Teratogenic causes of malformations

Abstract

Crucial morphogenetic processes during the blastogenesis period, which extends throughout the first 4 wk of development, from fertilization until the end of the gastrulation stage (days 27 to 28 postconception), can be altered and result in structural abnormalities, including patterns of multiple congenital anomalies (MCAs) arising from developmental field defects. Severe damage may cause death of the product of conception or, because of the pluripotential nature of the cells, the damage may be compensated allowing development to continue in a normal fashion. Most investigators believe that the all-or-none rule applies to the first 2 wk of development. Because the fetus is less susceptible to morphologic alterations when the developmental process of the majority of organs has been completed, the most common anomalies associated with teratogenic exposures during the fetal period are fetal growth restriction (intrauterine growth retardation) and mild errors of morphogenesis (abnormalities of phenogenesis), such as epicanthic folds, clinodactyly, and others. Thus, teratogenic exposures result in a wide variety of effects that range from infertility, prenatal onset growth restriction, structural defects, and functional CNS abnormalities to miscarriage or fetal death.