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Table of Contents

Magill’s Medical Guide, 9th Edition

Teratogens

by Earl Ma. Marshall, MD, BSN, RN, Nicholas Schenk, , MD

Category: Disease/Disorder

Anatomy or system affected: All

Specialties and related fields: Embryology, obstetrics

Definition: Any physical, chemical, metabolic, or infectious agent that disrupts embryological or fetal development when exposed to such agent during pregnancy.

BACKGROUND

“Teratology” is the study of birth defects. “Teratogen” is an umbrella term used to refer to agents that lead to birth defects or any disruption in the development of an embryo or fetus. Identifying teratogens has not been straight forward. The gold-standard in scientific research, the randomized control trial, exposes volunteers to an experimental variable and compares their outcomes with a similar group of volunteers that have not been exposed to the same variable. It is unethical to perform such experiments on pregnant humans, purposely exposing them to a potentially harmful agent. As such, much of our knowledge about teratology comes from lesser-reliable research avenues such as cohort studies, case-report studies, case-control studies, and animal studies. These types of studies typically have significant limitations. For example, thalidomide is an infamous medication that was used in pregnant women more than fifty years ago as a treatment for morning sickness. Extensive experiments in animals found the medication to be safe in many species including rodents, rabbits, primates, and most other mammals. Nonetheless, its use in humans led to thousands of birth defects. It was only after many years of case reports and retrospective study that the link between thalidomide and birth defects was proven, leading to its discontinued use in pregnancy.

TYPES

Teratogens are generally grouped into four broad categories, metabolic, physical, chemical, and infectious: Metabolic: Certain metabolic disorders can result in a spectrum of birth defects. Some examples of these are diabetes, thyroid disorders, and malnutrition. Diabetes during pregnancy can lead to neural tube defects, other defects of the nervous system, and a host of other complications with the pregnancy and fetal development including miscarriage and stillbirth. Untreated thyroid disorders can increase the risk of miscarriage, placental abruption, preterm labor, and delayed cognitive development. Maternal malnutrition leads to fetal malnutrition, resulting in alterations in fetal development.

Physical: This category includes agents such as ionizing radiation and heat. Exposure to excessive ionizing radiation has been linked to microcephaly (small head) and microphthalmia (small eyes). Examples of ionizing radiation include X-rays, heat or radiation for the run, and microwaves as well as gamma radiation from radioactive substances. Heat exposure, in the form of fever or use of saunas or hot tubs increases the risk of microcephaly, cleft palate, abdominal wall defects, and limb defects.

Chemical: This is the broadest category of teratogens and the category that people most closely associate with teratology. It includes medications, recreational drugs, and environmental exposures. Some of the most notable are mentioned here, though this list is not all-inclusive:

  • Alcohol—Alcohol use during pregnancy can lead to Alcohol Spectrum Disorder, which includes fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol-related birth defects, alcohol-related neurodevelopmental disorder, and neurobehavioral disorder associated with prenatal alcohol exposure. Fetal alcohol syndrome results in minor facial abnormalities, growth impairment, and central nervous system abnormalities. Other alcohol-related birth defects involve the kidneys, bones, eyes, and ears.

  • Tobacco—Smoking cigarettes increases the risk of stillbirth, miscarriage, and defects of the lungs and brain. The use of e-cigarettes exposes a developing fetus to nicotine, which alone can lead to cardiovascular, immune, nervous system, and respiratory system defects.

  • Recreational drugs—Amphetamines have been associated with small for gestational age newborns, hypertensive complications of pregnancy, placental abruption, preterm birth, and stillbirth. Cocaine use has been associated with preterm birth, placental abruption, low birth weight, and miscarriage.

  • Psychiatric/Antiepileptic medications—Valproic acid is the most dangerous within this class of medications. It is associated with major malformations and poor cognitive development. Carbamazepine, Phenytoin, Phenobarbital, and Topiramate have also been associated with birth defects. Lithium has been associated with Ebstein Anomoly and neonatal lithium toxicity. Lamotrigine and Levetiracetam are “safer” medications in this class and have not been linked to any pregnancy or developmental complications to date.

  • ACEIs/ARBs—Angiotensin converting enzyme inhibiters (ACEIs) and angiotensin receptor blockers (ARBs), used to treat hypertension, can lead to decreased blood flow to fetal kidneys. This can result in decreased or absent fetal urine output and POTTER Sequence. In the POTTER Sequence, decreased fetal urine output causes oligohydramnios (decreased amniotic fluid level). With less fluid to surround it, the fetus becomes compressed within the uterus, leading to fetal growth restriction and deformities of the face, skin, and limbs. Finally, because fetal lung maturation relies on the fetus breathing amniotic fluid in and out, lack of amniotic fluid leads to pulmonary hypoplasia. Medications in this category include Lisinopril, Prinivil, Losartan, Olmesartan, and others.

