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1. A novel clinical risk scoring system for neurodevelopmental outcomes among survivors of neonatal hypoxic-ischemic encephalopathy (HIE)

Author

Theresa Estiphan, Julie Sturza, Renée A. Shellhaas, and Martha D. Carlson

Subjects
Electroencephalography (EEG), Hypoxic-ischemic encephalopathy (HIE), Magnetic resonance imaging (MRI), Neonate, Neurodevelopment, Prognosis, Pediatrics, RJ1-570
Abstract

Objective: We aimed to develop a risk scoring system as a predictor of 24-month neurodevelopmental outcomes (cognitive, language, and motor) for neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). Methods: This was a chart review of infants with HIE treated with therapeutic hypothermia who were admitted to the Neonatal Intensive Care Unit (NICU) at the University of Michigan between 2009 and 2019 and followed in the neonatal developmental clinic until 24 months of age. We examined bivariate associations between the neonatal characteristics and Bayley-III scores. We then performed stepwise logistic regression. To create the risk scores, a participant was given one point for each of the factors included in the final model. Results: Fifty-five infants were included. The final model for Bayley cognitive abnormality included abnormal neonatal neurologic exam (p

Published
2024
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3. Lateralized neonatal EEG coherence during sleep predicts language outcome

Author

Martha D. Carlson, Ronald D. Chervin, Joseph W. Burns, Fauziya Hassan, Renée A. Shellhaas, and John D.E. Barks

Subjects
medicine.medical_specialty, Neonatal intensive care unit, medicine.diagnostic_test, business.industry, Gestational age, Eye movement, Polysomnography, Electroencephalography, Audiology, Non-rapid eye movement sleep, Sleep in non-human animals, 03 medical and health sciences, Language development, 0302 clinical medicine, 030225 pediatrics, Pediatrics, Perinatology and Child Health, medicine, business, 030217 neurology & neurosurgery
Abstract

Enriched language exposure may benefit infants in the neonatal intensive care unit. We hypothesized that changes in neonatal electroencephalogram (EEG) coherence during sleep, in response to maternal voice exposure, predict language development. Convalescent neonates underwent 12-h polysomnography. A recording of the mother’s voice was randomized to continuous playback in the first or second 6 h. We calculated the imaginary coherence (ICOH—a measure of functional connectivity) between EEG leads. Spearman correlations were computed between ICOH and 18-month Bayley-III language scores. Thirty-five neonates were included (N = 18 33-to

Published
2021
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4. Early-Life Outcomes in Relation to Social Determinants of Health for Children Born Extremely Preterm

