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 conferred by pharmaceutical agents or their metabolites that are present in breast milk.
Every drug has specific information listed in its product literature. In the UK, while no preset categories are applied, the British National Formulary gives a table of drugs to be avoided or used with caution in pregnancy, and does so using a limited number of key phrases.
In 1979, the United States Food and Drug Administration (FDA) introduced a classification of fetal risks due to pharmaceuticals. This was based on a similar system that was introduced in Sweden one year earlier. The same guidelines are followed in India as well.
These were the pregnancy categories:
|United States FDA Pharmaceutical Pregnancy Categories|
|Pregnancy Category A||Adequate and well-controlled human 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 OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.|
|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.|
There is one additional category, "Pregnancy Category N", which is a transitional identification indicating that the FDA has not yet classified the drug into a specified pregnancy category.
One characteristic of the FDA definitions of the pregnancy categories is that 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. See below.
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 that 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 fetus having been observed.|
|Pregnancy Category B1||Drugs that 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 fetus having been observed.
Studies in animals have not shown evidence of an increased occurrence of fetal damage.
|Pregnancy Category B2||Drugs that 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 fetus having been observed.
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||Drugs that 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 fetus having been observed.
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 that, owing to their pharmaceutical effects, have caused - or may be suspected of causing - harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible.|
|Pregnancy Category D||Drugs that have caused, are suspected to have caused - or may be expected to cause - an increased incidence of human fetal 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 fetus 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 that 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 those of Category X. In some cases, Category D was assigned to a drug on the basis of suspicion.
|Gr 1||Extensive human tests and animal studies have not shown the drug to be embryotoxic/teratogenic.|
|Gr 2||Extensive human tests of the drug have not shown the drug to be embryotoxic/teratogenic.|
|Gr 3||Extensive human tests of the drug have not shown the drug to be embryotoxic/teratogenic. However, the drug appears to be embryotoxic/teratogenic in animals.|
|Gr 4||No adequate and well-controlled studies of the drug's effects on humans are available. Animal studies have shown no embryotoxic/teratogenic effects.|
|Gr 5||No adequate and well-controlled studies of the drug's effects on humans are available.|
|Gr 6||No adequate and well-controlled studies of the drug's effects on humans are available. Animal studies have shown embryotoxic/teratogenic effects.|
|Gr 7||There is a risk that the drug is embryotoxic / teratogenic in humans, at least in the first trimester.|
|Gr 8||There is a risk that the drug is toxic to fetuses throughout the second and third trimesters.|
|Gr 9||There is a risk that the drug causes prenatal complications or abnormalities.|
|Gr 10||There is a risk that the drug causes hormone specific action on the human fetus.|
|Gr 11||There is a known risk that the drug is a mutagen/carcinogen.|
Categorization 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|
|Amoxicillin with clavulanic acid||B1||B|
- "Appendix 4: Pregnancy". British National Formulary (55 ed.). March 2008.[incomplete short citation]
- "Federal Register /Vol. 73, No. 104 /Thursday, May 29, 2008 / Proposed Rules". Archived from the original on 2012-09-16. Retrieved 2014-02-13.
- Wood, Wende. "FDA pregnancy categories: help or hindrance?". College of Psychiatric & Neurologic Pharmacists. Retrieved 3 March 2014.
- "Why poison your baby?". Prn2.usm.my. Archived from the original on 2003-05-17.
- Medicines in Pregnancy Working Party (14 February 2007). "Prescribing medicines in pregnancy". Australian Drug Evaluation Committee. Archived from the original on 2007-06-05. Retrieved 2008-05-21. – links provided for 1999 4th edition and subsequent updates
- Sannerstedt, R.; Lundborg, P.; Danielsson, B. R. et al. (February 1996). "Drugs during pregnancy: an issue of risk classification and information to prescribers". Drug Saf 14 (2): 69–77. doi:10.2165/00002018-199614020-00001. PMID 8852521.
- Food and Drug Administration. Federal Register 1980;44:37434-67
- "Specific requirements on content and format of labeling for human prescription drugs". Labeling Requirements for Prescription Drugs and/or Insulin. Food and Drug Administration. April 1, 1997. Archived from the original on 2008-03-26. Retrieved 2008-05-21.