Teratogens

DEFINITION: Agents that alter normal fetal development during pregnancy and cause birth defects.

Types and Effects

Teratogens are agents that cause fetal injury and result in birth defects. Various agents such as drugs, chemicals, infections, and environmental contaminants can cause birth defects through exposure during pregnancy. Teratogens can be found at home, in the workplace, or in the environment. The severity of fetal injury and subsequent birth defects that occur are the result of the amount and timing of exposure to a particular agent and the genetic susceptibility of the embryo and mother. At low doses of teratogen, there may be no effect; at intermediate doses, a characteristic pattern of malformations can result; and at high doses, severe malformations will occur that usually result in the death of the baby. The first trimester of pregnancy is the most vulnerable time.

Teratogens produce specific abnormalities at specific times during pregnancy. For example, thalidomide, sold in the late 1950s to help pregnant women with morning sickness, resulted in babies with phocomelia (lack of long bones and flipper-like hands and feet), while valproic acid and carbamazepine produced spinal cord and brain defects. Other teratogens are also associated with recognizable patterns of birth defects. For example, the antiepileptic drug dilantin/phenytoin results in craniofacial malformations, whereas coumarin anticoagulants, such as warfarin, result in neurological complications.

Teratogenic specificity also applies to individual species. For example, aspirin has been found to be teratogenic in mice and rats but appears to be safe in humans. Thalidomide, on the other hand, was shown not to be teratogenic in rats, cats, dogs, or rabbits but is highly teratogenic in humans, a fact that resulted in approximately ten thousand children born with severe birth defects before it was recognized. The most devastating effects of thalidomide occur with exposure within the first thirty days of pregnancy.

Classification and Reducing Risk

Known teratogens can be classified as infectious agents, environmental agents, and pharmaceutical drugs. Infectious agents include rubella, cytomegalovirus (CMV), varicella, herpes simplex, toxoplasmosis, and syphilis. Environmental agents include ionizing agents, radiation therapy, x-rays, organic mercury compounds, herbicides, polychlorinated biphenyls (PCBs), and industrial solvents. Pharmaceutical drugs include retinoic acid (isotretinoin, Accutane), aminopterin, steroid hormones, busulfan, angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril), cyclophosphamide, diethylstilbestrol, diphenylhydantoin (Phenytoin, Dilantin, Epanutin), etretinate, lithium, methimazole, penicillamine, tetracyclines, thalidomide, trimethadione, warfarin, and valproic acid.

Public awareness is essential for the prevention of teratogen exposure during pregnancy. Information about fetal malformations that can be caused by exposure to drugs or environmental agents is important because they are potentially preventable. Women who may become pregnant should be aware of any medications and environmental conditions that might be teratogenic, as severe fetal malformations occur very early before the pregnancy might be discovered.

Awareness of teratogenic agents and potential exposure during pregnancy has led to the development of teratogen information databases in many areas of the country. National databases, such as ReproTox and TERIS, and teratology society organizations, such as the Organization of Teratogen Information Specialists (OTIS), have been established to provide detailed information on numerous potential teratogenic agents.

Bibliography

“Appendix D: Teratogens/Prenatal Substance Abuse.” Understanding Genetics. Genetic Alliance, 2010. National Center for Biotechnology Information, US National Library of Medicine, www.ncbi.nlm.nih.gov/books/NBK132140. Accessed 15 Nov. 2024.

Barrow, Paul C. Teratogenicity Testing: Methods and Protocols. Humana Press, 2012.

Gupta, Ramesh C. Reproductive and Developmental Toxicology. Elsevier, 2012.

Kavlock, Robert J. Drug Toxicity in Embryonic Development II: Advances in Understanding Mechanisms of Birth Defects. Springer, 2011.

Ostensen, Monika. “How Safe Are Anti-Rheumatic Drugs during Pregnancy?” Current Opinion in Pharmacology, vol. 13, no. 3, 2013, pp. 470–475.

Shepard, Thomas H., and Ronald J. Lemire. Catalog of Teratogenic Agents. 11th ed., Johns Hopkins University Press, 2004.

Shepard, Thomas H. Catalog of Teratogenic Agents. 13th ed., Johns Hopkins University Press, 2010.

Shinde, M. U. “Prenatal Exposure to Nitrosatable Drugs, Vitamin C, and Risk of Selected Birth Defects.” Birth Defects Research: Clinical and Molecular Teratology, 2013.

Silverman, William A. “The Schizophrenic Career of a ‘Monster Drug.’” Pediatrics, vol. 110, no. 2, 2002, pp. 404–406.

"Teratogens." Cleveland Clinic, my.clevelandclinic.org/health/articles/24325-teratogens. Accessed 15 Nov. 2024.

Wilson, James G., and F. Clarke Fraser, eds. Handbook of Teratology. 4 vols., Plenum Press, 1977–1978.