Preterm Cerebellar Growth Impairment After Postnatal Exposure to Glucocorticoids

Overview

Journal Sci Transl Med

Specialties General Medicine
Science

Date 2011 Oct 21

PMID 22013125

Citations 54

Authors

Emily W Y Tam

Vann Chau

Donna M Ferriero

A James Barkovich

Kenneth J Poskitt

Colin Studholme

Eric D-Y Fok

Ruth E Grunau

David V Glidden

Steven P Miller

Affiliations

Soon will be listed here.

Abstract

As survival rates of preterm newborns improve as a result of better medical management, these children increasingly show impaired cognition. These adverse cognitive outcomes are associated with decreases in the volume of the cerebellum. Because animals exhibit reduced preterm cerebellar growth after perinatal exposure to glucocorticoids, we sought to determine whether glucocorticoid exposure and other modifiable factors increased the risk for these adverse outcomes in human neonates. We studied 172 preterm neonatal infants from two medical centers, the University of British Columbia and the University of California, San Francisco, by performing serial magnetic resonance imaging examinations near birth and again near term-equivalent age. After we adjusted for associated clinical factors, antenatal betamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone was associated with impaired cerebellar, but not cerebral, growth. Alterations in treatment after preterm birth, particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth.

Citing Articles

Cerebellar Development and the Burden of Prematurity.

Muehlbacher T, Dudink J, Steggerda S Cerebellum. 2025; 24(2):39.

PMID: 39885037 PMC: 11782465. DOI: 10.1007/s12311-025-01790-6.

Potential Benefits of a 'Trauma-Informed Care' Approach to Improve the Assessment and Management of Dogs Presented with Anxiety Disorders.

Corridan C, Dawson S, Mullan S Animals (Basel). 2024; 14(3).

PMID: 38338102 PMC: 10854685. DOI: 10.3390/ani14030459.

Impact of Nutritional Status on Total Brain Tissue Volumes in Preterm Infants.

Valdes C, Nataraj P, Kisilewicz K, Simenson A, Leon G, Kang D Children (Basel). 2024; 11(1).

PMID: 38255433 PMC: 10813841. DOI: 10.3390/children11010121.

Early, low-dose hydrocortisone and near-term brain connectivity in extremely preterm infants.

Dubner S, Rickerich L, Bruckert L, Poblaciones R, Sproul D, Scala M Pediatr Res. 2023; 95(4):1028-1034.

PMID: 38030826 DOI: 10.1038/s41390-023-02903-9.

Parent-Integrated Interventions to Improve Language Development in Children Born Very Preterm.

Synnes A, Luu T, Afifi J, Khairy M, de Cabo C, Moddemann D Children (Basel). 2023; 10(6).

PMID: 37371185 PMC: 10296804. DOI: 10.3390/children10060953.

References

Block A, McQuillen P, Chau V, Glass H, Poskitt K, Barkovich A . Clinically silent preoperative brain injuries do not worsen with surgery in neonates with congenital heart disease. J Thorac Cardiovasc Surg. 2010; 140(3):550-7. PMC: 2917479. DOI: 10.1016/j.jtcvs.2010.03.035. View

Needelman H, Hoskoppal A, Hoskappal A, Roberts H, Evans M, Bodensteiner J . The effect of hydrocortisone on neurodevelopmental outcome in premature infants less than 29 weeks' gestation. J Child Neurol. 2010; 25(4):448-52. DOI: 10.1177/0883073809348059. View

Rademaker K, Uiterwaal C, Groenendaal F, Uniken Venema M, van Bel F, Beek F . Neonatal hydrocortisone treatment: neurodevelopmental outcome and MRI at school age in preterm-born children. J Pediatr. 2007; 150(4):351-7. DOI: 10.1016/j.jpeds.2006.10.051. View

Yeh T, Lin Y, Lin H, Huang C, Hsieh W, Lin C . Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N Engl J Med. 2004; 350(13):1304-13. DOI: 10.1056/NEJMoa032089. View

Aden P, Goverud I, Liestol K, Loberg E, Paulsen R, Maehlen J . Low-potency glucocorticoid hydrocortisone has similar neurotoxic effects as high-potency glucocorticoid dexamethasone on neurons in the immature chicken cerebellum. Brain Res. 2008; 1236:39-48. DOI: 10.1016/j.brainres.2008.07.095. View

