Primary and secondary risk factors for birth defects.

Birth defects may be inherited in the germ line or may result primarily from a wide spectrum of predictable physical, chemical, and infectious processes that can operate in the mother, the father, or in the zygote. The systematic consideration of these mechanisms can lead to a fresh awareness of risk and possible strategies toward recognizing and avoiding such risks. Birth defects also depend heavily on secondary factors that may even be of greater concern than any single primary insult because they may simultaneously affect the consequences of more than one primary exposure. Under the influence of secondary factors, the frequency, timing, and intensity of developmental deficiencies can be quite varied. It is particularly interesting that expression can be delayed until quite late in life, and deficiencies may occur or be expressed only in response to the appropriate environmental stress or functional demand. Any discussion of teratogenic mechanisms, therefore, is not complete without taking into account the important concept of co-teratogenesis, or the operation of secondary risk mechanisms. The principle of secondary risk or co-teratogenesis has been demonstrated by means of enhancement of radiation-induced terata by the administration of drugs that inhibit DNA repair. An example of late-onset expression of prenatal damage was illustrated with postnatal retinal degeneration occurring after prenatal damage to the developing retina. It is suggested that a systematic consideration of primary and secondary risk mechanisms can lead to a better understanding of the problem of birth defects.