US EPA

4090737 

Journal Article 

Pregnancy Outcome in Women Exposed to Topical Tretinoin in the First Trimester 

Lourerio, KD; Kao, KK; Jones, KL; Chambers, CD 

2004 

Yes 

Birth Defects Research, Part A: Clinical and Molecular Teratology
ISSN: 1542-0752
EISSN: 1542-0760 

DART/TER/4001073 

70 

5 

English 

Topical tretinoin has been used for the treatment of acne vulgaris since the 1970s and recently has been demonstrated to be effective in the treatment of photodamaged skin. Evidence regarding the biologically available dose with topical application, and epidemiologic studies in humans have not suggested that topical tretinoin is teratogenic in humans. However, concerns persist based on case reports linking topical tretinoin use with major structural defects that are consistent with the oral isotretinoin embryopathy. Through the California Teratogen Information Service and Clinical Research Program, between 1979 and 2003, we prospectively ascertained and followed 107 women with first trimester exposure to topical tretinoin, and compared birth outcomes to 389 similarly ascertained women with no topical tretinoin exposure. There were no significant differences between groups on the proportion of pregnancies ending in spontaneous abortion (6.5% exposed vs. 8.5% unexposed; p = 0.52), or infants with major structural defects (2.2% exposed vs. 1.2% unexposed; p = 0.62). In addition, the groups were similar in mean birth weight, length and head circumference, and there were no significant differences between groups in length of gestation. Because a pattern of malformations has already been described for oral isotretinoin, we further evaluated pregnancy outcome in the 251 infants who had received a dysmorphological examination by creating a checklist of specific minor malformations that might represent the mild end of the spectrum of defects involved in the isotretinoin pattern. Using this restricted list, the prevalence of 1 or more or these specific minor malformations was not significantly different between the two groups (8/63 or 12.7% in exposed and 19/188 or 10.5% in unexposed; p = 0.51). We conclude that there is no evidence that topical tretinoin increases the risk of any of the adverse pregnancy outcomes evaluated, and specifically there is no indication that topical tretinoin is associated with an increased risk for minor structural defects that might be considered consistent with the isotretinoin embryopathy.