PEDIATRICS Vol. 107 No. 2 February 2001, pp. 217-221
Impaired Cerebral Cortical Gray Matter Growth After Treatment With Dexamethasone for Neonatal Chronic Lung Disease
Received Jul 26, 2000; accepted Sep 20, 2000.
,, ¶,
,,,, and
From the * Division of Newborn Medicine, Harvard Medical School
and Brigham & Women's Hospital, Boston, Massachusetts, Department
of Radiology, Harvard Medical School and Brigham & Women's Hospital,
Boston, Massachusetts, § Department of Paediatrics, University of
Otago, Christchurch School of Medicine and Hospital, Christchurch, New
Zealand, Department of Neurology, Children's Hospital, Boston,
Massachusetts, and ¶ Department of Pediatrics, University of Geneva,
Geneva, Switzerland.
Objective. The specific aim of this study was to quantify at term the influence of postnatal systemic dexamethasone treatment for neonatal chronic lung disease on subsequent brain growth and development in premature infants without evidence of severe intraventricular hemorrhage or white matter injury.
Methods. Eighteen premature (23 to 31 weeks) infants, 7 treated with dexamethasone and 11 not treated, were studied at term, ie, 38 to 41 postconceptional weeks, by an advanced quantitative volumetric 3-dimensional magnetic resonance imaging (MRI) technique to quantify cerebral tissue volumes. Fourteen healthy term infants also were studied for comparison. A sequence of image processing algorithms was used to segment each of the MRI slices into the following separate tissue classes: cerebral cortical gray matter, basal ganglia/thalami, unmyelinated white matter, myelinated white matter, and cerebrospinal fluid, all classified based on magnetic resonance signal intensity and anatomic location. A final summing of voxels for each tissue class was performed to compute absolute volumes in milliliters.
Results. Cerebral cortical gray matter volume in premature infants treated with dexamethasone was reduced 35% when compared with gray matter volume in premature infants not treated with dexamethasone (mean ± standard deviation, 130.3 ± 54.0 vs 200.6 ± 35.1 mL, respectively). Subcortical gray matter volumes (basal ganglia and thalami) and myelinated and unmyelinated white matter volumes were not significantly different among the treated and untreated groups. However, premature infants treated with dexamethasone exhibited a reduction (30%) in total cerebral tissue volume compared with total cerebral tissue volume in both the premature infants not treated with dexamethasone and the control term infants (312.7 ± 43.7 vs 448.2 ± 50.2 and 471.6 ± 36.4 mL respectively). This latter finding relates primarily to the decrease in cerebral cortical gray matter volume.
Conclusions. The data suggest an impairment in brain growth, principally affecting cerebral cortical gray matter, secondary to systemic dexamethasone therapy. Although the premature infants who received dexamethasone were smaller with more severe respiratory disease, these findings are consistent with growing evidence of a potential deleterious effect of dexamethasone on neonatal brain and subsequent neurodevelopmental outcome. This apparent deleterious effect should be taken into consideration by clinicians when weighing the potential risks and benefits of this therapy for low birth weight infants with neonatal chronic lung disease. Key words: prematurity, dexamethasone, cerebral cortical gray matter, volumetric 3D-MRI.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. Nagy, J. Ashburner, J. Andersson, S. Jbabdi, B. Draganski, S. Skare, B. Bohm, A.-C. Smedler, H. Forssberg, and H. Lagercrantz Structural Correlates of Preterm Birth in the Adolescent Brain Pediatrics, November 1, 2009; 124(5): e964 - e972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Volpe Cerebellum of the Premature Infant: Rapidly Developing, Vulnerable, Clinically Important J Child Neurol, September 1, 2009; 24(9): 1085 - 1104. [Abstract] [PDF]
|
|
|
|
|
|
