Jm. Reinisch et al., IN-UTERO EXPOSURE TO PHENOBARBITAL AND INTELLIGENCE DEFICITS IN ADULTMEN, JAMA, the journal of the American Medical Association, 274(19), 1995, pp. 1518-1525
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.