Prenatal Dexamethasone Treatment For Congenital Adrenal Hyperplasia

Objective: To assess the efficacy and safety of prenatal dexamethasone treatment in offspring at risk for congenital adrenal hyperplasia.Methods: MEDLINE,EMBASE,the Cochrane Library,the clinicaltrials.gov website databases was systematically searched from inception through March 2019.The Newcastle-Ottawa quality assessment scale(NOS)was applied to assess the quality of the methodology in the included studies.Outcome indicators include the short-term outcomes contained virilization of affected female,newborn physical outcomes and the long-term outcomes consisted of cognitive function,behavioral problems,temperament.WMD and SMD with 95%CI were calculated using random or fixed effects models.The I-squared(significance level,>50%)and Q statistic(significance level at P < 0.10)were used to assess heterogeneity among studies.If there is significant heterogeneity,a random effect model(Der Simonian-Laird method)was used to calculate the pooled effect;otherwise,the fixed model(Mantel-Haenszel method)was used.All statistical analyses were performed using STATA,version 15.0(Stata Corp).Results: Finally,18 articles met the inclusion criteria were included in the synthesis.All included studies were cohort studies conducted in diverse geographic locations,mainly from the United States and Europe.The methodological quality of all observational cohort studies assessed using the NOS score,only nine studies were high quality(scored ≥7).Among all articles,seven studies provided data regarding feminization,two studies each provided data on birth weight,body length,11 studies provided data on the long-term effects.There was a significant reduction of virilization in the DEX-treated group(WMD=-2.39,95%CI:-3.31,-1.47).No significant differences were found in newborn physical outcomes for birth weight(WMD= 0.09,95%CI:-0.09,0.27)and birth length(WMD= 0.27,95%CI:-0.68,1.21).Concerning cognitive functions,no significant differences in the domains of psychometric intelligence(SMD= 0.05,95%CI:-0.74,0.83),verbal memory(SMD=-0.17,95%CI:-0.58,0.23),visual memory(SMD= 0.10,95%CI:-0.14,0.34),learning(SMD=-0.02,95%CI:-0.27,0.22),verbal processing(SMD=-0.38,95%CI:-0.93,0.17).Regarding behavioral problems,no significant differences in the domains of internalizing problems(SMD= 0.16,95%CI:-0.49,0.81),externalizing problems(SMD= 0.07,95%CI:-0.30,0.43),total problems(SMD= 0.14,95%CI:-0.23,0.51).With respect to temperament,no significant differences in the domains of emotionality(SMD= 0.13,95%CI:-0.79,1.05),activity(SMD= 0.04,95%CI:-0.32,0.39),shyness(SMD= 0.25,95%CI:-0.70,1.20),sociability(SMD=-0.23,95%CI:-0.90,0.44).Conclusions: Prenatal DEX treatment reduced virilization with no significant differences in newborn physical outcomes,cognitive functions,behavioral problems,temperament.The results need to be interpreted cautiously due to the existence of limitations.