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1. Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia

Author

Soumyaroop Bhattacharya, Jared A. Mereness, Andrea M. Baran, Ravi S. Misra, Derick R. Peterson, Rita M. Ryan, Anne Marie Reynolds, Gloria S. Pryhuber, and Thomas J. Mariani

Subjects
lcsh:Immunologic diseases. Allergy, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Neonatal respiratory distress syndrome, Lymphocyte, Immunology, Gestational Age, Disease, CD8-Positive T-Lymphocytes, Lymphocyte Activation, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Internal medicine, mental disorders, bronchopulmonary dysplasia, medicine, Humans, Immunology and Allergy, RNA-Seq, Respiratory system, RNA-sequencing, Pathway, Original Research, Respiratory Distress Syndrome, Newborn, Lung, business.industry, Respiratory disease, Infant, Newborn, Gestational age, Prognosis, medicine.disease, CD8+ lymphocytes, prematurity and respiratory outcomes program, 030104 developmental biology, medicine.anatomical_structure, Bronchopulmonary dysplasia, Infant, Extremely Premature, 030220 oncology & carcinogenesis, Premature Birth, Female, lcsh:RC581-607, Transcriptome, business, Biomarkers, CD8, Newborn Lung, Peripheral Blood Mononucleated cells, Respiratory tract
Abstract

Many premature babies who are born with neonatal respiratory distress syndrome (RDS) go on to develop Bronchopulmonary Dysplasia (BPD) and later Post-Prematurity Respiratory Disease (PRD) at one year corrected age, characterized by persistent or recurrent lower respiratory tract symptoms frequently related to inflammation and viral infection. Transcriptomic profiles were generated from sorted peripheral blood CD8+ T cells of preterm and full-term infants enrolled with consent in the NHLBI Prematurity and Respiratory Outcomes Program (PROP) at the University of Rochester and the University at Buffalo. We identified outcome-related gene expression patterns following standard methods to identify markers for oxygen utilization and BPD as outcomes in extremely premature infants. We further identified predictor gene sets for BPD based on transcriptomic data adjusted for gestational age at birth (GAB). RNA-Seq analysis was completed for CD8+ T cells from 145 subjects. Among the subjects with highest risk for BPD (born at TGFB, NRF2, HIPPO, andCD40-associated pathways in BPD. Using gene expression data from both premature and full-term subjects (n=116), we identified a 28 gene set that predicted the PRD status with a moderately high level of accuracy, which also were involved inTGFBsignaling. Transcriptomic data from sort-purified peripheral blood CD8+ T cells from 145 preterm and full-term infants identified sets of molecular markers of inflammation associated with independent development of BPD in extremely premature infants at high risk for the disease and of PRD among the preterm and full-term subjects.

Published
2021

2. Behavior Profiles at 2 Years for Children Born Extremely Preterm with Bronchopulmonary Dysplasia

Author

Jane E. Brumbaugh, Edward F. Bell, Scott F. Grey, Sara B. DeMauro, Betty R. Vohr, Heidi M. Harmon, Carla M. Bann, Matthew A. Rysavy, J. Wells Logan, Tarah T. Colaizy, Myriam A. Peralta-Carcelen, Elisabeth C. McGowan, Andrea F. Duncan, Barbara J. Stoll, Abhik Das, Susan R. Hintz, Michael S. Caplan, Richard A. Polin, Abbot R. Laptook, Martin Keszler, Angelita M. Hensman, Elisa Vieira, Emilee Little, Robert T. Burke, Bonnie E. Stephens, Barbara Alksninis, Carmena Bishop, Mary L. Keszler, Teresa M. Leach, Victoria E. Watson, Andrea M. Knoll, Michele C. Walsh, Avroy A. Fanaroff, Nancy S. Newman, Deanne E. Wilson-Costello, Allison Payne, Monika Bhola, Gulgun Yalcinkaya, Bonnie S. Siner, Harriet G. Friedman, Elizabeth Roth, William E. Truog, Eugenia K. Pallotto, Howard W. Kilbride, Cheri Gauldin, Anne Holmes, Kathy Johnson, Allison Knutson, Kurt Schibler, Brenda B. Poindexter, Stephanie Merhar, Kimberly Yolton, Teresa L. Gratton, Cathy Grisby, Kristin Kirker, Sandra Wuertz, David P. Carlton, Ira Adams-Chapman, Ellen C. Hale, Yvonne C. Loggins, Diane I. Bottcher, Colleen Mackie, Sheena L. Carter, Maureen Mulligan LaRossa, Lynn C. Wineski, Gloria V. Smikle, Angela Leon-Hernandez, Salathiel Kendrick-Allwood, C. Michael Cotten, Ronald N. Goldberg, Ricki F. Goldstein, William F. Malcolm, Patricia L. Ashley, Joanne Finkle, Kimberley A. Fisher, Sandra Grimes, Kathryn E. Gustafson, Matthew M. Laughon, Carl L. Bose, Janice Bernhardt, Gennie Bose, Diane Warner, Janice Wereszczak, Stephen D. Kicklighter, Ginger Rhodes-Ryan, Rosemary D. Higgins, Stephanie Wilson Archer, Gregory M. Sokol, Lu Ann Papile, Abbey C. Hines, Dianne E. Herron, Susan Gunn, Lucy Smiley, Kathleen A. Kennedy, Jon E. Tyson, Julie Arldt-McAlister, Katrina Burson, Allison G. Dempsey, Patricia W. Evans, Carmen Garcia, Margarita Jiminez, Janice John, Patrick M. Jones, M. Layne Lillie, Karen Martin, Sara C. Martin, Georgia E. McDavid, Shawna Rodgers, Saba Khan Siddiki, Daniel Sperry, Patti L. Pierce Tate, Sharon L. Wright, Pablo J. Sánchez, Leif D. Nelin, Sudarshan R. Jadcherla, Patricia Luzader, Christine A. Fortney, Gail E. Besner, Nehal A. Parikh, Dennis Wallace, Marie G. Gantz, Jamie E. Newman, Jeanette O'Donnell Auman, Margaret Crawford, Jenna Gabrio, David Leblond, Carolyn M. Petrie Huitema, Kristin M. Zaterka-Baxter, Krisa P. Van Meurs, Valerie Y. Chock, David K. Stevenson, Marian M. Adams, M. Bethany Ball, Barbara Bentley, Maria Elena DeAnda, Anne M. Debattista, Beth Earhart, Lynne C. Huffman, Magdy Ismael, Casey E. Krueger, Andrew W. Palmquist, Melinda S. Proud, Elizabeth N. Reichert, Meera N. Sankar, Nicholas H. St. John, Heather L. Taylor, Hali E. Weiss, Ivan D. Frantz, John M. Fiascone, Brenda L. MacKinnon, Ellen Nylen, Anne Furey, Cecelia E. Sibley, Ana K. Brussa, Waldemar A. Carlo, Namasivayam Ambalavanan, Kirstin J. Bailey, Fred J. Biasini, Monica V. Collins, Shirley S. Cosby, Vivien A. Phillips, 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, Radmila West, Michelle L. Baack, Dan L. Ellsbury, Laurie A. Hogden, Jonathan M. Klein, John M. Dagle, Karen J. Johnson, Tracy L. Tud, Chelsey Elenkiwich, Megan M. Henning, Megan Broadbent, Mendi L. Schmelzel, Jacky R. Walker, Claire A. Goeke, Kristi L. Watterberg, Robin K. Ohls, Conra Backstrom Lacy, Sandra Brown, Janell Fuller, Carol Hartenberger, Jean R. Lowe, Sandra Sundquist Beauman, Mary Ruffner Hanson, Tara Dupont, Elizabeth Kuan, Barbara Schmidt, Haresh Kirpalani, Aasma S. Chaudhary, Soraya Abbasi, Toni Mancini, Dara M. Cucinotta, Judy C. Bernbaum, Marsha Gerdes, Hallam Hurt, Carl T. D'Angio, Ronnie Guillet, Gary J. Myers, Satyan Lakshminrusimha, Anne Marie Reynolds, Michelle E. Hartley-McAndrew, Holly I.M. Wadkins, Michael G. Sacilowski, Linda J. Reubens, Rosemary L. Jensen, Joan Merzbach, William Zorn, Osman Farooq, Deanna Maffett, Ashley Williams, Julianne Hunn, Stephanie Guilford, Kelley Yost, Mary Rowan, Diane M. Prinzing, Karen Wynn, Cait Fallone, Ann Marie Scorsone, Myra H. Wyckoff, Luc P. Brion, Roy J. Heyne, Diana M. Vasil, Sally S. Adams, Lijun Chen, Maria M. De Leon, Frances Eubanks, Alicia Guzman, Elizabeth T. Heyne, Linda A. Madden, Nancy A. Miller, Lizette E. Lee, Lara Pavageau, Pollieanna Sepulveda, Cathy Twell Boatman, Roger G. Faix, Bradley A. Yoder, Mariana Baserga, Karen A. Osborne, Shawna Baker, Karie Bird, Jill Burnett, Susan Christensen, Brandy Davis, Jennifer O. Elmont, Jennifer J. Jensen, Manndi C. Loertscher, Trisha Marchant, Earl Maxson, Stephen D. Minton, D. Melody Parry, Carrie A. Rau, Susan T. Schaefer, Mark J. Sheffield, Cynthia Spencer, Mike Steffen, Kimberlee Weaver-Lewis, Sarah Winter, Kathryn D. Woodbury, Karen Zanetti, Seetha Shankaran, Sanjay Chawla, Beena G. Sood, Athina Pappas, Girija Natarajan, Monika Bajaj, Rebecca Bara, Mary E. Johnson, Laura Goldston, Stephanie A. Wiggins, Mary K. Christensen, Martha Carlson, John Barks, Diane F. White, Richard A. Ehrenkranz, Harris Jacobs, Christine G. Butler, Patricia Cervone, Sheila Greisman, Monica Konstantino, JoAnn Poulsen, Janet Taft, and Elaine Romano

