Retinoic acid, an analogue of vitamin A, is known to be teratogenic in 
laboratory animals and has recently been implicated in a few clinical case 
reports. To study the human teratogenicity of this agent, we investigated 154 
human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for 
severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 
infants without major malformations, 12 spontaneous abortions, and 21 malformed 
infants. A subset of 36 of the 154 pregnancies was observed prospectively. The 
outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 
malformed infants. Exposure to isotretinoin was associated with an unusually 
high relative risk for a group of selected major malformations (relative risk = 
25.6; 95 per cent confidence interval, 11.4 to 57.5). Among the 21 malformed 
infants we found a characteristic pattern of malformation involving 
craniofacial, cardiac, thymic, and central nervous system structures. The 
malformations included microtia/anotia (15 infants), micrognathia (6), cleft 
palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic 
defects (7), retinal or optic-nerve abnormalities (4), and central nervous 
system malformations (18). The pattern of malformation closely resembled that 
produced in animal studies of retinoid teratogenesis. It is possible that a 
major mechanism of isotretinoin teratogenesis is a deleterious effect on 
cephalic neural-crest cell activity that results in the observed craniofacial, 
cardiac, and thymic malformations.