Structural Brain Abnormalities in Children Born Prematurely: New Detection Methods and Clinical-Pathological Correlates

Brain Injuries Clinical Trial

Official title:

Structural Brain Abnormalities in Children Born Prematurely: New Detection Methods and Clinical-Pathological Correlates

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00153855
• Other study ID #: 2004-6-3818
• Status: Terminated
• Phase: Phase 3
• First received: September 8, 2005
• Last updated: September 6, 2006
• Start date: January 2005
• Est. completion date: March 2006

Study information

• Verified date: September 2006
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 50
• Est. completion date: March 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 24 Months to 27 Months

Eligibility

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

Study Design

Observational Model: Defined Population, Primary Purpose: Screening, Time Perspective: Longitudinal

Related Conditions & MeSH terms

• Brain Injuries
• Infant, Premature

Locations

Country	Name	City	State
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	Children's Hospital Boston, Children's Mercy Hospital Kansas City

Country where clinical trial is conducted

United States, 

References & Publications (22)

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum in: Lancet 1999 Nov 20;354(9192):1826. — View Citation

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. — View Citation

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. — View Citation

Hüppi 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. — View Citation

Hüppi 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. — View Citation

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. — View Citation

Inder TE, Volpe JJ. Mechanisms of perinatal brain injury. Semin Neonatol. 2000 Feb;5(1):3-16. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Olsén P, Pääkkö E, Vainionpää L, Pyhtinen J, Järvelin MR. Magnetic resonance imaging of periventricular leukomalacia and its clinical correlation in children. Ann Neurol. 1997 Jun;41(6):754-61. — View Citation

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. — View Citation

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. — View Citation

Sie LT, van der Knaap 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 22 references in all — Click here to view all references