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1. Brain structural connectome in neonates with prenatal opioid exposure

Author

Ramana V. Vishnubhotla, Yi Zhao, Qiuting Wen, Jonathan Dietrich, Gregory M. Sokol, Senthilkumar Sadhasivam, and Rupa Radhakrishnan

Subjects
NOWS, DTI, diffusion tensor imaging, brain development, prenatal opioid exposure, brain networks, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

IntroductionInfants with prenatal opioid exposure (POE) are shown to be at risk for poor long-term neurobehavioral and cognitive outcomes. Early detection of brain developmental alterations on neuroimaging could help in understanding the effect of opioids on the developing brain. Recent studies have shown altered brain functional network connectivity through the application of graph theoretical modeling, in infants with POE. In this study, we assess global brain structural connectivity through diffusion tensor imaging (DTI) metrics and apply graph theoretical modeling to brain structural connectivity in infants with POE.MethodsIn this prospective observational study in infants with POE and control infants, brain MRI including DTI was performed before completion of 3 months corrected postmenstrual age. Tractography was performed on the whole brain using a deterministic fiber tracking algorithm. Pairwise connectivity and network measure were calculated based on fiber count and fractional anisotropy (FA) values. Graph theoretical metrics were also derived.ResultsThere were 11 POE and 18 unexposed infants included in the analysis. Pairwise connectivity based on fiber count showed alterations in 32 connections. Pairwise connectivity based on FA values showed alterations in 24 connections. Connections between the right superior frontal gyrus and right paracentral lobule and between the right superior occipital gyrus and right fusiform gyrus were significantly different after adjusting for multiple comparisons between POE infants and unexposed controls. Additionally, alterations in graph theoretical network metrics were identified with fiber count and FA value derived tracts.ConclusionComparisons show significant differences in fiber count in two structural connections. The long-term clinical outcomes related to these findings may be assessed in longitudinal follow-up studies.

Published
2022
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2. Global Brain Functional Network Connectivity in Infants With Prenatal Opioid Exposure

Author

Rupa Radhakrishnan, Ramana V. Vishnubhotla, Yi Zhao, Jingwen Yan, Bing He, Nicole Steinhardt, David M. Haas, Gregory M. Sokol, and Senthilkumar Sadhasivam

Subjects
prenatal opioid exposure, resting state brain networks, neonatal opioid withdrawal syndrome, rs-fMRI, opioid use disorder, Pediatrics, RJ1-570
Abstract

BackgroundInfants with prenatal opioid and substance exposure are at higher risk of poor neurobehavioral outcomes in later childhood. Early brain imaging in infancy has the potential to identify early brain developmental alterations that may help predict behavioral outcomes in these children. In this study, using resting-state functional MRI in early infancy, we aim to identify differences in global brain network connectivity in infants with prenatal opioid and substance exposure compared to healthy control infants.Methods and MaterialsIn this prospective study, we recruited 23 infants with prenatal opioid exposure and 29 healthy opioid naïve infants. All subjects underwent brain resting-state functional MRI before 3 months postmenstrual age. Covariate Assisted Principal (CAP) regression was performed to identify brain networks within which functional connectivity was associated with opioid exposure after adjusting for sex and gestational age. Associations of these significant networks with maternal comorbidities were also evaluated. Additionally, graph network metrics were assessed in these CAP networks.ResultsThere were four CAP network components that were significantly different between the opioid exposed and healthy control infants. Two of these four networks were associated with maternal psychological factors. Intra-network graph metrics, namely average flow coefficient, clustering coefficient and transitivity were also significantly different in opioid exposed infants compared to healthy controls.ConclusionPrenatal opioid exposure is associated with alterations in global brain functional networks compared to non-opioid exposed infants, with intra-network alterations in graph network modeling. These network alterations were also associated with maternal comorbidity, especially mental health. Large-scale longitudinal studies can help in understanding the clinical implications of these early brain functional network alterations in infants with prenatal opioid exposure.

Published
2022
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3. Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation

Author

Taeun Chang, Brenda Poindexter, Gregory M. Sokol, Patrick J Heagerty, Mark Smith, Jessica L Wisnowski, Amit M Mathur, Jeffrey Berman, Ping-Sun Keven Chen, James Dix, Trevor Flynn, Stanley Fricke, Seth D Friedman, Hayden W Head, Chang Y Ho, Beth Kline-Fath, Michael Oveson, Richard Patterson, Sumit Pruthi, Nancy Rollins, Yanerys M Ramos, John Rampton, Jerome Rusin, Dennis W Shaw, Jean Tkach, Shreyas Vasanawala, Arastoo Vossough, Matthew T Whitehead, Duan Xu, Kristen Yeom, Bryan Comstock, Sandra E Juul, Yvonne W Wu, Robert C McKinstry, Kaashif Ahmed, Mariana Beserga, Ellen Bendel-Stenzel, Lina Chalak, John Flibotte, Fernando Gonzalez, Andrea Lampland, Nathalie Maitre, Amit M. Mathur, Dennis Mayock, Ulrike Mietzsch, Rakesh Rao, David Riley, Krisa Van Meurs, Hendrik Weitkamp, Tai-Wei Wu, and Toby Yanowitz

Subjects
Medicine
Abstract

Introduction MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms.Methods and analysis Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation—thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans.Ethics and dissemination IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor.Trial registration number NCT02811263; Pre-result.

Published
2021
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5. Risk of seizures in neonates with hypoxic-ischemic encephalopathy receiving hypothermia plus erythropoietin or placebo

Author

Hannah C. Glass, Courtney J. Wusthoff, Bryan A. Comstock, Adam L. Numis, Fernando F. Gonzalez, Nathalie Maitre, Shavonne L. Massey, Dennis E. Mayock, Ulrike Mietzsch, Niranjana Natarajan, Gregory M. Sokol, Sonia L. Bonifacio, Krisa P. Van Meurs, Cameron Thomas, Kaashif A. Ahmad, Patrick J. Heagerty, Sandra E. Juul, and Yvonne W. Wu

Subjects
Pediatrics, Perinatology and Child Health
Published
2022

6. Safety of sildenafil in extremely premature infants: a phase I trial

Author

Dan L. Stewart, Daniel Gonzalez, Namasivayam Ambalavanan, Andrew M. Atz, Wesley M. Jackson, Gregory M Sokol, Michael Cohen-Wolkowiez, Brenda B. Poindexter, Mary Mills, Chi D. Hornik, Karen Martz, Shawn K. Ahlfeld, Matthew M. Laughon, Christoph P. Hornik, Gratias Mundakel, and P. Brian Smith

Subjects
Mean arterial pressure, Sildenafil, Infant, Premature, Diseases, Enteral administration, Sildenafil Citrate, Article, chemistry.chemical_compound, Humans, Medicine, Adverse effect, Respiratory tract diseases, business.industry, Infant, Newborn, Obstetrics and Gynecology, Infant, Low Birth Weight, medicine.disease, respiratory tract diseases, Clinical trial, chemistry, Outcomes research, Infant, Extremely Premature, Anesthesia, Pediatrics, Perinatology and Child Health, Cohort, cardiovascular system, Population study, Elevated transaminases, Hypotension, business
Abstract

Objective To characterize the safety of sildenafil in premature infants. Study design A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring. Results Twenty-four infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants received a single IV sildenafil dose of 0.25 mg/kg (n = 7) or 0.125 mg/kg (n = 2). In cohort 2, there was one serious AE related to study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases. Conclusion Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants. Clinical trial ClinicalTrials.gov Identifier: NCT01670136.

Published
2021

7. Acute and Chronic Placental Abnormalities in a Multicenter Cohort of Newborn Infants with Hypoxic–Ischemic Encephalopathy

Author

Dennis E. Mayock, Amy M. Goodman, Rakesh Rao, Raymond W. Redline, Ellen M. Bendel-Stenzel, Mariana Baserga, Andrea L. Lampland, Taeun Chang, Krisa P. Van Meurs, Joern Hendrik Weitkamp, Tai-Wei Wu, Yvonne W. Wu, Bryan A. Comstock, Gregory M Sokol, Ulrike Mietzsch, Nathalie L. Maitre, Fernando F. Gonzalez, Brenda B. Poindexter, Toby D Yanowitz, John Flibotte, Kaashif A. Ahmad, Lina F. Chalak, Sandra E. Juul, David Riley, and Amit M. Mathur

Subjects
Male, medicine.medical_specialty, Placenta Diseases, Encephalopathy, Gestational Age, Gastroenterology, Hypoxic Ischemic Encephalopathy, Cohort Studies, Double-Blind Method, Hypothermia, Induced, Pregnancy, Risk Factors, Internal medicine, Placenta, Humans, Medicine, Erythropoietin, Asphyxia, Clinical pathology, business.industry, Infant, Newborn, medicine.disease, medicine.anatomical_structure, Acute Disease, Chronic Disease, Hypoxia-Ischemia, Brain, Pediatrics, Perinatology and Child Health, Cohort, Gestation, Female, medicine.symptom, business, Villitis of unknown etiology
Abstract

To examine the frequency of placental abnormalities in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) and to determine the association between acuity of placental abnormalities and clinical characteristics of HIE.Infants born at ≥36 weeks of gestation (n = 500) with moderate or severe HIE were enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. A placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute and chronic placental abnormalities using a standard classification system.Complete placental pathologic examination was available for 321 of 500 (64%) trial participants. Placental abnormalities were identified in 273 of 321 (85%) and were more common in infants ≥40 weeks of gestation (93% vs 81%, P = .01). A combination of acute and chronic placental abnormalities (43%) was more common than either acute (20%) or chronic (21%) abnormalities alone. Acute abnormalities included meconium staining of the placenta (41%) and histologic chorioamnionitis (39%). Chronic abnormalities included maternal vascular malperfusion (25%), villitis of unknown etiology (8%), and fetal vascular malperfusion (6%). Infants with chronic placental abnormalities exhibited a greater mean base deficit at birth (-15.9 vs -14.3, P = .049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs 38.0, P .001) and greater rates of clinically diagnosed chorioamnionitis (25% vs 2%, P .001) than those without acute abnormalities.Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE.ClinicalTrials.gov: NCT02811263.

