Browsing by Author "Smyser, Christopher D."

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    Children born very preterm experience altered cortical expansion over the first decade of life
    (Oxford University Press, 2024-09-17) Gorham, Lisa S.; Latham, Aidan R.; Alexopoulos, Dimitrios; Kenley, Jeanette K.; Iannopollo, Emily; Lean, Rachel E.; Loseille, David; Smyser, Tara A.; Neil, Jeffrey J.; Rogers, Cynthia E.; Smyser, Christopher D.; Garcia, Kara; Radiology and Imaging Sciences, School of Medicine
    The brain develops rapidly from the final trimester of gestation through childhood, with cortical surface area expanding greatly in the first decade of life. However, it is unclear exactly where and how cortical surface area changes after birth, or how prematurity affects these developmental trajectories. Fifty-two very preterm (gestational age at birth = 26 ± 1.6 weeks) and 41 full-term (gestational age at birth = 39 ± 1.2 weeks) infants were scanned using structural magnetic resonance imaging at term-equivalent age and again at 9/10 years of age. Individual cortical surface reconstructions were extracted for each scan. Infant and 9/10 cortical surfaces were aligned using anatomically constrained Multimodal Surface Matching (aMSM), a technique that allows calculation of local expansion gradients across the cortical surface for each individual subject. At the neonatal time point, very preterm infants had significantly smaller surface area than their full-term peers (P < 0.001), but at the age 9/10-year time point, very preterm and full-term children had comparable surface area (P > 0.05). Across all subjects, cortical expansion by age 9/10 years was most pronounced in frontal, temporal, and supramarginal/inferior parietal junction areas, which are key association cortices (PSpin < 0.001). Very preterm children showed greater cortical surface area expansion between term-equivalent age and age 9/10 compared to their full-term peers in the medial and lateral frontal areas, precuneus, and middle temporal/banks of the superior sulcus junction (P < 0.05). Furthermore, within the very preterm group, expansion was highly variable within the orbitofrontal cortex and posterior regions of the brain. By mapping these patterns across the cortex, we identify differences in association cortices that are known to be important for executive functioning, emotion processing, and social cognition. Additional longitudinal work will be needed to understand if increased expansion in very preterm children is adaptive, or if differences persist into adulthood.
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    Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns
    (Massachusetts Medical Society, 2022) Wu, Yvonne W.; Comstock, Bryan A.; Gonzalez, Fernando F.; Mayock, Dennis E.; Goodman, Amy M.; Maitre, Nathalie L.; Chang, Taeun; Van Meurs, Krisa P.; Lampland, Andrea L.; Bendel-Stenzel, Ellen; Mathur, Amit M.; Wu, Tai-Wei; Riley, David; Mietzsch, Ulrike; Chalak, Lina; Flibotte, John; Weitkamp, Joern-Hendrik; Ahmad, Kaashif A.; Yanowitz, Toby D.; Baserga, Mariana; Poindexter, Brenda B.; Rogers, Elizabeth E.; Lowe, Jean R.; Kuban, Karl C. K.; O'Shea, T. Michael; Wisnowski, Jessica L.; McKinstry, Robert C.; Bluml, Stefan; Bonifacio, Sonia; Benninger, Kristen L.; Rao, Rakesh; Smyser, Christopher D.; Sokol, Gregory M.; Merhar, Stephanie; Schreiber, Michael D.; Glass, Hannah C.; Heagerty, Patrick J.; Juul, Sandra E.; HEAL Consortium; Pediatrics, School of Medicine
    Background: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown. Methods: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. Results: Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57). Conclusions: The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events.