D. Wilson-Costello, M. C. Walsh, J. C. Langer, R. Guillet, A. R. Laptook, B. J. Stoll, S. Shankaran, N. N. Finer, K. P. Van Meurs, W. A. Engle, et al. Impact of Postnatal Corticosteroid Use on Neurodevelopment at 18 to 22 Months' Adjusted Age: Effects of Dose, Timing, and Risk of Bronchopulmonary Dysplasia in Extremely Low Birth Weight Infants Pediatrics, March 1, 2009; 123(3): e430 - e437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Maunu, R. Parkkola, H. Rikalainen, L. Lehtonen, L. Haataja, H. Lapinleimu, and and the PIPARI Group Brain and Ventricles in Very Low Birth Weight Infants at Term: A Comparison Among Head Circumference, Ultrasound, and Magnetic Resonance Imaging Pediatrics, February 1, 2009; 123(2): 617 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Needelman, M. Evans, H. Roberts, M. Sweney, and J.B. Bodensteiner Effects of Postnatal Dexamethasone Exposure on the Developmental Outcome of Premature Infants J Child Neurol, April 1, 2008; 23(4): 421 - 424. [Abstract] [PDF]
|
|
|
|
|
|
T. M. O'Shea, L. K. Washburn, P. A. Nixon, and D. J. Goldstein Follow-up of a Randomized, Placebo-Controlled Trial of Dexamethasone to Decrease the Duration of Ventilator Dependency in Very Low Birth Weight Infants: Neurodevelopmental Outcomes at 4 to 11 Years of Age Pediatrics, September 1, 2007; 120(3): 594 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Wilkinson, D. M. Brosi, and Z. D. Jiang Functional Impairment of the Brainstem in Infants With Bronchopulmonary Dysplasia Pediatrics, August 1, 2007; 120(2): 362 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Watterberg, M. L. Shaffer, M. J. Mishefske, C. L. Leach, M. C. Mammel, R. J. Couser, S. Abbasi, C. H. Cole, S. W. Aucott, E. H. Thilo, et al. Growth and Neurodevelopmental Outcomes After Early Low-Dose Hydrocortisone Treatment in Extremely Low Birth Weight Infants Pediatrics, July 1, 2007; 120(1): 40 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Lindstrom, B. Winbladh, B. Haglund, and A. Hjern Preterm Infants as Young Adults: A Swedish National Cohort Study Pediatrics, July 1, 2007; 120(1): 70 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Stephenson, S. Wright, A. O'Connor, A. Fielder, A. Johnson, S. Ratib, and M. Tobin Children born weighing less than 1701 g: visual and cognitive outcomes at 11-14 years Arch. Dis. Child. Fetal Neonatal Ed., July 1, 2007; 92(4): F265 - F270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Thompson, S. K. Warfield, J. B. Carlin, M. Pavlovic, H. X. Wang, M. Bear, M. J. Kean, L. W. Doyle, G. F. Egan, and T. E. Inder Perinatal risk factors altering regional brain structure in the preterm infant Brain, March 1, 2007; 130(3): 667 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Parikh, R. E. Lasky, K. A. Kennedy, F. R. Moya, L. Hochhauser, S. Romo, and J. E. Tyson Postnatal Dexamethasone Therapy and Cerebral Tissue Volumes in Extremely Low Birth Weight Infants Pediatrics, February 1, 2007; 119(2): 265 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Airo, M Scarsi, A Brucato, T Benicchi, F Malacarne, I Cavazzana, E Danieli, M LiDestri, M Motta, L Caimi, et al. Characterization of T-cell population in children with prolonged fetal exposure to dexamethasone for anti-Ro/SS-A antibodies associated congenital heart block Lupus, September 1, 2006; 15(9): 553 - 561. [Abstract] [PDF]
|
|
|
|
 |
|
 L. J. Woodward, P. J. Anderson, N. C. Austin, K. Howard, and T. E. Inder Neonatal MRI to Predict Neurodevelopmental Outcomes in Preterm Infants. N. Engl. J. Med., August 17, 2006; 355(7): 685 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. U.J. Mewes, P. S. Huppi, H. Als, F. J. Rybicki, T. E. Inder, G. B. McAnulty, R. V. Mulkern, R. L. Robertson, M. J. Rivkin, and S. K. Warfield Regional Brain Development in Serial Magnetic Resonance Imaging of Low-Risk Preterm Infants Pediatrics, July 1, 2006; 118(1): 23 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Arya, V. G. Demarco, M. Issar, and G. Hochhaus CONTRARY TO ADULT, NEONATAL RATS SHOW PRONOUNCED BRAIN UPTAKE OF CORTICOSTEROIDS Drug Metab. Dispos., June 1, 2006; 34(6): 939 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zacharia, S. Zimine, K.O. Lovblad, S. Warfield, H. Thoeny, C. Ozdoba, E. Bossi, R. Kreis, C. Boesch, G. Schroth, et al. Early Assessment of Brain Maturation by MR Imaging Segmentation in Neonates and Premature Infants. AJNR Am. J. Neuroradiol., May 1, 2006; 27(5): 972 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Limperopoulos, J. S. Soul, H. Haidar, P. S. Huppi, H. Bassan, S. K. Warfield, R. L. Robertson, M. Moore, P. Akins, J. J. Volpe, et