Infants with Persistent Pulmonary Hypertension (PPHN) are among the most critically ill patients cared for in the Neonatal Intensive Care Unit and are at significant risk for neurodevelopmental abnormalities. These newborns often experience some degree of hypoxia with potential for ischemic insult to the brain during their acute illness. Currently, we approach these infants with several different therapies, depending on the severity of illness. To date, over 200 infants have received extracorporeal membrane oxygenation (ECMO) at Stanford, while many others have required treatment with conventional medical therapy high frequency ventilation and induction of alkalosis, or inhaled Nitric Oxide (NO). Survival results, both conventional medical therapy and ECMO are not without signficant long term neurodevelopmental sequelae. The outcome after NO is as yet unknown. Studies have demonstrated increased risk for neurologic abnormality, developmental delay and sensorineural hearing loss among newborns receiving conventional medical therapy. ECMO therapy is also not without significance. While early studies have demonstrated a reasonable outcome with a low incidence of major handicapping conditions given the critical perinatal illness of the infants with most studies finding normal outcomes in 60 to 70% of ECMO survivors in the first two years of life, survivors have been shown to be at increased risk of neuroradiographic and long term neurocognitive delay. A few investigators, including ourselves, have proceeded to examine the functioning of these children at age five and beyond. Despite mean IQ scores in the normal range, ECMO survivors were found to have a disturbing number of neurodevelopmental deficits suggesting that they are at substantial risk for subtle cognitive and behavioral problems that influence later academic and psychosocial adjustment. To date, the risk and benefits of conventional medical therapy in comparison to other therapies (i.e. ECMO and NO) has not been systematically assessed. The purpose of this study is to understand the abnormalities of growth and neurodevelopment in infants with neonatal hypertension and to determine if these abnormalities differ amongst patients who receive these various treatment modalities for neonatal pulmonary hypertension. A multidisciplinary evaluation will be conducted in the Mary L. Johnson Infant Development Clinic until seven years of age. Standard broad based testing will be assessments of hearing, speech/language development, higher cortical function and minor neuromotor development. Longitudinal outcome data between groups will be analyzed to characterize neurodevelopmental outcome and the types of sequelae associated with conventional medical therapy, ECMO and/or NO in the neonatal period.
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