Subjects
Male, Pediatrics, medicine.medical_specialty, CBCL, behavioral disciplines and activities, Language Development, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Cognition, 030225 pediatrics, mental disorders, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Child Behavior Checklist, Motor skill, Bronchopulmonary Dysplasia, Problem Behavior, business.industry, Confounding, Postmenstrual Age, Infant, Newborn, medicine.disease, Bronchopulmonary dysplasia, Motor Skills, Child, Preschool, Infant, Extremely Premature, Pediatrics, Perinatology and Child Health, Infant Behavior, Gestation, Female, business
Abstract

To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD).We studied children born at 22-26 weeks of gestation and assessed at 22-26 months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36 weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior.Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P .001) and pervasive developmental problems (P .001) increased with worsening BPD grade. Sleep problems (P = .008) and aggressive behavior (P = .023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values .05).BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.

Published
2019

3. Retrospective Analysis of Short-Term Respiratory Outcomes of Three Different Steroids Used in Clinical Practice in Intubated Preterm Infants

Author

Mark L. Hudak, Rita M. Ryan, Satyan Lakshminrusimha, Sfurti Nath, Chang-Xing Ma, and Anne Marie Reynolds

Subjects
Pediatrics, medicine.medical_specialty, Neonatal intensive care unit, Hydrocortisone, Anti-Inflammatory Agents, New York, Gestational Age, Infant, Premature, Diseases, Methylprednisolone, Severity of Illness Index, Dexamethasone, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, 030225 pediatrics, Intensive Care Units, Neonatal, medicine, Humans, 030212 general & internal medicine, Bronchopulmonary Dysplasia, Retrospective Studies, Respiratory Distress Syndrome, Newborn, business.industry, Infant, Newborn, Obstetrics and Gynecology, medicine.disease, Treatment Outcome, Bronchopulmonary dysplasia, Pediatrics, Perinatology and Child Health, Gestation, Female, Steroids, business, Infant, Premature, medicine.drug, Cohort study
Abstract

Objective This study aimed to compare short-term respiratory outcomes of three steroids (dexamethasone, hydrocortisone, and methylprednisolone) to facilitate extubation by improving respiratory status in preterm infants.Study Design This is a retrospective, single-center, cohort study of 98 intubated preterm infants ≤346/7 weeks' gestation, admitted to a 64-bed, level III neonatal intensive care unit at the Women & Children's Hospital of Buffalo, Buffalo, NY, between 2006 and 2012, who received a short course of low-dose steroids for lung disease after first week of life.Results Study infants received dexamethasone (34%), hydrocortisone (44%), or methylprednisolone (22%) based on clinical team preference. By day 7 after initiation of steroids, extubation occurred in 59, 44, and 41%, respectively, in infants on dexamethasone, hydrocortisone, and methylprednisolone (p = 0.3). The mean respiratory severity score (RSS = fraction of inspired oxygen × mean airway pressure), a quantitative measure of respiratory status, decreased by 44% for all infants and by 59% in the dexamethasone group by day 7.Conclusion Steroids improved short-term respiratory outcomes in all infants (RSS and extubation); by day 7, dexamethasone treatment was associated with the greatest decrease in RSS. Additional prospective, randomized trials of short-course low-dose steroids are warranted to substantiate these findings to guide clinical decision making and in evaluating differential steroid effects on long-term neurodevelopmental outcomes.

Published
2019

4. Umbilical Cord Milking vs Delayed Cord Clamping and Associations with In-Hospital Outcomes among Extremely Premature Infants