Published
2021

8. Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns

Author

Yvonne W, Wu, Bryan A, Comstock, Fernando F, Gonzalez, Dennis E, Mayock, Amy M, Goodman, Nathalie L, Maitre, Taeun, Chang, Krisa P, Van Meurs, Andrea L, Lampland, Ellen, Bendel-Stenzel, Amit M, Mathur, Tai-Wei, Wu, David, Riley, Ulrike, Mietzsch, Lina, Chalak, John, Flibotte, Joern-Hendrik, Weitkamp, Kaashif A, Ahmad, Toby D, Yanowitz, Mariana, Baserga, Brenda B, Poindexter, Elizabeth E, Rogers, Jean R, Lowe, Karl C K, Kuban, T Michael, O'Shea, Jessica L, Wisnowski, Robert C, McKinstry, Stefan, Bluml, Sonia, Bonifacio, Kristen L, Benninger, Rakesh, Rao, Christopher D, Smyser, Gregory M, Sokol, Stephanie, Merhar, Michael D, Schreiber, Hannah C, Glass, Patrick J, Heagerty, Sandra E, Juul, and Adam L, Numis

Subjects
Neuroprotective Agents, Double-Blind Method, Hypothermia, Induced, Cerebral Palsy, Hypoxia-Ischemia, Brain, Infant, Newborn, Humans, Infant, Administration, Intravenous, General Medicine, Erythropoietin
Abstract

Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown.In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57).The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).

Published
2022

9. 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

10. Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants

Author

Haresh, Kirpalani, Edward F, Bell, Susan R, Hintz, Sylvia, Tan, Barbara, Schmidt, Aasma S, Chaudhary, Karen J, Johnson, Margaret M, Crawford, Jamie E, Newman, Betty R, Vohr, Waldemar A, Carlo, Carl T, D'Angio, Kathleen A, Kennedy, Robin K, Ohls, Brenda B, Poindexter, Kurt, Schibler, Robin K, Whyte, John A, Widness, John A F, Zupancic, Myra H, Wyckoff, William E, Truog, Michele C, Walsh, Valerie Y, Chock, Abbot R, Laptook, Gregory M, Sokol, Bradley A, Yoder, Ravi M, Patel, C Michael, Cotten, Melissa F, Carmen, Uday, Devaskar, Sanjay, Chawla, Ruth, Seabrook, Rosemary D, Higgins, Abhik, Das, and Marian, Willinger

Subjects
Pediatrics, medicine.medical_specialty, Anemia, Vision Disorders, MEDLINE, Infant, Premature, Diseases, 030204 cardiovascular system & hematology, law.invention, Hemoglobins, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Humans, 030212 general & internal medicine, Hearing Loss, Survival rate, Obstetrics, Extramural, business.industry, Cerebral Palsy, Cognitive delay, Infant, Newborn, General Medicine, medicine.disease, Survival Rate, Multicenter study, Infant, Extremely Low Birth Weight, Neurodevelopmental Disorders, Infant, Extremely Premature, Hemoglobin, Cognition Disorders, Erythrocyte Transfusion, business, Algorithms, Infant, Premature
Abstract

Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia.We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity.A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively.In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).

Published
2020

11. Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia

Author

Kristi L, Watterberg, Michele C, Walsh, Lei, Li, Sanjay, Chawla, Carl T, D'Angio, Ronald N, Goldberg, Susan R, Hintz, Matthew M, Laughon, Bradley A, Yoder, Kathleen A, Kennedy, Georgia E, McDavid, Conra, Backstrom-Lacy, Abhik, Das, Margaret M, Crawford, Martin, Keszler, Gregory M, Sokol, Brenda B, Poindexter, Namasivayam, Ambalavanan, Anna Maria, Hibbs, William E, Truog, Barbara, Schmidt, Myra H, Wyckoff, Amir M, Khan, Meena, Garg, Patricia R, Chess, Anne M, Reynolds, Mohannad, Moallem, Edward F, Bell, Lauritz R, Meyer, Ravi M, Patel, Krisa P, Van Meurs, C Michael, Cotten, Elisabeth C, McGowan, Abbey C, Hines, Stephanie, Merhar, Myriam, Peralta-Carcelen, Deanne E, Wilson-Costello, Howard W, Kilbride, Sara B, DeMauro, Roy J, Heyne, Ricardo A, Mosquera, Girija, Natarajan, Isabell B, Purdy, Jean R, Lowe, Nathalie L, Maitre, Heidi M, Harmon, Laurie A, Hogden, Ira, Adams-Chapman, Sarah, Winter, William F, Malcolm, Rosemary D, Higgins, and Marian, Willinger

Subjects
Hydrocortisone, Infant, Newborn, Oxygen Inhalation Therapy, General Medicine, Respiration, Artificial, Double-Blind Method, Neurodevelopmental Disorders, Infant, Extremely Premature, Airway Extubation, Humans, Glucocorticoids, Infant, Premature, Bronchopulmonary Dysplasia, Follow-Up Studies
Abstract

Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown.We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age.We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups.In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).

Published
2022

12. Physiologically-Based Pharmacokinetic Modeling Characterizes the CYP3A-Mediated Drug-Drug Interaction Between Fluconazole and Sildenafil in Infants

Author

Jacqueline G Gerhart, Dan L. Stewart, Namasivayam Ambalavanan, Gregory M Sokol, Daniel Gonzalez, Matthew M. Laughon, Chi D. Hornik, Andrea N. Edginton, Sara Salerno, Mary Mills, and Karen Martz

Subjects
Adult, Male, Physiologically based pharmacokinetic modelling, Adolescent, CYP3A, Sildenafil, Pharmacology, 030226 pharmacology & pharmacy, Models, Biological, Article, Sildenafil Citrate, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Pharmacokinetics, Medicine, Cytochrome P-450 CYP3A, Humans, Pharmacology (medical), Drug Interactions, Fluconazole, Active metabolite, Aged, CYP3A4, business.industry, Middle Aged, medicine.disease, Pulmonary hypertension, chemistry, 030220 oncology & carcinogenesis, Area Under Curve, Cytochrome P-450 CYP3A Inhibitors, Female, business, Infant, Premature, medicine.drug
Abstract

Physiologically-based pharmacokinetic (PBPK) modeling can potentially predict pediatric drug-drug interactions (DDIs) when clinical DDI data are limited. In infants for whom treatment of pulmonary hypertension and prevention or treatment of invasive candidiasis are indicated, sildenafil with fluconazole may be given concurrently. To account for developmental changes in cytochrome P450 (CYP) 3A, we determined and incorporated fluconazole inhibition constants (KI ) for CYP3A4, CYP3A5, and CYP3A7 into a PBPK model developed for sildenafil and its active metabolite, N-desmethylsildenafil. Pharmacokinetic (PK) data in preterm infants receiving sildenafil with and without fluconazole were used for model development and evaluation. The simulated PK parameters were comparable to observed values. Following fluconazole co-administration, differences in the fold change for simulated steady-state area under the plasma concentration vs. time curve from 0 to 24 hours (AUCss,0-24 ) were observed between virtual adults and infants (2.11-fold vs. 2.82-fold change). When given in combination with treatment doses of fluconazole (12 mg/kg i.v. daily), reducing the sildenafil dose by ~ 60% resulted in a geometric mean ratio of 1.01 for simulated AUCss,0-24 relative to virtual infants receiving sildenafil alone. This study highlights the feasibility of PBPK modeling to predict DDIs in infants and the need to include CYP3A7 parameters.

Published
2020

13. Brain Resting State Functional Networks in Infants with Prenatal Opioid Exposure

Author

Nicole Steinhardt, Ramana Vishnubhotla, Yi Zhao, David M. Haas, Gregory M. Sokol, Senthilkumar Sadhasivam, and Rupa Radhakrishnan

Subjects
Ocean Engineering
Abstract

Purpose: Infants of mothers with opioid and substance use can present with postnatal withdrawal symptoms and are at risk of poor neurodevelopmental outcomes in later childhood. Identifying methods to evaluate the consequences of substance exposure on the developing brain can help initiate proactive therapies to improve outcomes for opioid-exposed neonates. Additionally, early brain imaging in infancy has the potential to identify early brain developmental alterations that could prognosticate neurodevelopmental outcomes in these children. In this study, we aim to identify differences in global brain network connectivity in infants with prenatal opioid exposure compared to healthy control infants, using resting-state functional MRI performed at less than 2 months completed gestational age. Materials and Methods: In this prospective, IRB-approved study, we recruited 20 infants with prenatal opioid exposure and 20 healthy, opioid naïve infants. Anatomic imaging and resting-state functional MRI were performed at less than 48 weeks corrected gestational age, and rs-fMRI images were co-registered to the UNC neonate brain template and 90 anatomic atlas-labelled regions. Covariate Assisted Principal (CAP) regression was performed to identify brain network functional connectivity that was significantly different among infants with prenatal opioid exposure compared to healthy neonates. Results: Of the 5 significantly different CAP components identified, the most distinct component (CAP5, p= 3.86 x 10-6) spanned several brain regions, including the right inferior temporal gyrus, bilateral Hesch’s gyrus, left thalamus, left supramarginal gyrus, left inferior parietal lobule, left superior parietal gyrus, right anterior cingulate gyrus, right gyrus rectus, left supplementary motor area, and left pars triangularis. Functional connectivity in this network was lower in the infants with prenatal opioid exposure compared to non-opioid exposed infants. Conclusion: This study demonstrates global network alterations in infants with prenatal opioid exposure compared to non-opioid exposed infants. Future studies should be aimed at identifying clinical significance of this altered connectivity.

