TERIS: The Teratogen Information System

TERIS (The Teratogen Information System) is a unique and authoritative clinical teratology resource designed to assist physicians and other health care professionals in assessing the risks of medication and other exposures during pregnancy. The computerized database consists of summaries with teratogenic risk ratings for over 1,800 agents, each of which is based on a thorough review of the published clinical and experimental literature.

All information in TERIS is analyzed and reviewed by the TERIS Advisory Board, a group of global experts in medicine, epidemiology and genetics. Based on the available evidence, teratogenic risk ratings are assigned to each agent contained in the database.

For more information about TERIS, see the TERIS Preamble below:

Every year, about 3-6% of infants worldwide are born with a serious birth defect (1). Birth defects are not restricted to structural congenital anomalies but also other important functional deficits which may not become apparent until later in life. The cause of most birth defects is unknown. Purely genetic factors, i.e., chromosomal aberrations and abnormalities of a single gene or gene pair, account for about 25%; while environmental factors such as exposure to medications, chemicals, or other agents during pregnancy may account for about 5-10% (2). Nevertheless, congenital anomalies caused by environmental agents are especially important because they can potentially be prevented (3,4).

A teratogen may be defined as an agent that can produce a permanent abnormality of structure or function in an organism exposed during embryonic or fetal life. Identification of human teratogens requires careful interpretation of data obtained from several kinds of studies (5). The first evidence that an agent is teratogenic in humans often comes from clinical case reports. Case reports are most useful if they reveal a pattern of anomalies in children who experienced similar well-defined exposures at similar points during embryonic or fetal development. Case reports cannot provide reliable quantitative estimates of the risk of anomalies in an exposed pregnancy. While case reports are important in raising causal hypotheses, most such hypotheses are incorrect. Coincidental occurrence of an environmental exposure in a pregnant woman and congenital anomalies in her child is very common, especially if the exposure or the defects or both are relatively frequent.

Controlled epidemiologic studies provide the only means of obtaining quantitative estimates regarding the strength and statistical significance of associations between agent exposures in pregnant women and abnormalities in their children. Epidemiologic investigations used in teratology are primarily of two types: cohort studies and case-control studies. In cohort studies, the frequencies of certain anomalies are compared in the children of women exposed and unexposed to the agent in question. In case-control studies, the frequency of prenatal agent exposure is compared among children with and without a given anomaly. If a teratogenic agent increases the risk of anomalies only slightly, very large studies may be necessary to demonstrate the increase. On the other hand, spurious associations often occur in investigations involving large numbers of comparisons between exposed and unexposed or affected and unaffected subjects. In interpreting epidemiologic studies, one must remember that the maternal disease or situation which occasioned the exposure rather than the agent itself may be responsible for an observed association. Biases of ascertainment and recall may also produce spurious associations. One can never assume that a statistically significant association in an epidemiologic study indicates causality without adducing other evidence to support such a conclusion. Moreover, the usefulness of most published epidemiological studies is limited by failure to consider the etiologic heterogeneity of human congenital abnormalities or the subtle patterns of anomalies characteristic of many human teratogens.

Although human investigations are necessary to demonstrate that an agent is teratogenic in humans, such studies are not informative until the agent has already damaged many children. Experimental animal studies can provide a means of identifying agents with teratogenic potential before humans have been harmed. Unfortunately, it is usually impossible to extrapolate findings in animals to a clinical situation involving an individual pregnant woman. Species differences in placentation, pharmacodynamics, embryonic development, and innate predisposition to various fetal anomalies are well recognized. Moreover, teratology experiments in animals often employ agent dosages which are many times greater than those likely to occur in humans, and maternal toxic effects may confound interpretation of fetal outcome. It is even more difficult to assess the relevance of in vitro teratology assays to pregnant women.

In TERIS, analysis of each agent’s teratogenicity has been made on the basis of the reproducibility, consistency, and biological plausibility of available clinical, epidemiological, and experimental data. Reproducibility is judged by whether similar findings have been obtained in independent studies. Concordance is considered to be particularly important if the studies are of different design and if the types of anomalies observed in various studies are consistent. Effects seen in animal investigations are weighed more heavily if the exposure is similar in dosage and route to that encountered clinically and if the species tested are closely related to humans phylogenetically.

