An investigation of sleep maturation and neurodevelopmental outcome in both a low and high-risk neonatal population is proposed using EEG-sleep analyses as a quantitative neurophysiologic probe. Brain disorders are expressed in many of these children as dysmaturity of EEG-sleep development without abnormal clinical signs, rather than severe encephalopathic patterns. EEG-sleep dysmaturity can be defined as delayed and/or accelerated physiologic behaviors as compared with healthy infants for a given postconceptional age. Ontogenetic adaptation continues during infant development, characterized by a balance between the needs of a present developmental stage with the anticipated needs of subsequent stages of maturation. Therefore, EEG-sleep dysmaturity in the high-risk neonate may affect both sleep ontogeny and neurodevelpment at older ages, modified by environmental/social influences in which the vulnerable child is nurtured. In the present proposal this conceptual framework is applied to a longitudinal study of EEG sleep and outcome in neonates who are healthy versus those recovering from medical illnesses. Three hypotheses will be investigated: 1) neonatal medical complications predetermine EEG-sleep dysmaturity; 2) EEG-sleep dysmaturity will persist during infancy in these children, modified environmental/social factors; and 3) dysmature EEG sleep during infancy more accurately predicts neurodevelopmental performance than a neonatal EEG-sleep profile. These hypotheses will be tested by the following specific aims: 1) to investigate if medical complications predetermine dysmature EEG sleep; 2) to investigate if dysmature neonatal EEG sleep predetermines ongoing EEG-sleep dysmaturity during infancy; 3) to determine if environmental/social factors modify this EEG-sleep dysmaturity; 4) to determine if EEG-sleep dysmaturity during infancy better correlates with lower neurodevelopmental scores.
These specific aims will be accomplished through a longitudinal study of 150 low through high-risk neonates recruited over a four-year time period from a level three neonatal intensive care unit (NICU), selected on the basis of a neuro-biologic complication score at the time of discharge. Serial EEG sleep recordings will be performed during the neonatal and infancy periods, beginning with monthly studies during the neonatal period until a term age, as well as studies at 3, 6, 9, and 12 months of age, using a multi-channel monitoring device in an EEG-sleep laboratory. Seven EEG-sleep measures will be used to define an EEG-sleep dysmaturity index, based on preliminary findings showing differences between healthy preterm and fullterm neonatal cohorts at postconceptional fullterm ages. Environmental/social measures will be socioeconomic status, a home environment inventory, and a maternal psychological profile, to be obtained throughout the two year testing period for each subject. Neurodevelopmental assessments at 6, 12 and 24 months of age will be performed. Analytic strategies will define dysmaturity at each age based on comparisons of EEG-sleep measures of each subject. Interactions among EEG-sleep measures, neonatal medical complications, and environmental/ social factors will be examined. The results of this study will form the basis of a neurophysiological screening procedure for the child with a pervasive, yet subclinical presentation of a static encephalopathy which evolves during early childhood, as modified by environmental/social factors.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Human Development and Aging Subcommittee 3 (HUD)
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Nichols, Paul L
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Case Western Reserve University
Schools of Medicine
United States
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Scher, Mark S; Johnson, Mark W; Ludington, Susan M et al. (2011) Physiologic brain dysmaturity in late preterm infants. Pediatr Res 70:524-8
Scher, Mark S (2011) Ontogeny of EEG sleep from neonatal through infancy periods. Handb Clin Neurol 98:111-29
Scher, Mark S; Ludington-Hoe, Susan; Kaffashi, Farhad et al. (2009) Neurophysiologic assessment of brain maturation after an 8-week trial of skin-to-skin contact on preterm infants. Clin Neurophysiol 120:1812-8
Scher, Mark S; Steppe, Doris A; Beggarly, Marquita (2008) Timing of neonatal seizures and intrapartum obstetrical factors. J Child Neurol 23:640-3
Scher, Mark S (2008) Ontogeny of EEG-sleep from neonatal through infancy periods. Sleep Med 9:615-36
Scher, Mark S; Kidder, Brenda M; Bangert, Barbara A (2007) Pediatric epilepsy evaluations from the prenatal perspective. J Child Neurol 22:396-401
Scher, Mark S; Turnbull, John; Loparo, Kenneth et al. (2005) Automated state analyses: proposed applications to neonatal neurointensive care. J Clin Neurophysiol 22:256-70
Scher, Mark S; Johnson, Mark W; Holditch-Davis, Diane (2005) Cyclicity of neonatal sleep behaviors at 25 to 30 weeks' postconceptional age. Pediatr Res 57:879-82
Scher, Mark S; Waisanen, Holly; Loparo, Kenneth et al. (2005) Prediction of neonatal state and maturational change using dimensional analysis. J Clin Neurophysiol 22:159-65
Scher, Mark S (2004) Automated EEG-sleep analyses and neonatal neurointensive care. Sleep Med 5:533-40

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