  • Cancer medications—Many cancer medications aim to interfere with rapid cellular division. A developing fetus relies on rapid cellular division for growth and development. Hence, cancer treatment medications are associated with a myriad of fetal malformations.

  • Retinoids—Retinoids are Vitamin A derivatives, including isotretinoin, acitretin, and bexarotene, that cause retinoic acid embryopathy when used in pregnancy. Birth defects involve the central nervous system, face, heart, and thymus. These medications are used to treat acne.

  • Heavy metals—Lead and mercury are the most commonly encountered heavy metals. There are many other heavy metals found in specific industrial environments and all can lead to neurological defects. Mercury is found in significant amounts in certain species of fish, which is why pregnant women are often counseled to avoid fish consumption.

Infectious: Toxoplasma, rubella, cytomegalovirus, and herpes simplex virus comprise the infamous “ToRCH” infections, which are known to cause birth defects. The o in ToRCH stands for “other” and includes infections such as syphilis, chickenpox, parvovirus B19, human immunodeficiency virus (HIV), and the Zika virus.

  • Toxoplasma—Toxoplasma, found in undercooked meat and cat feces, can cause fetal eye and nervous system defects, which is why pregnant women are counseled to avoid deli meats and cleaning litter boxes.

  • Rubella—Rubella causes Congenital Rubella syndrome, resulting in deafness, cataracts, and heart defects. Pregnant women are routinely screened for rubella immunity to assess their risk of contracting this virus during pregnancy.

  • Cytomegalovirus—Cytomegalovirus is a common virus that typically causes mild symptoms for healthy adults. However, maternal cytomegalovirus infection can result in birth defects including deafness, microcephaly, seizures, chorioretinitis, and intracranial calcifications.

  • Herpes simplex virus—If a pregnant woman experiences a herpes outbreak in the period surrounding birth, the virus can be transmitted to the newborn as it passes through the birth canal. This can lead to meningoencephalitis, a serious inflammatory condition of the brain.

  • Syphilis—Congenital syphilis infection can lead to craniofacial malformations, deafness, and fetal death.

  • Varicella zoster virus—Maternal chickenpox infection can lead to Congenital Varicella syndrome, especially in the first and second trimesters. Congenital Varicella syndrome can involve skin lesions, neurological defects, eye diseases, and skeletal abnormalities.

  • Parvovirus B19—Maternal infection with parvovirus B19 can lead to destruction of fetal red blood cells, resulting in fetal anemia.

  • HIV—Newborn HIV infection can present with low birth weight and recurrent bacterial infections. Pregnant women with HIV are encouraged to take antiretroviral therapy during pregnancy. The majority of HIV infections in newborns occur during delivery or breastfeeding. As such, HIV-infected pregnant women are often counseled to undergo cesarean delivery rather than vaginal delivery, though this is now dependent upon the woman’s viral load in the perinatal period. Women with HIV are also counseled to not breastfeed their newborn.

  • Zika Virus—Zika virus is a newer addition to the “ToRCH” list. Zika is a virus transmitted by Aedes mosquitos and causes Congenital Zika syndrome, which includes severe microcephaly, loss of brain tissue, eye defects, bone defects, and hypertonia.

AVOIDANCE AND PREVENTION

Avoidance of all teratogens is rarely possible. For example, women are commonly prescribed medication for hyperemesis gravidarum and antibiotics are often prescribed for urinary tract infection during pregnancy. The risk of untreated mental illness must be weighed against the risk of medication use during pregnancy. Nonetheless, teratogens are avoided as much as reasonably possible during pregnancy to reduce the risk of birth defects and pregnancy complications. A physician should always be consulted to discuss risks, benefits, and alternatives when medications must be used during pregnancy.

Several resources are available to provide information on teratogens, including the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), ReproTox (a database on the reproductive effects of chemicals, medications, physical agents, and biologics), the Teratogen Information System (TERIS), and the Organization of Teratogen Information Specialists (OTIS).

It is important to note that women are usually several weeks, if not months, pregnant before they realize they are pregnant. Hence, women who may become pregnant should also avoid teratogens. One extreme example of this is Isotretinoin. Isotretinoin use carries a high risk of causing serious birth defects. As a result, the FDA requires patients to register for the iPLEDGE program, which places strict requirements on the patient in an effort to avoid pregnancy while using Isotretinoin.