TERIS places a strong emphasis on ensuring that observed associations between prenatal exposures and embryo/fetal effects are biologically plausible. Exposures that produce malformations in the developing embryo or fetus should occur only during organogenesis or histogenesis, and affected structures should be susceptible to the teratogenic action of an agent only at specific gestational times. Systemic absorption of the agent by the mother and its presence at susceptible sites in the embryo or placenta should be demonstrable. In most cases, higher exposures should increase the likelihood of abnormalities. Such dose-response relationships are commonly observed in experimental studies but are often not demonstrable in human data due to the limited dose range encountered clinically. Finally, a causal inference is strengthened if a reasonable pathogenic mechanism can be established for the observed effect.

TERIS includes reviewed data on birth defects, childhood neurodevelopmental outcomes, other adverse pregnancy and neonatal outcomes and animal experimental studies related to exposures during pregnancy. Maternal exposures assessed in TERIS include medications, recreational drugs, infections, vaccines, and selected medical conditions, environmental agents, and vitamins. Information regarding the pharmacodynamics of the agents, their excretion in breast milk, and their maternal and neonatal pharmacology is not included but is available elsewhere (6-10). The mutagenicity of agents is also generally excluded. Although many agents have been shown to be mutagenic in experimental systems, there is no evidence in humans that exposure of an individual to any mutagen measurably increases the risk of congenital anomalies in his or her offspring (11).

TERIS was founded by Jan M. Friedman, M.D., Ph.D. (University of British Columbia), who wrote and updated TERIS along with Janine E. Polifka, Ph.D., TERIS Director Emeritus (University of Washington), until December 2019. Dr. Friedman continues to hold a key role inTERIS as an Advisory Board Member. The current members of the TERIS Advisory Board are Drs. Jan M. Friedman, Margaret L.P. Adam, Christina Chambers, Sonia Hernandez-Diaz, Kenneth L. Jones, Jennita Reefhuis, and Gary M. Shaw.

A special tribute goes to the following past board members and staff for their contribution toTERIS over the years:

Richard K. Miller, Ph.D. (Advisory Board Member, 37 years)

Robert L. Brent, M.D., Ph.D. (Advisory Board Member Emeritus, 35 years)

Thomas H. Shepard, M.D. (Advisory Board Member, 32 years)

Janine E. Polifka, Ph.D. (Director Emeritus, 31 years)

James W. Hansen, M.D., (Advisory Board Member, 14 years)

Jose F. Cordero, M.D. (Advisory Board Member, 14 years)

J. David Erickson, D.D.S., Ph.D. (Advisory Board Member, 14 years)

Cheryl Broussard, Ph.D. (Advisory Board Member, 8 years)

Cynthia Moore, M.D., Ph.D. (Advisory Board Member, 6 years)

TERIS agent summaries are written by Sura Alwan, M.Sc., PhD (University of British Columbia) and Kimberly S. Grant, Ph.D. (University of Washington). Each agent summary is based on a thorough review of published peer-reviewed data identified through PubMed, Google Scholar, and Europe PMC bibliographic searches. Statements regarding the absence of published studies are made on the basis of this literature review and are true to the best of our knowledge. Unpublished studies, such as those submitted by pharmaceutical or chemical companies to regulatory agencies, are not included because their unpublished state precludes conventional peer review and assessment. Mention of these unpublished studies is often included in package inserts, the Prescribers Digital Reference (12), and similar information provided by manufacturers. Such sources should be consulted to obtain a broader perspective on the teratogenicity of an agent. Lists of agent names and synonyms included in the index are obtained from PubChem of the National Library of Medicine (13) and DrugBank Online (14).

Near the beginning of each agent summary is a risk statement printed entirely in capital letters.This statement conveys the TERIS assessment of teratogenic risk associated with maternalexposure to the agent at clinically relevant doses. Exposures to unusually high doses, especially those that are toxic to the mother, may be associated with a higher risk. Other adverse outcomes, such as impaired perinatal adaptation or transplacental carcinogenesis, are considered separately in the narrative and, when sufficiently important, are mentioned in the risk statement under“Comments”. Each risk statement represents a consensus of ratings by the authors and the TERIS Advisory Board.

The teratogenic risk rating classifies the estimated magnitude of risk to the child followingmaternal exposure during pregnancy as None, Minimal, Small, Moderate, High, Undetermined,or Unlikely. In some instances, the rating is accompanied by a clarifying comment. For example, an agent may be rated as Undetermined with a comment that “a small risk cannot be excluded, but a high risk of congenital anomalies in the children of women treated with therapeutic doses of this agent during pregnancy is unlikely.” Similarly, an Unlikely rating may include the comment “unlikely to pose a substantial teratogenic risk, but the data are insufficient to state that there is no risk.” if available data are negative but insufficient to conclude that there is norisk. Such statements are made on the basis of general pharmacology, animal data, or analogy to a closely related agent that has been studied more thoroughly.

