Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up study
Abstract Introduction Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long‐lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-08-01
|
| Series: | Acta Obstetricia et Gynecologica Scandinavica |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/aogs.14885 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850211737302728704 |
|---|---|
| author | Florian Rakers Ekkehard Schleussner Amani Cornelius Steffen Kluckow Isabel Muth Dirk Hoyer Sven Rupprecht Torsten Schultze Karin Schiecke Carolin Ligges Matthias Schwab Heike Hoyer |
| author_facet | Florian Rakers Ekkehard Schleussner Amani Cornelius Steffen Kluckow Isabel Muth Dirk Hoyer Sven Rupprecht Torsten Schultze Karin Schiecke Carolin Ligges Matthias Schwab Heike Hoyer |
| author_sort | Florian Rakers |
| collection | DOAJ |
| description | Abstract Introduction Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long‐lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8–9 years. This follow‐up study aimed to examine whether these findings persisted into adolescence. Material and Methods Prospective observational follow‐up study involving twenty‐one 14‐ to 15‐year‐old adolescents born to mothers who received betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty‐five children not exposed to betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention‐deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus–pituitary–adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm. Results No statistically significant group difference was observed in global IQ (adjusted mean: betamethasone 103.9 vs references 105.9, mean difference −2.0, 95% confidence interval [CI]: −7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress‐induced activity of the HPAA and the ANS did not differ significantly between groups. However, the betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency–adjusted means: 16.0 Hz vs 17.8 Hz, mean difference −1.83 Hz, 95% CI: −3.21 to −0.45, p = 0.01). Conclusions In 14‐ to 15‐year‐old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow‐up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions. |
| format | Article |
| id | doaj-art-417cf1bea27943f18ef244e8faa8449e |
| institution | OA Journals |
| issn | 0001-6349 1600-0412 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Acta Obstetricia et Gynecologica Scandinavica |
| spelling | doaj-art-417cf1bea27943f18ef244e8faa8449e2025-08-20T02:09:30ZengWileyActa Obstetricia et Gynecologica Scandinavica0001-63491600-04122024-08-0110381530154010.1111/aogs.14885Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up studyFlorian Rakers0Ekkehard Schleussner1Amani Cornelius2Steffen Kluckow3Isabel Muth4Dirk Hoyer5Sven Rupprecht6Torsten Schultze7Karin Schiecke8Carolin Ligges9Matthias Schwab10Heike Hoyer11Hans Berger Department of Neurology Jena University Hospital Jena GermanyDepartment of Obstetrics Jena University Hospital Jena GermanyDepartment of Obstetrics Jena University Hospital Jena GermanyHans Berger Department of Neurology Jena University Hospital Jena GermanyDepartment of Obstetrics Jena University Hospital Jena GermanyHans Berger Department of Neurology Jena University Hospital Jena GermanyHans Berger Department of Neurology Jena University Hospital Jena GermanyHans Berger Department of Neurology Jena University Hospital Jena GermanyInstitute of Medical Statistics, Computer and Data Sciences Jena University Hospital Jena GermanyDepartment of Child and Adolescent Psychiatry, Psychosomatic Medicine and Psychotherapy Jena University Hospital Jena GermanyHans Berger Department of Neurology Jena University Hospital Jena GermanyInstitute of Medical Statistics, Computer and Data Sciences Jena University Hospital Jena GermanyAbstract Introduction Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long‐lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8–9 years. This follow‐up study aimed to examine whether these findings persisted into adolescence. Material and Methods Prospective observational follow‐up study involving twenty‐one 14‐ to 15‐year‐old adolescents born to mothers who received betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty‐five children not exposed to betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention‐deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus–pituitary–adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm. Results No statistically significant group difference was observed in global IQ (adjusted mean: betamethasone 103.9 vs references 105.9, mean difference −2.0, 95% confidence interval [CI]: −7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress‐induced activity of the HPAA and the ANS did not differ significantly between groups. However, the betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency–adjusted means: 16.0 Hz vs 17.8 Hz, mean difference −1.83 Hz, 95% CI: −3.21 to −0.45, p = 0.01). Conclusions In 14‐ to 15‐year‐old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow‐up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions.https://doi.org/10.1111/aogs.14885fetal physiologyfetal programmingglucocorticoidsneurodevelopmentpreterm birth |
| spellingShingle | Florian Rakers Ekkehard Schleussner Amani Cornelius Steffen Kluckow Isabel Muth Dirk Hoyer Sven Rupprecht Torsten Schultze Karin Schiecke Carolin Ligges Matthias Schwab Heike Hoyer Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up study Acta Obstetricia et Gynecologica Scandinavica fetal physiology fetal programming glucocorticoids neurodevelopment preterm birth |
| title | Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up study |
| title_full | Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up study |
| title_fullStr | Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up study |
| title_full_unstemmed | Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up study |
| title_short | Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up study |
| title_sort | association between prenatal glucocorticoid exposure and adolescent neurodevelopment an observational follow up study |
| topic | fetal physiology fetal programming glucocorticoids neurodevelopment preterm birth |
| url | https://doi.org/10.1111/aogs.14885 |
| work_keys_str_mv | AT florianrakers associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT ekkehardschleussner associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT amanicornelius associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT steffenkluckow associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT isabelmuth associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT dirkhoyer associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT svenrupprecht associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT torstenschultze associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT karinschiecke associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT carolinligges associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT matthiasschwab associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy AT heikehoyer associationbetweenprenatalglucocorticoidexposureandadolescentneurodevelopmentanobservationalfollowupstudy |