Safety of Topical Dermatologic Medications in Pregnancy

supranumerary ribs and delayed ossification. Of 6 woman that became pregnant while using adapalene, one patient terminated her pregnancy, two patients delivered healthy babies, two patients delivered premature babies that reached a healthy state after intensive care, and one patient was lost to follow up.⁴⁶ One report was published of a woman using topical adapalene from 1 month prior to conception to 13 weeks of gestation, who terminated her pregnancy after ultrasound revealed a small for gestational age fetus with anophthalmia. Post-abortion examination revealed anophthalmia and agenesis of optic chiasm. It was concluded that such defects were not typical of retinoids (heart, CNS, craniofacial, thymus, and limb defects).⁴⁷ It is possible that the drug is safe in pregnancy, but due to nearly absent human data, it is best to avoid this drug especially in first-trimester.^7,18

A commonly used drug to treat acne, it has not been well studied in animals or humans to accurately assess safety profile in pregnancy. About 5% of topical dose is absorbed systemically.²⁰ It is also broadly used in plastics and the food industry and despite its widespread use, there are no indications of teratogenic effects. Therefore, it may be used in pregnant women on limited areas.¹⁴

This bacteriostatic agent has not been studied in human or animals to assess safety profile in pregnancy. When applied topically, about 4% is absorbed.⁴⁸ Oral sulfonamide use during pregnancy has been reported to cause neonatal jaundice, although no problems with topical sulfacetamide have been reported.⁴⁹ Use only if there are clear indications and benefits outweigh risks.⁵⁰

This anti-inflammatory agent that is absorbed between 9-25% when used topically.^51,52 In third trimester, its use can potentially cause early closure of ductus arteriosus and oligohydramnios, so it should not be applied over large surface areas for prolonged time periods, or under occlusive dressings which may enhance systemic absorption.²⁸

About 4% of topical azelaic acid is absorbed systemically after one application.⁵³ Animal studies show no teratogenic potential even when used in high doses.⁴⁸ Human studies are lacking. It should only be used on small skin surfaces and preferably not in first trimester.^54,55

Minoxidil is antihypertensive and a vasodilator that is topically used for androgenic and other types of alopecia. In a prospective study of 17 women treated with topical minoxidil, 1 fetus had heart malformations.⁵⁶ One case report of a women who applied topical minoxidil on scalp at least twice daily had numerous fetal malformations such as heart with distal stenosis of aorta, longer sigmoideum, ventricular broadening of brain, cerebral hemorrhages, and ischemic areas of placenta.⁵⁷ In another case, a woman used topical 2% minoxidil over many years who had a fetus that had suffered significant caudal regression syndrome with aplasia of the lower spine, lower extremity and urinary tract malformations, renal agenesis, and esophageal atresia.58 As there is insufficient and inconclusive data on topical use of minoxidil, its use in pregnancy should be avoided.^14,25

When used topically, camphor has a cooling and local anesthetic effect, which makes it useful for pruritic skin conditions. In animal studies, maternally toxic doses of camphor failed to produce evidence of embryotoxicity or teratogenicity.^59,60 When it is ingested, it has the potential to cause fetal demise and neonatal respiratory failure, as camphor can cross the placenta. ⁶¹ The collaborative perinatal project followed 168 women with first trimester exposure to topical camphor and found no evidence of congenital malformations.⁶² Furthermore, 763 patients used camphor at any time in their pregnancies, but no congenital defects were found.⁶² Therefore, topical camphor is safe to use during pregnancy.^7,14,16,63

Echinacea is a commonly used herbal product that has not been well studied. In a small study, 206 women reported use of Echinacea (112 women in first trimester). This cohort was matched to women exposed to nonteratogenic substances. There was no statistically significant difference in abortions, mode of birth, birth weight, gestational age at delivery, fetal distress, and fetal malformations.⁶⁴ Despite these results, this small study lacked sufficient statistical power. In animal studies, extracts of plant E. purpurae interfered with embryonic angiogenesis and caused decreased levels of growth factors compared to control group.^65,66 Many authors are skeptical about Echinacea use in pregnancy since it has not been studied in detail, and thus, do not support its use in pregnancy.⁶⁷ Furthermore, herbal supplements may be mixtures of numerous plants and may have contaminates, raising questions about their safety.

The authors have no conflicts of interests to declare.