Case‐control study of cleft lip or palate after maternal use of topical corticosteroids during pregnancy

Abstract

A case-control survey of 48 children with nonsyndromic cleft lip or palate showed a significant increase in prevalence of maternal use of topical corticosteroid preparations in the first trimester of pregnancy, compared to 58 controls born in the same hospital; the odds ratio was 13.154, 95% confidence interval 1.67-586, P = 0.0049 on Fisher's exact two-tail test. The results were statistically significant although the wide confidence interval reflected the small sample size. Although older epidemiological studies have not detected any association between systemic corticosteroid treatment and the combined incidence of all congenital malformations, experimental studies over several decades have shown that maternal corticosteroid exposure in several species of animals is specifically associated with oral clefts. This association has been confirmed by more specific case-control surveys where the cases were children with cleft lip or palate and the exposure was maternal systemic corticosteroid treatment in the first trimester. Only one previous survey also analyzed topical corticosteroids, and it demonstrated an increased odds ratio for cleft lip or palate. A national survey of children with cleft palate will be necessary to evaluate the results of this pilot study.

Corticosteroid use during pregnancy and risk of orofacial clefts

“…Studies specifically evaluating topical corticosteroids and orofacial clefts are uncommon. [4][5][6]8,9 A recent Cochrane review of the safety of topical corticosteroids during pregnancy concluded that the current studies were limited and inconclusive and that cohort studies with very large samples were needed. 33 …”

“…[3][4][5][6][8][9][10] However, many of the previous studies were limited by a lack of statistical power. The largest study to date, an American case-control study, included 39 instances of orofacial clefts associated with exposure to corticosteroids, 4 whereas our study included 84 instances associated with exposure during the first trimester.…”

“…The association between risk of orofacial clefts and the use of corticosteroids during pregnancy remains unclear. [3][4][5][6][7][8][9][10] We conducted a nationwide cohort study in Denmark with independent and prospective determination of cortico steroid use during pregnancy and the diagnosis of orofacial clefts. Our study comprised all live births from January 1996 to September 2008.…”

The Role of Corticosteroids in Today's Oral and Maxillofacial Surgery

“…Several investigations have reported that the use of corticosteroids during early pregnancy is associated with a 3-to 6-fold increased risk of orofacial clefts. [71][72][73][74][75] Although systemic corticosteroids are associated with a higher risk of orofacial clefts than topical corticosteroids, the latter is not without risk. It has been shown that application of hydrocortisone cream on eczematous skin is associated with significant increase in the level of plasma cortisol.…”

“…[76] In a study by Edwards et al, a significant association between topical corticosteroids and orofacial cleft was observed. [77] Epidemiologic data have shown that low-to-moderate doses of inhaled corticosteroids taken during the first trimester of pregnancy are safe but raise concerns about high doses. [78] The mechanism of cleft palate production by corticosteroids is uncertain; it is a complicated interference in a complex developmental program involving many genetic and biochemical processes.…”