IN-UTERO EXPOSURE TO PHENOBARBITAL AND INTELLIGENCE DEFICITS IN ADULTMEN

Objective.-To test whether exposure to phenobarbital in utero is assoc iated with deficits in intelligence scores in adult men and whether th e magnitude of the postnatal effect is mediated by exposure parameters and/or postnatal environmental factors. Design.-Two double-blind stud ies were conducted on independent samples of adult men prenatally expo sed to phenobarbital and matched control samples using different measu res of general intelligence, Based on data from control subjects, regr ession models were built relating intelligence scores to relevant pre- exposure matching variables and age at testing, Models generated predi cted scores for each exposed subject, Group mean differences between t he individually predicted and observed scores estimated exposure effec ts. Setting.-Copenhagen, Denmark. Participants.-Exposed subjects were adult men born at the largest hospital in Copenhagen between 1959 and 1961 who were exposed to phenobarbital during gestation via maternal m edical treatment and whose mothers had no history of a central nervous system disorder and no treatment during pregnancy with any other psyc hopharmacological drug. Study 1 included 33 men and study 2, 81 men. C ontrols were unexposed members of the same birth cohort matched on a w ide spectrum of maternal variables recorded prenatally and perinatally . Controls for studies 1 and 2 included 52 and 101 men, respectively. Main Outcome Measures.-In study 1: Wechsler Adult intelligence Scale ( Danish version); in study 2: Danish Military Draft Board Intelligence Test (Borge Priens Prove). Result.-Men exposed prenatally to phenobarb ital had significantly lower verbal intelligence scores (approximately 0.5 SD) than predicted, Lower socioeconomic status and being the offs pring of an ''unwanted'' pregnancy increased the magnitude of the nega tive effects; Exposure that included the last trimester was the most d etrimental. Conclusion.-Phenobarbital exposure during early developmen t can have long-term deleterious effects on cognitive performance. Det rimental environmental conditions can interact with prenatal biologica l insult to magnify negative outcomes, Physicians are urged to use inc reased caution in prescribing such medications during pregnancy.