Published
2021

14. Thalamocortical functional connectivity in infants with prenatal opioid exposure correlates with severity of neonatal opioid withdrawal syndrome

Author

Rupa, Radhakrishnan, Ramana V, Vishnubhotla, Zoe, Guckien, Yi, Zhao, Gregory M, Sokol, David M, Haas, and Senthilkumar, Sadhasivam

Subjects
Analgesics, Opioid, Thalamus, Pregnancy, Infant, Newborn, Humans, Infant, Female, Prospective Studies, Magnetic Resonance Imaging
Abstract

Prenatal opioid exposure (POE) is a growing public health concern due to its associated adverse outcomes including neonatal opioid withdrawal syndrome (NOWS). The aim of this study was to assess alterations in thalamic functional connectivity in neonates with POE using resting-state functional magnetic resonance imaging (rs-fMRI) and identify whether these altered connectivity measures were associated with NOWS severity.In this prospective, IRB-approved study, we performed rs-fMRI in 19 infants with POE and 20 healthy control infants without POE. Following standard pre-processing, we performed seed-based functional connectivity analysis with the right and left thalamus as the regions of interest. We performed post hoc analysis in the prenatal opioid exposure group to identify associations of altered thalamocortical connectivity with severity of NOWS. P value of .05 was considered statistically significant.There were several regions of significantly altered thalamic to cortical functional connectivity in infants with POE compared to the healthy infants. Distinct regions of thalamocortical functional connectivity correlated with maximum modified Finnegan score. Association between thalamocortical connectivity and severity of NOWS was nominally modified by maternal psychological conditions and polysubstance use.Our findings reveal prenatal opioid exposure-related alterations in thalamic functional connectivity in the infant brain that are correlated with severity of NOWS. Future studies may benefit from evaluation of thalamocortical resting state functional connectivity in infants with POE to help stratify risk of long term neurodevelopmental outcomes.

Published
2021

15. Early brain and abdominal oxygenation in extremely low birth weight infants

Author

Valerie Y, Chock, Emily, Smith, Sylvia, Tan, M Bethany, Ball, Abhik, Das, Susan R, Hintz, Haresh, Kirpalani, Edward F, Bell, Lina F, Chalak, Waldemar A, Carlo, C Michael, Cotten, John A, Widness, Kathleen A, Kennedy, Robin K, Ohls, Ruth B, Seabrook, Ravi M, Patel, Abbot R, Laptook, Toni, Mancini, Gregory M, Sokol, Michele C, Walsh, Bradley A, Yoder, Brenda B, Poindexter, Sanjay, Chawla, Carl T, D'Angio, Rosemary D, Higgins, and Krisa P, Van Meurs

Subjects
Oxygen, Hemoglobins, Pregnancy, Infant, Extremely Low Birth Weight, Cerebrovascular Circulation, Infant, Newborn, Humans, Birth Weight, Brain, Female, Prospective Studies, Infant, Premature
Abstract

Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined.A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables.In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions in the first week had the lowest Csat and highest cFTOE (p 0.001).Brain oxygen extraction preferentially increased in more immature and anemic preterm infants. NIRS monitoring may enhance understanding of cerebral and mesenteric oxygenation patterns and inform future protective strategies in the preterm ELBW population.Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.

Published
2021

16. Initial Laparotomy Versus Peritoneal Drainage in Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis or Isolated Intestinal Perforation

Author

Michele C. Walsh, Rachel Geller, Ivan D. Frantz, David E. Skarda, Claudia Pedroza, Seetha Shankaran, Leif D. Nelin, Shawn D. St. Peter, Henry E. Rice, Isabell B. Purdy, Kara L. Calkins, Walter J. Chwals, Kimberly Yolton, Troy A. Markel, Brenda B. Poindexter, Christina M Shanti, Gail E. Besner, David K. Stevenson, Pablo J. Sánchez, William E Truog, Barry Eggleston, Myriam Peralta-Carcelen, Krisa P. Van Meurs, Nathalie L. Maitre, James C.Y. Dunn, R.A. Mosquera, Rebeccah L. Brown, Bradley A. Yoder, Howard W. Kilbride, Satyanarayana Lakshminrusimha, Carroll M. Harmon, Robin K. Ohls, Ricki F. Goldstein, Barbara J. Stoll, Kristi L. Watterberg, Abbey C. Hines, Ravi Mangal Patel, Matthew M. Laughon, Jon E. Tyson, Karl G. Sylvester, Kathryn D. Bass, Alan W. Flake, Carl T. D'Angio, Rosemary D. Higgins, Martin L. Blakely, Reed A. Dimmitt, Arlet G. Kurkchubasche, Colin A. Martin, Girija Natarajan, C. Michael Cotten, David G Lemon, Sarah Winter, Elisabeth C. McGowan, Edward F. Bell, Abhik Das, Diana L. Diesen, Kevin P. Lally, Waldemar A. Carlo, Kelley Yost, Walter Pegoli, Amina M. Bhatia, Susan R. Hintz, Tarah T. Colaizy, Myra H. Wyckoff, Gregory M Sokol, Betty R. Vohr, Sara B. DeMauro, Kathleen A. Kennedy, Abbot R. Laptook, Roy J. Heyne, and Joel Shilyansky

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Perforation (oil well), Infant, Premature, Diseases, Article, law.invention, Randomized controlled trial, Enterocolitis, Necrotizing, law, Laparotomy, medicine, Humans, Survival rate, Enterocolitis, business.industry, Infant, Newborn, medicine.disease, Confidence interval, Surgery, Survival Rate, Treatment Outcome, Infant, Extremely Low Birth Weight, Intestinal Perforation, Neurodevelopmental Disorders, Relative risk, Necrotizing enterocolitis, Drainage, Feasibility Studies, Female, medicine.symptom, business, Infant, Premature
Abstract

OBJECTIVE: To determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18–22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage (adjusted relative risk [aRR] = 1.0; 95% confidence interval [CI]: 0.87–1.14). A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (p = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR=0.81; 95% CI: 0.64 to 1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference

Published
2021

17. Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections

Author

Gratias Mundakel, Gregory M. Sokol, Sherry E. Courtney, Daniel K. Benjamin, Joseph M. Bliss, Jörn-Hendrik Weitkamp, Mark L. Hudak, Gaurav Sharma, Jinson Erinjeri, Matthew A. Saxonhouse, Jamie Gao, P. Brian Smith, Christiane E.L. Dammann, Julie Debski, Gloria P Heresi, Catherine M. Bendel, Barry T. Bloom, C. Michael Cotten, Julie Autmizguine, Angelique E Boutzoukas, Adrian Lavery, Erin K. Zinkhan, Michael J. Smith, Susan R. Mendley, Christoph P. Hornik, and Michael Cohen-Wolkowiez

Subjects
Microbiology (medical), medicine.medical_specialty, Intraabdominal infection, medicine.drug_class, Antibiotics, Population, Article, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Internal medicine, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, education, education.field_of_study, Study drug, business.industry, Mortality rate, Infant, Newborn, Gestational age, Infant, Confidence interval, Anti-Bacterial Agents, Clinical trial, Infectious Diseases, Treatment Outcome, Pediatrics, Perinatology and Child Health, Intraabdominal Infections, business, Infant, Premature
Abstract

BACKGROUND: In premature infants, complicated intra-abdominal infections (cIAIs) are a leading cause of morbidity and mortality. Although universally prescribed, the safety and effectiveness of commonly used antibiotic regimens has not been established in this population. METHODS: Infants ≤33 weeks gestational age and 4) 30 days after study drug completion. RESULTS: 180 infants (128 randomized [R], 52 non-randomized [NR]) were enrolled: 63 in group 1 (45 R, 18 NR), 47 in group 2 (41 R, 6 NR), and 70 in group 3 (42 R, 28 NR). Thirty-day mortality was 8%, 7%, and 9% in groups 1, 2, and 3, respectively. There were no differences in safety outcomes between antibiotic regimens. After adjusting for treatment group and gestational age, mortality rates through end of follow-up were 4.22 (95% confidence interval [CI] 1.39–12.13), 4.53 (95% CI 1.21–15.50), and 4.07 (95% CI 1.22–12.70) for groups 1, 2, and 3, respectively. CONCLUSIONS: Each of the antibiotic regimens are safe in premature infants with cIAI. CLINICAL TRIAL REGISTRATION: NCT0199499

Published
2021

18. Safety of Metronidazole in Late Preterm and Term Infants with Complicated Intraabdominal Infections

Author

Julie Debski, Erin K Zinkhan, Fernando Moya, Sarah Jane Commander, Paula Delmore, Gaurav Sharma, Gloria Heresi, Christoph P. Hornik, Jinson Erinjeri, Tedryl G Bumpass, Gregory M Sokol, P. Brian Smith, Adrian Lavery, Sherry E. Courtney, Jamie Gao, Michael Cohen-Wolkowiez, Elisabeth T. Tracy, and Daniel K. Benjamin

Subjects
Microbiology (medical), Male, Pediatrics, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Exploratory laparotomy, medicine.drug_class, medicine.medical_treatment, Antibiotics, Gestational Age, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Multicenter trial, Ampicillin, Metronidazole, medicine, Humans, 030212 general & internal medicine, business.industry, Infant, Newborn, Gestational age, Infant, Rash, United States, Anti-Bacterial Agents, Infectious Diseases, Pediatrics, Perinatology and Child Health, Vancomycin, Intraabdominal Infections, Drug Therapy, Combination, Female, medicine.symptom, business, medicine.drug
Abstract

BACKGROUND: Metronidazole is frequently used off-label in infants with complicated intra-abdominal infections (cIAI) to provide coverage against anaerobic organisms, but its safety and efficacy in this indication are unknown. METHODS: In the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP) open-label multicenter trial infants ≥34 weeks gestation at birth and 4. A blinded adjudication committee reviewed all safety events of special interest. RESULTS: Fifty-five infants were included; median gestational age was 36 weeks (range: 34–41) and postnatal age was 7 days (0–63). The most common additional antibiotics received included gentamicin, piperacillin-tazobactam, ampicillin, and vancomycin. Only one adverse event, a candidal rash, was identified to be potentially caused by metronidazole administration. One infant died of cardiopulmonary failure, which was deemed unrelated to metronidazole. The most common events of special interest included feeding intolerance in 18 (33%) infants, and exploratory laparotomy in 10 (18%) requiring intestinal anastomosis in 7 (13%) infants. There was one (2%) intestinal stricture. Fifty-three infants (96%) achieved overall therapeutic success, 54 (98%) were alive through 30 days post-study therapy, and 54 (98%) had 30-day clinical cure score >4. CONCLUSIONS: In a cohort of late pre-term and term infants with cIAIs, combination antibiotic therapy that included metronidazole was safe, and therapeutic success was high.

