Risk classification systems for drug use during pregnancy: are they a reliable source of information?

Drug Saf. 2000 Sep;23(3):245-53. doi: 10.2165/00002018-200023030-00006.


Background: In several countries, risk classification systems have been set up to summarise the sparse data on drug safety during pregnancy. However, these have resulted in ambiguous statements that are often difficult to interpret and use with accuracy when counselling patients on drug use in pregnancy.

Objectives: The objective of this study was to compare and analyse the consistency between and the criteria for risk classification for medications used during pregnancy included in 3 widely used international risk classification systems. All 3 systems use categories based on risk factors to summarise the degree to which available clinical information has ruled out the risk to unborn offspring, balanced against the drug's potential benefit to the patient.

Methods: Drugs included in the risk classification systems from the US Food and Drug Administration (FDA), the Australian Drug Evaluation Committee (ADEC) and the Swedish Catalogue of Approved Drugs (FASS), were reviewed and compared on basis of the risk factor category to which they had been assigned. Agreement between the systems was calculated as the number of drugs common to all 3 and assigned to the same risk factor category. In addition, evidence on teratogenicity and adverse effects during pregnancy was retrieved using a MEDLINE search (from 1966 up to 1998) for common drugs classified as teratogenic.

Results: Differences in the allocation of drugs to different risk factor categories were found. Risk factor category allocation for 645 drugs classified by the FDA, 446 classified by ADEC and 527 classified by FASS was compared. Only 61 (26%) of the 236 drugs common to all 3 systems were placed in the same risk factor category. Analysis of studies on the safety of common drugs during pregnancy of drugs classified as X by the FDA indicated that the variability in category allocation was not only attributable to the different definitions for the categories, but also depended on how the available scientific literature was handled.

Conclusions: Differences in category allocation for the same drug can be a source of great confusion among users of the classification systems as well as for those who require information regarding risk for drug use during pregnancy, and may limit the usefulness and reliability of risk classification systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Australia
  • Drug-Related Side Effects and Adverse Reactions*
  • Female
  • Fetus / drug effects
  • Humans
  • Pharmaceutical Preparations / classification*
  • Pregnancy
  • Risk Assessment*
  • Sweden
  • Teratogens / classification*
  • United States
  • United States Food and Drug Administration


  • Pharmaceutical Preparations
  • Teratogens