Craniofacial and central nervous system malformations induced by triamcinolone acetonide in nonhuman primates: I. General teratogenicity.

Eighteen pregnant Macaca mulatta, 15 Macaca radiata, and six Papio cynocephalus were treated with 5--20 mg/kg triamcinolone acetonide (TAC) between 21 and 43 days of gestation on single- or multiple-day treatment schedules. Prenatal deaths and stillbirths were tripled in the bonnet monkey and doubled in the rhesus monkey, but did not significantly increase in the baboon. The central nervous system and cranium were the most commonly malformed areas in all three species. The incidence of severe defects, e.g., cranium bifidum, encephalocele, meningocele, and hydrocephalus, was increased in multiple-day treated cases. Minor abnormalities such as aplasia cutis congenita, cranium bifidum occultum, and occipital lobe hypoplasia were more prevalent in single-day treated cases. The sensitive period (days 23--31) for TAC for this group of defects encompasses neural tube closure, rostral demarcation of the midbrain, and development of the primordial collicular plate and two midbrain neuromeres. The results of this study indicate that TAC is a valuable chemical tool for the study of malformations and pathogenesis of the brain and accompanying cranio-facial defects.