In general, risks rated Minimal or lower should not influence decisions regarding continuation or termination of an exposed pregnancy. Moderate or High risks may be considered important enough to influence such decisions in some circumstances.

The data quality rating describes the strength of evidence upon which the risk assessment is based, using the categories None, Limited, Fair, Good, or Excellent. Risk assessments based on evidence rated Limited or Fair ought to be considered tentative and may change as more information becomes available. Even when the quality of data is rated Good, only approximateestimates of risk magnitude are often possible.

The risk statement is followed by a detailed discussion of the evidence on which it is based. Emphasis is placed primarily on information obtained from human studies, with relevant animal studies (only in mammals) included to clarify or support interpretation. The risk statement should always be read in the context of this discussion.

References cited in each agent summary have been selected for their relevance and quality. They are not intended to provide a comprehensive bibliography but to assist clinicians in obtaining a broader understanding of the agent’s potential effects on the embryo and fetus.

TERIS is not intended as a guide for prescribing medications to pregnant women. Physicians should consult approved package inserts and professional guidelines for such guidance. Proprietary names are used solely for identification purposes, and do not imply endorsement or recommendation of the agent.

The agent summaries are designed to assist physicians and other health professionals in counseling pregnant patients concerned about potential effects of drugs or other exposures on their developing babies. These summaries form only one component of a comprehensive pregnancy risk assessment which must consider the route and dose of the exposure. Accurate determination of timing is particularly important, as the highest risk of teratogenesis occurs during organogenesis (approximately 18-60 days post-conception). Exposures before this period are less likely to cause malformations but may result in embryonic death, while exposures later in pregnancy are unlikely to produce structural malformations but can cause growth restriction, functional deficits, or fetal death.

Evaluation of each patient should also include assessment of their overall health, previous and current pregnancy history, and family history. Counseling should be tailored to the patient’s intellectual, educational, psychosocial, and cultural background. Risk should be presented in the context of the baseline risk of congenital anomalies that occurs in every pregnancy. Decisions regarding prenatal diagnosis and continuation or termination of pregnancy should be made by the patient in consultation with their physician, family, and other appropriate individuals.

Counseling regarding potential effects of environmental or drug exposure on the developing embryo or fetus is an important component of medical care. Such counseling should be provided by physicians and other health professionals with competence in clinical teratology. Difficult or complex cases should be referred to appropriate specialists.

1. Centers for Disease Control and Prevention: Birth Defects. Atlanta, Ga.: U.S. Department of Health and Human Services, 2024. Available at https://www.cdc.gov/birth-defects/about/index.html

2. Brent RL: The role of the pediatrician in preventing congenital malformations. Pediatr Rev32(10):411-421, 2011.

3. Chambers C: Over-the-counter medications: risk and safety in pregnancy. Semin Perinatol39(7):541-544, 2015.

4. Kiernan E, Jones KL: Medications that cause fetal anomalies and possible prevention strategies. Clin Perinatol 46(2):203-213, 2019.

5. Friedman JM: Editorial In Bed with The Devil: Recognizing human teratogenic exposures. Birth Defects Res 109(18):1407-1413, 2017.

6. O’Neil MJ (ed): The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th ed. Cambridge: The Royal Society of Chemistry, 2013.

7. Briggs GG, Towers CV, Forinash AB: Briggs Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 12th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins, 2021.

8. National Institute of Child Health and Human Development: Drugs and Lactation Database (LactMed®) [Internet]. Bethesda, Md.: National Library of Medicine; 2006-. Available at https://www.ncbi.nlm.nih.gov/books/NBK501922/

9. Brunton LL, Knollmann BC (eds): Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 14th ed. New York: The McGraw-Hill Companies, 2022.

10. Pharmaceutical Press: Martindale: The Complete Drug Reference [Internet]. London. Available at https://www.pharmaceuticalpress.com/products/martindale-the-complete-drug-reference/

11. European Medicines Agency: ICH Guideline S2(R1) on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use. London: European Medicines Agency, 2012. Available at https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-s2-r1-genotoxicity-testing-and-data-interpretation-pharmaceuticals-intended-human-use-step-5_en.pdf

12. Prescribers Digital Reference [Internet]. Whippany, N.J.: PDR by ConnectiveRx. Available from: https://www.pdr.net/

13. PubChem [Internet]. Bethesda, Md.: U.S. National Library of Medicine. Available from:https://pubchem.ncbi.nlm.nih.gov/

14. DrugBank [Internet]. Edmonton (AB): DrugBank Online; 2025. Available from: https://go.drugbank.com/