The relationship between maternal corticosteroid use and orofacial clefts-a meta-analysis

•Corticosteroids likely increase the risk of orofacial clefts, although it is small.•The study implies that maternal corticosteroid use during the first trimester is associated with fetal cleft lip with or without palate.•The clinicians and pregnant women need make more informed decisions regarding the use of corticosteroids during pregnancy. The aim was to evaluate the relationship between maternal corticosteroid use during first trimester of pregnancy and risk of orofacial clefts (OC). The overall findings showed a certain association between maternal corticosteroid use and occurrence of OC, compared with non-users (OR=1.16 [95% CI: 1.01–1.33]). When study type was considered this association was significant only for case-control studies (OR=1.22 [95% CI: 1.02–1.47]), and not for cohort studies (OR=1.09 [95% CI: 0.88–1.34]) when there are many confounders (dose, route of application, disease etc.) and biases (re-call, loss-to follow-up etc.) that still need to be considered. A subgroup analysis based on the type of OC gave an overall OR of 1.41 (95% CI: 1.14–1.74) in the case-control studies for cleft lip with or without palate (CL/P) and 1.09 (95% CI: 0.80–1.48) for cleft palate only (CPO), when comparing maternal corticosteroid users with non-users. However, for cohort studies, the overall OR for CL/P is 1.06 (95% CI: 0.82–1.37) and 1.20 (95% CI: 0.83–1.75) for CPO. The absolute risk of facial cleft after prenatal exposure to corticosteroids, if any, is small.