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Purpose: To determine whether health-related quality of life (HRQL) in a cohort of adolescents who were born prematurely is related to the severity of brain ultrasound examination findings during the newborn period., Methods: This study uses a historical, prospective methodology to investigate the 84 members of a cohort of infants born prematurely (<33 weeks gestation) at Thomas Jefferson University Hospital during a 25-month period, from 1979 to 1981. We extracted the following information from their neonatal intensive care unit (NICU) records: ultrasound examination findings (graded for intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL); and records of medical illness (respiratory, gastrointestinal, and other) during the NICU stay. We followed-up the members of this cohort 18-19 years later, obtaining data on 53 (63%). We correlated the NICU data with the following self-report outcome measures: HRQL, Disabilities Questionnaire [parental report indicating the severity of complications of prematurity (DISAB)] and psychological assessment tests [Beck Depression Inventory (BDI), Coopersmith Self-Esteem Inventory (CSEI), and Body Shape Questionnaire (BSQ)]. We used the method of multiple discriminant function analysis to determine statistical significance of differences between the two ultrasound groups, grades 0-2 IVH, no PVL vs. grades 3-4 IVH and/or PVL., Results: A statistically significant difference was obtained between the two ultrasound groups (grades 0-2 IVH, no PVL vs. grades 3-4 IVH and/or PVL) among the HRQL variables (Wilks' lambda =.764, df = 5, p <.470). The relative contribution of dependent variables (HRQL1, HRQL2, HRQL3, HRQL4, DISAB) to the group separation was assessed through the interpretation of discriminant function-variable correlation. HRQL1 and DISAB made the largest discriminant between groups, which is supported by results from univariate Student's t-tests. Study subjects with grades 3-4 IVH and/or PVL ultrasound findings obtained much lower HRQL1 scores (better overall estimation of HRQL) and much higher DISAB scores than subjects with grades 0-2 IVH, no PVL ultrasound findings., Conclusions: It appears that the lower an adolescent's score on overall HRQL (HRQL1), (i.e., the better the self-perceived overall quality of life), the more likely he or she displayed the higher severity of brain ultrasound examination findings during the NICU hospitalization. A larger study of premature infants who are followed into adolescence is required to better understand the factors that determine the association of IVH and PVL with HRQL.