al. Impaired Trophic Interactions Between the Cerebellum and the Cerebrum Among Preterm Infants Pediatrics, October 1, 2005; 116(4): 844 - 850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Lodygensky, K. Rademaker, S. Zimine, M. Gex-Fabry, A. F. Lieftink, F. Lazeyras, F. Groenendaal, L. S. de Vries, and P. S. Huppi Structural and Functional Brain Development After Hydrocortisone Treatment for Neonatal Chronic Lung Disease Pediatrics, July 1, 2005; 116(1): 1 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Volpe Encephalopathy of Prematurity Includes Neuronal Abnormalities Pediatrics, July 1, 2005; 116(1): 221 - 225. [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Bruder, P. C. Lee, and H. Raff Dexamethasone treatment in the newborn rat: fatty acid profiling of lung, brain, and serum lipids J Appl Physiol, March 1, 2005; 98(3): 981 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Stark Pharmacology Review: Risks and Benefits of Postnatal Corticosteroids NeoReviews, February 1, 2005; 6(2): e99 - e103. [Full Text] [PDF]
|
|
|
|
|
|
T. E. Inder, S. K. Warfield, H. Wang, P. S. Huppi, and J. J. Volpe Abnormal Cerebral Structure Is Present at Term in Premature Infants Pediatrics, February 1, 2005; 115(2): 286 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Johnsen, J. B. Bodensteiner, and T. E. Lotze Frequency and Nature of Cerebellar Injury in the Extremely Premature Survivor with Cerebral Palsy J Child Neurol, January 1, 2005; 20(1): 60 - 64. [Abstract] [PDF]
|
|
|
|
 |
|
 E. D. Bruder, P. C. Lee, and H. Raff Metabolic Consequences of Hypoxia from Birth and Dexamethasone Treatment in the Neonatal Rat: Comprehensive Hepatic Lipid and Fatty Acid Profiling Endocrinology, November 1, 2004; 145(11): 5364 - 5372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Vasileiadis, N. Gelman, V. K.M. Han, L.-A. Williams, R. Mann, Y. Bureau, and R. T. Thompson Uncomplicated Intraventricular Hemorrhage Is Followed by Reduced Cortical Volume at Near-Term Age Pediatrics, September 1, 2004; 114(3): e367 - e372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Neal Jr., G. Weidemann, M. Kabbaj, and D. M. Vazquez Effect of neonatal dexamethasone exposure on growth and neurological development in the adult rat Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2004; 287(2): R375 - R385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. F. Yeh, Y. J. Lin, H. C. Lin, C. C. Huang, W. S. Hsieh, C. H. Lin, and C. H. Tsai Outcomes at School Age after Postnatal Dexamethasone Therapy for Lung Disease of Prematurity N. Engl. J. Med., March 25, 2004; 350(13): 1304 - 1313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Parikh, R. G. Locke, A. Chidekel, K. H. Leef, J. Emberger, D. A. Paul, and J. L. Stefano Effect of Inhaled Corticosteroids on Markers of Pulmonary Inflammation and Lung Maturation in Preterm Infants With Evolving Chronic Lung Disease J Am Osteopath Assoc, March 1, 2004; 104(3): 114 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O Baud Postnatal steroid treatment and brain development Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2004; 89(2): F96 - F100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Costedoat-Chalumeau, Z Amoura, D Le Thi Hong, B Wechsler, D Vauthier, P Ghillani, T Papo, O Fain, L Musset, and J-C Piette Questions about dexamethasone use for the prevention of anti-SSA related congenital heart block Ann Rheum Dis, October 1, 2003; 62(10): 1010 - 1012. [Abstract] [Full Text]
|
|
|
|
|
|
S. J. Counsell, J. M. Allsop, M. C. Harrison, D. J. Larkman, N. L. Kennea, O. Kapellou, F. M. Cowan, J. V. Hajnal, A. D. Edwards, and M. A. Rutherford Diffusion-Weighted Imaging of the Brain in Preterm Infants With Focal and Diffuse White Matter Abnormality Pediatrics, July 1, 2003; 112(1): 1 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S J Counsell, M A Rutherford, F M Cowan, and A D Edwards Magnetic resonance imaging of preterm brain injury Arch. Dis. Child. Fetal Neonatal Ed., July 1, 2003; 88(4): F269 - F274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R W I Cooke and L Foulder-Hughes Growth impairment in the very preterm and cognitive and motor performance at 7 years