title: 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.
authors.affiliation: Department of Women's and Children's Health (L.W., M.Z., M.T.S., A.G., A.N., S.L.), Karolinska Institutet, Pediatric Endocrinology Unit (Q2:08), Karolinska University Hospital, and Department of Women's and Children's Health (T.H.), Karolinska Institutet, Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Wallensteen
authors.affiliation: Department of Women's and Children's Health (L.W., M.Z., M.T.S., A.G., A.N., S.L.), Karolinska Institutet, Pediatric Endocrinology Unit (Q2:08), Karolinska University Hospital, and Department of Women's and Children's Health (T.H.), Karolinska Institutet, Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Marius
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Department of Women's and Children's Health (L.W., M.Z., M.T.S., A.G., A.N., S.L.), Karolinska Institutet, Pediatric Endocrinology Unit (Q2:08), Karolinska University Hospital, and Department of Women's and Children's Health (T.H.), Karolinska Institutet, Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Thomsen Sandberg
authors.affiliation: Department of Women's and Children's Health (L.W., M.Z., M.T.S., A.G., A.N., S.L.), Karolinska Institutet, Pediatric Endocrinology Unit (Q2:08), Karolinska University Hospital, and Department of Women's and Children's Health (T.H.), Karolinska Institutet, Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Anton
authors.initials: A
authors.lastname: Gezelius
authors.affiliation: Department of Women's and Children's Health (L.W., M.Z., M.T.S., A.G., A.N., S.L.), Karolinska Institutet, Pediatric Endocrinology Unit (Q2:08), Karolinska University Hospital, and Department of Women's and Children's Health (T.H.), Karolinska Institutet, Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Nordenström
authors.affiliation: Department of Women's and Children's Health (L.W., M.Z., M.T.S., A.G., A.N., S.L.), Karolinska Institutet, Pediatric Endocrinology Unit (Q2:08), Karolinska University Hospital, and Department of Women's and Children's Health (T.H.), Karolinska Institutet, Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Tatja
authors.initials: T
authors.lastname: Hirvikoski
authors.affiliation: Department of Women's and Children's Health (L.W., M.Z., M.T.S., A.G., A.N., S.L.), Karolinska Institutet, Pediatric Endocrinology Unit (Q2:08), Karolinska University Hospital, and Department of Women's and Children's Health (T.H.), Karolinska Institutet, Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Lajic
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy; D002648:Child; D003071:Cognition / Q000502:physiology*; D003907:Dexamethasone / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D007360:Intelligence / Q000502:physiology*; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D012727:Sex Characteristics; D012737:Sex Factors; D014770:Virilism / Q000188:drug therapy
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone