Topical therapy constitutes one of the pillars of treatment of dermatological disorders. In 1952, the first report of the successful use of topical corticosteroids in dermatological disorders was published by Sulzberger and Witten [1]. Topical corticosteroids as one of the major components of the dermatologist’s therapeutic armamentarium are prescribed to up to 6% of pregnant women for cutaneous manifestations such as chronic cutaneous lupus erythematosus, pemphigoid gestationis, chronic plantar pustulosis, pruritic urticarial papules and plaques of pregnancy (PUPPP), and atopic eruptions [2]. Topical corticosteroids during pregnancy should be used only if the adequate benefit justifies the potential risk to the fetus. The US Food and Drug Administration (FDA) labels topical corticosteroids as pregnancy risk category C [3].

The percutaneous absorption of topical corticosteroid and its potential for systemic exposure [4] is determined by several factors including:

Depending on certain pharmacokinetic properties, lipophilicity and degradability, different topical corticosteroids have different systemic bioavailability. In patients suffering from severe skin disease, the least potent corticosteroid hydrocortisone, after percutaneous absorption are capable to suppress the adrenals [5]. Clobetasol propionate ointment which is the most potent topical corticosteroid can result in adrenal insufficiency at doses as low as 2 g daily⁻¹ for 1 week [6]. Under extreme conditions adrenal insufficiency can be seen after topical application of lipophilic corticosteroids (i.e., mometasone furoate, fluticasone propionate and methylprednisolone aceponate) [7, 8]. The systemic availability of topical corticosteroids is affected during pregnancy due to alterations in the cutaneous blood circulation and hydration [9].

Once corticosteroids get absorb, more than 90% of cortisol in plasma is reversibly bound to transcortin or corticosteroid-binding globulin (CBG) which is an α-globulin secreted by the liver and albumin. The corticosteroid effect is mediated by the unbound fraction which enters the cells. Albumin has large binding capacity for corticosteroids and low affinity whereas CBG has relatively low total binding capacity for corticosteroids but high affinity. Most of the hormone gets bound at low as well as normal concentrations of corticosteroids. The protein binding capacity increases due to higher corticosteroid concentrations, and a greater fraction of the corticosteroid exists in the free state. During pregnancy due to physiological hypercorticism, there is increase in the circulating oestrogen levels which induces CBG production, results in increased total plasma cortisone. The synthetic congeners of biologically active adrenocortical corticosteroids gets metabolized in the liver and excreted via kidneys.

The topical corticosteroids effects on fetus also depend on the penetrating efficiency of corticosteroid through placenta. The cortisol (hydrocortisone, the active form) gets converted to cortisone (biologically inactive) by 11β-hydroxysteroid dehydrogenase (11βHSD) which metabolizes corticosteroids in the placenta. Thus, 11βHSD protects the fetus from potential harm by playing an important role in regulating the amount of maternal cortisol that crosses the placenta [10]. In the placenta, because of low potency and high metabolism, hydrocortisone is considered safe for use in antenatal cases, but a study based on maternal–fetal cortisol transfer in the fetal–placental unit before abortion showed that 15% of ³H-cortisol crossed the placenta unmetabolized [11] and another study found a linear relation between maternal and fetal serum cortisol concentrations [12, 13]. Only 1/8th to 1/10th of prednisolone reaches to the fetus by placental transfer [14]. Betamethasone, dexamethasone, and methylprednisolone are less metabolized while fluticasone propionate and budesonide are not metabolized by placental 11βHSD [15, 16] therefore, leads to placental transfer in high concentration. There are no studies available on the other corticosteroids.

Topical corticosteroids required to be used during maternal skin conditions in pregnancy:

To the best of our knowledge, certain animal studies have found that corticosteroids are present in the fetal blood after topical application, but there are no human studies evaluating the amounts of topical corticosteroids that reach the fetus after topical application. In mice and rabbits, significant amounts of betamethasone 17,21-dipropionate appeared in the fetal blood after topical application to their mothers’ skin [17]. Furthermore, corticosteroids are teratogenic not only through systemic administration but also through topical application in animals. For example, diflorasone diacetate cream on topical application induced cleft palate at a dose of 0.001 mg/kg which is about 30% of the human topical dose, when applied to the chest skin of pregnant rats. The application dose when increased to 0.5 mg/kg per day, the rate of fetal death increased to the untreated controls. It has been observed that rabbits suffered from depressed fetal growth, external anomalies (31.9%), cleft palate (22.2%) and visceral defects (45.5%) on receiving a topical dose of diflorasone diacetate 0.016 mg/kg per day [3]. Taken together, the studies suggest that for pregnant women who need treatment with topical corticosteroids, medium potency topical corticosteroids should be preferred to high potency preparations. If potent or superpotent topical corticosteroids are needed, the amount used should be kept to a minimum and fetal growth should be monitored.

In humans, the available data on the safety of topical corticosteroids in pregnancy are limited and mainly based upon observational studies [2]. The systemic effects of topical corticosteroids depend largely on the extent of skin absorption, which varies from 0.7% to 7% through intact skin [18], which may have an impact on the fetus as well as lead to systemic effects [5]. However, for inflammatory dermatoses where cutaneous absorption is more, topical corticosteroids are often prescribed. Hydrocortisone cream 1% is the low potency corticosteroid, its absorption during exacerbation of atopic dermatitis was 11–31 times that in remission [18]. Although the application of hydrocortisone cream 1% beyond 1 month in patients with severe cutaneous manifestations was shown to suppress the adrenal glands [5]. Administration of hydrocortisone in pregnancy may still affect the fetus and the fetotoxic effects of corticosteroids depend on their ability to cross the placenta [18]. The ability to cross the placental barrier varies among other corticosteroids as stated.