Sex-dimorphic effects of prenatal treatment with dexamethasone
Abstract
CONTEXT: 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. OBJECTIVE: To evaluate long-term cognitive effects of prenatal DEX therapy in healthy (non-CAH) DEX-treated children. DESIGN AND SETTING: Observational study with patient and control groups from a single research institute. PARTICIPANTS: Healthy (non-CAH) DEX-treated subjects (n = 34) and untreated population controls (n = 66) from Sweden, aged 7-17 years. INTERVENTION: DEX-treatment used in unborn children at risk of CAH, during first trimester of fetal life. MAIN OUTCOME MEASURES: Standardized neuropsychological tests and questionnaires were used. RESULTS: 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. CONCLUSIONS: 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.
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In two cohorts of girls with CAH treated throughout gestation, neurocognitive outcomes were negatively affected for mental processing and spatial memory and broad deficits were found in most measures of cognition.
“In two cohorts of girls with CAH treated throughout gestation, neurocognitive outcomes were negatively affected for mental processing and spatial memory (480) and broad deficits were found in most measures of cognition (488).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [480]
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Favero, D., Lapuchesky, L. S., Poggio, F. B., Nardin, S., Perachino, M., Arecco, L., Scavone, G., Ottonello, S., Latocca, M. M., Borea, R., et al. (2023) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2023.2293167 · Cited by 2 · see citing works
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Family planning and preimplantation testing: family experiences in congenital adrenal hyperplasia
Sandy, J., Betts, G. A., Harper, J. L., Nevin, S. M., Deans, R., & Neville, K. A. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1482902 · Cited by 1 · see citing works
Has the Era of Individualized Intrauterine Treatment for Congenital Adrenal Hyperplasia Arrived?
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Management of Pregnancy in a Patient with Nonclassical Congenital Adrenal Hyperplasia
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Epigenetic alterations associated with early prenatal dexamethasone treatment
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Prenatal Diagnosis and Treatment of Congenital Adrenal Hyperplasia
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Prenatal dexamethasone affects female cognitive functions
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Debates and controversies in genetic steroid disorders
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Antenatal dexamethasone treatment and long-term programming
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Update on prenatal diagnosis and treatment of congenital adrenal hyperplasia
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Self-citationReproductive and fertility challenges in adolescents with congenital adrenal hyperplasia
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Hippocampal volume and white matter impairments in patients with congenital adrenal hyperplasia
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Self-citation
- Authors
- Wallensteen, L., Zimmermann, M., Thomsen Sandberg, M., Gezelius, A., Nordenström, A., Hirvikoski, T., & Lajic, S.
- Affiliations
- Karolinska University Hospital (SE)
- 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, SE-171 76 Stockholm, Sweden
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-08-02
- Volume
- 101
- Issue
- 10
- Pages
- 3838-3846
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2502708865
- Cited by
- 67
- References
- 46
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 8 · 2021: 3 · 2020: 7 · 2019: 8 · 2018: 14 · 2017: 8 · 2016: 1
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- dexamethasone, prenatal glucocorticoid exposure, sex differences, congenital adrenal hyperplasia, cognitive effects, intelligence, visuospatial working memory, children, neuropsychological outcomes, drug safety in pregnancy
- MeSH terms
- Adolescent, Adrenal Hyperplasia, Congenital, Child, Cognition, Dexamethasone, Female, Follow-Up Studies, Glucocorticoids, Humans, Intelligence, Male, Memory, Short-Term, Pregnancy, Prenatal Exposure Delayed Effects, Sex Characteristics, Sex Factors, Virilism
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