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Cognitive Functions in Children at Risk for Congenital Adrenal Hyperplasia Treated Prenatally with Dexamethasone

Departments of Psychiatry (T.H.), Molecular Medicine and Surgery (T.H., A.N., A.W., S.L.), Clinical Sciences (A.N.), Public Health Sciences/National Institute for Psychosocial Medicine (F.L.), and Woman and Child Health (E.M.R.), Karolinska Institutet, 171 76 Stockholm, Sweden; and the Department of Psychology (T.L.), Stockholm University, 106 91 Stockholm, Sweden

Address all correspondence and requests for reprints to: Dr. Svetlana Lajic, Department of Molecular Medicine and Surgery, Center for Molecular Medicine L8:02, Karolinska Institutet/Karolinska University Hospital, 171 76 Stockholm, Sweden. E-mail: Svetlana.Lajic{at}ki.se.

Context and Objective: In Sweden, from 1985 through 1995, 40 fetuses at risk for congenital adrenal hyperplasia (CAH) were treated with dexamethasone (DEX) to prevent virilization of affected females. We report long-term effects on neuropsychological functions and scholastic performance of this controversial treatment.

Design and Patients: Prenatally treated children, 7 to 17 yr old, were assessed with standardized neuropsychological tests (A Developmental Neuropsychological Assessment and Wechsler Intelligence Scales for Children) and child-completed questionnaires measuring self-perceived scholastic competence (Self-Perception Profile for Children). A parent-completed questionnaire (Child Behavior Checklist/4–18 School Scale) was used to evaluate whether the treatment had any impact on the children’s school performance. In addition, a child-completed questionnaire measuring social anxiety (The Social Anxiety Scale for Children–Revised) was completed by the prenatally treated children aged 8 to 17 yr (n = 21) and age- and sex-matched controls (n = 26).

Results: Of 40 DEX-treated children, 26 (median age, 11 yr) participated in the study. Thirty-five sex- and age-matched healthy children were controls. There were no between-group differences concerning psychometric intelligence, measures of cerebral lateralization, memory encoding, and long-term memory. Short-term treated, CAH-unaffected children performed poorer than the control group on a test assessing verbal working memory (P = 0.003), and they rated lower on a questionnaire assessing self-perception of scholastic competence (P = 0.003). This group also showed increased self-rated social anxiety assessed by The Social Anxiety Scale for Children–Revised (P = 0.026). Prenatally treated, CAH-affected children performed poorer than controls on tests measuring verbal processing speed, although this difference disappeared when controlling for the child’s full-scale IQ.

Conclusions: This study indicates that prenatal DEX treatment is associated with previously not described long-term effects on verbal working memory and on certain aspects of self-perception that could be related to poorer verbal working memory. These findings may thus question future DEX treatment of congenital adrenal hyperplasia. Therefore, we encourage additional retrospective studies of larger cohorts to either confirm or challenge the present findings.

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