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Editor's note

Editor's note The ensuing paper by Barwell et al. [ 2002 ] reports an infant with apparently an isolated choanal atresia in association with a history of maternal exposure to carbimazole during pregnancy. The authors suggest that their case supports the notion of a methimazole/carbimazole embryopathy. From a quick glance at a single case report, the astute reader should ask, why publish a single case? However, there is good reason: As the authors point out, there are other reports of methimazole or carbimazole exposure and the occurrence of choanal atresia. In a recent review, Diav‐Citrin and Ornoi [ 2002 ] summarize six other cases with this exposure and choanal atresia most of which have other malformations as well. The reasoning process here is one that has been called the astute clinician model : the recognition of the co‐occurrence of a rare exposure in pregnancy and a rare outcome. The logic of drawing the conclusion of causual inference is based on this type of clinical evidence (rare exposure associated with rare outcome) for a number of well‐established human teratogens in which there is no (or minimal) available epidemiologic evidence to support causation. The underlying concept is that the combination of this uncommon pregnancy exposure with a distinctive outcome is so unlikely to be due to chance that causation is inferred. Examples of well‐established teratogens where causual inference is drawn in this way include fluconazole, penicillamine, and aminopterin/methotrexate. While the notion of causation in these latter exposures is also supported by evidence from biologic plausibility or animal models, the most solid evidence comes, in fact, from clinical documentation. In this reasoning process, the more distinctive and unique the outcome the more likely the conclusion of cause and effect relationship can be drawn. For example, the fetal aminopterin syndrome is so distinctive as a pattern of malformation that the conclusion of cause and effect seems straightforward. In the case here of carbimazole and choanal atresia, one can say that methimazole/carbimazole exposure is likely less than 1 in 1,000 pregnancies. The prevalence at birth of choanal atresia is estimated at about 1 in 12,000 to 1 in 15,000 births (Feldkamp, Utah Birth Defects Network, personal communication, 2002). Therefore, in the United States, the co‐occurrence of carbimazole exposure and choanal atresia would be about 1 in 12–15 million births. This would mean that about every 3–4 years in the U.S. there would be a coincidental occurrence of this exposure and this outcome. Thus in the context of the other reported cases of choanal atresia and methimazole/carbimazole exposure, the idea then of another case of this becomes important. A symposium entitled “The Criteria for the Assessment of Teratogenicity” occurred in June 2002, at the meeting of the Organization of Teratology Information Services (OTIS), which this year was held with the Teratology Society meeting in Tucson, Arizona. Further discussion to establish a consensus surrounding this reasoning process is recommended, and certainly this symposium at the OTIS meeting was a good continuing step. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Medical Genetics Part A Wiley

Editor's note

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References (2)

Publisher
Wiley
Copyright
Copyright © 2002 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1552-4825
eISSN
1552-4833
DOI
10.1002/ajmg.10622
Publisher site
See Article on Publisher Site

Abstract

The ensuing paper by Barwell et al. [ 2002 ] reports an infant with apparently an isolated choanal atresia in association with a history of maternal exposure to carbimazole during pregnancy. The authors suggest that their case supports the notion of a methimazole/carbimazole embryopathy. From a quick glance at a single case report, the astute reader should ask, why publish a single case? However, there is good reason: As the authors point out, there are other reports of methimazole or carbimazole exposure and the occurrence of choanal atresia. In a recent review, Diav‐Citrin and Ornoi [ 2002 ] summarize six other cases with this exposure and choanal atresia most of which have other malformations as well. The reasoning process here is one that has been called the astute clinician model : the recognition of the co‐occurrence of a rare exposure in pregnancy and a rare outcome. The logic of drawing the conclusion of causual inference is based on this type of clinical evidence (rare exposure associated with rare outcome) for a number of well‐established human teratogens in which there is no (or minimal) available epidemiologic evidence to support causation. The underlying concept is that the combination of this uncommon pregnancy exposure with a distinctive outcome is so unlikely to be due to chance that causation is inferred. Examples of well‐established teratogens where causual inference is drawn in this way include fluconazole, penicillamine, and aminopterin/methotrexate. While the notion of causation in these latter exposures is also supported by evidence from biologic plausibility or animal models, the most solid evidence comes, in fact, from clinical documentation. In this reasoning process, the more distinctive and unique the outcome the more likely the conclusion of cause and effect relationship can be drawn. For example, the fetal aminopterin syndrome is so distinctive as a pattern of malformation that the conclusion of cause and effect seems straightforward. In the case here of carbimazole and choanal atresia, one can say that methimazole/carbimazole exposure is likely less than 1 in 1,000 pregnancies. The prevalence at birth of choanal atresia is estimated at about 1 in 12,000 to 1 in 15,000 births (Feldkamp, Utah Birth Defects Network, personal communication, 2002). Therefore, in the United States, the co‐occurrence of carbimazole exposure and choanal atresia would be about 1 in 12–15 million births. This would mean that about every 3–4 years in the U.S. there would be a coincidental occurrence of this exposure and this outcome. Thus in the context of the other reported cases of choanal atresia and methimazole/carbimazole exposure, the idea then of another case of this becomes important. A symposium entitled “The Criteria for the Assessment of Teratogenicity” occurred in June 2002, at the meeting of the Organization of Teratology Information Services (OTIS), which this year was held with the Teratology Society meeting in Tucson, Arizona. Further discussion to establish a consensus surrounding this reasoning process is recommended, and certainly this symposium at the OTIS meeting was a good continuing step.

Journal

American Journal of Medical Genetics Part A – Wiley

Published: Oct 22, 2003

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