Published
2020

19. Association Between Increased Seizures During Rewarming After Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy and Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up

Author

Lina F. Chalak, Meena Garg, Abbot R. Laptook, Roy J. Heyne, Gregory M Sokol, Jon E. Tyson, William E Truog, Alexis S. Davis, Rebecca Bara, Kurt Schibler, Carl T. D'Angio, Brenda B. Poindexter, M. Bethany Ball, Waldemar A. Carlo, Claudia Pedroza, Cathy Grisby, Pablo J. Sánchez, Seetha Shankaran, Krisa P. Van Meurs, Rosemary D. Higgins, Sylvia Tan, Kevin Dysart, Christopher J. Timan, Edward F. Bell, Shannon E. G. Hamrick, Abhik Das, Athina Pappas, Kristi L. Watterberg, and C. Michael Cotten

Subjects
Male, Pediatrics, medicine.medical_specialty, Encephalopathy, Group B, Hypothermia, Induced, Seizures, Humans, Medicine, EPOCH (chemotherapy), Rewarming, Original Investigation, Asphyxia Neonatorum, business.industry, Infant, Newborn, Correction, Gestational age, Electroencephalography, Odds ratio, Hypothermia, medicine.disease, Case-Control Studies, Relative risk, Hypoxia-Ischemia, Brain, Female, Neurology (clinical), medicine.symptom, business, Cohort study
Abstract

Importance Compared with normothermia, hypothermia has been shown to reduce death or disability in neonatal hypoxic ischemic encephalopathy but data on seizures during rewarming and associated outcomes are scarce. Objective To determine whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and whether they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy. Design, setting, and participants This prespecified nested cohort study of infants enrolled in the Optimizing Cooling (OC) multicenter Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network trial from December 2011 to December 2013 with 2 years' follow-up randomized infants to either 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, 10 declined consent, and 120 met all predefined inclusion criteria. A total of 112 (90%) had complete data for death or disability. Data were analyzed from January 2018 to January 2020. Interventions Serial amplitude electroencephalography recordings were compared in the 12 hours prior and 12 hours during rewarming for evidence of electrographic seizure activity by 2 central amplitude-integrated electroencephalography readers blinded to treatment arm and rewarming epoch. Odds ratios and 95% CIs were evaluated following adjustment for center, prior seizures, depth of cooling, and encephalopathy severity. Main outcomes and measures The primary outcome was the occurrence of electrographic seizures during rewarming initiated at 72 or 120 hours compared with the preceding 12-hour epoch. Secondary outcomes included death or moderate or severe disability at age 18 to 22 months. The hypothesis was that seizures during rewarming were associated with higher odds of abnormal neurodevelopmental outcomes. Results A total of 120 newborns (70 male [58%]) were enrolled (66 in group A and 54 in group B). The mean (SD) gestational age was 39 (1) weeks. There was excellent interrater agreement (κ, 0.99) in detection of seizures. More infants had electrographic seizures during the rewarming epoch compared with the preceding epoch (group A, 27% vs 14%; P = .001; group B, 21% vs 10%; P = .03). Adjusted odd ratios (95% CIs) for seizure frequency during rewarming were 2.7 (1.0-7.5) for group A and 3.2 (0.9-11.6) for group B. The composite death or moderate to severe disability outcome at 2 years was significantly higher in infants with electrographic seizures during rewarming (relative risk [95% CI], 1.7 [1.25-2.37]) after adjusting for baseline clinical encephalopathy and seizures as well as center. Conclusions and relevance Findings that higher odds of electrographic seizures during rewarming are associated with death or disability at 2 years highlight the necessity of electroencephalography monitoring during rewarming in infants at risk. Trial registration ClinicalTrials.gov Identifier: NCT01192776.

Published
2021

20. Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial

Author

Abhik Das, Seetha Shankaran, Richard A. Ehrenkranz, David P. Carlton, Lina F. Chalak, Claudia Pedroza, Valerie Y. Chock, Brenda B. Poindexter, Kristi L. Watterberg, Jon E. Tyson, Rosemary D. Higgins, Pablo J. Sánchez, Heidi M. Harmon, Roger G. Faix, Myra H. Wyckoff, Ronald N. Goldberg, William E. Truog, Michele C. Walsh, Elisabeth C. McGowan, Angelita M. Hensman, Nehal A. Parikh, Uday Devaskar, Edward F. Bell, Athina Pappas, Anna Maria Hibbs, Shannon E. G. Hamrick, Abbot R. Laptook, Krisa P. Van Meurs, Namasivayam Ambalavanan, Gregory M. Sokol, Aasma S. Chaudhary, Jane E. Brumbaugh, Breda Munoz, Ivan D. Frantz, Ronnie Guillet, and C. Michael Cotten

Subjects
Pediatrics, medicine.medical_specialty, Randomization, business.industry, Encephalopathy, Obstetrics and Gynecology, Posterior risk, General Medicine, Hypothermia, medicine.disease, Hypoxic Ischemic Encephalopathy, law.invention, Randomized controlled trial, law, medicine, Gestation, Risk of death, medicine.symptom, business
Abstract

Importance Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks’ or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. Objective To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks’ or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Interventions Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). Main Outcomes and Measures The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks’ gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, −1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. Conclusions and Relevance Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness. Trial Registration clinicaltrials.gov Identifier:NCT00614744

Published
2018

21. Developmental Outcomes of Extremely Preterm Infants with a Need for Child Protective Services Supervision

Author

Elisabeth C. McGowan, Abbot. R. Laptook, Jean Lowe, Myriam Peralta-Carcelen, Dhuly Chowdhury, Rosemary D. Higgins, Susan R. Hintz, Betty R. Vohr, Richard A. Polin, Abbott R. Laptook, Martin Keszler, Angelita M. Hensman, Barbara Alksninis, Kristin M. Basso, Robert Burke, Melinda Caskey, Katharine Johnson, Mary Lenore Keszler, Andrea M. Knoll, Theresa M. Leach, Emilee Little, Elisa Vieira, Victoria E. Watson, Suzy Ventura, Michele C. Walsh, Avroy A. Fanaroff, Anna Marie Hibbs, Deanne E. Wilson-Costello, Nancy S. Newman, Allison H. Payne, 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, Edward F. Donovan, Cathy Grisby, Kate Bridges, Barbara Alexander, Estelle E. Fischer, Holly L. Mincey, Jody Hessling, Teresa L. Gratton, Lenora Jackson, Kristin Kirker, Greg Muthig, Jean J. Steichen, Stacey Tepe, Kimberly Yolton, Ronald N. Goldberg, C. Michael Cotten, Ricki F. Goldstein, Patricia L. Ashley, William F. Malcolm, Kathy J. Auten, Kimberley A. Fisher, Sandra Grimes, Kathryn E. Gustafson, Melody B. Lohmeyer, Joanne Finkle, Matthew M. Laughon, Carl L. Bose, Janice Bernhardt, Gennie Bose, Cindy Clark, Linda Manor, Diane Warner, Janice Wereszczak, David P. Carlton, Barbara J. Stoll, Ira Adams-Chapman, Ellen C. Hale, Yvonne Loggins, Stephanie Wilson Archer, Gregory M. Sokol, Brenda B. Poindexter, Anna M. Dusick, Lu-Ann Papile, Susan Gunn, Faithe Hamer, Dianne E. Herron, Abbey C. Hines, Carolyn Lytle, Heike M. Minnich, Lucy Smiley, Leslie Dawn Wilson, Pablo J. Sanchez, Leif D. Nelin, Sudarshan R. Jadcherla, Patricia Luzader, Christine A. Fortney, Gail E. Besner, Nehal A. Parikh, Abhik Das, Dennis Wallace, Marie G. Gantz, W. Kenneth Poole, Jamie E. Newman, Jeanette O'Donnell Auman, Margaret M. Crawford, Carolyn M. Petrie Huitema, Kristin M. Zaterka-Baxter, Krisa P. Van Meurs, David K. Stevenson, M. Bethany Ball, Alexis S. Davis, Andrew W. Palmquist, Melinda S. Proud, Barbara Bentley, Elizabeth Bruno, Maria Elena DeAnda, Anne M. DeBattista, Beth Earhart, Lynne C. Huffman, Jean G. Kohn, Casey Krueger, Hali E. Weiss, Ivan D. Frantz, John M. Fiascone, Brenda L. MacKinnon, Anne Furey, Ellen Nylen, Waldemar A. Carlo, Namasivayam Ambalavanan, Monica V. Collins, Shirley S. Cosby, Fred J. Biasini, Kristen C. Johnston, Kathleen G. Nelson, Cryshelle S. Patterson, Vivien A. Phillips, 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, Edward F. Bell, Tarah T. Colaizy, Michael J. Acarregui, Dan L. Ellsbury, John A. Widness, Karen J. Johnson, Donia B. Campbell, Diane L. Eastman, Jacky R. Walker, Jane E. Brumbaugh, 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, Jean R. Lowe, Janell F. Fuller, Robin K. Ohls, Conra Backstrom Lacy, Andrea F. Duncan, Rebecca Montman, Barbara Schmidt, Haresh Kirpalani, Sara B. DeMauro, Aasma S. Chaudhary, Soraya Abbasi, Toni Mancini, Dara M. Cucinotta, Judy C. Bernbaum, Marsha Gerdes, Hallam Hurt, Carl T. D'Angio, Dale L. Phelps, Ronnie Guillet, Satyan Lakshminrusimha, Julie Babish Johnson, Linda J. Reubens, Cassandra A. Horihan, Diane Hust, Rosemary L. Jensen, Emily Kushner, Joan Merzbach, Gary J. Myers, Mary Rowan, Holly I.M. Wadkins, Melissa Bowman, Julianne Hunn, Stephanie Guilford, Deanna Maffett, Farooq Osman, Diane Prinzing, Anne Marie Reynolds, Michael G. Sacilowski, Ashley Williams, Karen Wynn, Kelley Yost, William Zorn, Lauren Zwetsch, Kathleen A. Kennedy, Jon E. Tyson, Georgia E. McDavid, Nora I. Alaniz, Julie Arldt-McAlister, Katrina Burson, Patricia W. Evans, Carmen Garcia, Charles Green, Beverly Foley Harris, Margarita Jiminez, Janice John, Patrick M. Jones, Layne M. Lillie, Anna E. Lis, Karen Martin, Sara C. Martin, Brenda H. Morris, M. Layne Poundstone, Peggy Robichaux, Shawna Rodgers, Saba Siddiki, Maegan C. Simmons, Daniel Sperry, Patti L. Pierce Tate, Sharon L. Wright, Myra H. Wyckoff, Luc P. Brion, Roy J. Heyne, Walid A. Salhab, Charles R. Rosenfeld, Diana M. Vasil, Lijun Chen, Alicia Guzman, Gaynelle Hensley, Melissa H. Leps, Nancy A. Miller, Janet S. Morgan, Sally S. Adams, Catherine Twell Boatman, Elizabeth T. Heyne, Linda A. Madden, Lizette E. Torres, Roger G. Faix, Bradley A. Yoder, Karen A. Osborne, Cynthia Spencer, Kimberlee Weaver-Lewis, Shawna Baker, Karie Bird, Jill Burnett, Michael Steffen, Jennifer J. Jensen, Sarah Winter, Karen Zanetti, T. Michael O'Shea, 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, Athina Pappas, John Barks, Rebecca Bara, Laura A. Goldston, Girija Natarajan, Mary Christensen, Stephanie A. Wiggins, Diane White, Richard A. Ehrenkranz, Harris Jacobs, Christine G. Butler, Patricia Cervone, Sheila Greisman, Monica Konstantino, JoAnn Poulsen, Janet Taft, Joanne Williams, and Elaine Romano

