Tretinoin (all-trans retinoic acid, ATRA) is an endogenous metabolite of vitamin A which is normally present in plasma. Tretinoin is used topically in the treatment of acne, hyperpigmentation, and repair of dermal photodamage, and orally for the induction of remission in acute promyelocytic leukemia (APL; FAB classification AML-M3).
Although sporadic case reports have described malformations, including cardiovascular defects, limb defects, ear defects and CNS defects following maternal use of topical tretinoin during the first trimester of pregnancy, no increased risk of congenital malformation has been shown in subsequent larger cohort studies of topical first trimester tretinoin exposure. These data are, however, too limited to definitively exclude a fetal risk and use during pregnancy is therefore not generally recommended. An individual risk assessment is advised where exposure to supratherapeutic doses of topical tretinoin has occurred, or risk factors which increase absorption of the drug are present in association with pregnancy.
There are insufficient data (particularly relating to first trimester exposure) to quantify the risks posed to a developing fetus following oral exposure to tretinoin. The risk-benefit balance of maternal vs. fetal wellbeing must be addressed on an individual basis. Other retinoids are known to be teratogenic at therapeutic doses and the likelihood of an increased risk of structural malformation and neurodevelopmental impairment with tretinoin use in the first trimester should therefore be considered and discussed with the patient. The manufacturer advises that there is a high risk of severe malformations and that effective contraception (progesterone-only pills are not considered to be an effective measure of contraception during treatment with tretinoin) must be used for the duration of oral treatment and for one month afterwards.
Data regarding the risk of adverse neurodevelopmental effects following in utero tretinoin exposure are limited, but adverse effects are well described for other retinoids. Clinicians and patients should, therefore, be aware of the potential risk of neurodevelopmental impairment following tretinoin exposure in utero at any stage of pregnancy, and that such effects cannot be screened for antenatally.
Exposure to oral, or in some cases topical, tretinoin during pregnancy may warrant additional fetal monitoring. Other risk factors may also be present in individual cases which independently increase the risk of adverse pregnancy outcomes. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments. Due to the known teratogenicity of retinoids, enhanced fetal monitoring may be warranted following exposure to tretinoin in pregnancy by any route. Discussion with UKTIS is recommended.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.