Abstract: We included 7 new observational studies in this update, bringing the total number to 14, including 5 cohort and 9 case-control studies, with 1,601,515 study subjects. Most studies found no causal associations between maternal exposure to topical corticosteroids of any potency and pregnancy outcomes when compared with no exposure. These outcomes included: mode of delivery (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.15, 1 cohort study, n = 9904, low quality evidence); congenital abnormalities, including orofacial cleft or cleft palate and hypospadias (where the urethral opening is on the underside of the penis) (RR 0.82, 95% CI 0.34 to 1.96, 2 cohort studies, n = 9512, low quality evidence; and odds ratio (OR) 1.07, 95% CI 0.71 to 1.60, 1 case-control study, n = 56,557); low birth weight (RR 1.08, 95% CI 0.86 to 1.36; n = 59,419, 4 cohort studies; very low quality evidence); preterm delivery (RR 0.93, 95% CI 0.81 to 1.08, 4 cohort studies, n = 59,419, low quality evidence); foetal death (RR 1.02, 95% CI 0.60 to 1.73, 4 cohort studies, n = 63,885, very low quality evidence); and low Apgar score (RR 0.84, 95% CI 0.54 to 1.31, 1 cohort study, n = 9220, low quality evidence). We conducted stratified analyses of mild or moderate potency, and potent or very potent topical corticosteroids, but we found no causal associations between maternal exposure to topical corticosteroid of any potency and congenital abnormality, orofacial clefts, preterm delivery, or low Apgar score. For low birth weight, although the meta-analysis based on study-level data was not significant for either mild to moderate corticosteroids (pooled RR 0.90, 95% CI 0.74 to 1.09, 3 cohort studies, n > 55,713) or potent to very potent corticosteroids (pooled RR 1.58, 95% CI 0.96 to 2.58, 4 cohort studies, n > 47,651), there were significant differences between the two subgroups (P = 0.04). The results from three of the individual studies in the meta-analysis indicated an increased risk of low birth weight in women who received potent to very potent topical corticosteroids. Maternal use of mild to moderate potency topical steroids was associated with a decreased risk of foetal death (pooled RR 0.70, 95% CI 0.64 to 0.77, 2 studies, n = 48,749; low quality evidence), but we did not observe this effect when potent to very potent topical corticosteroids were given during pregnancy (pooled RR 1.14, 95% CI 0.69 to 1.88, 3 studies, n = 37,086, low quality evidence). We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group approach to rate the overall quality of the evidence. Data from observational studies started at low quality. We further downgraded the evidence because of imprecision in low birth weight and inconsistency in foetal death. Lower quality evidence resulted in lower confidence in the estimate of effect for those outcomes. This update adds more evidence showing no causal associations between maternal exposure to topical corticosteroids of all potencies and pregnancy outcomes including mode of delivery, congenital abnormalities, preterm delivery, foetal death, and low Apgar score, which is consistent with the previous version of this review. This update provides stratified analyses based on steroid potency; we found no association between maternal use of topical corticosteroids of any potency and an increase in adverse pregnancy outcomes, including mode of delivery, congenital abnormality, preterm delivery, foetal death, and low Apgar score. Similar to the previous version of the review, this update identified a probable association between low birth weight and maternal use of potent to very potent topical corticosteroids, especially when the cumulative dosage of topical corticosteroids throughout the pregnancy is very large, which warrants further investigation. The finding of a possible protective effect of mild to moderate topical corticosteroids on foetal death could also be examined.

Plain-language summary: We updated the review that was previously published in 2009. We examined the research published up to July 2015 and found seven new studies. All in all, this updated review included a total of 14 observational studies that assessed 1,601,515 pregnancies. Observational studies are generally regarded as less rigorous than randomised controlled clinical trials. The funding source was from academic or governmental institutions in 10 studies and was not reported in 4 studies. We found no associations between mothers' use of topical steroids of any potency and type of delivery, birth defects, premature births, or low Apgar score. There is some evidence indicating a relation between low birth weight and maternal use of potent or very potent topical steroids, especially when high doses are used in pregnancy, and this may warrant more research. On the other hand, maternal use of mild or moderate topical corticosteroids is not related to low birth weight. We even found that mild or moderately potent topical steroids protect against death of the baby, but this was not seen when the mothers used potent or very potent topical steroids. This finding needs further examination. The overall quality of evidence is low because all available studies were observational. The high quality study design of the randomised controlled trial that allocates participants to receive either topical corticosteroids or no treatment is not generally feasible in pregnant women due to ethical concerns about possible exposure of the foetus to an experimental treatment. Where we further downgraded the quality of the evidence to 'very low', it was because we had detected variation in the results from the studies that we found, which means that we have low confidence in our estimates of the effects for our outcomes.