues of risk assessment: lessons from the use and abuse of drugs during pregnancy

Therapeutic uses and risks associated with the opioids, cannabis, cocaine, and phencyclidine are discussed as well as limitations of the developmental animal and clinical pediatric literature, especially with respect to problems of quantitative risk assessment. Human and animal developmental findings for methadone and cannabis are compared with respect to long-term behavioral effects with special emphasis on pharmacological and interpretive issues. It is suggested that neonatal withdrawal is the most serious neurobehavioral sequela associated with maternal use of opioid and other sedative-hypnotic compounds. Withdrawal phenomena are described and attempts to develop animal models are discussed. Methodological considerations including surrogate fostering, pair-feeding, and problems associated with the administration of compounds to lactating dams are discussed in the context of the adequacy of the EPA developmental neurotoxicity battery to characterize risk for abuse substances as well as the new NIDA medication compounds.