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Teratogen Information

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Introduction to Teratogen Counseling

Psychiatric disorders are among the most common serious diseases occurring in women of childbearing age. Many women initially manifest symptoms and require medications during their reproductive years. Unfortunately, high relapse rates occur in patients with medication-responsive illness who discontinue their medication(s). Data also show that stopping and restarting psychiatric medications can render them less effective, and that stopping or tapering off these medications can have implications for the patient's competency and ability to manage her pregnancy. Therefore, health-care providers in consultation with patients often find themselves weighing the risks and the benefits of psychiatric medications during the preconception period and pregnancy.

A woman planning a pregnancy or one already pregnant must work with her health-care providers (such as the prescribing physician, OB/GYN, and genetic counselor) to determine whether her current medication regimen poses a teratogenic risk that outweighs the benefits of this therapy. This is not always a simple task. As with many types of exposures, data that clearly define and assess teratogenic risk are in many cases unavailable or inconclusive. In some cases, alternative medications with less potential for adverse pregnancy outcome can be prescribed, or doses can be lowered or eliminated during critical developmental periods. Each case must be evaluated individually to ensure that a proper risk assessment occurs for each patient.

As counselors are aware, pregnancies often are unplanned, and any pregnant woman may inadvertently expose a fetus to a teratogen. If possible, the counselor, physicians, and patient should discuss the potential teratogenicity of any medication used by a woman of childbearing age, especially if the drug is used on an ongoing basis.

Counselors also must keep in mind that there is a high incidence of tobacco, drug, and alcohol use among individuals with psychiatric disorders. In some cases, the potential adverse effects of these exposures outweigh the concerns relating to psychiatric medications. This is one reason that teratogen counseling may become the focus of the session even when it was not the indication for genetic counseling. When booking appointments, it is helpful to have an idea before the session of what, if any, medications your patients are taking and exposures they have experienced.

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Collecting Data on Exposure to Medications

When counseling a pregnant patient, the counselor should

  • Be sure to get accurate indications and doses for all medications.
  • Often a patient will be taking more than one medication. Ask about each medication used, the dosage used for each medication, and the reason each medication is prescribed.
  • Determine how compliant she has been with the medication regimen.
  • Get specific start and stop dates for all exposures.
  • Ask about other exposures, such as illicit drugs, alcohol, cigarettes, over-the-counter medications, herbal remedies, chemicals, and medications used to treat non-psychiatric disorders.

Counselors also should ask the patient:

  • how she is doing on this regimen,
  • how long a particular regimen been in place, and
  • her history with respect to other medications, and why the other medications were discontinued.

The answers to these questions will give the counselor a better idea of whether the current medication is likely to be used long term, and may suggest possible alternatives that may be prescribed by a treating physician. It may be appropriate in such cases to discuss the lower teratogenic potential of such medications.

If the patient is not pregnant, the counselor still may want to address issues related to medication use during pregnancy. The counselor may inquire about

  • birth control practices (especially important because although some psychiatric medications reduce fertility, patients may not be aware that some of the newer medications do not have this side effect, making an unplanned pregnancy more likely), and
  • other exposures, such as drugs, alcohol, cigarettes, over-the-counter medications, herbal remedies, chemicals, and medications used to treat non-psychiatric disorders.

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Risk Assessment

When assessing risk, keep the following in mind (Friedman and Polifka, 1998):

  • Ideally, a pregnant woman should not take any drug unless it is necessary for her health or the health of her fetus. Because of the normal variability in fetal development and drug response, it is impossible to state that a drug poses no risk.
  • A woman of childbearing age should not be given any drug unless the benefit clearly outweighs the risk. Because of uncertain data, this may be difficult to determine in clinical practice.
  • The greatest risk for malformations occurs during organogenesis. Before that time, exposures are likely to lead to fetal death or have no effect on the fetus.
  • After organogenesis, teratogenic agents can cause death, growth retardation, disruptions, or intellectual deficits.
  • Any drug in a dose high enough to produce toxic effects in a pregnant woman (i.e., in a suicide attempt) poses a potential risk to the fetus.
  • Simultaneous exposure to more than one drug can have more than additive effects; little is known about the likely teratogenicity of a combination of agents. In this case, the counselor should use the risks associated with the individual medications, but explain limitations to the client.

