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1. Limitations of Conventional Magnetic Resonance Imaging as a Predictor of Death or Disability Following Neonatal Hypoxic–Ischemic Encephalopathy in the Late Hypothermia Trial

Author

Abbot R. Laptook, Seetha Shankaran, Patrick Barnes, Nancy Rollins, Barbara T. Do, Nehal A. Parikh, Shannon Hamrick, Susan R. Hintz, Jon E. Tyson, Edward F. Bell, Namasivayam Ambalavanan, Ronald N. Goldberg, Athina Pappas, Carolyn Huitema, Claudia Pedroza, Aasma S. Chaudhary, Angelita M. Hensman, Abhik Das, Myra Wyckoff, Amir Khan, Michelle C. Walsh, Kristi L. Watterberg, Roger Faix, William Truog, Ronnie Guillet, Gregory M. Sokol, Brenda B. Poindexter, Rosemary D. Higgins, Michael S. Caplan, Richard A. Polin, Martin Keszler, William Oh, Betty R. Vohr, Elizabeth C. McGowan, Barbara Alksninis, Kristin Basso, Joseph Bliss, Carmena Bishop, Robert T. Burke, William Cashore, Melinda Caskey, Dan Gingras, Nicholas Guerina, Katharine Johnson, Mary Lenore Keszler, Andrea M. Knoll, Theresa M. Leach, Martha R. Leonard, Emilee Little, Bonnie E. Stephens, Elisa Vieira, Victoria E. Watson, Anna Maria Hibbs, Deanne E. Wilson-Costello, Nancy S. Newman, Beau Batton, Monika Bhola, Juliann M. Di Fiore, Harriet G. Friedman, Bonnie S. Siner, Eileen K. Stork, Gulgun Yalcinkaya, Arlene Zadell, Eugenia K. Pallotto, Howard W. Kilbride, Cheri Gauldin, Anne Holmes, Kathy Johnson, Allison Knutson, Kurt Schibler, Kimberly Yolton, Cathy Grisby, Teresa L. Gratton, Stephanie Merhar, Sandra Wuertz, C. Michael Cotten, Kimberley A. Fisher, Sandra Grimes, Joanne Finkle, Ricki F. Goldstein, Kathryn E. Gustafson, William F. Malcolm, Patricia L. Ashley, Kathy J. Auten, Melody B. Lohmeyer, Matthew M. Laughon, Carl L. Bose, Janice Bernhardt, Cindy Clark, Diane D. Warner, Janice Wereszcsak, Sofia Aliaga, David P. Carlton, Barbara J. Stoll, Ellen C. Hale, Yvonne Loggins, Diane I. Bottcher, Colleen Mackie, Maureen Mulligan LaRossa, Ira Adams-Chapman, Lynn C. Wineski, Sheena L. Carter, Stephanie Wilson Archer, Heidi M. Harmon, Lu-Ann Papile, Anna M. Dusick, Susan Gunn, Dianne E. Herron, Abbey C. Hines, Darlene Kardatzke, Carolyn Lytle, Heike M. Minnich, Leslie Richard, Lucy C. Smiley, Leslie Dawn Wilson, Kathleen A. Kennedy, Elizabeth Allain, Carrie M. Mason, Julie Arldt-McAlister, Katrina Burson, Allison G. Dempsey, Andrea F. Duncan, Patricia W. Evans, Carmen Garcia, Charles E. Green, Margarita Jimenez, Janice John, Patrick M. Jones, M. Layne Lillie, Karen Martin, Sara C. Martin, Georgia E. McDavid, Shannon McKee, Patti L. Pierce Tate, Shawna Rodgers, Saba Khan Siddiki, Daniel K. Sperry, Sharon L. Wright, Pablo J. Sánchez, Leif D. Nelin, Sudarshan R. Jadcherla, Patricia Luzader, Christine A. Fortney, Jennifer L. Grothause, Dennis Wallace, Marie G. Gantz, Kristin M. Zaterka-Baxter, Margaret M. Crawford, Scott A. McDonald, Jamie E. Newman, Jeanette O'Donnell Auman, Carolyn M. Petrie Huitema, James W. Pickett, Patricia Yost, Krisa P. Van Meurs, David K. Stevenson, M. Bethany Ball, Barbara Bentley, Valerie Y. Chock, Elizabeth F. Bruno, Alexis S. Davis, Maria Elena DeAnda, Anne M. DeBattista, Beth Earhart, Lynne C. Huffman, Jean G. Kohn, Casey E. Krueger, Melinda S. Proud, William D. Rhine, Nicholas H. St. John, Heather Taylor, Hali E. Weiss, Waldemar A. Carlo, Myriam Peralta-Carcelen, Monica V. Collins, Shirley S. Cosby, Vivien A. Phillips, Richard V. Rector, Sally Whitley, Tarah T. Colaizy, Jane E. Brumbaugh, Karen J. Johnson, Diane L. Eastman, Michael J. Acarregui, Jacky R. Walker, Claire A. Goeke, Jonathan M. Klein, Nancy J. Krutzfield, Jeffrey L. Segar, John M. Dagle, Julie B. Lindower, Steven J. McElroy, Glenda K. Rabe, Robert D. Roghair, Lauritz R. Meyer, Dan L. Ellsbury, Donia B. Campbell, Cary R. Murphy, Vipinchandra Bhavsar, Robin K. Ohls, Conra Backstrom Lacy, Sandra Sundquist Beauman, Sandra Brown, Erika Fernandez, Andrea Freeman Duncan, Janell Fuller, Elizabeth Kuan, Jean R. Lowe, Barbara Schmidt, Haresh Kirpalani, Sara B. DeMauro, Kevin C. Dysart, Soraya Abbasi, Toni Mancini, Dara M. Cucinotta, Judy C. Bernbaum, Marsha Gerdes, Hallam Hurt, Carl D'Angio, Satyan Lakshminrusimha, Nirupama Laroia, Gary J. Myers, Kelley Yost, Stephanie Guilford, Rosemary L. Jensen, Karen Wynn, Osman Farooq, Anne Marie Reynolds, Holly I.M. Wadkins, Ashley Williams, Joan Merzbach, Patrick Conway, Melissa Bowman, Michele Hartley-McAndrew, William Zorn, Cait Fallone, Kyle Binion, Constance Orme, Ann Marie Scorsone, Luc P. Brion, Lina F. Chalak, Roy J. Heyne, Lijun Chen, Diana M. Vasil, Sally S. Adams, Catherine Twell Boatman, Alicia Guzman, Elizabeth T. Heyne, Lizette E. Lee, Melissa H. Leps, Linda A. Madden, Nancy A. Miller, Emma Ramon, Bradley A. Yoder, Karen A. Osborne, Cynthia Spencer, R. Edison Steele, Mike Steffen, Karena Strong, Kimberlee Weaver-Lewis, Shawna Baker, Sarah Winter, Karie Bird, Jill Burnett, Beena G. Sood, Rebecca Bara, Kirsten Childs, Lilia C. De Jesus, Bogdan Panaitescu, Sanjay M.D. Chawla, Jeannette E. Prentice, Laura A. Goldston, Eunice Hinz Woldt, Girija Natarajan, Monika Bajaj, John Barks, Mary Christensen, and Stephanie A. Wiggins