Tam E, Miller S, Studholme C, Chau V, Glidden D, Poskitt K . Differential effects of intraventricular hemorrhage and white matter injury on preterm cerebellar growth. J Pediatr. 2010; 158(3):366-71. PMC: 3025266. DOI: 10.1016/j.jpeds.2010.09.005. View

Doyle L, Anderson P . Adult outcome of extremely preterm infants. Pediatrics. 2010; 126(2):342-51. DOI: 10.1542/peds.2010-0710. View

Papile L, BURSTEIN J, Burstein R, KOFFLER H . Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978; 92(4):529-34. DOI: 10.1016/s0022-3476(78)80282-0. View

Noguchi K, Walls K, Wozniak D, Olney J, Roth K, Farber N . Acute neonatal glucocorticoid exposure produces selective and rapid cerebellar neural progenitor cell apoptotic death. Cell Death Differ. 2008; 15(10):1582-92. PMC: 2636573. DOI: 10.1038/cdd.2008.97. View

10.

Benders M, Groenendaal F, van Bel F, Ha Vinh R, Dubois J, Lazeyras F . Brain development of the preterm neonate after neonatal hydrocortisone treatment for chronic lung disease. Pediatr Res. 2009; 66(5):555-9. PMC: 4495650. DOI: 10.1203/PDR.0b013e3181b3aec5. View

11.

Spittle A, Doyle L, Anderson P, Inder T, Lee K, Boyd R . Reduced cerebellar diameter in very preterm infants with abnormal general movements. Early Hum Dev. 2009; 86(1):1-5. DOI: 10.1016/j.earlhumdev.2009.11.002. View

12.

Ment L, Kesler S, Vohr B, Katz K, Baumgartner H, Schneider K . Longitudinal brain volume changes in preterm and term control subjects during late childhood and adolescence. Pediatrics. 2009; 123(2):503-11. PMC: 2679898. DOI: 10.1542/peds.2008-0025. View

13.

Limperopoulos C, Soul J, Haidar H, Huppi P, Bassan H, Warfield S . Impaired trophic interactions between the cerebellum and the cerebrum among preterm infants. Pediatrics. 2005; 116(4):844-50. DOI: 10.1542/peds.2004-2282. View

14.

Lodygensky G, Rademaker K, Zimine S, Gex-Fabry M, Lieftink A, Lazeyras F . Structural and functional brain development after hydrocortisone treatment for neonatal chronic lung disease. Pediatrics. 2005; 116(1):1-7. DOI: 10.1542/peds.2004-1275. View

15.

Jacobs C, Trinh M, Rootwelt T, Lomo J, Paulsen R . Dexamethasone induces cell death which may be blocked by NMDA receptor antagonists but is insensitive to Mg2+ in cerebellar granule neurons. Brain Res. 2006; 1070(1):116-23. DOI: 10.1016/j.brainres.2005.10.093. View

16.

Miller S, Ferriero D, Leonard C, Piecuch R, Glidden D, Partridge J . Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. J Pediatr. 2005; 147(5):609-16. DOI: 10.1016/j.jpeds.2005.06.033. View

17.

Parikh N, Lasky R, Kennedy K, Moya F, Hochhauser L, Romo S . Postnatal dexamethasone therapy and cerebral tissue volumes in extremely low birth weight infants. Pediatrics. 2007; 119(2):265-72. DOI: 10.1542/peds.2006-1354. View

18.

Dobbing J, Sands J . Quantitative growth and development of human brain. Arch Dis Child. 1973; 48(10):757-67. PMC: 1648530. DOI: 10.1136/adc.48.10.757. View

19.

Watterberg K . Policy statement--postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia. Pediatrics. 2010; 126(4):800-8. DOI: 10.1542/peds.2010-1534. View

20.

Limperopoulos C, Soul J, Gauvreau K, Huppi P, Warfield S, Bassan H . Late gestation cerebellar growth is rapid and impeded by premature birth. Pediatrics. 2005; 115(3):688-95. DOI: 10.1542/peds.2004-1169. View