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Animal Models

Often, the only data available on a medication are derived from animal studies. Exercise care when attempting to extrapolate these data to human exposures. Chick and frog embryos are inappropriate human models because maternal metabolism does not play a role in these species. When evaluating data from animal models, counselors should consider the following:

  • If multiple studies in the same species report conflicting results, then use the worst-case scenario.
  • Weigh most heavily those studies where the route (i.e., oral) and mode (i.e., diet or drinking water) of administration are similar to those in humans.
  • Weigh positive results (increase in malformations) more heavily when they are found in all species; weigh less heavily when positive results occur in only one species and negative results occur (no increase in malformations) in all others.
  • When using data from animals that produce litters, weigh results more heavily if major effects occur in all litters versus only one litter.
  • Weigh results most heavily if there is a significant increase in rare malformations; question the validity if there is a marginal increase in common malformations.
  • Weigh most heavily those studies that find an increase in malformations at doses that have not caused maternal toxicity.

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Counseling Breastfeeding Mothers

Women are advised not to take any unnecessary medications while breastfeeding, since the majority of drugs may be secreted in varying amounts into breast milk. Unfortunately, there often are limited data available for risk assessment. The same resources available to evaluate prenatal exposure are useful in investigating breastfeeding issues. If medication is necessary, the risk to the infant must be weighed against the benefits of breastfeeding. If a woman chooses to breastfeed while on psychiatric medications, the safest effective drug should be used, the dose should be kept minimal, if possible, and the infant should be monitored for toxic effects. The American Academy of Pediatrics considers some psychiatric medications to be contraindicated during breastfeeding, and many physicians will recommend against breastfeeding unless the risk associated with a particular medication is well established and minimal.

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Paternal Exposures

The vast majority of exposures that produce birth defects are those where the fetus is directly exposed. Medications or drugs taken by the father of a pregnancy or by environmental hazards to which he is exposed can only affect the pregnancy if they are present in semen in significant amounts, or if they change the genetic material in the sperm. Animal studies have found an increased rate of miscarriage prior to implantation following exposure to certain chemicals present in semen. Other animal studies have reported increased pregnancy loss, decreased fetal weight, or birth defects in association with exposures to chemicals present in semen. Such findings, however, have not been reported in humans. Since humans continue to have intercourse during pregnancy, it is possible that the fetus may be exposed to drugs or chemicals in semen, but most drugs and chemicals are found at such low levels that no effect would be expected.

Many studies have reported possible associations between various paternal occupational exposures and pregnancy loss, birth defects, adverse pregnancy outcomes, and childhood cancers. The evidence, however, is not strong enough at this time to allow for any definite conclusions. In summary, while there is evidence of increased risks following paternal exposure in some animal studies, there is no conclusive evidence for such an effect in humans.

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Resource List

Resources to Help with Risk Assessment

There are numerous resources available to counselors and physicians assess teratogenic risk, including

  • current literature, available through the National Library of Medicine (www.nlm.nih.gov), including Medline, Toxline, Developmental and Reproductive Toxicology (DART), and Hazardous Substances Data Bank (HSDB),
  • textbooks, and
  • on-line references and computer databases.

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Reference Texts

Berkowitz, Richard et al. Handbook for Prescribing Medications during Pregnancy, 2nd ed. Little, Brown and Company, Boston (1986).

Braunwald, Eugene, et al. Harrison’s Principles of Internal Medicine, 11th ed. McGraw-Hill Book Company, New York (1987).

Briggs, Gerald et al. Drugs in Pregnancy and Lactation, 5TH ed. Williams and Wilkins, Baltimore (1998).

Creasy, R and Resnik, R. Maternal Fetal Medicine: Principles and Practice, 2nd ed. W.B. Saunders Company, Philadelphia (1989).

Friedman JM, Polifka JE. The Effects of Neurologic and Psychiatric Drugs on the Fetus and Nursing Infant. Johns Hopkins University Press, Baltimore (1998).

Gleicher, Norbert, ed. Principles and Practice of Medical Therapy in Pregnancy, 2nd ed. Appleton & Lange, Norwalk, CT (1992).

Heinonen, G.P. et al. Birth Defects and Drugs in Pregnancy, 3rd ed. PSG Publishing Company, Inc., Littleton, MA (1977).

Koren, Gideon, ed. Maternal-Fetal Toxicology, 2nd ed. Marcel Dekker, Inc., New York (1994).

Larsen, William J. Human Embryology. Churchill Livingstone, New York (1993).