Author

Jane E. Brumbaugh, Betty R. Vohr, Edward F. Bell, Carla M. Bann, Colm P. Travers, Elisabeth C. McGowan, Heidi M. Harmon, Waldemar A. Carlo, Andrea F. Duncan, Susan R. Hintz, Alan H. Jobe, Michael S. Caplan, Richard A. Polin, Abbot R. Laptook, Martin Keszler, Angelita M. Hensman, Barbara Alksninis, Carmena Bishop, Robert T. Burke, Melinda Caskey, Laurie Hoffman, Katharine Johnson, Mary Lenore Keszler, Andrea M. Knoll, Vita Lamberson, Teresa M. Leach, Emilee Little, Bonnie E. Stephens, Elisa Vieira, Lucille St. Pierre, Suzy Ventura, Victoria E. Watson, Anna Maria Hibbs, Michele C. Walsh, Deanne E. Wilson-Costello, Nancy S. Newman, Monika Bhola, Allison H. Payne, Bonnie S. Siner, Gulgun Yalcinkaya, William E. Truog, Eugenia K. Pallotto, Howard W. Kilbride, Cheri Gauldin, Anne Holmes, Kathy Johnson, Allison Scott, Prabhu S. Parimi, Lisa Gaetano, Brenda B. Poindexter, Kurt Schibler, Suhas G. Kallapur, Edward F. Donovan, Stephanie Merhar, Cathy Grisby, Kimberly Yolton, Barbara Alexander, Traci Beiersdorfer, Kate Bridges, Tanya E. Cahill, Juanita Dudley, Estelle E. Fischer, Teresa L. Gratton, Devan Hayes, Jody Hessling, Lenora D. Jackson, Kristin Kirker, Holly L. Mincey, Greg Muthig, Sara Stacey, Jean J. Steichen, Stacey Tepe, Julia Thompson, Sandra Wuertz, C. Michael Cotten, Ronald N. Goldberg, Ricki F. Goldstein, William F. Malcolm, Deesha Mago-Shah, Patricia L. Ashley, Joanne Finkle, Kathy J. Auten, Kimberley A. Fisher, Sandra Grimes, Kathryn E. Gustafson, Melody B. Lohmeyer, Matthew M. Laughon, Carl L. Bose, Janice Bernhardt, Gennie Bose, Cindy Clark, Jennifer Talbert, Diane Warner, Andrea Trembath, T. Michael O'Shea, Janice Wereszczak, Stephen D. Kicklighter, Ginger Rhodes-Ryan, Donna White, Ravi M. Patel, David P. Carlton, Barbara J. Stoll, Ellen C. Hale, Yvonne C. Loggins, Ira Adams-Chapman, Ann Blackwelder, Diane I. Bottcher, Sheena L. Carter, Salathiel Kendrick-Allwood, Judith Laursen, Maureen Mulligan LaRossa, Colleen Mackie, Amy Sanders, Irma Seabrook, Gloria Smikle, Lynn C. Wineski, Rosemary D. Higgins, Andrew A. Bremer, Stephanie Wilson Archer, Gregory M. Sokol, Anna M. Dusick, Lu Ann Papile, Susan Gunn, Faithe Hamer, Dianne E. Herron, Abbey C. Hines, Carolyn Lytle, Lucy C. Miller, Heike M. Minnich, Leslie Richard, Lucy Smiley, Leslie Dawn Wilson, Jon E. Tyson, Kathleen A. Kennedy, Amir M. Khan, Andrea Duncan, Ricardo Mosquera, Emily K. Stephens, Georgia E. McDavid, Nora I. Alaniz, Elizabeth Allain, Julie Arldt-McAlister, Katrina Burson, Allison G. Dempsey, Elizabeth Eason, Patricia W. Evans, Carmen Garcia, Charles Green, Donna Hall, Beverly Foley Harris, Margarita Jiminez, Janice John, Patrick M. Jones, M. Layne Lillie, Anna E. Lis, Karen Martin, Sara C. Martin, Carrie M. Mason, Shannon McKee, Brenda H. Morris, Kimberly Rennie, Shawna Rodgers, Saba Khan Siddiki, Maegan C. Simmons, Daniel Sperry, Patti L. Pierce Tate, Sharon L. Wright, Pablo J. Sánchez, Leif D. Nelin, Sudarshan R. Jadcherla, Jonathan L. Slaughter, Keith O. Yeates, Sarah Keim, Nathalie L. Maitre, Christopher J. Timan, Patricia Luzader, Erna Clark, Christine A. Fortney, Julie Gutentag, Courtney Park, Julie Shadd, Margaret Sullivan, Melanie Stein, Mary Ann Nelin, Julia Newton, Kristi Small, Stephanie Burkhardt, Jessica Purnell, Lindsay Pietruszewski, Katelyn Levengood, Nancy Batterson, Pamela Morehead, Helen Carey, Lina Yoseff-Salameh, Rox Ann Sullivan, Cole Hague, Jennifer Grothause, Erin Fearns, Aubrey Fowler, Jennifer Notestine, Jill Tonneman, Krystal Hay, Michelle Chao, Kyrstin Warnimont, Laura Marzec, Bethany Miller, Demi R. Beckford, Hallie Baugher, Brittany DeSantis, Cory Hanlon, Jacqueline McCool, Abhik Das, Marie G. Gantz, Dennis Wallace, Margaret M. Crawford, Jenna Gabrio, David Leblond, Jamie E. Newman, Carolyn M. Petrie Huitema, Jeanette O'Donnell Auman, W. Kenneth Poole, Kristin M. Zaterka-Baxter, Krisa P. Van Meurs, Valerie Y. Chock, David K. Stevenson, Marian M. Adams, M. Bethany Ball, Barbara Bentley, Elizabeth Bruno, Alexis S. Davis, Maria Elena DeAnda, Anne M. DeBattista, Lynne C. Huffman, Magdy Ismael, Jean G. Kohn, Casey Krueger, Janice Lowe, Ryan