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Time Factors, Birth weight, Gestational Age, Prenatal care, Article, 03 medical and health sciences, 0302 clinical medicine, Child Development, stomatognathic system, Pregnancy, 030225 pediatrics, medicine, Hospital discharge, Humans, 030212 general & internal medicine, School education, Retrospective Studies, business.industry, Extremely preterm, Child Protective Services, Infant, Newborn, Infant, Cognition, Prenatal Care, Patient Discharge, United States, stomatognathic diseases, Foster care, Increased risk, Child, Preschool, Infant, Extremely Premature, Pediatrics, Perinatology and Child Health, Female, business, Follow-Up Studies
Abstract

OBJECTIVE: To evaluate neurodevelopmental outcomes of preterm infants with need for Child Protective Services (CPS) supervision at hospital discharge compared with those discharged without CPS supervision. STUDY DESIGN: For infants born at

Published
2019

22. 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

23. Timing of postnatal steroids for bronchopulmonary dysplasia: association with pulmonary and neurodevelopmental outcomes

Author

Heidi M, Harmon, Erik A, Jensen, Sylvia, Tan, Aasma S, Chaudhary, Jonathan L, Slaughter, Edward F, Bell, Myra H, Wyckoff, Angelita M, Hensman, Gregory M, Sokol, Sara B, DeMauro, and Elaine, Romano

Subjects
Male, Pediatrics, medicine.medical_specialty, Perinatal Death, Dexamethasone, Drug Administration Schedule, Infant Death, Article, Cohort Studies, Severe BPD, mental disorders, medicine, Odds Ratio, Humans, Glucocorticoids, Bronchopulmonary Dysplasia, Retrospective Studies, Respiratory Distress Syndrome, Newborn, business.industry, Postmenstrual Age, Age Factors, Infant, Newborn, Patient Acuity, Obstetrics and Gynecology, Gestational age, Infant, Retrospective cohort study, Odds ratio, medicine.disease, Infant mortality, Logistic Models, Bronchopulmonary dysplasia, nervous system, Neurodevelopmental Disorders, Infant, Extremely Premature, Pediatrics, Perinatology and Child Health, Female, business, Cohort study
Abstract

Objective: To determine the associations between age at first postnatal corticosteroids (PNS) exposure and risk for severe bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI). Study Design: Cohort study of 951 infants born

Published
2019

24. 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

25. 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

26. Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies

Author

Kristi L. Watterberg, Krisa P. Van Meurs, Carl T. D'Angio, Michele C. Walsh, Waldemar A. Carlo, Myra H. Wyckoff, Karen M. Puopolo, Monica V. Collins, Gregory M Sokol, Bradley A. Yoder, Brenda B. Poindexter, Pablo J. Sánchez, Nellie I. Hansen, Uday Devaskar, Rosemary D. Higgins, Edward F. Bell, Carol J. Baker, Stephanie J. Schrag, Abbot R. Laptook, Barbara J. Stoll, Abhik Das, S. Nadya J. Kazzi, Ellen C. Hale, and C. Michael Cotten

Subjects
Male, Pediatrics, medicine.medical_specialty, Birth weight, Gestational Age, Group B, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Ampicillin, Escherichia coli, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Escherichia coli Infections, Original Investigation, Neonatal sepsis, business.industry, Incidence, Incidence (epidemiology), Infant, Newborn, Correction, Gestational age, medicine.disease, United States, Practice Guidelines as Topic, Pediatrics, Perinatology and Child Health, Female, Gentamicin, Neonatal Sepsis, business, Infant, Premature, medicine.drug
Abstract

Importance Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, setting, and participants This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main outcomes and measures Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). Conclusions and relevance In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.

Published
2020

27. Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial

Author

Seetha Shankaran, Edward F. Bell, Abbot R. Laptook, Shampa Saha, Nancy S. Newman, S. Nadya J. Kazzi, John Barks, Barbara J. Stoll, Rebecca Bara, Jenna Gabrio, Kirsten Childs, Abhik Das, Rosemary D. Higgins, Waldemar A. Carlo, Pablo J. Sánchez, David P. Carlton, Lara Pavageau, William F. Malcolm, Carl T. D'Angio, Robin K. Ohls, Brenda B. Poindexter, Gregory M. Sokol, Krisa P. Van Meurs, Tarah T. Colaizy, Ayman Khmour, Karen M. Puopolo, Meena Garg, Michele C. Walsh, Richard A. Polin, Martin Keszler, Angelita M. Hensman, Elisa Vieira, Anna Marie Hibbs, Bonnie S. Siner, William E. Truog, Eugenia K. Pallotto, Howard W. Kilbride, Cheri Gauldin, Anne Holmes, Kathy Johnson, Kurt Schibler, Suhas G. Kallapur, Cathy Grisby, Barbara Alexander, Estelle E. Fischer, Lenora Jackson, Kristin Kirker, Jennifer Jennings, Sandra Wuertz, Greg Muthig, C. Michael Cotten, Ronald N. Goldberg, Theresa Roach, Joanne Finkle, Kimberley A. Fisher, Matthew M. Laughon, Carl L. Bose, Janice Bernhardt, Cindy Clark, Stephen D. Kicklighter, Ginger Rhodes-Ryan, Ellen C. Hale, Yvonne Loggins, Diane I. Bottcher, Stephanie Wilson Archer, Heidi Harmon, Dianne E. Herron, Shirley I. Wright-Coltart, Leif D. Nelin, Sudarshan R. Jadcherla, Patricia Luzader, Julie Gutentag, Courtney Park, Julie C. Shadd, Margaret Sullivan, Jennifer L. Grothause, Melanie Stein, Erna Clark, Rox Ann Sullivan, Dennis Wallace, Kristin M. Zaterka-Baxter, Margaret Crawford, Jeanette O'Donnell Auman, David K. Stevenson, Lou Ann Herfert, M. Bethany Ball, Gabrielle T. Goodlin, Melinda S. Proud, R. Jordan Williams, Namasivayam Ambalavanan, Monica V. Collins, Shirley S. Cosby, Teresa Chanlaw, Rachel Geller, Dan L. Ellsbury, Jane E. Brumbaugh, Karen J. Johnson, Donia B. Campbell, Jacky R. Walker, Kristi Watterberg, Conra Backstrom Lacy, Sandy Sundquist Beauman, Carol Hartenberger, Haresh Kirpalani, Eric C. Eichenwald, Sara B. DeMauro, Noah Cook, Aasma S. Chaudhary, Soraya Abbasi, Toni Mancini, Dara Cucinotta, Satyan Lakshminrusimha, Ronnie Guillet, Ann Marie Scorsone, Julianne Hunn, Rosemary Jensen, Holly I.M. Wadkins, Stephanie Guilford, Ashley Williams, Myra Wyckoff, Luc P. Brion, Diana M. Vasil, Lijun Chen, Lizette E. Torres, Athina Pappas, Bogdan Panaitescu, Shelley Handel, Diane F. White, Mary Christensen, and Stephanie A. Wiggins

