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Structural Brain Abnormalities in Children Born Prematurely: New Detection Methods and Clinical-Pathological Correlates
This study has been terminated.
First Received: September 8, 2005   Last Updated: September 6, 2006   History of Changes
Sponsors and Collaborators: Children's Hospital of Philadelphia
Children's Hospital Boston
Children's Mercy Hospital Kansas City
Information provided by: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00153855
  Purpose

The purpose of the study is to detect structural brain changes using MRI and to correlate these findings with neurodevelopmental assessments in two-year old children previously enrolled in the NIH sponsored trial of inhaled Nitric Oxide (iNO) for the prevention of Chronic Lung Disease in preterm ventilated infants. It is hypothesized that this imaging will identify children with previously undiagnosed brain abnormalities and that the presence of structural abnormalities will be associated with deficits in motor, cognitive, and neurosensory development.


Condition Phase
Infant, Premature
Brain Injuries
Phase III

Study Type: Observational
Study Design: Screening, Longitudinal, Defined Population, Prospective Study
Official Title: Structural Brain Abnormalities in Children Born Prematurely: New Detection Methods and Clinical-Pathological Correlates

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Estimated Enrollment: 50
Study Start Date: January 2005
Estimated Study Completion Date: March 2006
Detailed Description:

Infants born prematurely are at significant risk for hemorrhagic and ischemic brain injury. Despite improved survival rates among this population in recent years, these forms of brain injury remain frequent and have considerable consequences. Periventricular leukomalacia (PVL), a disease characterized by necrosis of the cerebral white matter in a characteristic distribution, is one of the most common types of brain injury seen in premature infants. MRI technology now allows for better anatomical resolution resulting in improvements in diagnostic accuracy. The current standard practice is not to perform routine MRI examinations on premature infants, nor is it routine to perform surveillance brain imaging in children after leaving the NICU. In their 2002 Practice Parameter for neuroimaging in the neonate, the American Academy of Neurology and the Practice Committee of the Child Neurology Society acknowledge the superiority of MRI in detection of brain lesions in premature infants, but fall short of recommending routine MRI scanning on the basis of a lack of information correlating MRI findings to neurodevelopmental outcomes. We now have a unique opportunity to help provide such information.

  Eligibility

Ages Eligible for Study:   24 Months to 27 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • must be participants in trial (NHLBI-UO1-HL62514-05A1 and FDA IND # 58,146 - Roberta A Ballard PI) of inhaled Nitric Oxide (iNO) for the prevention of Chronic Lung Disease in preterm ventilated infants
  • gestational age between 24 months and 27 months

Exclusion Criteria:

  • history of allergy to sedation agents
  • medical conditions which may pose a threat to airway integrity (i.e., Pierre-Robin sequence, intercurrent respiratory illness)
  • other conditions which may otherwise place subjects at increased risk for complications from sedation and MRI examination
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00153855

Locations
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
Children's Hospital Boston
Children's Mercy Hospital Kansas City
Investigators
Principal Investigator: Roberta A Ballard, M.D. Children's Hospital of Philadelphia
  More Information

