Pregnancy category

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. It does not include any risks confered by pharmaceutical agents or their metabolites that are present in breast milk.

In 1979, the United States FDA introduced a classification of fetal risks due to pharmaceuticals. This was based on a similar system that was introduced in Sweden just one year earlier.

The United States FDA has the following definitions for the pregnancy categories:

United States FDA Pharmaceutical Pregnancy Categories
Pregnancy Category A	Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
Pregnancy Category B	Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
Pregnancy Category C	Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Pregnancy Category D	There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Pregnancy Category X	Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

A shortcoming of the FDA definitions of the pregnancy categories is that the FDA requires an unrealistic amount of high-quality data on a pharmaceutical for it to be defined as Pregnancy Category A. As a consequence of this, many drugs that would be considered Pregnancy Category A in other countries are allocated to Category C by the FDA.

As an example of a different category system, following is the pregnancy category system for Australia, established by the Congenital Abnormalities Sub-committee of the Australian Drug Evaluation Committee:

Australian Pharmaceutical Pregnancy Categories
Pregnancy Category A	Drugs which have been taken by a large number of pregnant women and women of childbearing age without an increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.
Pregnancy Category B	Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed.
Pregnancy Category B1	Studies in animals have not shown evidence of an increased occurrence of fetal damage.
Pregnancy Category B2	Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
Pregnancy Category B3	Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
Pregnancy Category C	Drugs which, owing to their pharmaceutical effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible.
Pregnancy Category D	Drugs which have caused an increased incidence of human fetal malformations or irreversible damage. They may also have adverse pharmacological effects.
Pregnancy Category X	Drugs that have such a high risk of causing permanent damage to the foetus that they should NOT be used in pregnancy or when there is a possibility of pregnancy.

Classifications of some agents

Classification of some agents, based on different national bodies
Pharmaceutical agent	Australia	United States
Acetaminophen	A	B
Amoxycillin	A	B
Amoxycillin with clavulanic acid	B	B
Phenytoin	D	D
Rifampin	C	C
Thalidomide	X	X
Theophylline	A	C

References

1. http://www.prn2.usm.my/mainsite/bulletin/sun/1995/sun24.html
2. Australian categories
3. Sannerstedt R, Lundborg P, Danielsson BR, Kihlstrom I, Alvan G, Prame B, Ridley E. Drugs during pregnancy: an issue of risk classification and information to prescribers. Drug Saf. 1996 Feb;14(2):69-77. (Medline abstract)