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March 18, 1968

Maternal Exposure to Potential Teratogens

JAMA. 1968;203(12):1075-1076. doi:10.1001/jama.1968.03140120073030

To the Editor:—  The demonstration of a teratogenic effect in human subjects is a formidable problem.To the best of our understanding at this time there are at least three major factors involved in the teratogenic production of congenital malformations:

  1. Hereditary predisposition to the malformation.

  1. Hereditary predisposition to the effects of a given teratogen.

  1. Administration of the teratogen at a vulnerable period of embryogenesis.

In animal models it is not difficult to control these factors to produce a malformation. For example, in studying atrial septal defect, we select the A/Jax mouse which is both predisposed to atrial septal defect and is sensitive to the teratogenic effects of dextroamphetamine.1 We administer this drug at day eight of gestation, the vulnerable time for cardiac development. The result is that 12% of the offspring have congenital heart anomalies, mainly atrial septal defect. This same drug is capable of causing