A teratogen is an environmental agent that can cause abnormalities of form or function in a fetus exposed to the agent. Susceptibility to teratogenesis depends on the genotype of the conceptus, timing of exposure, dosage and interaction with other environmental factors and maternal genetic factors.

Timing of exposure

If exposure to the teratogen occurs before the differentiation of the three germ layers, either embryonic death results or no abnormalities are apparent. A high degree of sensitivity then occurs during organogenesis from about days 18 to 60, with a peak susceptibility at approximately 30 days. The type of malformation is dependent on which organ is susceptible at exposure, an organ being most susceptible early in its differentiation. Because the fetal period (second to ninth months) is characterised by histogenesis (refined cellular and tissue changes) and functional maturation, teratogenic insults during this time will result mainly in mental and growth retardation.

Dose and interaction with other environmental and genetic factors

For some, but not all, teratogens there is a dose related effect, higher doses resulting in more malformations. The potency of some teratogens can be increased in the presence of other environmental factors: the teratogenicity of some anticonvulsants is increased, for example, if used in combination with another drug.

There also appears to be a difference in susceptibility between individuals: the same dose of sodium valproate is associated with a neural tube defect in the fetus of one mother but not another.

Mechanisms of teratogens in the causation of malformations

Teratogens affect morphogenesis, development and differentiation through cell death, failed cell interactions or alterations in the movement of cells. As these affect the basic processes of cells, a teratogen may have a general effect on several tissues. Likewise, different teratogens may produce common effects. The teratogens listed in the table, do, however, produce a characteristic pattern of anomalies.