Subjects
Male, Pediatrics, Incubators, Infant, and Human Development Neonatal Research Network, Reproductive health and childbirth, Low Birth Weight and Health of the Newborn, Infant Equipment, law.invention, incubator, Incubators, 0302 clinical medicine, Randomized controlled trial, law, Neonatal, Infant Mortality, 030212 general & internal medicine, Pediatric, Obstetrics, weaning, Incubator, General Medicine, Patient Discharge, Intensive Care Units, Gestation, Female, Patient Safety, medicine.symptom, Infant, Premature, medicine.medical_specialty, Clinical Trials and Supportive Activities, MEDLINE, Weaning, Article, Child health, Paediatrics and Reproductive Medicine, moderately preterm infants, 03 medical and health sciences, Preterm, Clinical Research, 030225 pediatrics, Intensive Care Units, Neonatal, medicine, Humans, Trial registration, Adverse effect, Premature, business.industry, Body Weight, Infant, Newborn, Infant, temperature, Human Movement and Sports Sciences, Perinatal Period - Conditions Originating in Perinatal Period, Length of Stay, Newborn, Eunice Kennedy Shriver National Institute of Child Health, Good Health and Well Being, randomized controlled trial, Pediatrics, Perinatology and Child Health, business, Weight gain
Abstract

ObjectiveTo assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight.Study designThis trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight

Published
2018

28. Expired Tidal Volume Variation in Extremely Low Birth Weight and Very Low Birth Weight Infants on Volume-Targeted Ventilation

Author

Honglang Wang, Samuel Wong, Robert S. Tepper, Gregory M. Sokol, and Rebecca Rose

Subjects
Male, congenital, hereditary, and neonatal diseases and abnormalities, Expired tidal volume, medicine.medical_treatment, Birth weight, Gestational Age, Infant, Premature, Diseases, Intermittent Positive-Pressure Ventilation, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Intensive Care Units, Neonatal, medicine, Tidal Volume, Humans, Infant, Very Low Birth Weight, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, reproductive and urinary physiology, Tidal volume, Mechanical ventilation, business.industry, Infant, Newborn, Gestational age, Volume targeted ventilation, Low birth weight, Exhalation, Infant, Extremely Low Birth Weight, Anesthesia, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, business, Follow-Up Studies
Abstract

In a prospective study we describe the delivery of small tidal volumes to extremely low birth weight (ELBW) and very low birth weight (VLBW) infants using a volume-targeted ventilation mode (VTV). Tidal volume delivery was consistent for both ELBW and VLBW infants independent of gestational age, birth weight, and the target volume.

Published
2018

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

Author

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

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

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

Published
2018

30. 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

31. Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants

Author

Abhik Das, Sandy Sundquist Beauman, Barbara J. Stoll, William E Truog, B. Carper, Erika Fernandez, Myra H. Wyckoff, Satyanarayana Lakshminrusimha, Gregory M Sokol, Waldemar A. Carlo, Brenda B. Poindexter, Kathleen A. Kennedy, Pablo J. Sánchez, Sanjay Chawla, Cheri Gauldin, Rosemary D. Higgins, C M Cotten, K. P. Van Meurs, Edward F. Bell, W. F. Buss, Uday Devaskar, M.C. Walsh, María V. Fraga, Andrea F. Duncan, Conra Backstrom Lacy, and Kristi L. Watterberg

Subjects
Inotrope, Pediatrics, Hydrocortisone, Reproductive health and childbirth, Low Birth Weight and Health of the Newborn, law.invention, Congenital, 0302 clinical medicine, Randomized controlled trial, law, Informed consent, Infant Mortality, 030212 general & internal medicine, Heart Defects, Pediatric, education.field_of_study, Informed Consent, Obstetrics and Gynecology, Early Termination of Clinical Trials, Gestation, Infant, Premature, medicine.drug, Heart Defects, Congenital, medicine.medical_specialty, Cardiotonic Agents, Critical Illness, Clinical Trials and Supportive Activities, Population, Clinical Sciences, MEDLINE, Article, Paediatrics and Reproductive Medicine, 03 medical and health sciences, Double-Blind Method, Clinical Research, Preterm, 030225 pediatrics, medicine, Humans, education, Premature, Heart Failure, business.industry, Patient Selection, Infant, Newborn, Infant, Perinatal Period - Conditions Originating in Perinatal Period, Newborn, Good Health and Well Being, Neurodevelopmental Disorders, Pediatrics, Perinatology and Child Health, Observational study, business
Abstract

Objective To analyze reasons for low enrollment in an RCT of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late-preterm newborns. Study Design The original study was a multicenter RCT. Eligibility: ≥34 weeks’ gestation

Published
2017

32. Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial

Author

Angelita M. Hensman, Athina Pappas, Krisa P. Van Meurs, Jane E. Brumbaugh, Aasma S. Chaudhary, Breda Munoz, Ivan D. Frantz, Jon E. Tyson, Ronnie Guillet, William E. Truog, David P. Carlton, Myra H. Wyckoff, Claudia Pedroza, Anna Maria Hibbs, Abhik Das, Richard A. Ehrenkranz, Namasivayam Ambalavanan, Elisabeth C. McGowan, Brenda B. Poindexter, Abbot R. Laptook, Rosemary D. Higgins, Pablo J. Sánchez, Seetha Shankaran, Michele C. Walsh, Nehal A. Parikh, Heidi M. Harmon, Roger G. Faix, Ronald N. Goldberg, Gregory M. Sokol, Lina F. Chalak, Edward F. Bell, C. Michael Cotten, Shannon E. G. Hamrick, Kristi L. Watterberg, Uday Devaskar, and Valerie Y. Chock

Subjects
Male, Randomization, Developmental Disabilities, Encephalopathy, Gestational Age, Hypoxic Ischemic Encephalopathy, Article, law.invention, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Hypothermia, Induced, Pregnancy, 030225 pediatrics, Medicine, Humans, business.industry, Infant, Newborn, Gestational age, Bayes Theorem, General Medicine, Hypothermia, medicine.disease, Pregnancy Complications, Anesthesia, Hypoxia-Ischemia, Brain, Gestation, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Importance Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks’ or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. Objective To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks’ or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Interventions Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). Main Outcomes and Measures The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks’ gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, −1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. Conclusions and Relevance Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness. Trial Registration clinicaltrials.gov Identifier:NCT00614744

Published
2017

33. 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

34. Admission Temperature and Associated Mortality and Morbidity among Moderately and Extremely Preterm Infants

Author

Abbot R. Laptook, Edward F. Bell, Seetha Shankaran, Nansi S. Boghossian, Myra H. Wyckoff, Sarah Kandefer, Michele Walsh, Shampa Saha, Rosemary Higgins, Richard A. Polin, Martin Keszler, Betty R. Vohr, Angelita M. Hensman, Elisa Vieira, Emilee Little, Avroy A. Fanaroff, Anna Marie Hibbs, Nancy S. Newman, Bonnie S. Siner, William E. Truog, Eugenia K. Pallotto, Howard W. Kilbride, Cheri Gauldin, Anne Holmes, Kathy Johnson, Kurt Schibler, Suhas G. Kallapur, Cathy Grisby, Barbara Alexander, Estelle E. Fischer, Lenora Jackson, Kristin Kirker, Jennifer Jennings, Sandra Wuertz, Greg Muthig, Edward F. Donovan, Jody Hessling, Marcia Worley Mersmann, Holly L. Mincey, C. Michael Cotten, Ronald N. Goldberg, Joanne Finkle, Kimberley A. Fisher, Kathy J. Auten, Matthew M. Laughon, Carl L. Bose, Janice Bernhardt, Cindy Clark, Barbara J. Stoll, David P. Carlton, Ellen C. Hale, Yvonne Loggins, Diane I. Bottcher, Stephanie Wilson Archer, Linda L. Wright, Elizabeth M. McClure, Brenda B. Poindexter, Gregory M. Sokol, Dianne E. Herron, James A. Lemons, Diana D. Appel, Lucy C. Miller, Pablo J. Sanchez, Leif D. Nelin, Sudarshan R. Jadcherla, Patricia Luzader, Nehal A. Parikh, Marliese Dion Nist, Jennifer Fuller, Julie Gutentag, Marissa E. Jones, Sarah McGregor, Elizabeth Rodgers, Jodi A. Ulloa, Tara Wolfe, Abhik Das, Dennis Wallace, W. Kenneth Poole, Kristin M. Zaterka-Baxter, Margaret Crawford, Jenna Gabrio, Jeanette O'Donnell Auman, Carolyn Petrie Huitema, Betty K. Hastings, Krisa P. Van Meurs, David K. Stevenson, M. Bethany Ball, Melinda S. Proud, Waldemar A. Carlo, Namasivayam Ambalavanan, Monica V. Collins, Shirley S. Cosby, Uday Devaskar, Meena Garg, Teresa Chanlaw, Rachel Geller, Tarah T. Colaizy, Dan L. Ellsbury, Jane E. Brumbaugh, Karen J. Johnson, Donia B. Campbell, Jacky R. Walker, Kristi L. Watterberg, Robin K. Ohls, Conra Backstrom Lacy, Sandra Sundquist Beauman, Carol Hartenberger, Barbara Schmidt, Haresh Kirpalani, Noah Cook, Sara B. DeMauro, Aasma S. Chaudhary, Soraya Abbasi, Toni Mancini, Dara Cucinotta, Carl T. D'Angio, Ronnie Guillet, Satyan Lakshminrusimha, Dale L. Phelps, Ann Marie Reynolds, Julianne Hunn, Rosemary Jensen, Holly I.M. Wadkins, Stephanie Guilford, Ashley Williams, Michael Sacilowski, Linda Reubens, Erica Burnell, Mary Rowan, Karen Wynn, Deanna Maffett, Luc P. Brion, Diana M. Vasil, Lijun Chen, Lizette E. Torres, Walid A. Salhab, Susie Madison, Gay Hensley, Nancy A. Miller, Alicia Guzman, Kathleen A. Kennedy, Jon E. Tyson, Julie Arldt-McAlister, Carmen Garcia, Karen Martin, Georgia E. McDavid, Sharon L. Wright, Esther G. Akpa, Patty A. Cluff, Anna E. Lis, Claudia I. Franco, Athina Pappas, John Barks, Rebecca Bara, Shelley Handel, Geraldine Muran, Diane F. White, Mary Christensen, and Stephanie A. Wiggins

