Glycolic Acid—Limited data exist on the safety of glycolic acid during pregnancy. In vitro studies have shown up to 27% systemic absorption depending on pH, concentration, and duration of application.33 Animal reproductive studies involving rats have shown fetal multisystem malformations and developmental abnormalities with oral administration of glycolic acid at doses far exceeding those used in humans.34 Although no human reproductive studies exist, topical glycolic acid is unlikely to reach the developing fetus in notable amounts, and the medication is likely safe for use.17,35
Clindamycin—Topical clindamycin phosphate is an effective and well-tolerated agent for the treatment of mild to moderate acne.36 Its systemic absorption is minimal, and it is considered safe for use during all trimesters of pregnancy.14,17,26,27,35,37
Erythromycin—Topical erythromycin is another commonly prescribed topical antibiotic used to target mild to moderate acne. However, its use recently has been associated with a decrease in efficacy secondary to the rise of antibacterial resistance in the community.38-40 Nevertheless, it remains a safe treatment for use during all trimesters of pregnancy.14,17,26,27,35,37
Topical Retinoids—Vitamin A derivatives (also known as retinoids) are the mainstay for the treatment of mild to moderate acne. Limited data exist regarding pregnancy outcomes after in utero exposure.41 A rare case report suggested topical tretinoin has been associated with fetal otocerebral anomalies.42 For tazarotene, teratogenic effects were seen in animal reproductive studies at doses exceeding maximum recommended human doses.41,43 However, a large meta-analysis failed to find a clear risk for increased congenital malformations, spontaneous abortions, stillbirth, elective termination of pregnancy, low birthweight, or prematurity following first-trimester exposure to topical retinoids.44 As the level of exposure that could lead to teratogenicity in humans is unknown, avoidance of both tretinoin and tazarotene is recommended in pregnant women.41,45 Nevertheless, women inadvertently exposed should be reassured.44
Conversely, adapalene has been associated with 1 case of anophthalmia and agenesis of the optic chiasma in a fetus following exposure until 13 weeks’ gestation.46 However, a large, open-label trial prior to the patient transitioning from adapalene to over-the-counter treatment showed that the drug harbors a large and reassuring margin of safety and no risk for teratogenicity in a maximal usage trial and Pregnancy Safety Review.47 Therefore, adapalene gel 0.1% is a safe and effective medication for the treatment of acne in a nonprescription environment and does not pose harm to the fetus.
Clascoterone—Clascoterone is a novel topical antiandrogenic drug approved for the treatment of hormonal and inflammatory moderate to severe acne.48-51 Human reproductive data are limited to 1 case of pregnancy that occurred during phase 3 trial investigations, and no adverse outcomes were reported.51 Minimal systemic absorption follows topical use.52 Nonetheless, dose-independent malformations were reported in animal reproductive studies.53 As such, it remains better to avoid the use of clascoterone during pregnancy pending further safety data.
Minocycline Foam—Minocycline foam 4% is approved to treat inflammatory lesions of nonnodular moderate to severe acne in patients 9 years and older.54 Systemic absorption is minimal, and the drug has limited bioavailability with minimal systemic accumulation in the patient’s serum.55 Given this information, it is unlikely that topical minocycline will reach notable levels in the fetal serum or harbor teratogenic effects, as seen with the oral formulation.56 However, it may be best to avoid its use during the second and third trimesters given the potential risk for tooth discoloration in the fetus.57,58