Otocerebral anomalies associated with topical tretinoin use


      Topical preparations of tretinoin are used for the treatment of various skin conditions and for rejuvenation of the skin. Published information on pregnancy outcome following maternal exposure to topical tretinoin is limited to three case reports. We report a case of a patient with anomalies involving the ear and central nervous system with exposure to topical tretinoin during the first trimester. Though the potential link between the use of topical tretinoin and the existence of fetal malformations remains to be further documented by animal as well as epidemiological studies, we strongly recommend that the use of topical tretinoin during pregnancy should be discouraged, and effective contraception should be used in patients of childbearing age.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lammer E.J.
        • Chen D.T.
        • Hoar R.M.
        • Agnish N.D.
        • Benke P.J.
        • Braun J.T.
        • et al.
        Retinoic acid embryopathy.
        N Engl J Med. 1985; 313: 837-841
        • Camera G.
        • Pregliasco P.
        Ear malformation in baby born to mother using tretinoin cream (letter).
        Lancet. 1992; 339: 687
        • Lipson A.H.
        • Collins F.
        • Webster W.S.
        Multiple congenital defects associated with maternal use of topical tretinoin.
        Lancet. 1993; 341: 1352-1353
        • Navarre-Belhassen C.
        • Blanchet P.
        • Hillaire-Buys D.
        • Sarda P.
        • Blayac J.P.
        Multiple congenital malformations associated with topical tretinoin.
        Ann. Pharmacother. 1998; 32: 505-506
        • Christian M.S.
        • Mitala J.J.
        • Powers Jr, W.J.
        • McKenzie B.E.
        • Latriano L.
        A developmental toxicity study of tretinoin emollient cream (Renova) applied topically to New Zealand white rabbits.
        J Am Acad Dermatol. 1997; 36: S67-S76
        • Shapiro L.
        • Pastuszak A.
        • Curto G.
        • Koren G.
        Safety of first-trimester exposure to topical tretinoin: prospective cohort study.
        Lancet. 1997; 350: 1143-1144
        • Seegmiller R.E.
        • Carter M.W.
        • Ford W.H.
        • White R.D.
        Induction of maternal toxicity in the rat by dermal application of retinoic acid and its effect on fetal outcome.
        Reprod Toxicol. 1990; 4: 277-281
        • Pratt R.M.
        • Goulding E.H.
        • Abbott B.D.
        Retinoic acid inhibits migration of cranial neural crest cells in the cultured mouse embryo.
        J Craniofac Genet Dev Biol. 1987; 7: 205-217
        • Lammer E.J.
        • Armstrong D.L.
        Malformations of hindbrain structures among humans exposed to isotretinoin (13-cis-retinoic acid) during early embryogenesis.
        in: Morriss-Kay G. Retinoids in normal development and teratogenesis. Oxford University Press, New York1991: 281-295
        • Jahn A.F.
        Embryological development of human ear.
        Univ. Toronto Med. J. 1972; 50: 16-20