E. Lucash, Andrew W. Palmquist, Jessica Patel, Melinda S. Proud, Elizabeth N. Reichert, Nicholas H. St. John, Dharshi Sivakumar, Heather L. Taylor, Natalie Wager, R. Jordan Williams, Hali Weiss, Ivan D. Frantz, John M. Fiascone, Brenda L. MacKinnon, Anne Furey, Ellen Nylen, Paige T. Church, Cecelia E. Sibley, Ana K. Brussa, Namasivayam Ambalavanan, Myriam Peralta-Carcelen, Kathleen G. Nelson, Kirstin J. Bailey, Fred J. Biasini, Stephanie A. Chopko, Monica V. Collins, Shirley S. Cosby, Kristen C. Johnston, Mary Beth Moses, Cryshelle S. Patterson, Vivien A. Phillips, Julie Preskitt, Richard V. Rector, Sally Whitley, Uday Devaskar, Meena Garg, Isabell B. Purdy, Teresa Chanlaw, Rachel Geller, Neil N. Finer, Yvonne E. Vaucher, David Kaegi, Maynard R. Rasmussen, Kathy Arnell, Clarence Demetrio, Martha G. Fuller, Wade Rich, Tarah T. Colaizy, John A. Widness, Michael J. Acarregui, Karen J. Johnson, Diane L. Eastman, Claire A. Goeke, Mendi L. Schmelzel, Jacky R. Walker, Michelle L. Baack, Laurie A. Hogden, Megan Broadbent, Chelsey Elenkiwich, Megan M. Henning, Sarah Van Muyden, Dan L. Ellsbury, Donia B. Campbell, Tracy L. Tud, Shahnaz Duara, Charles R. Bauer, Ruth Everett-Thomas, Sylvia Fajardo-Hiriart, Arielle Rigaud, Maria Calejo, Silvia M. Frade Eguaras, Michelle Harwood Berkowits, Andrea Garcia, Helina Pierre, Alexandra Stoerger, Kristi L. Watterberg, Janell Fuller, Robin K. Ohls, Sandra Sundquist Beauman, Conra Backstrom Lacy, Mary Hanson, Carol Hartenberger, Elizabeth Kuan, Jean R. Lowe, Rebecca A. Thomson, Sara B. DeMauro, Eric C. Eichenwald, Barbara Schmidt, Haresh Kirpalani, Aasma S. Chaudhary, Soraya Abbasi, Toni Mancini, Christine Catts, Noah Cook, Dara M. Cucinotta, Judy C. Bernbaum, Marsha Gerdes, Sarvin Ghavam, Hallam Hurt, Jonathan Snyder, Saritha Vangala, Kristina Ziolkowski, Carl T. D'Angio, Dale L. Phelps, Ronnie Guillet, Gary J. Myers, Michelle Andrews-Hartley, Julie Babish Johnson, Kyle Binion, Melissa Bowman, Elizabeth Boylin, Erica Burnell, Kelly R. Coleman, Cait Fallone, Osman Farooq, Julianne Hunn, Diane Hust, Rosemary L. Jensen, Rachel Jones, Jennifer Kachelmeyer, Emily Kushner, Deanna Maffett, Kimberly G. McKee, Joan Merzbach, Constance Orme, Diane Prinzing, Linda J. Reubens, Daisy Rochez, Mary Rowan, Premini Sabaratnam, Ann Marie Scorsone, Holly I.M. Wadkins, Kelley Yost, Lauren Zwetsch, Satyan Lakshminrusimha, Anne Marie Reynolds, Michael G. Sacilowski, Stephanie Guilford, Emily Li, Ashley Williams, William A. Zorn, Myra H. Wyckoff, Luc P. Brion, Walid A. Salhab, Charles R. Rosenfeld, Roy J. Heyne, Diana M. Vasil, Sally S. Adams, Lijun Chen, Maria M. De Leon, Francis Eubanks, Alicia Guzman, Gaynelle Hensley, Elizabeth T. Heyne, Lizette E. Lee, Melissa H. Leps, Linda A. Madden, E. Rebecca McDougald, Nancy A. Miller, Janet S. Morgan, Lara Pavageau, Pollieanna Sepulveda, Kristine Tolentino-Plata, Cathy Twell Boatman, Azucena Vera, Jillian Waterbury, Bradley A. Yoder, Mariana Baserga, Roger G. Faix, Sarah Winter, Stephen D. Minton, Mark J. Sheffield, Carrie A. Rau, Shawna Baker, Karie Bird, Jill Burnett, Susan Christensen, Laura Cole-Bledsoe, Brandy Davis, Jennifer O. Elmont, Jennifer J. Jensen, Manndi C. Loertscher, Jamie Jordan, Trisha Marchant, Earl Maxson, Kandace M. McGrath, Karen A. Osborne, D. Melody Parry, Brixen A. Reich, Susan T. Schaefer, Cynthia Spencer, Michael Steffen, Katherine Tice, Kimberlee Weaver-Lewis, Kathryn D. Woodbury, Karen Zanetti, Robert G. Dillard, Lisa K. Washburn, Barbara G. Jackson, Nancy Peters, 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, Girija Natarajan, Athina Pappas, Katherine Abramczyk, Prashant Agarwal, Monika Bajaj, Rebecca Bara, Elizabeth Billian, Sanjay Chawla, Kirsten Childs, Lilia C. De Jesus, Debra Driscoll, Melissa February, Laura A. Goldston, Mary E. Johnson, Geraldine Muran, Bogdan Panaitescu, Jeannette E. Prentiss, Diane White, Eunice Woldt, John Barks, Stephanie A. Wiggins, Mary K. Christensen, Martha D. Carlson, Richard A. Ehrenkranz, Harris Jacobs, Christine G. Butler, Patricia Cervone, Sheila Greisman, Monica Konstantino, JoAnn Poulsen, Janet Taft, Joanne Williams, and Elaine Romano

Subjects
Pediatrics, Perinatology and Child Health
Published
2023
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5. Lateralized neonatal EEG coherence during sleep predicts language outcome

Author

Renée A, Shellhaas, Ronald D, Chervin, John D E, Barks, Fauziya, Hassan, Martha D, Carlson, and Joseph W, Burns

Subjects
Intensive Care Units, Neonatal, Polysomnography, Infant, Newborn, Voice, Humans, Infant, Electroencephalography, Female, Sleep
Abstract

Enriched language exposure may benefit infants in the neonatal intensive care unit. We hypothesized that changes in neonatal electroencephalogram (EEG) coherence during sleep, in response to maternal voice exposure, predict language development.Convalescent neonates underwent 12-h polysomnography. A recording of the mother's voice was randomized to continuous playback in the first or second 6 h. We calculated the imaginary coherence (ICOH-a measure of functional connectivity) between EEG leads. Spearman correlations were computed between ICOH and 18-month Bayley-III language scores.Thirty-five neonates were included (N = 18 33-to-35 weeks gestation; N = 17 ≥ 35 weeks). Predictive value of ICOH during neonatal non-rapid eye movement (NREM) sleep was left lateralized, and varied with gestational age and voice playback. ICOH in the left-hemispheric (C3-Cz; T3-Cz) channels across multiple EEG frequency bands was associated with 18-month language scores (rho = -0.34 to -0.48). The association was driven by neonates born at 33-34 weeks gestation, and a trend suggested a possible effect of maternal voice at some EEG frequencies. Right hemisphere ICOH (C4-Cz; T4-Cz) was not associated with language outcome.Left-hemispheric EEG functional connectivity during neonatal NREM sleep shows early signs of physiologic asymmetry that may predict language development. We speculate that sleep analyses could have unique prognostic value.During neonatal NREM sleep, EEG functional connectivity predicts future language development. Left temporal and central EEG coherence-specifically the imaginary component of coherence-is predictive, whereas the same analysis from the right hemisphere is not. These results appear to vary according to the infant's gestational age, and a trend suggests they may be enhanced by measuring functional connectivity during exposure to the mother's voice. These findings identify early evidence of physiologic differentiation within the cerebral hemispheres and raise the possibility that neonatal NREM sleep has a role to play in language development.

Published
2020

6. Thrombocytopenia in pediatric patients on concurrent cannabidiol and valproic acid

Author

Steven M. Leber, Louis T. Dang, Patricia L. Robertson, Sucheta M. Joshi, Renée A. Shellhaas, Martha D. Carlson, Julie Sturza, Garnett C. Smith, Julie Ziobro, Erin M. Fedak Romanowski, and Nancy A. McNamara

Subjects
Male, 0301 basic medicine, Drug Resistant Epilepsy, medicine.medical_specialty, Adolescent, Side effect, Combination therapy, Epilepsies, Myoclonic, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Dravet syndrome, Internal medicine, medicine, Cannabidiol, Humans, Child, Valproic Acid, Epilepsy, Lennox Gastaut Syndrome, business.industry, Infant, medicine.disease, Thrombocytopenia, Regimen, 030104 developmental biology, Neurology, Child, Preschool, Epilepsy syndromes, Anticonvulsants, Drug Therapy, Combination, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug, Lennox–Gastaut syndrome
Abstract

In January 2019, a new plant-derived purified cannabidiol preparation, approved by the US Food and Drug Administration, became commercially available for patients ≥2 years old with Lennox-Gastaut syndrome or Dravet syndrome. Among our patients who were prescribed the new cannabidiol formulation, we observed several cases of thrombocytopenia and therefore embarked on this study. We conducted a single-center systematic chart review of all pediatric patients (

Published
2020
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7. Sleep‐disordered breathing is common among term and near term infants in the NICU

Author

John D.E. Barks, Fauziya Hassan, Martha D. Carlson, Renée A. Shellhaas, Ronald D. Chervin, and Meera S. Meerkov

Subjects
Male, Risk, Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Neonatal intensive care unit, Term Birth, Polysomnography, Bayley Scales of Infant Development, Sleep medicine, Article, 03 medical and health sciences, Sleep Apnea Syndromes, 0302 clinical medicine, Seizures, Intensive Care Units, Neonatal, 030225 pediatrics, Intensive care, Epidemiology, medicine, Humans, Prospective Studies, Sleep Apnea, Obstructive, medicine.diagnostic_test, business.industry, Infant, Newborn, Infant, Sleep Apnea, Central, nervous system diseases, respiratory tract diseases, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Breathing, Female, business, Neurocognitive, Follow-Up Studies
Abstract

OBJECTIVE: Among older infants and children, sleep-disordered breathing (SDB) has negative neurocognitive consequences. We evaluated the frequency and potential impact of SDB among newborns who require intensive care. STUDY DESIGN: Term and near-term newborns at risk for seizures underwent 12-h attended polysomnography in the neonatal intensive care unit (NICU). Bayley Scales of Infant Development, third edition (Bayley-III) were administered at 18–22 months. RESULT: The 48 newborns (EGA 39.3 ± 1.6) had a median pediatric apnea-hypopnea index (AHI) of 10.1 (3.3–18.5) and most events were central (vs obstructive). Maternal and prenatal factors were not associated with AHI. Moreover, neonatal PSG results were not associated with Bayley-III scores (P > 0.05). CONCLUSION: SDB is common among term and near-term newborns at risk for seizures. Follow-up at ages when more nuanced testing can be performed may be necessary to establish whether neonatal SDB is associated with long-term neurodevelopmental disability.

Published
2019
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8. Differential Diagnosis of Autism Spectrum Disorder Versus Language Disorder in Children Ages 2 to 5 Years: Contributions of Parent-Reported Development and Behavior

Author

Elise K. Hodges, Martha D. Carlson, and Annette E. Richard

Subjects
Male, Parents, Autism Spectrum Disorder, Child Behavior, behavioral disciplines and activities, Parent ratings, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Child Development, mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Language disorder, Early childhood, Retrospective Studies, Language Disorders, business.industry, 05 social sciences, Social change, medicine.disease, Autism spectrum disorder, Child, Preschool, Pediatrics, Perinatology and Child Health, Autism, Female, Differential diagnosis, business, 030217 neurology & neurosurgery, Neurotypical, 050104 developmental & child psychology, Clinical psychology
Abstract

Early diagnosis of autism spectrum disorder (ASD) has focused on differentiating children with ASD from neurotypical children. However, many children presenting with concern for ASD are ultimately diagnosed with language disorder (LD). This study aimed to identify differences in parent-rated development and behavior among children ages 2 to 5 years presenting with concern for ASD who were diagnosed with either ASD or LD. Children with ASD were rated as more socially withdrawn and more delayed in social development and self-help skills than those with LD. Parent-rated developmental delays were positively correlated with scores on an autism screening measure and with social withdrawal and pervasive developmental problems among children with ASD. Among those with LD, parent-rated social and self-help development were positively correlated with social withdrawal and attention problems. Thus, parent ratings of social withdrawal and development of social and self-help skills may facilitate differential diagnosis of ASD and LD in children ages 2 to 5 years.

Published
2019

9. Neurodevelopmental and Behavioral Outcomes in Extremely Premature Neonates With Ventriculomegaly in the Absence of Periventricular-Intraventricular Hemorrhage

Author

Heike M. Minnich, Ivan D. Frantz, Karen J. Johnson, William E Truog, Sandra Brown, Ronnie Guillet, Myriam Peralta-Carcelen, Rosemary D. Higgins, Haresh Kirpalani, Kathryn E. Gustafson, Leslie Dawn Wilson, Gregory M Sokol, Catherine Twell Boatman, Edward F. Bell, Janet S. Morgan, W. Kenneth Poole, Amanda D. Soong, Jeanette O'Donnell Auman, Avroy A. Fanaroff, Katrina Burson, Gulgun Yalcinkaya, Monica Konstantino, Leif D. Nelin, Bradley A. Yoder, Carin Kiser, Kristin M. Basso, Marian M. Adams, Neil N. Finer, Dennis Wallace, Hali E. Weiss, Deanna Maffett, Hallam Hurt, Fred J. Biasini, Meena Garg, Laura Cole, Kathleen A. Kennedy, Julianne Hunn, Lucy Miller, Anne Holmes, Farooq Osman, Barbara Schmidt, Anna Marie Hibbs, Walid A. Salhab, Karen A. Osborne, M. Bethany Ball, Laura A. Goldston, Silvia M. Frade Eguaras, Faithe Hamer, Julie Babish Johnson, Ruth Everett-Thomas, Patti L. Pierce Tate, Maria Calejo, Michele C. Walsh, Eugenia K. Pallotto, Rachel Geller, Roger G. Faix, Melissa H. Leps, Maria Elena DeAnda, Ronald N. Goldberg, Marie G. Gantz, Sally Whitley, Nehal A. Parikh, Michelle Harwood Berkowits, Seetha Shankaran, Andrew W. Palmquist, Andrea Halbrook, Kimberlee Weaver-Lewis, Theresa M. Leach, Ira Adams-Chapman, Janice Bernhardt, Sarah Ryan, Maynard Rasmussen, Edward F. Donovan, Diana M. Vasil, Carroll Peterson, Jamie E. Newman, Bonnie E. Stephens, Karen A. Wynn, Myra H. Wyckoff, David P. Carlton, Jody Hessling, Barbara Alexander, Katherine A. Foy, Abbot R. Laptook, Michael Steffen, Sudarshan R. Jadcherla, Suzy Ventura, Raquel Halfond, Ana K. Brussa, Charles R. Rosenfeld, Ellen Waldrep, Peggy Robichaux, Donald J. Goldstein, Monika Bhola, Brenda H. Morris, Clarence Demetrio, Erica Burnell, Brenda B. Poindexter, Martha D. Carlson, Sharon L. Wright, Linda A. Madden, Michael S. Caplan, Isabell B. Purdy, Athina Pappas, Barbara Bentley, Carol Hartenberger, Patricia W. Evans, John A. Widness, Marsha Gerdes, Stephanie Wilson Archer, Kimberly Yolton, Christine G. Butler, Roy J. Heyne, Joanne Williams, Gaynelle Hensley, Carl L. Bose, Lu Ann Papile, Richard A. Polin, Brenda L. MacKinnon, JoAnn Poulsen, Anne Marie Reynolds, T. Michael O'Shea, Charles R. Bauer, Gary J. Myers, Joanne Finkle, Maegan C. Simmons, Shahnaz Duara, Arielle Rigaud, Jill Burnett, Jacky R. Walker, Lauren Zwetsch, Ellen Nylen, Margarita Jiminez, Christine A. Fortney, Angelita M. Hensman, Ellen C. Hale, Joan Merzbach, Teresa L. Gratton, Yvonne E. Vaucher, Kathy Arnell, Holly I.M. Wadkins, Sara Kryzwanski, Nancy A. Miller, Susan R. Hintz, Elaine Romano, Betty R. Vohr, Sara B. DeMauro, Donia B. Campbell, Dara M. Cucinotta, Anna Bodnar, Kristy Domnanovich, Angela Argento, Georgia E. McDavid, Kurt Schibler, Patricia L. Ashley, Margaret M. Crawford, Casey E. Krueger, Bonnie S. Siner, Sally S. Adams, Jane E. Brumbaugh, Korinne Chiu, Janice Wereszczak, Satyanarayana Lakshminrusimha, Jon E. Tyson, Carolyn Lytle, Toni Mancini, Nancy Peters, Gennie Bose, Cryshelle S. Patterson, Katharine Johnson, Barbara J. Stoll, Kristin Kirker, Gail Hounshell, Melinda S. Proud, Janet Taft, Dale L. Phelps, Keith Owen Yeates, Kathy Johnson, Dan L. Ellsbury, Martin Keszler, Leslie Rodrigues, Jennifer J. Jensen, Barbara Alksninis, Sandra Grimes, Wade Rich, Stephanie A. Wiggins, Krisa P. Van Meurs, Yvonne Loggins, M. Layne Poundstone, David Kaegi, Elizabeth T. Heyne, Sheena L. Carter, Patricia Cervone, Richard V. Rector, John M. Fiascone, Nora I. Alaniz, Helina Pierre, Waldemar A. Carlo, Kimberley A. Fisher, Elisabeth C. McGowan, Robert G. Dillard, Greg Muthig, Sarah Martin, Carolyn M. Petrie Huitema, Barbara G. Jackson, Brian G. Tang, Melinda Caskey, Vivien Phillips, Soraya Abbasi, Michael J. Acarregui, Andrea Garcia, Robert T. Burke, Aasma S. Chaudhary, Luc P. Brion, Jean G. Kohn, Kelley Yost, Melody B. Lohmeyer, Allison F. Payne, Harriet Friedman, Victoria E. Watson, William Oh, Nancy S. Newman, John Barks, Andrea H. Duncan, Pablo J. Sánchez, Mary Lenore Keszler, Deborah Evans Allred, Rosemary L. Jensen, Karie Bird, Kristin M. Zaterka-Baxter, Ann B. Cook, Alicia Guzman, Holly L. Mincey, Gail E. Besner, Kate Bridges, Sylvia Fajardo-Hiriart, Matthew M. Laughon, Cathy Grisby, Robin K. Ohls, Rebecca Bara, Karen Zanetti, Anne M. DeBattista, Tarah T. Colaizy, William F. Malcolm, Cherrie D. Welch, Judy Bernbaum, Melissa Whalen Morris, Kathleen G. Nelson, Scott A. McDonald, Emily Kushner, Abbey C. Hines, Sheila Greisman, Ashley Williams, Estelle E. Fischer, Lenora Jackson, Harris C. Jacobs, Cheri Gauldin, Alexandra Stoerger, Deanne E. Wilson-Costello, Rebecca Montman, Monica V. Collins, Mary Christensen, Charles Green, Mary Johnson, David K. Stevenson, Lijun Chen, Cecelia E. Sibley, Lisa K. Washburn, Maureen Mulligan LaRossa, Lizette E. Torres, Kathy J. Auten, Chris Henderson, U. Devaskar, Leigh Ann Smith, Janell Fuller, Diane L. Eastman, Anna E. Lis, Dianne E. Herron, Kristen C. Johnston, Anna M. Dusick, Martha G. Fuller, Anne Furey, Howard W. Kilbride, Jean R. Lowe, Elizabeth F. Bruno, Saba Siddiki, Abhik Das, Linda J. Reubens, Richard A. Ehrenkranz, Namasivayam Ambalavanan, Cynthia Spencer, Ricki F. Goldstein, Lynne C. Huffman, Teresa Chanlaw, Patricia Luzader, Carl T. D'Angio, Diane Hust, Radmila West, Beverly Foley Harris, Sarah Winter, Conra Backstrom Lacy, Shawna Baker, Shirley S. Cosby, C. Michael Cotten, and Kristi L. Watterberg

Subjects
Male, Pediatrics, medicine.medical_specialty, Gestational Age, Infant, Premature, Diseases, Bayley Scales of Infant Development, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, medicine, Humans, Longitudinal Studies, Original Investigation, Cerebral Hemorrhage, Retrospective Studies, Ultrasonography, business.industry, Cerebral Palsy, Infant, Newborn, Gestational age, Brain, Gross Motor Function Classification System, Odds ratio, medicine.disease, Prognosis, Intraventricular hemorrhage, Bronchopulmonary dysplasia, Neurodevelopmental Disorders, Infant, Extremely Premature, Pediatrics, Perinatology and Child Health, Necrotizing enterocolitis, Female, business, 030217 neurology & neurosurgery, Ventriculomegaly, Hydrocephalus
Abstract

Importance Studies of cranial ultrasonography and early childhood outcomes among cohorts of extremely preterm neonates have linked periventricular-intraventricular hemorrhage and cystic periventricular leukomalacia with adverse neurodevelopmental outcomes. However, the association between nonhemorrhagic ventriculomegaly and neurodevelopmental and behavioral outcomes is not fully understood. Objective To characterize the outcomes of extremely preterm neonates younger than 27 weeks’ gestational age who experienced nonhemorrhagic ventriculomegaly that was detected prior to 36 weeks’ postmenstrual age. Design, Setting, and Participants This longitudinal observational study was conducted at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants born prior to 27 weeks’ gestational age in any network facility between July 1, 2006, and June 30, 2011, were included if they had a cranial ultrasonogram performed prior to 36 weeks’ postmenstrual age. Comparisons were made between those with ventriculomegaly and those with normal cranial sonograms. Data analysis was completed from August 2013 to August 2017. Main Outcomes and Measures The main outcome was neurodevelopmental impairment, defined as a Bayley Scales of Infant and Toddler Development III cognitive score less than 70, moderate/severe cerebral palsy, a Gross Motor Function Classification System score of level 2 or more, vision impairment, or hearing impairment. Secondary outcomes included Bayley Scales of Infant and Toddler Development III subscores, components of neurodevelopmental impairment, behavioral outcomes, and death/neurodevelopmental impairment. Logistic regression was used to evaluate the association of ventriculomegaly with adverse outcomes while controlling for potentially confounding variables and center differences as a random effect. Linear regression was used similarly for continuous outcomes. Results Of 4193 neonates with ultrasonography data, 300 had nonhemorrhagic ventriculomegaly (7%); 3045 had normal cranial ultrasonograms (73%), 775 had periventricular-intraventricular hemorrhage (18.5%), and 73 had cystic periventricular leukomalacia (1.7%). Outcomes were available for 3008 of 3345 neonates with ventriculomegaly or normal scans (90%). Compared with normal cranial ultrasonograms, ventriculomegaly was associated with lower gestational age, male sex, and bronchopulmonary dysplasia, late-onset sepsis, meningitis, necrotizing enterocolitis, and stage 3 retinopathy of prematurity. After adjustment, neonates with ventriculomegaly had higher odds of neurodevelopmental impairment (odds ratio [OR], 3.07; 95% CI, 2.13-4.43), cognitive impairment (OR, 3.23; 95% CI, 2.09-4.99), moderate/severe cerebral palsy (OR, 3.68; 95% CI, 2.08-6.51), death/neurodevelopmental impairment (OR, 2.17; 95% CI, 1.62-2.91), but not death alone (OR, 1.09; 95% CI, 0.76-1.57). Behavioral outcomes did not differ. Conclusions and Relevance Nonhemorrhagic ventriculomegaly is associated with increased odds of neurodevelopmental impairment among extremely preterm neonates.