See also: Addiction; Alcoholism; Birth defects; Carcinogens; Chickenpox; Childbirth; Childbirth complications; Cytomegalovirus (CMV); DNA and RNA; Embryology; Environmental diseases; Environmental health; Fetal alcohol syndrome; Herpes; Imaging and radiology; Intellectual disability; Mercury poisoning; Mutation; Obstetrics; Occupational health; Over-the-counter medications; Pharmacology; Pregnancy and gestation; Premature birth; Radiation therapy; Rubella; Self-medication; Sexually transmitted diseases (STDs); Syphilis; Thalidomide; Toxoplasmosis; Viral infections.

For Further Information:

1 

Arth, A., V. Kancherla, H. Pachón, et al. “A 2015 Global Update on Folic Acid-Preventable Spina Bifida and Anencephaly.” Birth Defects Research Part A: Clinical and Molecular Teratology, vol. 106, no. 7, 2016, pp. 520-9, doi: 10.1002/bdra.23529. PMID: 27418029.

2 

Bagatin, E., and C. S. Costa. “The Use of Isotretinoin for Acne—An Update on Optimal Dosing, Surveillance, and Adverse Effects.” Expert Review of Clinical Pharmacology, vol. 13, no. 8, Aug. 2020, pp. 885-97, doi10.1080/17512433.2020.1796637. PMID: 32744074.

3 

Belanger, B. G., and F. Lui. “Embryology, Teratology TORCH.” StatPearls, 26 July 2021. PMID: 31424732.

4 

“Birth Defects?” Centers for Disease Control and Prevention, 5 Nov. 2021, www.cdc.gov/ncbddd/birthdefects/facts.html.

5 

Brittney, D., and M. D. Bastow. “Teratology and Drug Use during Pregnancy.” Medscape, 26 June 2021, emedicine.medscape.com/article/260725-overview.

6 

Georgieff, M. K., P. V. Tran, and E. S. Carlson. “Atypical Fetal Development: Fetal Alcohol Syndrome, Nutritional Deprivation, Teratogens, and Risk for Neurodevelopmental Disorders and Psychopathology.” Development Psychopathology, vol. 30, no. 3, Aug. 2018, pp. 1063-86, doi:10.1017/S0954579418000500. PMID: 30068419; PMCID: PMC6074054.

7 

Rasmussen, S. A., and D. J. Jamieson. “Teratogen Update: Zika Virus and Pregnancy.” Birth Defects Research, vol. 112, no. 15, Sept. 2020, pp. 1139-49, doi:10.1002/bdr2.1781. PMID: 32830420.

8 

Tomson, T., D. Battino, and E. Perucca. “Teratogenicity of Antiepileptic Drugs.” Current Opinion in Neurology, vol. 21, no. 2, 2018, pp. 246-52, doi:10.1097/WCO.0000000000000659. PMID: 30664067.

9 

Vargesson, N. “Thalidomide-Induced Teratogenesis: History and Mechanisms.” Birth Defects Research Part C: Embryo Today: Reviews, vol. 105, no. 2, June 2015, pp. 140-56, doi:10.1002/bdrc.21096. PMID: 26043938; PMCID: PMC4737249.

10 

Wachholz, G. E., B. D. Rendel, N. Vargesson, and L. R. Fraga. “From the Farm to the Lab: How Chicken Embryos Contribute to the Field of Teratology.” Frontiers in Genetics, vol. 12, July 2021, p. 666726, doi:10.3389/fgene.2021.666726. PMID: 34367238; PMCID: PMC8339958.

Citation Types

Type
Format
MLA 9th
Marshall, Earl Ma., and Nicholas Schenk. "Teratogens." Magill’s Medical Guide, 9th Edition, edited by Anubhav Agarwal,, Salem Press, 2022. Salem Online, online.salempress.com/articleDetails.do?articleName=MMG2022_1340.
APA 7th
Marshall, E. M., & Schenk, N. (2022). Teratogens. In A. Agarwal, (Ed.), Magill’s Medical Guide, 9th Edition. Salem Press. online.salempress.com.
CMOS 17th
Marshall, Earl Ma. and Schenk, Nicholas. "Teratogens." Edited by Anubhav Agarwal,. Magill’s Medical Guide, 9th Edition. Hackensack: Salem Press, 2022. Accessed October 22, 2025. online.salempress.com.