Elsevier

Obstetrics & Gynecology

Volume 100, Issue 3, September 2002, Pages 465-473
Obstetrics & Gynecology

Original research
Teratogenicity of recently introduced medications in human pregnancy

https://doi.org/10.1016/S0029-7844(02)02122-1Get rights and content

Abstract

OBJECTIVE:

To determine how long it takes after a new drug is marketed to establish whether or not its use by pregnant women is likely to pose a substantial teratogenic risk.

METHODS:

We used standard clinical teratology resources to assess the teratogenic risks in human pregnancy of therapeutic treatment with 468 drugs approved by the US Food and Drug Administration between 1980 and 2000. The teratogenic risk of each treatment was classified using the current online version of TERIS into one of three categories: 1) no risk, minimal risk, or unlikely to produce an increased risk; 2) associated with a small, moderate, or high risk; or 3) risk undetermined.

RESULTS:

We found that the teratogenic risk in human pregnancy was still undetermined for 91.2% of drug treatments approved in the United States between 1980 and 2000. The proportion of treatments classified as having an “undetermined” teratogenic risk was more than 80% for drugs approved for marketing 0–4, 5–9, 10–14, or 15–20 years ago, but the highest proportion of drugs with an “undetermined” teratogenic risk was found among those approved 15–20 years ago. The agreement between TERIS risk ratings and Food and Drug Administration Use-in-Pregnancy Categories for 163 drugs that had been assessed by both systems was poor (κ ± standard error = 0.082 ± 0.042).

CONCLUSION:

We conclude that inadequate information is available for pregnant women and their physicians to determine whether the benefits exceed the teratogenic risks for most drug treatments introduced in the past 20 years.

Section snippets

Materials and methods

We obtained from the FDA a list of 511 drugs that were approved for marketing in the United States between 1980 and 2000. We excluded radioactive agents and drugs that were subsequently withdrawn from the US market. For drugs that were structural variants of a single active entity (eg, insulin, lispro insulin, and insulin glargine), we only considered the one that was first approved. The remaining 469 drugs were selected for this study.

The risk of teratogenic effects associated with use of each

Results

According to information available in standard clinical teratology knowledgebases, the teratogenic risk in human pregnancy associated with therapeutic use of 91.2% of 468 drug treatments approved by the FDA between 1980 and 2000 was still undetermined at the time of this study (Table 1). The distribution of treatments among the three categories—1) teratogenic risk “none,” “minimal,” or “unlikely”; 2) teratogenic risk “small,” “moderate,” or “high”; or 3) “undetermined” teratogenic

Discussion

Teratology testing in rodents and rabbits is usually required before a new drug is approved for marketing. Such preclinical testing provides an important means of recognizing treatments that may have teratogenic potential in human pregnancy.14 However, preclinical studies are not always predictive of what will occur in humans, and both “false-positives” and “false-negatives” occur. It is, therefore, essential to perform studies of the outcome of pregnancies in women who have been treated by a

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  • Cited by (0)

    1

    Statement of potential conflict of interest: Dr. Friedman is senior author of the TERIS database.

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