Moore, Keith L. The Developing Human, 3rd ed. W. B. Saunders Company, Philadelphia (1982).

Newall et al. Herbal Medicines: A Guide For Health-Care Professionals. The Pharmaceutical Press, London (1996).

PDR for Herbal Medicines, 1st ed. Medical Economics Company, Montvale, NJ (1998).

Physicians’ Desk Reference, 54th ed. Medical Economics Company, Montvale, NJ (2000).

Schardein, James L. Chemically Induced Birth Defects, 2nd ed. Marcel Dekker, Inc., New York (1993).

Scialli, Anthony. A Clinical Guide to Reproductive and Developmental Toxicology. CRC Press, Inc., Boca Raton, FL (1992).

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On-Line Resources and Computer Databases

Many of these resources require a subscription. Each has a unique format and reviews data in different ways; it is best to review at least two different resources.

The Organization of Teratogen Information Services (OTIS):

The Organization of Teratology Information Services web site contains a continually expanding set of fact sheets. These fact sheets are designed for patient readability, and the information is kept current. Counselors also may locate the TIS that services their state on the OTIS website, and can contact that TIS for detailed information about a wide variety of exposures. www.OTISpregnancy.org

Reprorisk (MICROMEDEX): 

The Reprorisk system, produced by MICROMEDEX, is a compilation of four reproductive risk information databases, Reprotext (provides reviews on the health effects of industrial chemicals that are commonly encountered in the workplace), Reprotox (see below), Shepard’s Catalog of Teratogenic Agents (provides information on teratogenic agents including chemicals, food additives, household products, environmental pollutants, pharmaceuticals, and viruses), and TERIS (see below). http://www.micromedex.com/products/reprorisk/ or (800) 525-9083

Reprotox:

Reprotox provides current assessments on the potentially harmful effects of environmental exposure to chemicals and physical agents on human pregnancy, reproduction, and development. www.reprotox.org

TERIS:

The Teratogen Information Service provides information on the teratogenic effects of drugs and environmental agents. http://depts.washington.edu/~terisweb/teris/

Poisondex:

Poisondex identifies the ingredients for hundreds of thousands of commercial, biological, and pharmaceutical products. The index also provides data on clinical effects, range of toxicity, and treatment protocols for exposure. http://www.micromedex.com/products/poisindex/

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References

ACOG educational bulletin: Teratology. International Journal of Gynecology and Obstetrics. 57 (236): 319-326 (1997).

Bologa M et al . Drugs and chemicals most commonly used by pregnant women. In: Maternal-Fetal Toxicology 2nd ed. Ed Koren, Marcel Dekker, New York, pp 89 — 113 (1994).

Cohen LS, Rosenbaum JF. Psychotropic drug use during pregnancy: weighing the risks. J Clin Psychiatry 59(supp2): 18-28 (1998).

Cordero J et al. Drug exposure during pregnancy: Some epidemiologic considerations. Clinical Obstetrics and Gynecology 26 (2): 418 — 428 (June 1983).

Friedman JM, Polifka JE. The Effects of Neurologic and Psychiatric Drugs on the Fetus and Nursing Infant. Johns Hopkins University Press, Baltimore (1998).
Goethe J, Price A. Herbal medicines with psychiatric indications: a review for practitioners. Connecticut Medicine. 64 (6): 347-351 (2000).

Holmes LB, et al. The teratogenicity of anticonvulsant drugs. NEJM 344 (15): 1132-1138 (2001).

Huan J, Ormond K, eds. Clinical Teratology Educational Modules. National Society of Genetic Counselors, GLaRGG Teratogen Subcommittee, and the Perinatal Foundation (2000).

Kelley-Buchanan, Christine. Peace of Mind during Pregnancy. Dell Publishing, New York (1988).

Koren G, et al. Women’s perception of teratogenic risk. Canadian Journal of Public Health. 82: S11-S14 (1991).

Koren G, Pastuszak A, Ito S. Drugs in pregnancy. NEJM 338 (16): 1128-1137 (1998).

Rubin P. Drug treatment during pregnancy. BMJ 317:1503 —1506 (1998).

Sampson PD et al. Incidence of Fetal Alcohol Syndrome and Prevalence of Alcohol-Related Neurodevelopmental Disorder. Teratology 56: 317 — 326 (1997).

Werler M. Teratogen Update: Smoking and reproductive outcomes. Teratology 55: 382-388 (1997).

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