Arch. Dis. Child., June 1, 2003; 88(6): 482 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Peterson, A. W. Anderson, R. Ehrenkranz, L. H. Staib, M. Tageldin, E. Colson, J. C. Gore, C. C. Duncan, R. Makuch, and L. R. Ment Regional Brain Volumes and Their Later Neurodevelopmental Correlates in Term and Preterm Infants Pediatrics, May 1, 2003; 111(5): 939 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hayakawa, A. Okumura, F. Hayakawa, Y. Kato, M. Ohshiro, N. Tauchi, and K. Watanabe Nutritional State and Growth and Functional Maturation of the Brain in Extremely Low Birth Weight Infants Pediatrics, May 1, 2003; 111(5): 991 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Burch, W. Rhine, R. Baker, F. Litman, J. W. Kaempf, E. Schwarz, S. Sun, N. R. Payne, and P. J. Sharek Implementing Potentially Better Practices to Reduce Lung Injury in Neonates Pediatrics, April 1, 2003; 111(4): e432 - 436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Kaempf, B. Campbell, R. S. Sklar, C. Arduza, R. Gallegos, M. Zabari, A. Brown, and J. V. McDonald Implementing Potentially Better Practices to Improve Neonatal Outcomes After Reducing Postnatal Dexamethasone Use in Infants Born Between 501 and 1250 Grams Pediatrics, April 1, 2003; 111(4): e534 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Davis, R. B. Parad, T. Michele, E. Allred, A. Price, and W. Rosenfeld Pulmonary Outcome at 1 Year Corrected Age in Premature Infants Treated at Birth With Recombinant Human CuZn Superoxide Dismutase Pediatrics, March 1, 2003; 111(3): 469 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Hoon JR, K. M. Belsito, and L. M. Nagae-Poetscher Neuroimaging in Spasticity and Movement Disorders J Child Neurol, January 1, 2003; 18(1_suppl): S25 - S39. [Abstract] [PDF]
|
|
|
|
|
|
I. E. Olsen, D. K. Richardson, C. H. Schmid, L. M. Ausman, and J. T. Dwyer Intersite Differences in Weight Growth Velocity of Extremely Premature Infants Pediatrics, December 1, 2002; 110(6): 1125 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Perlman Concern About Fetus and Newborn Committee Statement on Corticosteroid Use Pediatrics, November 1, 2002; 110(5): 1034 - 1034. [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, J. L. Pongrac, and D. B. DeFranco Glucocorticoid Receptors in Hippocampal Neurons that Do Not Engage Proteasomes Escape from Hormone-Dependent Down-Regulation but Maintain Transactivation Activity Mol. Endocrinol., September 1, 2002; 16(9): 1987 - 1998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. LeFlore, W. A. Salhab, R. S. Broyles, and W. D. Engle Association of Antenatal and Postnatal Dexamethasone Exposure With Outcomes in Extremely Low Birth Weight Neonates Pediatrics, August 1, 2002; 110(2): 275 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. Jacobs, R. L. Chapman, I. Gross, K. J. Barrington, and A. R. Stark Premature Conclusions on Postnatal Steroid Effects Pediatrics, July 1, 2002; 110(1): 200 - 201. [Full Text] [PDF]
|
|
|
|
|
|
C Romagnoli, E Zecca, R Luciano, G Torrioli, and G Tortorolo A three year follow up of preterm infants after moderately early treatment with dexamethasone Arch. Dis. Child. Fetal Neonatal Ed., July 1, 2002; 87(1): F55 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Banks Postnatal Dexamethasone for Bronchopulmonary Dysplasia: A Systematic Review and Meta-analysis of 20 Years of Clinical Trials NeoReviews, February 1, 2002; 3(2): e24 - 34. [Full Text]
|
|
|
|
|
|
S. B. Flagel, D. M. Vazquez, S. J. Watson Jr., and C. R. Neal Jr. Effects of tapering neonatal dexamethasone on rat growth, neurodevelopment, and stress response Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2002; 282(1): R55 - R63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Richardson A Woman With an Extremely Premature Newborn JAMA, September 26, 2001; 286(12): 1498 - 1505. [Full Text] [PDF]
|
|
|
|
|
|
K. J. Barrington Postnatal Steroids and Neurodevelopmental Outcomes: A Problem In the Making Pediatrics, June 1, 2001; 107(6): 1425 - 1426. [Full Text]
|
|
|
|
|
|
B. S. Peterson and L. R. Ment The Necessity and Difficulty of Conducting Magnetic Resonance Imaging Studies on Infant Brain Development Pediatrics, March 1, 2001; 107(3): 593 - 594. [Full Text]
|
|