Subjects
Male, Pediatrics, medicine.medical_specialty, Developmental Disabilities, Subgroup analysis, Severity of Illness Index, Article, Hypoxic Ischemic Encephalopathy, 03 medical and health sciences, 0302 clinical medicine, Hypothermia, Induced, Predictive Value of Tests, 030225 pediatrics, Multicenter trial, medicine, Humans, 030212 general & internal medicine, medicine.diagnostic_test, Neonatal encephalopathy, business.industry, Infant, Newborn, Area under the curve, Infant, Magnetic resonance imaging, Hypothermia, medicine.disease, Magnetic Resonance Imaging, Hypoxia-Ischemia, Brain, Pediatrics, Perinatology and Child Health, Gestation, Female, medicine.symptom, business, Infant, Premature
Abstract

Objective To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours. Study design Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age. Results Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n = 119) or died (n = 9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted kappa 0.56, 95% CI 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% CI 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively. Conclusions MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia–ischemia. Trial registration Clinicaltrials.gov: NCT00614744 .

Published
2021
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2. Behavioral Deficits at 18-22 Months of Age Are Associated with Early Cerebellar Injury and Cognitive and Language Performance in Children Born Extremely Preterm

Author

Andrea F. Duncan, Carla M. Bann, Allison Dempsey, Myriam Peralta-Carcelen, Susan Hintz, Alan H. Jobe, Michael S. Caplan, Abbot R. Laptook, Betty R. Vohr, William Oh, Angelita M. Hensman, Barbara Alksninis, Dawn Andrews, Kristen Angela, Susan Barnett, Bill Cashore, Melinda Caskey, Kim Francis, Dan Gingras, Katharine Johnson, Theresa M. Leach, Bonnie E. Stephens, Victoria E. Watson, Michele C. Walsh, Avroy A. Fanaroff, Nancy S. Newman, Deanne E. Wilson-Costello, Bonnie S. Siner, Arlene Zadell, Julie DiFiore, Monika Bhola, Harriet G. Friedman, Gulgun Yalcinkaya, Dorothy Bulas, Ronald N. Goldberg, C. Michael Cotten, Ricki F. Goldstein, Patricia Ashley, Kathy J. Auten, Kimberley A. Fisher, Katherine A. Foy, Sharon F. Freedman, Kathryn E. Gustafson, Melody B. Lohmeyer, William F. Malcolm, David K. Wallace, David P. Carlton, Barbara J. Stoll, Ira Adams-Chapman, Susie Buchter, Anthony J. Piazza, Sheena Carter, Sobha Fritz, Ellen C. Hale, Amy K. Hutchinson, Maureen Mulligan LaRossa, Rosemary D. Higgins, Stephanie Wilson Archer, Gregory M. Sokol, Brenda B. Poindexter, Anna M. Dusick, James A. Lemons, Leslie D. Wilson, Faithe Hamer, Ann B. Cook, Dianne E. Herron, Carolyn Lytle, Heike M. Minnich, Mary Anne Berberich, Carol J. Blaisdell, Dorothy B. Gail, James P. Kiley, Abhik Das, Marie G. Gantz, Jamie E. Newman, Helen Cheng, Betty K. Hastings, Elizabeth M. McClure, Jeanette O'Donnell Auman, Carolyn Petrie Huitema, W. Kenneth Poole, James W. Pickett, Dennis Wallace, Lisa A. Wrage, Kristin M. Zaterka-Baxter, Krisa P. Van Meurs, David K. Stevenson, M. Bethany Ball, Patrick D. Barnes, Barbara Bentley, Elizabeth F. Bruno, Maria Elena DeAnda, Anne M. DeBattista, Jean G. Kohn, Melinda S. Proud, Renee P. Pyle, Hali E. Weiss, Ivan D. Frantz, John M. Fiascone, Elisabeth C. McGowan, Anne Furey, Brenda L. MacKinnon, Ellen Nylen, Ana Brussa, Cecelia Sibley, Waldemar A. Carlo, Namasivayam Ambalavanan, Monica V. Collins, Shirley S. Cosby, Vivien A. Phillips, Kirstin J. Bailey, Fred J. Biasini, Maria Hopkins, Kristen C. Johnston, Kathleen G. Nelson, Cryshelle S. Patterson, Richard V. Rector, Leslie Rodriguez, Amanda Soong, Sally Whitley, Sheree York, Neil N. Finer, Maynard R. Rasmussen, Paul R. Wozniak, Yvonne E. Vaucher, Wade Rich, Kathy Arnell, Rene Barbieri-Welge, Ayala Ben-Tall, Renee Bridge, Clarence Demetrio, Martha G. Fuller, Elaine Ito, Meghan Lukasik, Deborah Pontillo, Donna Posin, Cheryl Runyan, James Wilkes, Paul Zlotnik, Edward F. Bell, John A. Widness, Michael J. Acarregui, Jonathan M. Klein, Tarah T. Colaizy, Karen J. Johnson, Diane L. Eastman, Shahnaz Duara, Charles R. Bauer, Ruth Everett-Thomas, Maria Calejo, Alexis N. Diaz, Silvia M. Frade Eguaras, Andrea Garcia, Kasey Hamlin-Smith, Michelle Harwood Berkowits, Sylvia Hiriart-Fajardo, Elaine O. Mathews, Helina Pierre, Arielle Riguard, Alexandra Stroerger, Kristi L. Watterberg, Robin K. Ohls, Janell Fuller, Julie Rohr, Conra Backstrom Lacy, Jean Lowe, Rebecca Montman, Sandra Brown, Nirupama Laroia, Dale L. Phelps, Gary J. Myers, Gary D. Markowitz, Linda J. Reubens, Diane Hust, Lisa Augostino, Julie Babish Johnson, Erica Burnell, Harris Gelbard, Rosemary L. Jensen, Emily Kushner, Joan Merzbach, Jonathan Mink, Carlos Torres, David Wang, Kelley Yost, Pablo J. Sánchez, Charles R. Rosenfeld, Walid A. Salhab, Roy J. Heyne, Sally S. Adams, James Allen, Laura Grau, Alicia Guzman, Gaynelle Hensley, Elizabeth T. Heyne, Jackie F. Hickman, Melissa H. Leps, Linda A. Madden, Melissa Martin, Nancy A. Miller, Janet S. Morgan, Araceli Solis, Lizette E. Torres, Catherine Twell Boatman, Diana M. Vasil, Kathleen A. Kennedy, Jon E. Tyson, Patricia W. Evans, Esther G. Akpa, Nora I. Alaniz, Beverly Foley Harris, Charles Green, Margarita Jiminez, Anna E. Lis, Sarah Martin, Georgia E. McDavid, Brenda H. Morris, Margaret L. Poundstone, Stacy Reddoch, Saba Siddiki, Patti L. Pierce Tate, Sharon L. Wright, Bradley A. Yoder, Roger G. Faix, Shawna Baker, Karie Bird, Anna E. Bullwinkle, Jill Burnett, Laura Cole, Karen A. Osborne, Cynthia Spencer, R. Edison Steele, Michael Steffen, Kimberlee Weaver-Lewis, T. Michael O'Shea, Robert G. Dillard, Lisa K. Washburn, Nancy J. Peters, Barbara G. Jackson, Korinne Chiu, Deborah Evans Allred, Donald J. Goldstein, Raquel Halfond, Carroll Peterson, Ellen L. Waldrep, Cherrie D. Welch, Melissa Whalen Morris, Gail Wiley Hounshell, Seetha Shankaran, Beena G. Sood, Thomas L. Slovis, Athina Pappas, Rebecca Bara, Elizabeth Billian, Laura A. Goldston, and Mary Johnson

Subjects
Male, Pediatrics, medicine.medical_specialty, Ultrasonography, Doppler, Transcranial, Neuroimaging, Neuropsychological Tests, Bayley Scales of Infant Development, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Child Development, Cerebellar Diseases, 030225 pediatrics, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Competence (human resources), business.industry, Brain, Infant, Cognition, Child development, Magnetic Resonance Imaging, Language development, Neurodevelopmental Disorders, Infant, Extremely Premature, Pediatrics, Perinatology and Child Health, Female, business, Cohort study
Abstract

Objective To investigate associations in toddlers born extremely preterm ( Study design Cohort analysis from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Trial Neuroimaging and Neurodevelopmental Outcomes Study of infants born extremely preterm. Subjects underwent cranial ultrasonography and near-term magnetic resonance imaging (MRI). At 18-22 months of corrected age, the assessment included the Brief Infant Toddler Social Emotional Assessment (BITSEA) Problem and Competence Scale scores and the Bayley Scales of Infant Development, Third Edition (Bayley-III). The BITSEA Problem Scale assesses dysregulation; the Competence Scale assesses social-emotional competence. We examined associations of Problem and Competence scores and positive screen rates with cranial ultrasonography and near-term MRI. Mean BITSEA and Bayley-III scores were compared using ANOVA and positive screen rates with the χ2 test. We computed correlations between BITSEA and Bayley-III scores. Results Of the 397 children, positive BITSEA screens were found in 34% for the Problem score and 26% for the Competence score. Presence of lesions on near-term MRI that included cerebellar lesions were significantly associated with lower BITSEA Competence but not with Problem scores; Competence scores were inversely related to the presence/significance of lesions. Positive screens on Competence scores and on both Competence and Problem scores were significantly associated with Bayley-III cognitive and language scores Conclusions Social–emotional competence contributes to deficits in cognitive and language development. Presence of injury on near-term MRI that includes cerebellar lesions is associated with later social–emotional competence and may be a useful predictor to guide early assessment and intervention. Trial registration ClinicalTrials.gov : NCT00063063 and NCT00233324 .

Published
2018

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