Subjects
Male, Pediatrics, medicine.medical_specialty, Fever, Hospital mortality, Hypothermia, Infant, Premature, Diseases, Logistic regression, Child health, Article, Body Temperature, 03 medical and health sciences, 0302 clinical medicine, Patient Admission, Risk Factors, 030225 pediatrics, Intensive Care Units, Neonatal, Medicine, Humans, 030212 general & internal medicine, Hospital Mortality, business.industry, Extremely preterm, Infant, Newborn, Infant newborn, United States, Logistic Models, Infant, Extremely Premature, Pediatrics, Perinatology and Child Health, Female, business
Abstract

To evaluate the temperature distribution among moderately preterm (MPT, 29-33 weeks) and extremely preterm (EPT,29 weeks) infants upon neonatal intensive care unit (NICU) admission in 2012-2013, the change in admission temperature distribution for EPT infants between 2002-2003 and 2012-2013, and associations between admission temperature and mortality and morbidity for both MPT and EPT infants.Prospectively collected data from 18 centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were used to examine NICU admission temperature of inborn MPT and EPT infants. Associations between admission temperature and mortality and morbidity were determined by multivariable logistic regression. EPT infants from 2002-2003 and 2012-2013 were compared.MPT and EPT cohorts consisted of 5818 and 3213 infants, respectively. The distribution of admission temperatures differed between the MPT vs EPT (P .01), including the percentage36.5°C (38.6% vs 40.9%), 36.5°C-37.5°C (57.3% vs 52.9%), and37.5°C (4.2% vs 6.2%). For EPT infants in 2012-2013 compared with 2002-2003, the percentage of temperatures between 36.5°C and 37.5°C more than doubled and the percentage of temperatures37.5°C more than tripled. Admission temperature was inversely associated with in-hospital mortality.Low and high admission temperatures are more frequent among EPT than MPT infants. Compared with a decade earlier, fewer EPT infants experience low admission temperatures but more have elevated temperatures. In spite of a change in distribution of NICU admission temperature, an inverse association between temperature and mortality risk persists.

Published
2017

35. Effects of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-ischemic Encephalopathy

Author

Jon E. Tyson, Roger G. Faix, Ronald N. Goldberg, Heidi M. Harmon, Athina Pappas, Angelita M. Hensman, Ivan D. Frantz, Ronnie Guillet, William E Truog, Claudia Pedroza, Lina F. Chalak, Jane E. Brumbaugh, K. P. Van Meurs, Rosemary D. Higgins, Brenda B. Poindexter, Elisabeth C. McGowan, Pablo J. Sánchez, Valerie Y. Chock, Gregory M Sokol, Seetha Shankaran, Myra H. Wyckoff, Richard A. Ehrenkranz, Edward F. Bell, Anna Maria Hibbs, Aasma S. Chaudhary, David P. Carlton, Kristi L. Watterberg, Abhik Das, A. R. Laptook, M.C. Walsh, Shannon E. G. Hamrick, Breda Munoz, Nehal A. Parikh, Namasivayam Ambalavanan, C M Cotten, and U. Devaskar

Subjects
03 medical and health sciences, 0302 clinical medicine, business.industry, Anesthesia, medicine, 030212 general & internal medicine, Hypothermia, medicine.symptom, business, 030217 neurology & neurosurgery, Hypoxic Ischemic Encephalopathy
Published
2018

36. Association between Policy Changes for Oxygen Saturation Alarm Settings and Neonatal Morbidity and Mortality in Infants Born Very Preterm

Author

David P. Carlton, Julie Arldt-McAlister, Maegan C. Simmons, Jody Hessling, Rebecca Bara, W. Kenneth Poole, Charles R. Rosenfeld, Brenda B. Poindexter, Andrea M. Knoll, Colleen Mackie, Kurt Schibler, Gregory M. Sokol, Dennis Wallace, Kathy J. Auten, Karen J. Johnson, Georgia E. McDavid, Yvonne Loggins, M. Bethany Ball, Carmen Garcia, Lucy Miller, Nancy A. Miller, Athina Pappas, Ellen C. Hale, Allison H. Payne, Kristin M. Basso, Carol H. Hartenberger, Carolyn M. Petrie Huitema, Shawna Rodgers, Edward F. Donovan, Estelle E. Fischer, Kristi L. Watterberg, Karen Martin, Gaynelle Hensley, Michele C. Walsh, Avroy A. Fanaroff, Luc P. Brion, Tarah T. Colaizy, Jon E. Tyson, David K. Stevenson, Lijun Chen, Kate Bridges, Andrew W. Palmquist, Seetha Shankaran, Marian M. Adams, Anna Maria Hibbs, Sara B. DeMauro, Dianne E. Herron, Diane I. Bottcher, Anna E. Lis, Girija Natarajan, John A. Widness, Marie G. Gantz, Emilee Little, Stephanie Wilson Archer, Shirley S. Cosby, Melissa H. Leps, Namasivayam Ambalavanan, Rosemary D. Higgins, Leslie Dawn Wilson, Joanne Finkle, C. Michael Cotten, Walid A. Salhab, Barbara D. Alexander, Ronald N. Goldberg, Barbara J. Stoll, Abhik Das, Elizabeth E. Foglia, Mary Hanson, Elisa Vieira, Beverly Foley Harris, Myra H. Wyckoff, Conra Backstrom Lacy, Diana M. Vasil, Kimberley A. Fisher, Holly L. Mincey, Magdy Ismail, Martin Keszler, A. R. Laptook, Sara C. Martin, Kristin Kirker, Melinda S. Proud, Robin K. Ohls, Kristin M. Zaterka-Baxter, Alicia Guzman, Angelita M. Hensman, Margaret M. Crawford, Nancy S. Newman, Lizette E. Lee, Benjamin Carper, Waldemar A. Carlo, Jennifer A. Keller, Krisa P. Van Meurs, Lenora Jackson, Greg Muthig, Monica V. Collins, Cathy Grisby, Patti L. Pierce Tate, Satyan Lakshminrusimha, Stacey Tepe, Katrina Burson, Kathleen A. Kennedy, Michael S. Caplan, Jeanette O'Donnell Auman, Sandra Sundquist Beauman, Jacky R. Walker, Lara Pavageau, Edward F. Bell, Janet S. Morgan, and Barbara Schmidt

Subjects
Pediatrics, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Retinopathy of prematurity, Retrospective cohort study, medicine.disease, Odds, 03 medical and health sciences, Pulse oximetry, ALARM, 0302 clinical medicine, Bronchopulmonary dysplasia, 030225 pediatrics, Pediatrics, Perinatology and Child Health, Necrotizing enterocolitis, medicine, sense organs, 030212 general & internal medicine, skin and connective tissue diseases, business, Oxygen saturation (medicine)
Abstract

Objective To determine the impact of policy changes for pulse oximetry oxygen saturation (SpO2) alarm limits on neonatal mortality and morbidity among infants born very preterm. Study design This was a retrospective cohort study of infants born very preterm in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants were classified based on treatment at a hospital with an SpO2 alarm policy change and study epoch (before vs after policy change). We used a generalized linear mixed model to determine the effect of hospital group and epoch on the primary outcomes of mortality and severe retinopathy of prematurity (ROP) and secondary outcomes of necrotizing enterocolitis, bronchopulmonary dysplasia, and any ROP. Results There were 3809 infants in 10 hospitals with an SpO2 alarm policy change and 3685 infants in 9 hospitals without a policy change. The nature of most policy changes was to narrow the SpO2 alarm settings. Mortality was lower in hospitals without a policy change (aOR 0.63; 95% CI 0.50-0.80) but did not differ between epochs in policy change hospitals. The odds of bronchopulmonary dysplasia were greater for hospitals with a policy change (aOR 1.65; 95% CI 1.36-2.00) but did not differ for hospitals without a policy change. Severe ROP and necrotizing enterocolitis did not differ between epochs for either group. The adjusted odds of any ROP were lower in recent years in both hospital groups. Conclusions Changing SpO2 alarm policies was not associated with reduced mortality or increased severe ROP among infants born very preterm.