Author

Jennifer O. Elmont, Holly I.M. Wadkins, M. Bethany Ball, Michele C. Walsh, Satyan Lakshminrusimha, Susan T. Schaefer, Toni Mancini, Melody Parry, Haresh Kirpalani, Jon E. Tyson, Gennie Bose, Namasivayam Ambalavanan, Megan M. Henning, Ann Marie Scorsone, Sanjay Chawla, Marie G. Gantz, Carl L. Bose, Seetha Shankaran, Kimberlee Weaver-Lewis, Diane I. Bottcher, John D.E. Barks, Rosemary D. Higgins, Leif D. Nelin, Kathryn D. Woodbury, Karen J. Johnson, Jennifer Donato, Stephanie Wilson Archer, Dennis Wallace, David Leblond, Tracy L. Tud, Chelsey Elenkiwich, Stephen D. Minton, Prabhu S. Parimi, Sandra Sundquist Beauman, Meena Garg, Andrew A. Bremer, Constance Orme, Anna Maria Hibbs, Mary Hanson, Joanne Finkle, Pablo J. Sánchez, Michael G. Sacilowski, Courtney Park, Laurie A. Hogden, Elizabeth Kuan, Diane F. White, Mendi L. Schmelzel, Deanna Maffett, Kathleen A. Kennedy, Sarvin Ghavam, Brandy Davis, Edward F. Bell, Martin Keszler, David P. Carlton, Emily Li, Jacky R. Walker, Elizabeth N. Reichert, Sharon L. Wright, Claire A. Goeke, Elizabeth Eason, Tara McNair, Sara B. DeMauro, Brenda B. Poindexter, Colleen Mackie, Eugenia K. Pallotto, Rachel Geller, Yvonne Loggins, Carol Hartenberger, Daisy Rochez, Waldemar A. Carlo, Frances Eubanks, Hallie Baugher, Barry Eggleston, Diane Prinzing, Teresa Chanlaw, Kandace McGrath, Carrie A. Rau, Barbara Schmidt, Stephanie Guilford, Kristin Kirker, Melinda S. Proud, Kristin M. Zaterka-Baxter, Ginger Rhodes-Ryan, Premini Sabaratnam, Georgia E. McDavid, Pollieanna Sepulvida, Cathy Grisby, Ronnie Guillet, Soraya Abbasi, Gregory M. Sokol, Mary Rowan, Abbot R. Laptook, Patricia Luzader, Myra H. Wyckoff, Luc P. Brion, Melanie Stein, Bogdan Panaitescu, Sara C. Handley, Karen Martin, Carl T. D'Angio, William E. Truog, Elisa Vieira, Kristi L. Watterberg, Allison Knutson, Cheri Gauldin, Manndi C. Loertscher, Rachel A. Jones, Jacqueline McCool, Lisa Gaetano, Bradley A. Yoder, Monica V. Collins, Ronald N. Goldberg, Michelle L. Baack, Julie C. Shadd, John M. Dagle, Mariana Baserga, Jill Burnett, Anne Marie Reynolds, Sudarshan R. Jadcherla, Emily K. Stephens, Anne Holmes, Earl Maxson, Ravi Mangal Patel, Kimberley A. Fisher, Jonathan Snyder, Rosemary L. Jensen, Jeanette O'Donnell Auman, Kirsten Childs, Stephanie L. Merhar, Angelita M. Hensman, Neha Kumbhat, Jane E. Brumbaugh, R. Jordan Williams, Eric C. Eichenwald, Maria M. DeLeon, Carla Bann, Krisa P. Van Meurs, Mark J. Sheffield, Trisha Marchant, Christine Catts, Robin K. Ohls, Claudia Pedrozza, Amir M. Khan, Conra Backstrom Lacy, Shirley S. Cosby, C. Michael Cotten, Aasma S. Chaudhary, Diana M. Vasil, Donna Hall, Janice Bernhardt, Alexis S. Davis, Kurt Schibler, Valerie Y. Chock, Erna Clark, Kyle Binion, Jonathan M. Klein, Dan L. Ellsbury, Richard A. Polin, Janell Fuller, Abhik Das, Julie Gutentag, Susan Christensen, Dianne E. Herron, Jenna Gabrio, Megan Broadbent, Lucille St. Pierre, Donna White, Cindy Clark, Elizabeth E. Foglia, Matthew M. Laughon, Stephen D. Kicklighter, Tarah T. Colaizy, David K. Stevenson, Girija Natarajan, and Uday Devaskar

Subjects
Male, medicine.medical_specialty, Gestational Age, Umbilical cord, Article, Umbilical Cord, Milking, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, 030225 pediatrics, medicine, Humans, Hospital Mortality, 030212 general & internal medicine, Cerebral Intraventricular Hemorrhage, Retrospective Studies, Extremely premature, Obstetrics, business.industry, Infant, Newborn, Retrospective cohort study, medicine.disease, Constriction, medicine.anatomical_structure, Intraventricular hemorrhage, Hospital outcomes, Infant, Extremely Premature, Pediatrics, Perinatology and Child Health, Female, Cord clamping, business
Abstract

OBJECTIVE: To compare in-hospital outcomes after umbilical cord milking versus delayed cord clamping among infants

Published
2021

5. 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

6. Comparisons and Limitations of Current Definitions of Bronchopulmonary Dysplasia for the Prematurity and Respiratory Outcomes Program

Author

Alan H. Jobe, Rui Feng, Roberta A. Ballard, Barbara Schmidt, Anne Marie Reynolds, Pamela A. Shaw, Aaron Hamvas, Brenda B. Poindexter, and Judy L. Aschner

Subjects
Male, Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Supplemental oxygen, Infant, Premature, Diseases, medicine, Humans, Prospective Studies, Prospective cohort study, Survival rate, Original Research, Bronchopulmonary Dysplasia, business.industry, Extremely preterm, Infant, Newborn, Oxygen Inhalation Therapy, Postmenstrual Age, Disease Management, Prognosis, medicine.disease, United States, Survival Rate, Bronchopulmonary dysplasia, Infant, Extremely Premature, Cohort, Female, Observational study, Morbidity, business, Follow-Up Studies, Program Evaluation
Abstract

Bronchopulmonary dysplasia is the most common morbidity of prematurity, but the validity and utility of commonly used definitions have been questioned.To compare three commonly used definitions of bronchopulmonary dysplasia in a contemporary prospective, multicenter observational cohort of extremely preterm infants.At 36 weeks postmenstrual age, the following definitions of bronchopulmonary dysplasia were applied to surviving infants with and without imputation: need for supplemental oxygen (Shennan definition), National Institutes of Health Workshop definition, and "physiologic" definition after a room-air challenge.Of 765 survivors assessed at 36 weeks, bronchopulmonary dysplasia was diagnosed in 40.8, 58.6, and 32.0% of infants, respectively, with the Shennan, workshop and physiologic definitions. The number of unclassified infants was lowest with the workshop definition (2.1%) and highest with the physiologic definition (16.1%). After assigning infants discharged home in room air before 36 weeks as no bronchopulmonary dysplasia, the modified Shennan definition compared favorably to the workshop definition, with 2.9% unclassified infants. Newer management strategies with nasal cannula flows up to 4 L/min or more and 0.21 FiO2 at 36 weeks obscured classification of bronchopulmonary dysplasia status in 12.4% of infants.Existing definitions of bronchopulmonary dysplasia differ with respect to ease of data collection and number of unclassifiable cases. Contemporary changes in management of infants, such as use of high-flow nasal cannula, limit application of existing definitions and may result in misclassification. A contemporary definition of bronchopulmonary dysplasia that correlates with respiratory morbidity in childhood is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01435187).

Published
2015

7. T cell developmental arrest in former premature infants increases risk of respiratory morbidity later in infancy

Author

Deanna Maffett, Gloria S. Pryhuber, Karan Arul, Tanya Scalise, Jeanne Holden-Wiltse, Thomas J. Mariani, Heidie Huyck, Kelly Schooping Tripi, Kristin Scheible, Andrew G. Straw, Rita M. Ryan, Derick R. Peterson, Andrea Baran, Anne Marie Reynolds, Elizabeth Werner, David J. Topham, Nathan Laniewski, John M. Ashton, Sanjukta Bandyopadhyay, Jason Emo, Mary T. Caserta, and Clement L. Ren

Subjects
CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, medicine.medical_specialty, T cell, lcsh:Medicine, Gestational Age, Development, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Humans, Longitudinal Studies, Interleukin 8, Respiratory system, Respiratory Tract Infections, Obstetrics, business.industry, Interleukin-8, lcsh:R, Infant, Newborn, Infant, Gestational age, Cell Differentiation, General Medicine, Acquired immune system, medicine.disease, Platelet Endothelial Cell Adhesion Molecule-1, 030104 developmental biology, medicine.anatomical_structure, In utero, Chronic Disease, Gestation, Female, business, Infant, Premature, Research Article, 030215 immunology
Abstract

The inverse relationship between gestational age at birth and postviral respiratory morbidity suggests that infants born preterm (PT) may miss a critical developmental window of T cell maturation. Despite a continued increase in younger PT survivors with respiratory complications, we have limited understanding of normal human fetal T cell maturation, how ex utero development in premature infants may interrupt normal T cell development, and whether T cell development has an effect on infant outcomes. In our longitudinal cohort of 157 infants born between 23 and 42 weeks of gestation, we identified differences in T cells present at birth that were dependent on gestational age and differences in postnatal T cell development that predicted respiratory outcome at 1 year of age. We show that naive CD4+ T cells shift from a CD31-TNF-α+ bias in mid gestation to a CD31+IL-8+ predominance by term gestation. Former PT infants discharged with CD31+IL8+CD4+ T cells below a range similar to that of full-term born infants were at an over 3.5-fold higher risk for respiratory complications after NICU discharge. This study is the first to our knowledge to identify a pattern of normal functional T cell development in later gestation and to associate abnormal T cell development with health outcomes in infants.

Published
2018

8. 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

9. Outcomes of Preterm Infants following Discussions about Withdrawal or Withholding of Life Support

Author

Jennifer James, David Munson, Sara B. DeMauro, John C. Langer, April R. Dworetz, Girija Natarajan, Margarita Bidegain, Christine A. Fortney, Ruth Seabrook, Betty R. Vohr, Jon E. Tyson, Edward F. Bell, Brenda B. Poindexter, Seetha Shankaran, Rosemary D. Higgins, Abhik Das, Barbara J. Stoll, Haresh Kirpalani, Michael S. Caplan, Abbot R. Laptook, Angelita M. Hensman, Elisa Vieira, Emilee Little, Robert Burke, Melinda Caskey, Katharine Johnson, Barbara Alksninis, Mary Lenore Keszler, Andrea M. Knoll, Theresa M. Leach, Elisabeth C. McGowan, Victoria E. Watson, Suzy Ventura, Michele C. Walsh, Avroy A. Fanaroff, Anna Marie Hibbs, Nancy S. Newman, Allison H. Payne, Deanne E. Wilson-Costello, Bonnie S. Siner, Monika Bhola, Gulgun Yalcinkaya, Harriet G. Friedman, William E. Truog, Eugenia K. Pallotto, Howard W. Kilbride, Cheri Gauldin, Anne Holmes, Kathy Johnson, Allison Knutson, Kurt Schibler, Barbara Alexander, Cathy Grisby, Teresa L. Gratton, Jean J. Steichen, Estelle E. Fischer, Lenora Jackson, Kristin Kirker, Greg Muthig, Stacey Tepe, Kimberly Yolton, Ronald N. Goldberg, C. Michael Cotten, Ricki F. Goldstein, William F. Malcolm, Patricia L. Ashley, Kimberley A. Fisher, Joanne Finkle, Kathryn E. Gustafson, Matthew M. Laughon, Carl L. Bose, Janice Bernhardt, Gennie Bose, Janice Wereszczak, David P. Carlton, Ellen C. Hale, Ira Adams-Chapman, Yvonne Loggins, Stephanie Wilson Archer, Gregory M. Sokol, Lu-Ann Papile, Leslie Dawn Wilson, Dianne E. Herron, Susan Gunn, Lucy Smiley, Abbey C. Hines, Leif D. Nelin, Sudarshan R. Jadcherla, Pablo J. Sánchez, Patricia Luzader, Gail E. Besner, Nehal A. Parikh, Dennis Wallace, Marie G. Gantz, Jamie E. Newman, Jeanette O'Donnell Auman, Margaret Crawford, Carolyn M. Petrie Huitema, Kristin M. Zaterka-Baxter, Krisa P. Van Meurs, David K. Stevenson, M. Bethany Ball, Susan R. Hintz, Melinda S. Proud, Barbara Bentley, Maria Elena DeAnda, Anne M. DeBattista, Beth Earhart, Lynne C. Huffman, Casey E. Krueger, Hali E. Weiss, Waldemar A. Carlo, Namasivayam Ambalavanan, Myriam Peralta-Carcelen, Monica V. Collins, Shirley S. Cosby, Fred J. Biasini, Kristen C. Johnston, Cryshelle S. Patterson, Vivien A. Phillips, Sally Whitley, Uday Devaskar, Meena Garg, Isabell B. Purdy, Teresa Chanlaw, Rachel Geller, Dan L. Ellsbury, Tarah T. Colaizy, Jane E. Brumbaugh, John A. Widness, Karen J. Johnson, Jacky R. Walker, Donia B. Campbell, Diane L. Eastman, Kristi L. Watterberg, Jean R. Lowe, Janell F. Fuller, Robin K. Ohls, Conra Backstrom Lacy, Andrea F. Duncan, Barbara Schmidt, Aasma S. Chaudhary, Soraya Abbasi, Toni Mancini, Judy C. Bernbaum, Marsha Gerdes, Hallam Hurt, Carl T. D'Angio, Ronnie Guillet, Satyan Lakshminrusimha, Anne Marie Reynolds, Rosemary L. Jensen, Joan Merzbach, Gary J. Myers, Ashley Williams, Kelley Yost, William Zorn, Karen Wynn, Deanna Maffett, Diane Prinzing, Julianne Hunn, Stephanie Guilford, Farooq Osman, Mary Rowan, Michael G. Sacilowski, Holly I.M. Wadkins, Melissa Bowman, Kathleen A. Kennedy, Julie Arldt-McAlister, Katrina Burson, Andrea Freeman Duncan, Carmen Garcia, Beverly Foley Harris, Janice John, Patrick M. Jones, Layne M. Lillie, Karen Martin, Sara C. Martin, Georgia E. McDavid, Shawna Rodgers, Saba Siddiki, Daniel Sperry, Patti L. Pierce Tate, Sharon L. Wright, Myra Wyckoff, Luc P. Brion, Diana M. Vasil, Lijun Chen, Roy J. Heyne, Sally S. Adams, Linda A. Madden, Elizabeth Heyne, Alicia Guzman, Lizette E. Torres, Catherine Twell Boatman, Athina Pappas, Rebecca Bara, Laura A. Goldston, John Barks, Mary Christensen, Stephanie Wiggins, and Diane White

Subjects
Male, Pediatrics, medicine.medical_specialty, Palliative care, Birth weight, Decision Making, Article, 03 medical and health sciences, 0302 clinical medicine, Early onset sepsis, 030225 pediatrics, Intensive care, Infant Mortality, Outcome Assessment, Health Care, medicine, Humans, 030212 general & internal medicine, Registries, Retrospective Studies, business.industry, Infant, Newborn, Gestational age, Infant, medicine.disease, Life Support Care, Survival Rate, Withholding Treatment, Life support, Pediatrics, Perinatology and Child Health, Necrotizing enterocolitis, Gestation, Female, Morbidity, business, Infant, Premature
Abstract

Objectives To describe the frequency of postnatal discussions about withdrawal or withholding of life-sustaining therapy (WWLST), ensuing WWLST, and outcomes of infants surviving such discussions. We hypothesized that such survivors have poor outcomes. Study design This retrospective review included registry data from 18 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Infants born at 22-28 weeks of gestation who survived >12 hours during 2011-2013 were included. Regression analysis identified maternal and infant factors associated with WWLST discussions and factors predicting ensuing WWLST. In-hospital and 18- to 26-month outcomes were evaluated. Results WWLST discussions occurred in 529 (15.4%) of 3434 infants. These were more frequent at 22-24 weeks (27.0%) compared with 27-28 weeks of gestation (5.6%). Factors associated with WWLST discussion were male sex, gestational age (GA) of ≤24 weeks, birth weight small for GA, congenital malformations or syndromes, early onset sepsis, severe brain injury, and necrotizing enterocolitis. Rates of WWLST discussion varied by center (6.4%-29.9%) as did WWLST (5.2%-20.7%). Ensuing WWLST occurred in 406 patients; of these, 5 survived to discharge. Of the 123 infants for whom intensive care was continued, 58 (47%) survived to discharge. Survival after WWLST discussion was associated with higher rates of neonatal morbidities and neurodevelopmental impairment compared with babies for whom WWLST discussions did not occur. Significant predictors of ensuing WWLST were maternal age >25 years, necrotizing enterocolitis, and days on a ventilator. Conclusions Wide center variations in WWLST discussions occur, especially at ≤24 weeks GA. Outcomes of infants surviving after WWLST discussions are poor. Trial registration ClinicalTrials.gov : NCT00063063 .

Published
2017

10. Respiratory Medications in Infants <29 Weeks during the First Year Postdischarge: The Prematurity and Respiratory Outcomes Program (PROP) Consortium

Author

Rita M. Ryan, Roberta L. Keller, Brenda B. Poindexter, Carl T. D'Angio, Pamela A. Shaw, Scarlett L. Bellamy, Paul E. Moore, Christopher McPherson, James M. Greenberg, Barbara Alexander, Tari Gratton, Cathy Grigsby, Beth Koch, Kelly Thornton, Pamela Bates, Claudia Cleveland, Julie Hoffmann, Laura Linneman, Jayne Sicard-Su, Gina Simpson, Jeanette M. Asselin, Samantha Balan, Katrina Burson, Cheryl Chapin, Erna Josiah-Davis, Carmen Garcia, Hart Horneman, Rick Hinojosa, Christopher Johnson, Susan Kelley, Karin L. Knowles, M. Layne Lillie, Karen Martin, Sarah Martin, Julie Arldt-McAlister, Georgia E. McDavid, Lori Pacello, Shawna Rodgers, Daniel K. Sperry, Amy B. Beller, Mark O’ Hunt, Theresa J. Rogers, Odessa L. Settles, Steven Steele, Sharon Wadley, Shannon Castiglione, Aimee Horan, Deanna Maffet, Jane O'Donnell, Michael Sacilowski, Tanya Scalise, Elizabeth Werner, Jason Zayac, Heidie Huyck, Valerie Lunger, Kim Bordeaux, Pam Brown, Julia Epping, Lisa Flattery-Walsh, Donna Germuga, Nancy Jenks, Mary Platt, Eileen Popplewell, Sandra Prentice, Kim Ciccio, Charles Clem, Susan Gunn, Lauren Jewett, Maria Blanco, Denise Cifelli, Sara DeMauro, Melissa Fernando, Ann Tierney, Lynn M. Taussig, Carol J. Blaisdell, Claire Chougnet, William Hardie, Alan H. Jobe, Karen McDowell, Thomas Ferkol, Aaron Hamvas, Mark R. Holland, James Kemp, Philip T. Levy, Phillip Tarr, Gautam K. Singh, Barbara Warner, Philip L. Ballard, Roberta A. Ballard, David J. Durand, Eric C. Eichenwald, Amir M. Khan, Leslie Lusk, Jeffrey D. Merrill, Dennis W. Nielson, Elizabeth E. Rogers, Judy Aschner, Candice Fike, Scott Guthrie, Tina Hartert, Nathalie Maitre, Marshall Summar, Vasanth Kumar, Tom Mariani, Gloria Pryhuber, Clement Ren, Anne Marie Reynolds, Kristin Scheible, Timothy Stevens, C. Michael Cotten, Kim Fisher, Jack Sharp, Judith A. Voynow, Stephanie Davis, Jonas Ellenberg, Rui Feng, Howard Panitch, and Barbara Schmidt

Subjects
Male, Pediatrics, medicine.medical_specialty, Neonatal intensive care unit, medicine.drug_class, medicine.medical_treatment, Anti-Inflammatory Agents, Gestational Age, Infant, Premature, Diseases, Article, 03 medical and health sciences, 0302 clinical medicine, Prednisone, Intensive Care Units, Neonatal, Surveys and Questionnaires, 030225 pediatrics, Bronchodilator, Administration, Inhalation, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Respiratory system, Diuretics, Prospective cohort study, Bronchopulmonary Dysplasia, business.industry, Infant, Newborn, Infant, Gestational age, medicine.disease, Patient Discharge, Bronchodilator Agents, Oxygen, Treatment Outcome, Bronchopulmonary dysplasia, Pediatrics, Perinatology and Child Health, Female, Steroids, Diuretic, business, Infant, Premature, medicine.drug
Abstract

OBJECTIVE: To determine patterns of respiratory medications used in neonatal intensive care unit (NICU) graduates. STUDY DESIGN: The Prematurity Respiratory Outcomes Program enrolled 835 babies

Published
2019

11. Black Race Is Associated with a Lower Risk of Bronchopulmonary Dysplasia

Author

Rita M. Ryan, Rui Feng, Catalina Bazacliu, Thomas W. Ferkol, Clement L. Ren, Thomas J. Mariani, Brenda B. Poindexter, Fan Wang, Paul E. Moore, Claire Chougnet, James M. Greenberg, William Hardie, Alan H. Jobe, Karen McDowell, Aaron Hamvas, Mark R. Holland, James Kemp, Philip T. Levy, Christopher McPherson, Phillip Tarr, Gautam K. Singh, Barbara Warner, Philip L. Ballard, Roberta A. Ballard, David J. Durand, Eric C. Eichenwald, Amir M. Khan, Leslie Lusk, Jeffrey D. Merrill, Dennis W. Nielson, Elizabeth E. Rogers, Judy Aschner, Candice Fike, Scott Guthrie, Tina Hartert, Nathalie Maitre, Marshall Summar, Carl T. D'Angio, Vasanth Kumar, Gloria Pryhuber, Anne Marie Reynolds, Kristin Scheible, Timothy Stevens, C. Michael Cotten, Kim Fisher, Jack Sharp, Judith A. Voynow, Stephanie Davis, Scarlett A. Bellamy, Jonas Ellenberg, Melissa Fernando, Howard Panitch, Pamela A. Shaw, Barbara Schmidt, Lynn M. Taussig, and Carol J. Blaisdell

Subjects
Pediatrics, medicine.medical_specialty, Gestational Age, Infant, Premature, Diseases, Lower risk, Black race, Risk Assessment, behavioral disciplines and activities, White People, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Intensive Care Units, Neonatal, 030225 pediatrics, mental disorders, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Bronchopulmonary Dysplasia, business.industry, Respiratory disease, Follow up studies, Gestational age, medicine.disease, United States, Large cohort, Black or African American, Hospitalization, Survival Rate, Bronchopulmonary dysplasia, Pediatrics, Perinatology and Child Health, Morbidity, business, Infant, Premature, Follow-Up Studies
Abstract

To use a large current prospective cohort of infants29 weeks to compare bronchopulmonary dysplasia (BPD) rates in black and white infants.The Prematurity and Respiratory Outcome Program (PROP) enrolled 835 infants born in 2011-2013 at29 weeks of gestation; 728 black or white infants survived to 36 weeks postmenstrual age (PMA). Logistic regression was used to compare BPD outcomes (defined as supplemental oxygen requirement at 36 weeks PMA) between the races, adjusted for gestational age (GA), antenatal steroid use, intubation at birth, and surfactant use at birth.Of 707 black or white infants with available BPD outcomes, BPD was lower in black infants (38% vs 45%), even though they were of significantly lower GA. At every GA, BPD was more common in white infants. The aOR for BPD was 0.60 (95% CI, 0.42-0.85; P = .004) for black infants compared with white infants after adjusting for GA. Despite the lower rate of BPD, black infants had a higher rate of first-year post-prematurity respiratory disease (black, 79%; white, 63%).In this large cohort of recently born preterm infants at29 weeks GA, compared with white infants, black infants had a lower risk of BPD but an increased risk of persistent respiratory morbidity.

Published
2019

12. Bronchopulmonary Dysplasia and Perinatal Characteristics Predict 1-Year Respiratory Outcomes in Newborns Born at Extremely Low Gestational Age: A Prospective Cohort Study

Author

Julia Epping, Theresa J. Rogers, Carl T. D'Angio, Nathalie L. Maitre, Marshall L. Summar, Erna Josiah-Davis, Maria Blanco, Jane O'Donnell, T.J. Mariani, Samantha Balan, Vasantha H.S. Kumar, Rita M. Ryan, Scarlett L. Bellamy, Dennis W. Nielson, Philip T. Levy, Melissa Fernando, Barbara Warner, David J. Durand, Shawna Rodgers, Steven Steele, Susan Kelley, Scott O Guthrie, Carmen Garcia, Anne Marie Reynolds, Karin L. Knowles, William D. Hardie, Jeffrey D. Merrill, Barbara Alexander, Timothy P. Stevens, Claudia Cleveland, Valerie Lunger, Julie A. Hoffmann, Karen M. McDowell, Donna Germuga, Elizabeth E. Rogers, Karen Martin, Jason Zayac, Laura Linneman, Gautam K. Singh, Kim Bordeaux, Deanna Maffet, Clement L. Ren, Lisa Flattery-Walsh, Stephanie D. Davis, Jack K. Sharp, Gina Simpson, Jonas H. Ellenberg, Aimee Horan, Lynn M. Taussig, Hart F. Horneman, Mark O'Hunt, Amy Beller, Elizabeth R. Werner, Charles Clem, Roberta A. Ballard, Thomas W. Ferkol, Katrina Burson, Jayne Sicard-Su, Tanya Scalise, Sarah Martin, Eileen Popplewell, M. Layne Lillie, Kim Ciccio, Shannon Castiglione, Carol J. Blaisdell, Lori Pacello, Philip L. Ballard, C. Michael Cotten, Brenda B. Poindexter, Tari Gratton, Sharon Wadley, Mary Jane Platt, Ann Tierney, Daniel K. Sperry, Kelly Thornton, Kristin Scheible, Roberta L. Keller, Pamela A. Shaw, Judith A. Voynow, Claire A. Chougnet, Kim Fisher, Georgia E. McDavid, Rick Hinojosa, Sandra Prentice, James M. Greenberg, Rui Feng, Jeanette M. Asselin, Barbara Schmidt, Pamela Bates, Susan Gunn, Denise Cifelli, Christopher Johnson, Howard B. Panitch, Cheryl J. Chapin, Heidie Huyck, Cathy Grisby, Tina V. Hartert, Amir M. Khan, Sara B. DeMauro, Lauren Jewett, Judy L. Aschner, Julie Arldt-McAlister, Aaron Hamvas, Leslie A. Lusk, James Kemp, Beth Koch, Pam Brown, Gloria S. Pryhuber, Candice D. Fike, Alan H. Jobe, Mark R. Holland, Michael G. Sacilowski, Odessa L. Settles, Nancy Jenks, Paul E. Moore, and Eric C. Eichenwald

Subjects
Male, Pediatrics, medicine.medical_specialty, Intrauterine growth restriction, Gestational Age, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, 030225 pediatrics, Wheeze, medicine, Humans, Infant, Very Low Birth Weight, Prospective Studies, Prospective cohort study, Lung, Bronchopulmonary Dysplasia, Obstetrics, business.industry, Parturition, Infant, Newborn, Gestational age, Infant, medicine.disease, Prognosis, Health Surveys, medicine.anatomical_structure, 030228 respiratory system, Bronchopulmonary dysplasia, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, Morbidity, business, Cohort study
Abstract

To assess the utility of clinical predictors of persistent respiratory morbidity in extremely low gestational age newborns (ELGANs).We enrolled ELGANs (29 weeks' gestation) at ≤7 postnatal days and collected antenatal and neonatal clinical data through 36 weeks' postmenstrual age. We surveyed caregivers at 3, 6, 9, and 12 months' corrected age to identify postdischarge respiratory morbidity, defined as hospitalization, home support (oxygen, tracheostomy, ventilation), medications, or symptoms (cough/wheeze). Infants were classified as having postprematurity respiratory disease (PRD, the primary study outcome) if respiratory morbidity persisted over ≥2 questionnaires. Infants were classified with severe respiratory morbidity if there were multiple hospitalizations, exposure to systemic steroids or pulmonary vasodilators, home oxygen after 3 months or mechanical ventilation, or symptoms despite inhaled corticosteroids. Mixed-effects models generated with data available at 1 day (perinatal) and 36 weeks' postmenstrual age were assessed for predictive accuracy.Of 724 infants (918 ± 234 g, 26.7 ± 1.4 weeks' gestational age) classified for the primary outcome, 68.6% had PRD; 245 of 704 (34.8%) were classified as severe. Male sex, intrauterine growth restriction, maternal smoking, race/ethnicity, intubation at birth, and public insurance were retained in perinatal and 36-week models for both PRD and respiratory morbidity severity. The perinatal model accurately predicted PRD (c-statistic 0.858). Neither the 36-week model nor the addition of bronchopulmonary dysplasia to the perinatal model improved accuracy (0.856, 0.860); c-statistic for BPD alone was 0.907.Both bronchopulmonary dysplasia and perinatal clinical data accurately identify ELGANs at risk for persistent and severe respiratory morbidity at 1 year.ClinicalTrials.gov: NCT01435187.

Published
2016

13. Pilot trial of late booster doses of surfactant for ventilated premature infants

Author

Aaron Hamvas, Anna Maria Hibbs, Robin H. Steinhorn, William E Truog, David J. Durand, K. W. Lu, Sherry E. Courtney, Roberta A. Ballard, Anne Marie Reynolds, Kimberly Spence, Philip L. Ballard, Rita M. Ryan, Eric C. Eichenwald, and Jeffrey D. Merrill

Subjects
Male, Bradycardia, Calfactant, Birth weight, Pilot Projects, Mean airway pressure, Proinflammatory cytokine, Pulmonary surfactant, medicine, Humans, Adverse effect, Bronchopulmonary Dysplasia, business.industry, Infant, Newborn, Obstetrics and Gynecology, Pulmonary Surfactants, medicine.disease, Respiration, Artificial, Treatment Outcome, Bronchopulmonary dysplasia, Anesthesia, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, business, Infant, Premature, medicine.drug
Abstract

Many premature infants at risk for bronchopulmonary dysplasia experience episodes of surfactant dysfunction with reduced surfactant protein B (SP-B). In this study, we investigated the safety and responses to booster doses of surfactant. A total of 87 infants, 500 to 1250 g birth weight, who were ventilated at 7 to 10 days received 2 or 3 doses of Infasurf (Calfactant, Forest Pharmaceuticals, St Louis, MO, USA) within a 1-week period. For 184 doses, occurrence rates of transient bradycardia (13) and plugged endotracheal tube (5) were low, and no other adverse effects were noted. Treatment transiently improved the respiratory severity score (FiO2 × mean airway pressure), SP-B content (+75%) and surface properties of isolated surfactant. Levels of eight proinflammatory cytokines in tracheal aspirate were interrelated and unchanged from baseline after surfactant treatment. Booster doses of surfactant for premature infants with lung disease are safe and transiently improve respiratory status as well as composition and function of endogenous surfactant.

Published
2011

14. Maternal Black Race and Persistent Wheezing Illness in Former Extremely Low Gestational Age Newborns: Secondary Analysis of a Randomized Trial

