First-trimester exposure to topical tretinoin: Its safety is not warranted
✍ Scribed by Mart�nez-Fr�as, Mar�a Luisa; Rodriguez-Pinilla, Elvira
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 23 KB
- Volume
- 60
- Category
- Article
- ISSN
- 0040-3709
No coin nor oath required. For personal study only.
✦ Synopsis
Teratology Information Services (TIS), including the Spanish one (SITTE), provide information about the potential effect of prenatal exposures to different agents, including drugs and maternal diseases. TIS use the published information to elaborate the risk assessment. One of the questions that are received at present in TIS regards the potential risk after first-trimester exposure to topical tretinoin. We are concerned because the information in the literature is quite confusing, and we would like to call attention to this matter.
We cannot ignore that there are at least two case reports of malformed infants with defects that are consistent with the classical effects of systemic isotretinoine; the mothers used tretinoin cream during the critical period of prenatal development (Camera and Pregliasco, '92; Lipson and Collins, '93). On the other hand, there is a controlled study on 215 women with pregnancy exposure to tretinoin and 430 matched controls, in which the authors found no evidence of risk. However, this study has as an important limitation, in that prescription records for pregnant women were used without determining how many women actually used the prescription (Jick et al., '93). Consequently, the results were not very conclusive. More recently, Shapiro et al. ('97), using data from Motherisk, performed a prospective study of 94 tretinoin-exposed cases and 133 controls, and concluded that first-trimester exposure to topical tretinoin is safe. Nevertheless, this study had serious limitations that were not commented on in the report. First of all, the authors did not indicate how many women, exposed and nonexposed to tretinoin, who contacted Motherisk were lost to follow-up. Second, they did not comment on possible biases involved in having data collected from voluntary callings, and that those biases may have been different in women exposed and nonexposed to tretinoin. Third, due to the very low frequency of defects observed in isotretinoine embryopathy, and considering that the risk of topical tretinoin exposure, if it exists, should be much lower than the risk of systemic exposure, this study did not have enough power either to identify a low risk or to conclude that the exposure is safe. For instance, using the prevalence figure for any type of cardiac defect (1.4 per 1,000 births) and microtia (0.16 per 1,000 births), observed in the Spanish Collaborative Study of Congenital Malformations (ECEMC) (Bermejo and Martı ´nez-Frı ´as, '98), and accepting that, for instance, first-trimester exposure to topical tretinoin could imply a risk, let us say, as high as 5, the risk of a mother with topical tretinoin exposure for having a Grant sponsor: Direccio ´n General de Farmacia y Productos Sanitarios,