Document Detail

Determination of human teratogenicity by the astute clinician method: review of illustrative agents and a proposal of guidelines.
MedLine Citation:
PMID:  19107954     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The determination that an exposure is a human teratogen is a complex process involving the application of the principles of teratology, epidemiology, biology, and clinical medicine. Shepard suggested that the "rare exposure/rare defect" or "case report method", the astute clinician model, was one approach for establishing teratogenicity. The purpose of this article is to review selected exposures with the goal of identifying principles that lead to a working proposal for the application of this approach.
METHODS: We selected three known exposures--penicillamine, fluconazole and mycophenolate mofetil--for detailed review. These agents were chosen because their evidence for causation arises mostly from clinical observations in the context of biologic plausibility.
RESULTS: All three agents were originally detected based on astute observations by clinicians reporting on individual cases of a distinctive pattern of malformation or, in the case of penicillamine distinctive phenotype, after the rare exposure. All three have varying degrees of biologic evidence that support the hypothesis that each represents a human teratogen. All three meet Shepard's criteria for "proof."
CONCLUSIONS: The basic premise of this approach depends on the rarity of both the exposure and the outcome. We propose guidelines for utilization of this approach in the determination of human teratogenicity.
John C Carey; Lynn Martinez; Elizabeth Balken; Marsha Leen-Mitchell; Julia Robertson
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Publication Detail:
Type:  Case Reports; Journal Article; Review    
Journal Detail:
Title:  Birth defects research. Part A, Clinical and molecular teratology     Volume:  85     ISSN:  1542-0760     ISO Abbreviation:  Birth Defects Res. Part A Clin. Mol. Teratol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-15     Completed Date:  2009-02-13     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101155107     Medline TA:  Birth Defects Res A Clin Mol Teratol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  63-8     Citation Subset:  IM    
Department of Pediatrics, Division of Medical Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
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MeSH Terms
Abnormalities, Drug-Induced / etiology*
Antifungal Agents / toxicity
Antirheumatic Agents / toxicity
Congenital Abnormalities / etiology*
Evidence-Based Medicine
Fetus / drug effects
Fluconazole / toxicity
Immunosuppressive Agents / toxicity
Infant, Newborn
Mycophenolic Acid / analogs & derivatives,  toxicity
Penicillamine / toxicity
Practice Guidelines as Topic
Teratogens / toxicity*
Reg. No./Substance:
0/Antifungal Agents; 0/Antirheumatic Agents; 0/Immunosuppressive Agents; 0/Teratogens; 24280-93-1/Mycophenolic Acid; 52-67-5/Penicillamine; 86386-73-4/Fluconazole; 9242ECW6R0/mycophenolate mofetil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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