The current available evidence on the safety of topical corticosteroid use in human pregnancy is limited. Many of the previous studies only investigated the relation between topical corticosteroid use in early pregnancy and orofacial cleft. A 2009 Cochrane review has highlighted potential problems with low birth weight (LBW). The objective of this retrospective cohort study was to investigate whether maternal exposure to topical dermal corticosteroids has adverse effects on pregnancy by examining a comprehensive set of outcomes.
This study included 2658 exposed women (including 757 exposed to topical corticosteroids during the first 12 gestational weeks) and 7246 unexposed women. The exposed group were pregnant women aged 15 to 44 years who received 1 or more dispensed prescriptions for topical corticosteroids during pregnancy. Women who had received 1 or more dispensed prescriptions for any other form (systemic, injection, inhalation, or nasal) of corticosteroids during pregnancy and women with multiple pregnancy or pregnancy following assisted reproduction were excluded. The unexposed group consisted of pregnant women aged 15 to 44 years who did not receive any dispensed prescription for any form of corticosteroids during pregnancy. For each exposed woman, we selected up to 3 unexposed pregnant women by matching for maternal age (5-year bands), as well as the calendar year of pregnancy.
The primary analysis found no association between maternal topical corticosteroid exposure and orofacial cleft, low birth weight, preterm delivery, foetal death, low Apgar score, and mode of delivery (adjusted risk ratio [RR], 1.85 [95% CI, 0.22-15.20] [P = .57]; 0.97 [95% CI, 0.78-1.19] [P = 0.75]; 1.20 [95% CI, 0.73-1.96] [P = 0.48]; 1.07 [95% CI, 0.56-2.05] [P = 0.84]; 0.84 [95% CI, 0.54-1.31] [P = 0.45]; and P = 0.76, respectively). Stratified analyses based on potency did not reveal any significant associations in most of these categories either, but an exploratory analysis showed a significantly increased risk of low birth weight when the dispensed amount of potent or very potent topical corticosteroids exceeded 300 g during the entire pregnancy (adjusted RR, 7.74 [95% CI, 1.49-40.11]; P = 0.02).
The authors noted the following study limitations:
• The critical period for the fusion of the lip and palate is from the 5th to the 12th gestational week. This study used an early exposed group composed of women who received a dispensed prescription for topical corticosteroids during the first 12 gestational weeks and thus had a better estimate of the association with orofacial cleft. However, there were only 8 orofacial clefts; the statistical power regarding this outcome was thus limited.
• A previous study reported a significant association of maternal exposure to potent or very potent topical corticosteroids with foetal growth restriction (adjusted RR, 2.08 [95% CI, 1.40-3.10]) and also a significant dose-response relationship (P = 0.02). However, the number needed to harm was 168, i.e., 1 additional foetal growth restriction would occur for every 168 pregnant women prescribed potent or very potent topical corticosteroids. Therefore, the absolute risk of LBW may be small when the quantity of topical corticosteroid used is limited and may not have been detected by the present study which had a smaller sample size and where mothers used a smaller dispensed quantity of stronger topical corticosteroids compared to the study which showed the significant association.
• Similar to previous studies using data from prescription databases, maternal adherence to topical corticosteroids was unknown in the present study. However, if pregnant women did not apply topical corticosteroids or applied smaller amounts than prescribed, the risk of adverse pregnancy outcomes might have been underestimated. Also, information on topical corticosteroids prescribed in hospital or purchased over-the-counter was not recorded.
• Another study reported that women with severe psoriasis had an increased risk of LBW infants but did not consider the confounding from pharmacological treatments. Pemphigoid gestationis is associated with LBW and preterm birth. This study did not have data on which skin conditions were being treated with topical corticosteroids. The authors adjusted for previous exposure to topical corticosteroids within 1 year before pregnancy in the multivariate analyses to mitigate the confounding from chronic dermatoses, but could not control the confounding from acute skin conditions such as pemphigoid gestationis because it lacked relevant data.