Safety of topical corticosteroids in pregnancy.
BACKGROUND
Topical corticosteroids are the most frequently prescribed dermatological treatment and are often used by pregnant women with skin conditions. However, little is known about their safety in pregnancy.


OBJECTIVE
To assess the effects of topical corticosteroids on pregnancy outcomes in pregnant women.


METHODS
This is an update of a review previously published in 2009. We updated our searches of the following databases to July 2015: the Cochrane Skin Group Specialised Register, the Cochrane Pregnancy and Childbirth Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 6), MEDLINE, EMBASE, and LILACS. We also searched five trials registers and checked the reference lists of included studies, published reviews, articles that had cited the included studies, and one author's literature collection, for further references to relevant RCTs.


METHODS
Randomised controlled trials and cohort studies of topical corticosteroids in pregnant women, as well as case-control studies comparing maternal exposure to topical corticosteroids between cases and controls when studies reported pre-specified outcomes. The primary outcomes included mode of delivery, major congenital abnormality, birth weight, and preterm delivery (delivery before 37 completed weeks gestation); the secondary outcomes included foetal death, minor congenital abnormality, and low Apgar score (less than seven at 5 min).


METHODS
We used standard methodological procedures expected by Cochrane. Two authors independently applied selection criteria, extracted data, and assessed the quality of the included studies. A third author was available for resolving differences of opinion. A further author independently extracted data from included studies that were conducted by authors of this systematic review.


RESULTS
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.


CONCLUSIONS
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.
Department of Dermatology and Centre for Evidence-Based Medicine, Chang Gung Memorial Hospital, 6, Sec West, Chia-Pu Road, Puzih, Chiayi, Taiwan, 61363.
Ching-Chi
CC
Chi
Shu-Hui
SH
Wang
Fenella
F
Wojnarowska
Gudula
G
Kirtschig
Emily
E
Davies
Cathy
C
Bennett
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D001724:Birth Weight / Q000187:drug effects; D016022:Case-Control Studies; D002971:Cleft Lip / Q000139:chemically induced; D002972:Cleft Palate / Q000139:chemically induced; D015331:Cohort Studies; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight; D064887:Observational Studies as Topic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D047928:Premature Birth / Q000139:chemically induced; D012880:Skin Pigmentation
D000305:Adrenal Cortex Hormones; D003879:Dermatologic Agents