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OBJECTIVE: To evaluate the relationship between brain volumes at term and neurodevelopmental outcome through early school age in preterm infants. STUDY DESIGN: One hundred twelve preterm infants (born mean gestational age 28.6 ± 1.7 weeks) were studied prospectively with magnetic resonance imaging (imaged at mean 41.6 ± 1.0 weeks). T2- and T1-weighted images were automatically segmented, and volumes of 6 tissue types were related to neurodevelopmental outcome assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (cognitive, fine, and gross motor scores) at 24 months corrected age (n = 112), Griffiths Mental Development Scales (developmental quotient) at age 3.5 years (n = 98), Movement Assessment Battery for Children, Second Edition (n = 85), and Wechsler Preschool and Primary Scale of Intelligence, Third Edition at age 5.5 years (n = 44). Corrections were made for intracranial volume, maternal education, and severe brain lesions. RESULTS: Ventricular volumes were negatively related to neurodevelopmental outcome at age 24 months and 3.5 years, as well as processing speed at age 5.5 years. Unmyelinated white matter (UWM) volume was positively associated with motor outcome at 24 months and with processing speed at age 5.5 years. Cortical gray matter (CGM) volume demonstrated a negative association with motor performance and cognition at 24 months and with developmental quotient at age 3.5 years. Cerebellar volume was positively related to cognition at these time points. Adjustment for brain lesions attenuated the relations between cerebellar and CGM volumes and cognition. CONCLUSIONS: Brain volumes of ventricles, UWM, CGM, and cerebellum may serve as biomarkers for neurodevelopmental outcome in preterm infants. The relationship between larger CGM volumes and adverse neurodevelopment may reflect disturbances in neuronal and/or axonal migration at the UWM-CGM boundary and warrants further investigation.

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OBJECTIVE: To evaluate the differential impact of germinal matrix-intraventricular hemorrhage (GMH-IVH) and posthemorrhagic ventricular dilatation (PHVD) on brain and cerebrospinal fluid (CSF) volumes and diffusion variables in preterm born infants at term-equivalent age (TEA). STUDY DESIGN: Nineteen infants (gestational age <31 weeks) with GMH-IVH grade II-III according to Papile et al and subsequent PHVD requiring intervention were matched against 19 controls with GMH-IVH grade II but no PHVD and 19 controls without GMH-IVH. Outcome variables on magnetic resonance imaging (MRI) including diffusion weighted imaging at TEA were volumes of white matter, cortical gray matter, deep gray matter, brainstem, cerebellum, ventricles, extracerebral CSF, total brain tissue, and intracranial volume (ICV), as well as white matter and cerebellar apparent diffusion coefficients (ADCs). Effects of GMH-IVH and PHVD on TEA-MRI measurements were evaluated using multivariable regression analysis. Brain and CSF volumes were adjusted for ICV to account for differences in bodyweight at TEA-MRI and ICV between cases and controls. RESULTS: PHVD was independently associated with volumes of deep gray matter (ß [95% CI]: -1.4 cc [-2.3; -.5]), cerebellum (-2.7 cc [-3.8; -1.6]), ventricles (+12.7 cc [7.9; 17.4]), and extracerebral CSF (-11.2 cc [-19.2; -3.3]), and with ADC values in occipital, parieto-occipital, and parietal white matter (ß: +.066-.119×10(-3) mm(2)/s) on TEA-MRI (P < .05). No associations were found between GMH-IVH grade II-III and brain and CSF volumes or ADC values at TEA. CONCLUSIONS: PHVD was negatively related to deep gray matter and cerebellar volumes and positively to white matter ADC values on TEA-MRI, despite early intervention for PHVD in the majority of the infants. These relationships were not observed for GMH-IVH.

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OBJECTIVE: To perform a feasibility and safety study with recombinant human erythropoietin (rhEPO) in neonates with perinatal arterial ischemic stroke. STUDY DESIGN: Neonates with a magnetic resonance imaging-confirmed perinatal arterial ischemic stroke (n = 21) were treated with 1000 IU/kg rhEPO immediately after diagnosis and at 24 and 48 hours after the first dose. Repeat magnetic resonance imaging was performed when the patients were 3 months of age. Coagulation and hematologic variables (red blood cells, white blood cells, platelet counts) were performed in the first week after initiation of treatment. We also compared 10 patients who were treated with rhEPO with 10 historic infants with perinatal arterial ischemic stroke matched for the involved arterial branch to investigate whether rhEPO reduces the residual size of the infarction and subsequent brain growth between first and second scan. RESULTS: Seizures were a first symptom in 20 of 21 neonates. Heart rate, blood pressure, and coagulation function were in the normal range, as were red blood cells, white blood cells, and platelet counts. In a subgroup of 10 rhEPO-treated neonates, no differences were detected in residual infarction volumes or neurodevelopmental outcome compared with their historical nontreated counterparts. CONCLUSIONS: rhEPO in neonates with perinatal arterial ischemic stroke had no adverse effects on red blood cells, white blood cells, platelets counts, or coagulation. rhEPO, 3000 IU/kg in total, given during a 3-day period, appears to be a safe therapy. The beneficial effects remains to be demonstrated in a larger, randomized, double-blind, placebo-controlled trial.

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