Teratogens

Maternal exposure to drugs, toxins, and other environmental insults may have an effect upon the developing embryo and fetus. Some associations are well known, such as the drug thalidomide and risk for phocomelia (short limbs). Other exposures may result in sporadic appearance of birth defects. The most common teratogen is alcohol.

Fetal Alcohol Syndrome

Fetal alcohol syndrome (FAS) may affect at least one out of every 750 live births. Thirty to forty percent of babies whose mothers drink heavily throughout pregnancy develop FAS. There is no threshold amount of alcohol consumption by the mother to produce the disease--no amount is safe. The probability of having a child with FAS increases with the amount and frequency of alcohol consumed. Whenever a pregnant woman stops drinking, she reduces the risk of having a baby with FAS. Damage to the fetus from FAS cannot be reversed.

The most common deformity with FAS is moderate to severe growth retardation. Anomalies include microcephaly, frontal bossing, long and narrow forehead, hypotelorism, maxillary and mandibular hypoplasia, narrow palpebal fissures, thin elongated philtrum and vermillion border of the upper lip, temporomandibular joint disorders, and dental malocclusion, wide roof of the nose, saddle nose, tooth enamel hypoplasia, and uvular hypoplasia. Ocular problems include microphthalmia, corneal clouding, coloboma, nystagmus, strabismus, and ptosis. Internal anomalies include congenital heart disease, particularly ventricular septal defect. Vertebral abnormalities including scoliosis can be present. The liver can have fatty metamorphosis with hepatomegaly and elevated serum transaminases. The physical anomalies tend to become less apparent as the child ages.

The effect of FAS on the brain results in varying degrees of mental retardation and behavioral problems. Adverse psychosocial, behavioral, physical, and intellectual consequences of prenatal alcohol exposure continue into adulthood.

Anti-convulsant Drug Teratogenicity

Several anticonvulsant drugs, including phenytoin, carbamazepine, and phenobarbital, are metabolized by the liver through the arene oxide pathway that leads to increased epoxide intermediate metabolites that may have teratogenicity. Fetuses of mothers who require such medications can be at risk for malformations. The risk of birth defects can be up to 10%.

The best known of these is the fetal hydantoin syndrome with use of phenytoin. Features of this syndrome may include facial dysmorphology with epicanthal folds, hypertelorism, upturned nose, and flat nasal bridge, along with distal digital hypoplasia, growth retardation, and mental retardation.

Fetal valproate (valproic acid) syndrome has a facial appearance characterized by a small broad nose, small ears, flat philtrum, a long upper lip with shallow philtrum, and micro/retrognathia. In addition, there can be musculoskeletal abnormalities, minor skin defects, cardiovascular abnormalities, genital abnormalities, pulmonary abnormalities, and neural tube defects. Fetal loss may occur in 12% of cases, and 29% of survivors have developmental deficits and/or mental retardation. Growth retardation occurs in one-sixth of cases.

Maternal use of other anticonvulsant drugs, including phenobarbital, primidone (which is metabolized to phenobarbital), and carbamazepine has been associated with a variety of birth defects, but the findings vary in published studies.