Author

Katherine C. Wai, Anna M. Hibbs, Martina A. Steurer, Dennis M. Black, Jeanette M. Asselin, Eric C. Eichenwald, Philip L. Ballard, Roberta A. Ballard, Roberta L. Keller, Suzanne Hamilton Strong, Jill Immamura-Ching, Margaret Orfanos-Villalobos, Cassandra Williams, David J. Durand, Jeffrey D. Merrill, Dolia Horton, Loretta Pacello, April Willard, William E. Truog, Cheryl Gauldin, Anne Holmes, Patrice Johnson, Kerrie Meinert, Anne Marie Reynolds, Janine Lucie, Patrick Conway, Michael Sacilowski, Michael Leadersdorff, Pam Orbank, Karen Wynn, Robin H. Steinhorn, Maria deUngria, Janine Yasmin Khan, Karin Hamann, Molly Schau, Brad Hopkins, James Jenson, Carmen Garcia, Aruna Parekh, Jila Shariff, Rose McGovern, Jeff Adelman, Adrienne Combs, Mary Tjersland, Dennis E. Mayock, Elizabeth Howland, Susan Walker, Jim Longoria, Holly Meo, Amir Khan, Georgia McDavid, Katrina Burson, Richard Hinojosa, Christopher Johnson, Karen Martin, Sarah Martin, Shawna Rogers, Sharon Wright, Mark L. Hudak, Kimberly Barnette, Amanda Kellum, Michelle Burcke, Christie Hayes, Stephanie Chadwick, Danielle Howard, Carla Kennedy, Renee Prince, Jennifer Helderman, T. Michael O'Shea, Beatrice Stefanescu, Kelly Warden, Patty Brown, Jennifer Griffin, Laura Conley, Catherine M. Bendel, Michael Georgieff, Bridget Davern, Marla Mills, Sharon Ritter, Carol Wagner, Rita M. Ryan, Deanna Fanning, Jimmy Roberson, Mark C. Mammel, Andrea Lampland, Pat Meyers, Angela Brey, Ellen M. Bendel-Stenzel, Neil Mulrooney, Cathy Worwa, Pam Dixon, Gerald Ebert, Cathy Hejl, Molly Maxwell, Kristin McCullough, Ramasubbareddy Dhanireddy, Mohammed T. El Abiad, Ajay Talati, Sheila Dempsey, Kathy Gammage, Gayle Gower, Kathy James, Pam LeNoue, Victor J. McKay, Suzi Bell, Dawn Bruton, Michelle Beaulieu, Richard Williams, Rajan Wadhawan, Robin Barron-Nelson, Shane Taylor, Sherry E. Courtney, Carol Sikes, Gary Lowe, Betty Proffitt, Elizabeth E. Rogers, Cheryl Chapin, Hart Horneman, Susan Kelley, Karin Knowles, Nancy Newton, Eric Vittinghoff, Jean Hietpas, Laurie Denton, Lisa Palermo, and Lucy Wu

Subjects
Male, Pediatrics, medicine.medical_specialty, Birth weight, Mothers, Infant, Premature, Diseases, Breast milk, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Risk Factors, law, 030225 pediatrics, Wheeze, medicine, Humans, 030212 general & internal medicine, Respiratory Sounds, Asthma, business.industry, Infant, Newborn, Infant, Gestational age, medicine.disease, Respiration, Artificial, Black or African American, Bronchopulmonary dysplasia, Child, Preschool, Infant, Extremely Premature, Pediatrics, Perinatology and Child Health, Gestation, Female, medicine.symptom, business
Abstract

Objective To evaluate the relationship between maternal self-reported race/ethnicity and persistent wheezing illness in former high-risk, extremely low gestational age newborns, and to quantify the contribution of socioeconomic, environmental, and biological factors on this relationship. Study design We assessed persistent wheezing illness determined at 18-24 months corrected (for prematurity) age in survivors of a randomized trial. Parents/caregivers were surveyed for wheeze and inhaled asthma medication use quarterly to 12 months, and at 18 and 24 months. We used multivariable analysis to evaluate the relationship of maternal race to persistent wheezing illness, and identified mediators for this relationship via formal mediation analysis. Results Of 420 infants (25.2 ± 1.2 weeks of gestation and 714 ± 166 g at birth, 57% male, 34% maternal black race), 189 (45%) had persistent wheezing illness. After adjustment for gestational age, birth weight, and sex, infants of black mothers had increased odds of persistent wheeze compared with infants of nonblack mothers (OR = 2.9, 95% CI 1.9, 4.5). Only bronchopulmonary dysplasia, breast milk diet, and public insurance status were identified as mediators. In this model, the direct effect of race accounted for 69% of the relationship between maternal race and persistent wheeze, whereas breast milk diet, public insurance status, and bronchopulmonary dysplasia accounted for 8%, 12%, and 10%, respectively. Conclusions Among former high-risk extremely low gestational age newborns, infants of black mothers have increased odds of developing persistent wheeze. A substantial proportion of this effect is directly accounted for by race, which may reflect unmeasured environmental influences, and acquired and innate biological differences. Trial registration ClinicalTrials.gov : NCT01022580 .

Published
2018

15. Pleural Effusion with Parenteral Nutrition Solution: An Unusual Complication of an 'Appropriately' Placed Umbilical Venous Catheter

Author

Anne Marie Reynolds, Maria Janina U. Pabalan, Satyanarayana Lakshminrusimha, Ralph J. Wynn, Rita M. Ryan, Veena Manja, and Mostafa Youssfi

Subjects
Adult, Male, Umbilical Veins, medicine.medical_specialty, Percutaneous, Pleural effusion, Vena Cava, Inferior, Inferior vena cava, Catheters, Indwelling, medicine, Humans, business.industry, Infant, Newborn, Obstetrics and Gynecology, respiratory system, medicine.disease, Venous Obstruction, respiratory tract diseases, Surgery, Pleural Effusion, Catheter, Parenteral nutrition, medicine.vein, Pediatrics, Perinatology and Child Health, cardiovascular system, Hydrothorax, Female, Parenteral Nutrition, Total, Radiology, Complication, business
Abstract

Pleural effusion is not an uncommon complication of percutaneous intravenous catheters in neonates. Umbilical venous catheters (UVCs) are associated with pleural effusion following abnormal placement in the left atrium or pulmonary veins due to venous obstruction. We report for the first time a case of right-sided pleural effusion with parenteral nutrition solution following a UVC that appeared to be positioned appropriately in the inferior vena cava.

Published
2007

16. Preterm Cord Blood CD4+ T Cells Exhibit Increased IL-6 Production in Chorioamnionitis and Decreased CD4+ T Cells in Bronchopulmonary Dysplasia

Author

Philip J. Katzman, Syed Sajid Hussain Shah, Anne Marie Reynolds, Ravi S. Misra, Hongyue Wang, Rita M. Ryan, Claire Wyman, Kristin Scheible, Thomas J. Mariani, Sara K. Misra, Gloria S. Pryhuber, Deborah J. Fowell, and Heidie Huyck

Subjects
medicine.medical_specialty, medicine.medical_treatment, T cell, Immunology, Chorioamnionitis, Peripheral blood mononuclear cell, T-Lymphocytes, Regulatory, Article, Pregnancy, T-Lymphocyte Subsets, Internal medicine, medicine, Immunology and Allergy, Humans, IL-2 receptor, Cells, Cultured, Bronchopulmonary Dysplasia, business.industry, Interleukin-6, Infant, Newborn, Interleukin-2 Receptor alpha Subunit, FOXP3, Gene Expression Regulation, Developmental, Forkhead Transcription Factors, General Medicine, medicine.disease, Fetal Blood, Endocrinology, Cytokine, medicine.anatomical_structure, Bronchopulmonary dysplasia, Cord blood, CD4 Antigens, Premature Birth, Female, Inflammation Mediators, business
Abstract

Background Chorioamnionitis (CA) is associated with premature delivery and bronchopulmonary dysplasia (BPD). We hypothesize that preterm infants exposed to CA have reduced suppressive regulatory T cells (Treg) and increased non-regulatory T cell pro-inflammatory cytokines, increasing risk for BPD. Objective To evaluate cord blood CD4+ T cell regulatory phenotype and pro-inflammatory cytokine production in CA and BPD groups. Study design Cord blood mononuclear cells from infants (GA ⩽32 weeks), with or without placental histological evidence of CA (hChorio), were analyzed by flow cytometry. Clinical information was collected by retrospective chart review. Numbers of putative Treg (CD4+FoxP3+CD25+CD127Dim), CD4+ non-Tregs, and CD4+ T cell intracellular cytokine content following in vitro stimulation were compared with CA status and oxygen requirement at 36 weeks postmenstrual age. Result Absolute Treg numbers were not different in CA and non-CA exposed samples. However, the infants who developed BPD had a significant decrease in Treg and non-regulatory T cell numbers. Greater IL-6 production was observed in hCA group. Conclusion A pro-inflammatory CD4+ T cell status is noted in CA and BPD but the later disease is also associated with decrease in Tregs, suggesting that the development of BPD is marked by distinct inflammatory changes from those of CA exposed infants.

