title: Retinoic acid embryopathy.
abstract: 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.
authors.forename: E J
authors.initials: EJ
authors.lastname: Lammer
authors.forename: D T
authors.initials: DT
authors.lastname: Chen
authors.forename: R M
authors.initials: RM
authors.lastname: Hoar
authors.forename: N D
authors.initials: ND
authors.lastname: Agnish
authors.forename: P J
authors.initials: PJ
authors.lastname: Benke
authors.forename: J T
authors.initials: JT
authors.lastname: Braun
authors.forename: C J
authors.initials: CJ
authors.lastname: Curry
authors.forename: P M
authors.initials: PM
authors.lastname: Fernhoff
authors.forename: A W
authors.initials: AW
authors.lastname: Grix
authors.forename: I T
authors.initials: IT
authors.lastname: Lott
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000022:Abortion, Spontaneous / Q000139:chemically induced; D000152:Acne Vulgaris / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D006330:Heart Defects, Congenital / Q000139:chemically induced; D006801:Humans; D007231:Infant, Newborn; D015474:Isotretinoin; D008297:Male; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D012189:Retrospective Studies; D012306:Risk; D014212:Tretinoin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D014212:Tretinoin; D015474:Isotretinoin