Publications:
Stevenson DK, Wright LL, Lemons JA, Oh W, Korones SB, Papile LA, Bauer CR, Stoll BJ, Tyson JE, Shankaran S, Fanaroff AA, Donovan EF, Ehrenkranz RA, Verter J. Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1993 through December 1994. Am J Obstet Gynecol. 1998 Dec;179(6 Pt 1):1632-9.
Volpe JJ. Brain injury in the premature infant: overview of clinical aspects, neuropathology, and pathogenesis. Semin Pediatr Neurol. 1998 Sep;5(3):135-51. Review.
Hack M, Fanaroff AA. Outcomes of children of extremely low birthweight and gestational age in the 1990s. Semin Neonatol. 2000 May;5(2):89-106. Review.
Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJ. Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA. 2002 Aug 14;288(6):728-37.
Sie LT, van der Knapp MS, van Wezel-Meijler G, Taets van Amerongen AH, Lafeber HN, Valk J. Early MR features of hypoxic-ischemic brain injury in neonates with periventricular densities on sonograms. AJNR Am J Neuroradiol. 2000 May;21(5):852-61.
Inder TE, Huppi PS, Warfield S, Kikinis R, Zientara GP, Barnes PD, Jolesz F, Volpe JJ. Periventricular white matter injury in the premature infant is followed by reduced cerebral cortical gray matter volume at term. Ann Neurol. 1999 Nov;46(5):755-60.
Olsen P, Paakko E, Vainionpaa L, Pyhtinen J, Jarvelin MR. Magnetic resonance imaging of periventricular leukomalacia and its clinical correlation in children. Ann Neurol. 1997 Jun;41(6):754-61.
Inder TE, Wells SJ, Mogridge NB, Spencer C, Volpe JJ. Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study. J Pediatr. 2003 Aug;143(2):171-9.
Huppi PS, Murphy B, Maier SE, Zientara GP, Inder TE, Barnes PD, Kikinis R, Jolesz FA, Volpe JJ. Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging. Pediatrics. 2001 Mar;107(3):455-60.
Huppi PS, Maier SE, Peled S, Zientara GP, Barnes PD, Jolesz FA, Volpe JJ. Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging. Pediatr Res. 1998 Oct;44(4):584-90.
Hoon AH Jr, Lawrie WT Jr, Melhem ER, Reinhardt EM, Van Zijl PC, Solaiyappan M, Jiang H, Johnston MV, Mori S. Diffusion tensor imaging of periventricular leukomalacia shows affected sensory cortex white matter pathways. Neurology. 2002 Sep 10;59(5):752-6.
Miller SP, Vigneron DB, Henry RG, Bohland MA, Ceppi-Cozzio C, Hoffman C, Newton N, Partridge JC, Ferriero DM, Barkovich AJ. Serial quantitative diffusion tensor MRI of the premature brain: development in newborns with and without injury. J Magn Reson Imaging. 2002 Dec;16(6):621-32.
Inder TE, Volpe JJ. Mechanisms of perinatal brain injury. Semin Neonatol. 2000 Feb;5(1):3-16. Review.
Melhem ER, Hoon AH Jr, Ferrucci JT Jr, Quinn CB, Reinhardt EM, Demetrides SW, Freeman BM, Johnston MV. Periventricular leukomalacia: relationship between lateral ventricular volume on brain MR images and severity of cognitive and motor impairment. Radiology. 2000 Jan;214(1):199-204.
Ment LR, Bada HS, Barnes P, Grant PE, Hirtz D, Papile LA, Pinto-Martin J, Rivkin M, Slovis TL. Practice parameter: neuroimaging of the neonate: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2002 Jun 25;58(12):1726-38. Review.
[No authors listed] Early compared with delayed inhaled nitric oxide in moderately hypoxaemic neonates with respiratory failure: a randomised controlled trial. The Franco-Belgium Collaborative NO Trial Group. Lancet. 1999 Sep 25;354(9184):1066-71.
Bennett AJ, Shaw NJ, Gregg JE, Subhedar NV. Neurodevelopmental outcome in high-risk preterm infants treated with inhaled nitric oxide. Acta Paediatr. 2001 May;90(5):573-6.
Cheung PY, Peliowski A, Robertson CM. The outcome of very low birth weight neonates (</=1500 g) rescued by inhaled nitric oxide: neurodevelopment in early childhood. J Pediatr. 1998 Dec;133(6):735-9.
Kinsella JP, Walsh WF, Bose CL, Gerstmann DR, Labella JJ, Sardesai S, Walsh-Sukys MC, McCaffrey MJ, Cornfield DN, Bhutani VK, Cutter GR, Baier M, Abman SH. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial. Lancet. 1999 Sep 25;354(9184):1061-5.
Rosenberg AA, Kennaugh JM, Moreland SG, Fashaw LM, Hale KA, Torielli FM, Abman SH, Kinsella JP. Longitudinal follow-up of a cohort of newborn infants treated with inhaled nitric oxide for persistent pulmonary hypertension. J Pediatr. 1997 Jul;131(1 Pt 1):70-5.
Subhedar NV, Ryan SW, Shaw NJ. Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants. Arch Dis Child Fetal Neonatal Ed. 1997 Nov;77(3):F185-90.
Schreiber MD, Gin-Mestan K, Marks JD, Huo D, Lee G, Srisuparp P. Inhaled nitric oxide in premature infants with the respiratory distress syndrome. N Engl J Med. 2003 Nov 27;349(22):2099-107.

Study ID Numbers: 2004-6-3818
Study First Received: September 8, 2005
Last Updated: September 6, 2006
ClinicalTrials.gov Identifier: NCT00153855     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
etiology
pathology

Study placed in the following topic categories:
Craniocerebral Trauma
Wounds and Injuries
Disorders of Environmental Origin
Central Nervous System Diseases
Trauma, Nervous System
Brain Diseases
Congenital Abnormalities
Brain Injuries

Additional relevant MeSH terms:
Craniocerebral Trauma
Nervous System Diseases
Wounds and Injuries
Disorders of Environmental Origin
Central Nervous System Diseases
Trauma, Nervous System
Brain Diseases
Brain Injuries

ClinicalTrials.gov processed this record on August 30, 2009