ENVIRONMENTAL INFLUENCES ON NEURODEVELOPMENTAL OUTCOME IN INFANTS BORN VERY PRETERM

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ABSTRACT Upwards of one-third of infants born <30 weeks postmenstrual age suffer long term neurodevelopmental deficits. The prevalence rate of Autism Spectrum Disorders (ASDs) is approximately 5 times higher in these infants than in the general population. The purpose of this Environmental Influences on Child Health Outcomes (ECHO) application is to leverage our ongoing NIH (1R01HD072267-01A) longitudinal multisite prospective study of approximately 600 infants born <30 weeks PMA from birth to age 2 entitled “Neonatal Neurobehavior and Outcomes in Very Preterm Infants.” Our long-term goal is to discern which of these infants are most likely to become developmentally impaired, a personalized medicine approach that could lead to interventions that prevent or mitigate later deficits. Our overall objective in ECHO is to follow these children through age 7 and determine potential mechanisms that lead to developmental outcome in these children. In order to do this, these children need to be studied in situ. Our hypothesis is that environmental exposures, behavioral, genetic variation and epigenetic factors are required to understand the mechanisms involved. We plan to determine how prenatal, perinatal and postnatal environmental exposures (e.g., physical, demographic, maternal psychological, medical, chemical), DNA methylation, and infant neurobehavior at NICU discharge) will be related to child measures of attention, cognition, emotion, social, language, behavioral and motor development at ages 5, 6, and 7 and ASD diagnosis. We expect genetic variation to modify the effects of environmental exposures on these child outcomes and plan to develop an algorithm to identify which individual infants will be developmentally impaired at ages 5-7. We also plan to determine the trajectories of DNA methylation and neurodevelopmental measures (attention, cognition, emotion, social, language, behavioral and motor development) over ages 4-7, determine how neurodevelopmental trajectories “track” the trajectory of DNA methylation and determine how these trajectories are modified by environmental exposures and genetic variation. Our cohort is of substantive import for the entire synthetic cohort effort of ECHO to address how pre-, peri-, and postnatal environmental exposures impact childhood development in a multitude of multi-level ways. The perspective proffered ECHO will help ECHO develop a unique model to better understand mechanisms of development, and use trajectory analysis to investigate sensitive periods and inflection points.