Published
2015

17. Developmentally determined reduction in CD31 during gestation is associated with CD8+ T cell effector differentiation in preterm infants

Author

Jeanne Holden-Wiltse, Andrew G. Straw, David J. Topham, Sara K. Misra, Hongmei Yang, Thomas J. Mariani, Heidie Huyck, Anne Marie Reynolds, Gloria S. Pryhuber, Kristin Scheible, Rita M. Ryan, and Jason Emo

Subjects
Male, medicine.medical_specialty, T cell, Cellular differentiation, Immunology, Biology, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Umbilical cord, Article, Pregnancy, Internal medicine, medicine, Immunology and Allergy, Cytotoxic T cell, Homeostasis, Humans, Cell Proliferation, Fetus, Infant, Newborn, Cell Differentiation, medicine.disease, Fetal Blood, Platelet Endothelial Cell Adhesion Molecule-1, Endocrinology, medicine.anatomical_structure, Bronchopulmonary dysplasia, Cord blood, Female, Immunologic Memory, CD8, Infant, Premature
Abstract

Homeostatic T cell proliferation is more robust during human fetal development. In order to understand the relative effect of normal fetal homeostasis and perinatal exposures on CD8+ T cell behavior in PT infants, we characterized umbilical cord blood CD8+ T cells from infants born between 23–42 weeks gestation. Subjects were recruited as part of the NHLBI-sponsored Prematurity and Respiratory Outcomes Program. Cord blood from PT infants had fewer naïve CD8+ T cells and lower regulatory CD31 expression on both naïve and effector, independent of prenatal exposures. CD8+ T cell in vitro effector function was greater at younger gestational ages, an effect that was exaggerated in infants with prior inflammatory exposures. These results suggest that CD8+ T cells earlier in gestation have loss of regulatory co-receptor CD31 and greater effector differentiation, which may place PT neonates at unique risk for CD8+ T cell-mediated inflammation and impaired T cell memory formation.

Published
2015

19. White blood cell left shift in a neonate: a case of mistaken identity

Author

Satyanarayana Lakshminrusimha, Ralph J. Wynn, K. Cominsky, Anne Marie Reynolds, Vasantha H.S. Kumar, Rita M. Ryan, and Ibrahim Mohamed

Subjects
Male, medicine.medical_specialty, Pediatrics, Neutrophils, Tachypnea, Leukocyte Count, White blood cell, Sepsis, Left shift, medicine, Humans, Blood culture, Neonatology, Family history, Diagnostic Errors, medicine.diagnostic_test, business.industry, Infant, Newborn, Obstetrics and Gynecology, Complete blood count, medicine.disease, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, Pelger–Huet anomaly, medicine.symptom, business, Pelger-Huet Anomaly
Abstract

We present a full-term male infant who presented with tachypnea and an increased band count on his complete blood count (CBC) with an immature to total neutrophil (I:T) ratio of 0.6 raising suspicion of early onset sepsis. A blood culture was drawn and he was started on appropriate antibiotics. The patient's clinical condition rapidly improved; however, the white cell count ‘left shift’ persisted. When a detailed family history was obtained, it was discovered that the father, paternal uncle and the grandfather had been diagnosed with Pelger-Huet anomaly (PHA). As the urine, blood and CSF cultures were all negative in this now well-appearing infant, the left shift on the CBC was believed to be due to inheritance of the PHA. We present this case to emphasize that even in this age of sophisticated laboratory evaluation, a good clinical history, including family history, and clinical evaluation, are essential for accurate diagnosis.

Published
2006

20. Ultrasound guided percutaneous relief of tension pneumomediastinum in a 1-day-old newborn

Author

Sami Fakir, Ibrahim Mohamed, Yi-Horng Lee, Sani Z. Yamout, and Anne Marie Reynolds

Subjects
medicine.medical_specialty, Images in Neonatal Medicine, Percutaneous, medicine.medical_treatment, Article, Catheterization, Intensive care, medicine, Humans, Intubation, Pneumomediastinum, Mediastinal Emphysema, Ultrasonography, Interventional, Mechanical ventilation, medicine.diagnostic_test, Vaginal delivery, business.industry, Infant, Newborn, Obstetrics and Gynecology, Gestational age, General Medicine, medicine.disease, Surgery, Pulse oximetry, Blood pressure, Chest Tubes, Pediatrics, Perinatology and Child Health, Breathing, business
Abstract

A 35-week gestational age baby with antenatal diagnosis of probable infantile polycystic kidney disease born via normal vaginal delivery required immediate intubation and ventilation in the delivery room. On admission, the baby’s blood pressure was normal (mean of 42 mm Hg) and pulse oximetry read 96% on 100% Fio2. An x ray showed moderate pneumomediastinum. Within 2 h the baby’s blood pressure …

Published
2009

21. 163 BOOSTER SURFACTANT THERAPY BEYOND THE FIRST WEEK OF LIFE IN VENTILATED EXTREMELY LOW GESTATIONAL AGE NEONATES

Author

Aaron Hamvas, Kimberly Spence, Philip L. Ballard, M. H. Godinez, X. Luan, A. M. Hibbs, Sherry E. Courtney, R. Ryan, D. Lisby, A. Ades, Roberta A. Ballard, Anne Marie Reynolds, Michael Posencheg, R. I. Godinez, and Jeffrey D. Merrill

Subjects
Mechanical ventilation, Pediatrics, medicine.medical_specialty, business.industry, medicine.medical_treatment, Gestational age, General Medicine, medicine.disease, Surfactant therapy, General Biochemistry, Genetics and Molecular Biology, law.invention, Bronchopulmonary dysplasia, Randomized controlled trial, law, Anesthesia, medicine, Breathing, Decompensation, Respiratory system, business
Abstract

Many extremely low gestational age neonates (≤ 28 wk, ELGANS) continue to require intubation and mechanical ventilation beyond the first week of life and many experience episodes of dysfunctional surfactant associated with low surfactant protein B content and clinically significant respiratory decompensations (Pediatr Res 2004;56:918-26). We hypothesized that booster surfactant treatment (booster) given during week 2-3 to these infants is safe and improves pulmonary outcome. Infants were enrolled in one of two booster pilot trials. ELGANS requiring ventilation at 7 to 10 days of life received one to two doses of “prophylactic” surfactant (Infasurf®, 3 mL/kg) 1 week apart. In a separate “Rescue” pilot trial, ventilated ELGANS at 5 to 21 days of life with respiratory decompensation received two doses of Infasurf over 12 to 24 hours. Tracheal aspirate (TA) samples were analyzed for minimum surface tension (STmin) in a pulsating bubble surfactometer and for concentrations of cytokines, growth factors, and chemokines. Clinical data including respiratory severity score (SS = mean airway press × FiO2) were collected. Twenty-six infants have been enrolled in the ongoing pilot trials. Mean GA and BW were 25.5 ± 1.3 week and 718.3 ± 151.8 g, respectively. Surfactant instillation was tolerated by infants in both trials. Changes in SS, as an index of initial clinical response, are shown as the number of infants with lower SS score/number with same SS score/number with higher SS score compared to the pr-treatment value (mean and range SS): Following treatment, there was an initial decrease in STmin for most infants, indicating improved function. Analysis of concentrations of IL-1α, IL-1β, IL-6, IL-8, TNFα, IL-10, RANTES, MIP-1α, TGF-β1, and VEGF after treatment revealed no significant changes as compared with pretreatment. These preliminary results support the safety of booster surfactant administration in ventilated ELGANS beyond 7 days of age and indicate a favorable initial response in respiratory status. This therapy will be tested for safety and prevention of bronchopulmonary dysplasia in a multicenter, randomized, controlled trial.

Published
2006

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