Published
2017

10. Neonatal Sleep–Wake Analyses Predict 18-month Neurodevelopmental Outcomes

Author

Ronald D. Chervin, Fauziya Hassan, Renée A. Shellhaas, Joseph W. Burns, John D.E. Barks, and Martha D. Carlson

Subjects
Male, medicine.medical_specialty, Time Factors, Critical Illness, Polysomnography, Sleep wake, Neurological examination, Electroencephalography, Audiology, Neurological Disorders, Bayley Scales of Infant Development, 03 medical and health sciences, Child Development, 0302 clinical medicine, Seizures, 030225 pediatrics, Physiology (medical), medicine, Humans, Prospective Studies, Wakefulness, Spectroscopy, Near-Infrared, medicine.diagnostic_test, business.industry, Infant, Newborn, Brain, Infant, Cognition, Oxygen, Female, Phenobarbital, Sleep Stages, Neurology (clinical), Sleep, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Objectives The neurological examination of critically ill neonates is largely limited to reflexive behavior. The exam often ignores sleep-wake physiology that may reflect brain integrity and influence long-term outcomes. We assessed whether polysomnography and concurrent cerebral near-infrared spectroscopy (NIRS) might improve prediction of 18-month neurodevelopmental outcomes. Methods Term newborns with suspected seizures underwent standardized neurologic examinations to generate Thompson scores and had 12-hour bedside polysomnography with concurrent cerebral NIRS. For each infant, the distribution of sleep-wake stages and electroencephalogram delta power were computed. NIRS-derived fractional tissue oxygen extraction (FTOE) was calculated across sleep-wake stages. At age 18-22 months, surviving participants were evaluated with Bayley Scales of Infant Development (Bayley-III), 3rd edition. Results Twenty-nine participants completed Bayley-III. Increased newborn time in quiet sleep predicted worse 18-month cognitive and motor scores (robust regression models, adjusted r2 = 0.22, p = .007, and 0.27, .004, respectively). Decreased 0.5-2 Hz electroencephalograph (EEG) power during quiet sleep predicted worse 18-month language and motor scores (adjusted r2 = 0.25, p = .0005, and 0.33, .001, respectively). Predictive values remained significant after adjustment for neonatal Thompson scores or exposure to phenobarbital. Similarly, an attenuated difference in FTOE, between neonatal wakefulness and quiet sleep, predicted worse 18-month cognitive, language, and motor scores in adjusted analyses (each p Conclusions These prospective, longitudinal data suggest that inefficient neonatal sleep-as quantified by increased time in quiet sleep, lower electroencephalogram delta power during that stage, and muted differences in FTOE between quiet sleep and wakefulness-may improve prediction of adverse long-term outcomes for newborns with neurological dysfunction.

Published
2017
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11. Whole Exome Sequencing in Pediatric Neurology Patients: Clinical Implications and Estimated Cost Analysis

Author

Martha D. Carlson and Danielle Nolan

Subjects
0301 basic medicine, Male, Pediatrics, medicine.medical_specialty, Adolescent, 030105 genetics & heredity, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Exome Sequencing, medicine, Insurance authorization, Humans, Genetic Testing, Child, Exome sequencing, Retrospective Studies, Insurance, Health, Genetic heterogeneity, business.industry, Infant, Health Care Costs, Phenotype, Neurology, Clinical diagnosis, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Cost analysis, Costs and Cost Analysis, Female, Neurology (clinical), Pediatric Neurology, Pediatric neurology clinic, Nervous System Diseases, business, 030217 neurology & neurosurgery
Abstract

Genetic heterogeneity in neurologic disorders has been an obstacle to phenotype-based diagnostic testing. The authors hypothesized that information compiled via whole exome sequencing will improve clinical diagnosis and management of pediatric neurology patients. The authors performed a retrospective chart review of patients evaluated in the University of Michigan Pediatric Neurology clinic between 6/2011 and 6/2015. The authors recorded previous diagnostic testing, indications for whole exome sequencing, and whole exome sequencing results. Whole exome sequencing was recommended for 135 patients and obtained in 53 patients. Insurance barriers often precluded whole exome sequencing. The most common indication for whole exome sequencing was neurodevelopmental disorders. Whole exome sequencing improved the presumptive diagnostic rate in the patient cohort from 25% to 48%. Clinical implications included family planning, medication selection, and systemic investigation. Compared to current second tier testing, whole exome sequencing can result in lower long-term charges and more timely diagnosis. Overcoming barriers related to whole exome sequencing insurance authorization could allow for more efficient and fruitful diagnostic neurological evaluations.

Published
2015

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