FDA pregnancy categories
Related Terms
Birth defects, category A, category B, category C, category D, category X, fetal development, pregnancy risk factor, teratogen.
Background
The term "Pregnancy Risk Factor" followed by letter A, B, C, D or X signifies a pregnancy category. The FDA established these five categories to indicate the potential of a systemically absorbed drug for causing birth defects. The categories are determined by the reliability of documentation and the risk to benefit (risk:benefit) ratio.
Pregnancy category X is particularly distinguished in that if any data exists that may implicate a drug as a teratogen (potentially causing birth defects) and the risk to benefit ratio is clearly negative, the drug is contraindicated (prohibited from use) during pregnancy.
Sometimes a drug taken by a woman during pregnancy may enter a fetus, causing damage or birth defects. The risk of damage done to a fetus is the greatest in the first few weeks of pregnancy, when major organs are developing. However, researchers do not know if taking medicines during pregnancy may also have negative effects on the baby later on.
Introduced in 1979, the pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does not include any risks given by pharmaceutical agents or their metabolites that are present in breast milk.
The FDA requires a relatively large amount of high-quality data on a pharmaceutical for it to be defined as pregnancy category A. As a result of this, many drugs that would be considered pregnancy category A in other countries are allocated to category C by the FDA.
Theory / Evidence
Unless research focuses on a pregnancy-related condition such as labor induction, drugs typically are not studied in pregnant women because of the risk of exposing the woman to an experimental drug and harming the fetus.
Currently there is a significant lack of adequate information on medications that sometimes must be used in pregnancy, such as antibiotics, and drugs to treat seizure disorders, hypertension, and psychiatric conditions. The FDA established the Labeling Task Force in 1996 to ensure pregnancy labeling of medical products is based on sound, scientific information.
Canadian pharmacologists at the Hospital for Sick Children in Toronto, Canada, have compiled a listing of common herbs, vitamins and supplements considered to be safe for use during pregnancy based on all available studies. Herbs were placed on a grading system to rate their safety for use during pregnancy and breastfeeding. Cranberries (for urinary tract infections), echinacea (for colds), garlic (for hypertension) and ginger (for nausea) have all been given an A rating for safety. An A rating means that large well-conducted trials showed no serious adverse effects. On the list of unsafe herbs is parsley, which could increase the chance of miscarriage. Doctors were uncertain how to grade substances like black cohosh which are used to induce labor.
Pregnant women have increased blood volume, which forces the heart and kidneys to work harder. Drugs may be cleared through a pregnant woman's kidneys faster than normal. However, often doctors may err on the side of caution by giving pregnant women a lower dose than for non-pregnant patients in hopes to protect the fetus, while because of the physiological changes that occur in pregnancy, there may be times when pregnant women need a higher dose.
Pregnancy registries have grown over the years. These registries follow women taking a certain drug until their pregnancy ends, allowing researchers to use the results to assess risks to mothers and their babies. Examples are the Antiepileptic Drug Pregnancy Registry run by Massachusetts General Hospital and the Organization of Teratology Information Services' (OTIS) Asthma Medications and Pregnancy Project.
Author information
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
Bibliography
Born D, Barron ML. Herb Use in Pregnancy: What Nurses Should Know. MCN Am J Matern Child Nurs. 2005 May/June;30(3):201-206.
de Groot RH, Hornstra G, van Houwelingen AC, et al. Effect of alpha-linolenic acid supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status and pregnancy outcome. Am J Clin Nutr. 2004 Feb;79(2):251-60.
Hardy JR, Leaderer BP, Holford TR, et al. Safety of medications prescribed before and during early pregnancy in a cohort of 81 975 mothers from the UK General Practice Research Database. Pharmacoepidemiol Drug Saf. 2006 Jun 12; [Epub ahead of print]
Jones K, Chambers C, Hill L, et al. Alcohol use in pregnancy: inadequate recommendations for an increasing problem. BJOG. 2006 Jun 2;
Lee E, Maneno MK, Smith L, et al. National patterns of medication use during pregnancy. Pharmacoepidemiol Drug Saf. 2006 May 15; [Epub ahead of print]
Nordeng H, Havnen GC. Use of herbal drugs in pregnancy: a survey among 400 Norwegian women. Pharmacoepidemiol Drug Saf. 2004 Jun;13(6):371-80.
Pregnancy and the Drug Dilemma. 15 June 2006.
Categories
Category A: Controlled studies in pregnant women fail to demonstrate a risk to the fetus in the first trimester with no evidence of risk in later trimesters. The possibility of fetal harm appears unlikely. Examples may include: folic acid, vitamin B6 and thyroid medicine in moderation or in prescribed doses.
Category B: Either animal-reproduction studies have not demonstrated a fetal risk, but there are no controlled studies in pregnant women, OR animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester and there is no evidence of a risk in later trimesters. Examples may include: some antibiotics, acetaminophen (Tylenol), aspartame (artificial sweetener), famotidine (Pepcid), prednisone (cortisone), insulin (for diabetes), and ibuprofin (Advil, Motrin) before the third trimester. Pregnant women should not take ibuprofen during the last three months of pregnancy.
Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women, OR studies in women and animals are not available. Drugs should be given only if the potential benefits justify the potential risk to the fetus. These drugs may include prochlorperazine (Compazine), Sudafed, fluconazole (Diflucan) and ciprofloxacin (Cipro). Some antidepressants are also included in this group.
Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g. if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective). Examples may include alcohol, lithium (used to treat manic depression), phenytoin (Dilantin) and most chemotherapy drugs to treat cancer. In some cases, chemotherapy drugs may be given during pregnancy.
Category X: Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience, or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant. Examples may include: drugs to treat skin conditions like cystic acne (Accutane) and psoriasis (Tegison or Soriatane); a sedative (thalidomide); and a drug to prevent miscarriage used up until 1971 in the United States and 1983 in Europe (diethylstilbestrol or DES).