Pregnancy category

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The pregnancy category of a pharmaceutical agent is an assessment of the risk of foetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does not include any risks conferred by pharmaceutical agents or their metabolites that are present in breast milk.

United States

The FDA-assigned pregnancy categories as used in the Drug Formulary are as follows:

United States FDA Pharmaceutical Pregnancy Categories
Pregnancy Category A	Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote.
Pregnancy 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 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).
Pregnancy Category C	Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal 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 benefit justifies the potential risk to the fetus.
Pregnancy 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).
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.

Australia

Australia has a slightly different pregnancy category system from the United States - notably the subdivision of Category B. The system, as outlined below, was established by the Congenital Abnormalities Sub-committee of the Australian Drug Evaluation Committee (ADEC).

ADEC Pregnancy Categories (Australia)
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 B1	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. Studies in animals have not shown evidence of an increased occurrence of foetal damage.
Pregnancy Category B2	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. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of foetal damage.
Pregnancy Category B3	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. Studies in animals have shown evidence of an increased occurrence of foetal 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, are suspected to have caused or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. These drugs 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.

The subcategorisation of Category B, while offering additional information which may be of benefit in evaluating the risk vs benefit, presents its own problem of data reliability - since human data is lacking or inadequate, the subcategorisation is based on animal data. Furthermore, allocation of a drug in Category B does not necessarily imply greater safety than Category C.

Drugs in Category D are not absolutely contraindicated in pregnancy, unlike Category X. In some cases Category D was assigned to a drug on the basis of suspicion.

Categorisation of selected agents

The data presented is for comparative and illustrative purposes only, and may have been superseded by updated data.

Classification of some agents, based on different national bodies
Pharmaceutical agent	Australia	United States
Acetaminophen/Paracetamol	A	B
Amoxicillin	A	B
Amoxicillin with clavulanic acid	B1	B
Isotretinoin	X	X
Phenytoin	D	D
Rifampicin	C	C
Thalidomide	X	X
Theophylline	A	C
Tetracycline	D	D

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. PMID 8852521.