The potential for teratogenicity of vitamin A and its congeners

To review the evidence for teratogenic potential associated with the use of vitamin A and synthetic retinoids in Australia.

Relevant indexed journal articles and standard drug information reference texts were identified by Medicine and library search. Information was also obtained from the Australian National Perinatal Statistics Unit.

We summarised human and animal data relating to the teratogenicity of vitamin A derivatives and synthetic retinoids, including case reports documenting systemic effects from topically administered drugs, pertinent information relating to the clinical pharmacokinetics and adverse effects of these compounds, and the approved and potential indications for the use of these agents.

Extensive experimental evidence points to the teratogenicity of natural and synthetic retinoids in animals. Data confirming an effect in humans are not as good. Nevertheless case series, case reports and some epidemiological data regarding isotretinoin suggest that synthetic retinoids are similarly teratogenic in humans. Although there are extensive guidelines and legislation dealing with the use of these compounds in the United States and Australia, the potential for teratogenicity induced by vitamin A still exists. This is because retinoids and vitamin A continue to be prescribed for women of child-bearing potential and documented evidence from the United States reveals that not all prescribers comply with recommendations that minimise the risk of malformations. Non-prescription forms of vitamin A are available without a pregnancy hazard warning, and potentially teratogenic amounts are available from dietary sources.

There exists a potential for teratogenicity in association with the use of both synthetic and natural retinoids in Australia. Monitoring systems currently in place in this country may not detect these malformations should they occur.