Drug use During Pregnancy and Breast‐Feeding: A classification sytem for drug information
Authors: Berglund Fredrik , Flodh Hans , Lundborg Per , Prame Britta , Sannerstedt Rune 
Published: December 2009

Since 1978 the Swedish catalogue of registered pharmaceutical specialities (FASS) has carried a special section entitled “Pregnancy and breast‐feeding” in each product presentation, intended to form an aid for the prescription of drugs to women during child‐bearing and lactation.

After a brief review of transplacental transport and milk secretion, reproduction‐toxicology studies in animals, and methods for clinical evaluation of drugs for use during pregnancy, the classification system is presented. On the basis of available data with regard to effects on early and late stages of pregnancy and labour, all the pharmaceutical specialities concerned are assigned to one of the following pregnancy categories: A, B 1, B 2, B 3, C or D. The letters refer to information based on findings in man, and the figures to information based on animal data. For drugs in categories B 3, C or D any harmful effects observed or likely to occur in man or animals are to be specified.

The pregnancy categories are defined as follows:Category A.Drugs which may be assumed to have been used by a large number of pregnant women and women of child‐bearing age, without any form of definite disturbance in the reproductive process having been noted so far, e.g. an increased incidence of malformations or other direct or indirect harmful effects on the fetus.

Category B.Drugs which may be assumed to have been used by only a limited number of pregnant women and women of child‐bearing age, without any form of definite disturbance in the reproduction process having been noted so far, e.g. an increased incidence of malformations or other direct or indirect harmful effects on the fetus.

Category C.Drugs which by their pharmacological effects have caused, or must be suspected of causing disturbances in the reproduction process that may involve risk to the fetus without being directly teratogenic.

Category D.Drugs which have caused an increased incidence of fetal malformations or other permanent damage in man or which on the basis of e.g. reproduction‐toxicology studies must be suspected of doing so. This category comprises drugs with primary teratogenic effects. If the drug also has pharmacological effects that may directly or indirectly have a harmful effect on the fetus, this must also be stated.

As experience of effects of drugs in Category B is limited, results of reproduction‐toxicology studies in animals are indicated by allocation to one of three subgroups according to the following definitions:Category B 1.Reproduction‐toxicology studies have not given evidence of an increased incidence of fetal damage or other deleterious effects on the reproduction process.

Category B 2.Reproduction‐toxicology studies are inadequate or may be lacking, but available data reveal no evidence of an increased incidence of fetal damage or other deleterious effects on the reproduction process.

Category B 3.Reproduction‐toxicology studies have revealed an increased incidence of fetal damage or other deleterious effects on the reproduction process, the significance of which is considered uncertain in man.

It should be noted that even drugs in Categories C and D may have important uses during pregnancy, e.g. β‐adrenoceptor blockers in the treatment of hypertension, chloroquine and hydroxychloroquine in the prophylaxis of malaria, prednisone and aspirine in the treatment of SLE, and anticonvulsants in the treatment of epilepsy. Other drugs in Categories C and D, e.g. dicoumarol and warfarin, should not be used during pregnancy.

Effects on fertility in patients are not included in the pregnancy classification. Information on these effects is usually given under the heading Adverse Reactions.

With respect to their use during breast‐feeding, each pharmaceutical specialty has been allocated to one of four groups. The breast‐feeding groups are defined as follows

Group I.Does not enter breast milk.

Group II.Enters breast milk but is not likely to affect the infant when therapeutic doses are used.

Group III.Enters breast milk in such quantities that there is a risk of affecting the infant when therapeutic doses are used.

Group IV.Not known whether it enters breast milk or not.

A number of drugs are exempted from the classification system. Such drugs are mainly those that due to type of use and administration should not represent a hazard to the fetus or the breast‐fed infant.

The classification system has now been used in seven successive editions of the FASS catalogue. During the seven years, the number of active ingredients in Category C has increased from 65 to 118, mainly by including ingredients that initially were totally exempted (26 substances), e.g. glucocorticoids for topical use (16 substances). Also, about 20 substances were transferred from Category A, notably benzodiazepines and inhibitors of prostaglandin synthesis. For drug use during breast‐feeding, Group IV unfortunately still comprises more than 50% of the drugs in the system.