Sex-Dimorphic Effects of Prenatal Treatment With Dexamethasone

Abstract

Dexamethasone (DEX) is used to prevent virilization in female fetuses at risk of congenital adrenal hyperplasia (CAH). Given that treatment has to be started before the genotype is known, 7 out of 8 fetuses will be exposed to DEX without benefit. To evaluate long-term cognitive effects of prenatal DEX therapy in healthy (non-CAH) DEX-treated children. Observational study with patient and control groups from a single research institute. Healthy (non-CAH) DEX-treated subjects (n = 34) and untreated population controls (n = 66) from Sweden, aged 7-17 years. DEX-treatment used in unborn children at risk of CAH, during first trimester of fetal life. Standardized neuropsychological tests and questionnaires were used. DEX treatment has widespread negative effects in girls. In Wechsler Intelligence Scales for Children-III scale subtests, we observed significant interactions between DEX and GENDER (coding, P = .044; block design, P = .013; vocabulary, P = .025) and a trend for the subtest digit span (P = .074). All interactions were driven by DEX effects in girls, but not boys, with DEX-treated females showing lower scores than female untreated controls (coding, P = .068, d = 0.66; block design, P = .021, d = 0.81; vocabulary, P = .014, d = 0.84; digit span, P = .001, d = 1.0). Likewise, DEX-treated girls tend to have poorer visual spatial working memory performance than controls (span board test forward: P = .065, d = .80). We observed no effects on long-term memory, handedness, speed of processing, nor self-perceived or parentally reported scholastic performance. Early prenatal DEX exposure affects cognitive functions in healthy girls, ie, children who do not benefit from the treatment. It can therefore not be considered safe to use this therapy in the context of CAH.