Published
2019

37. Inhaled Nitric Oxide Therapy for Pulmonary Disorders of the Term and Preterm Infant

Author

Gregory M. Sokol, Krisa P. Van Meurs, and Girija G. Konduri

Subjects
medicine.medical_specialty, Biomedical Research, Hypertension, Pulmonary, Vasodilator Agents, Context (language use), Infant, Premature, Diseases, Nitric Oxide, Extracorporeal, Article, law.invention, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Extracorporeal Membrane Oxygenation, Randomized controlled trial, law, 030225 pediatrics, Administration, Inhalation, medicine, Humans, 030212 general & internal medicine, Nitric oxide therapy, Intensive care medicine, Hypoxia, Bronchopulmonary Dysplasia, Randomized Controlled Trials as Topic, business.industry, Infant, Newborn, Obstetrics and Gynecology, medicine.disease, Pulmonary hypertension, Treatment Outcome, Respiratory failure, chemistry, Pediatrics, Perinatology and Child Health, Neonatology, business, Respiratory Insufficiency, Infant, Premature, Pulmonary disorders
Abstract

The 21st century began with the FDA approval of inhaled nitric oxide therapy for the treatment of neonatal hypoxic respiratory failure associated with pulmonary hypertension in recognition of the two randomized clinical trials demostrating a significant reduction in the need for extracorporeal support in the term and near-term infant. Inhaled nitric oxide is one of only a few therapeutic agents approved for use through clinical investigations primarily in the neonate. This article provides an overview of the pertinent biology and chemistry of nitric oxide, discusses potential toxicities, and reviews the results of pertinent clinical investigations and large randomized clinical trials including neurodevelopmental follow-up in term and preterm neonates. The clinical investigations conducted by the Eunice Kennedy Shriver NICHD Neonatal Research Network will be discussed and placed in context with other pertinent clinical investigations exploring the efficacy of inhaled nitric oxide therapy in neonatal hypoxic respiratory failure.

Published
2016

38. Effects ofMyo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks’ Gestational Age

Author

Kristin M. Zaterka-Baxter, Amy K. Hutchinson, Rosemary D. Higgins, Stephen D. Kicklighter, Abbot R. Laptook, C. Michael Cotten, Conra Backstrom Lacy, Carol A. Cole, David K. Wallace, Kristi L. Watterberg, Ann Marie Scorsone, Patricia R. Chess, Namasivayam Ambalavanan, Abhik Das, William Oh, David P. Carlton, Waldemar A. Carlo, Luc P. Brion, Michele C. Walsh, William E Truog, Kartik S. Kumar, Brenda B. Poindexter, Tarah T. Colaizy, Faruk H. Orge, Martin S. Cogen, Edward F. Bell, Matthew M. Laughon, John P Donahue, Michael B. Yang, Gregory M. Sokol, Anna Marie Hibbs, William R. Lucas, Graham E. Quinn, Heidi M. Harmon, Michael W. Gaynon, Krisa P. Van Meurs, Helen A. Mintz-Hittner, Kathleen A. Kennedy, Dale L. Phelps, Tracy L. Nolen, Seetha Shankaran, Denise Hug, Kurt Schibler, Meena Garg, Irena Tsui, Richard J. Olson, Sara B. DeMauro, Timothy W. Winter, Elisabeth C. McGowan, Yu Guang He, Amanda E. Graf, Satyanarayana Lakshminrusimha, Kathryn M. Haider, Don L. Bremer, and Mina Chung

Subjects
Male, medicine.medical_specialty, Gestational Age, Placebo, Infant, Newborn, Diseases, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, 030225 pediatrics, Intensive care, Internal medicine, Humans, Medicine, Retinopathy of Prematurity, Treatment Failure, 030212 general & internal medicine, Original Investigation, Cerebral Intraventricular Hemorrhage, Respiratory distress, business.industry, Infant, Newborn, Gestational age, Retinopathy of prematurity, General Medicine, medicine.disease, Infant, Extremely Premature, Relative risk, Necrotizing enterocolitis, Intensive Care, Neonatal, Female, business, Inositol, Follow-Up Studies
Abstract

IMPORTANCE: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. OBJECTIVE: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks’ gestational age. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial included 638 infants younger than 28 weeks’ gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. INTERVENTIONS: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. MAIN OUTCOMES AND MEASURES: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. RESULTS: Among 638 infants (mean, 26 weeks’ gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks’ postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). CONCLUSIONS AND RELEVANCE: Among premature infants younger than 28 weeks’ gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

Published
2018

39. Extreme Preterm Infant Rates of Overweight and Obesity at School Age in the SUPPORT Neuroimaging and Neurodevelopmental Outcomes Cohort

Author

Betty R. Vohr, Roy Heyne, Carla M. Bann, Abhik Das, Rosemary D. Higgins, Susan R. Hintz, Alan H. Jobe, Michael S. Caplan, Richard A. Polin, Abbot R. Laptook, Angelita M. Hensman, Elisabeth C. McGowan, Elisa Vieira, Emilee Little, Katharine Johnson, Barbara Alksninis, Mary Lenore Keszler, Andrea M. Knoll, Theresa M. Leach, Victoria E. Watson, Michele C. Walsh, Avroy A. Fanaroff, Deanne E. Wilson-Costello, Allison Payne, Nancy S. Newman, H. Gerry Taylor, Bonnie S. Siner, Arlene Zadell, Julie DiFiore, Monika Bhola, Harriet G. Friedman, Gulgun Yalcinkaya, Dorothy Bulas, Ronald N. Goldberg, C. Michael Cotten, Ricki F. Goldstein, Kathryn E. Gustafson, Patricia Ashley, Kathy J. Auten, Kimberley A. Fisher, Katherine A. Foy, Sharon F. Freedman, Melody B. Lohmeyer, William F. Malcolm, David K. Wallace, David P. Carlton, Barbara J. Stoll, Ira Adams-Chapman, Susie Buchter, Anthony J. Piazza, null Carter, Sobha Fritz, Ellen C. Hale, Amy K. Hutchinson, Maureen Mulligan LaRossa, Yvonne Loggins, Diane Bottcher, Stephanie Wilson Archer, Brenda B. Poindexter, Gregory M. Sokol, Heidi M. Harmon, Lu-Ann Papile, Abbey C. Hines, Leslie D. Wilson, Dianne E. Herron, Lucy Smiley, Kathleen A. Kennedy, Jon E. Tyson, Andrea Freeman Duncan, Allison G. Dempsey, Janice John, Patrick M. Jones, M. Layne Lillie, Saba Siddiki, Daniel K. Sperry, Mary Anne Berberich, Carol J. Blaisdell, Dorothy B. Gail, James P. Kiley, Dennis Wallace, Marie G. Gantz, Jamie E. Newman, Jeanette O'Donnell Auman, Jane A. Hammond, W. Kenneth Poole, Krisa P. Van Meurs, David K. Stevenson, Maria Elena DeAnda, M. Bethany Ball, Gabrielle T. Goodlin, Ivan D. Frantz, John M. Fiascone, Anne Furey, Brenda L. MacKinnon, Ellen Nylen, Ana Brussa, Cecelia Sibley, Waldemar A. Carlo, Namasivayam Ambalavanan, Myriam Peralta-Carcelen, Monica V. Collins, Shirley S. Cosby, Vivien A. Phillips, Kirstin J. Bailey, Fred J. Biasini, Maria Hopkins, Kristen C. Johnston, Kathleen G. Nelson, Cryshelle S. Patterson, Richard V. Rector, Leslie Rodriguez, Amanda Soong, Sally Whitley, Sheree York, Kristy Guest, Leigh Ann Smith, Neil N. Finer, Donna Garey, Maynard R. Rasmussen, Paul R. Wozniak, Yvonne E. Vaucher, Martha G. Fuller, Natacha Akshoomoff, Wade Rich, Kathy Arnell, Renee Bridge, Edward F. Bell, Tarah T. Colaizy, John A. Widness, Jonathan M. Klein, Karen J. Johnson, Michael J. Acarregui, Diane L. Eastman, Tammy L.V. Wilgenbusch, Kristi L. Watterberg, Robin K. Ohls, Janell Fuller, Jean Lowe, Julie Rohr, Conra Backstrom Lacy, Rebecca Montman, Sandra Brown, Pablo J. Sánchez, Charles R. Rosenfeld, Walid A. Salhab, Luc Brion, Sally S. Adams, James Allen, Laura Grau, Alicia Guzman, Gaynelle Hensley, Elizabeth T. Heyne, Jackie F. Hickman, Melissa H. Leps, Linda A. Madden, Melissa Martin, Nancy A. Miller, Janet S. Morgan, Araceli Solis, Lizette E. Lee, Catherine Twell Boatman, Diana M. Vasil, Bradley A. Yoder, Roger G. Faix, Sarah Winter, Shawna Baker, Karen A. Osborne, Carrie A. Rau, Sean Cunningham, Ariel Ford, Seetha Shankaran, Athina Pappas, Beena G. Sood, Rebecca Bara, Thomas L. Slovis, Elizabeth Billian, Laura A. Goldston, and Mary Johnson

Subjects
Male, Percentile, Pediatrics, medicine.medical_specialty, Waist, Neuroimaging, Overweight, Article, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 030225 pediatrics, medicine, Humans, Obesity, 030212 general & internal medicine, Child, Schools, business.industry, Incidence, Postmenstrual Age, nutritional and metabolic diseases, Infant, Low Birth Weight, Anthropometry, Prognosis, medicine.disease, United States, Neurodevelopmental Disorders, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, business, Weight gain, Body mass index, Infant, Premature
Abstract

OBJECTIVE: To identify rates of overweight (BMI ≥85(th) percentile) and obesity (BMI ≥95(th) percentile) at 6-7 years of age and associated risk factors among extremely preterm infants born at < 28 weeks of gestation. STUDY DESIGN: Anthropometrics, blood pressure, and active and sedentary activity levels were prospectively assessed. Three groups were compared, those with BMI≥85(th) percentile (overweight or obese for age, height and sex) and ≥95(th) percentile (obese) versus 85(th) percentile), central fat (waist circumference> 90(th) percentile), spent more time in sedentary activity (20.5 versus 18.2 versus 16.7 hours/week), and had either systolic and/or diastolic hypertension (24% versus 26% versus 14 %) respectively. Post discharge weight gain velocities from 36 weeks postmenstrual age (PMA) to 18 months, and 18 months to 6-7 years were independently associated with BMI ≥85(th) percentile whereas weight-gain velocity from 18 months to 6-7 years was associated with obesity. CONCLUSIONS: One in five former extremely preterm infants is overweight or obese and has central obesity at early school age. Post discharge weight gain velocities were associated with overweight and obesity. These findings suggest the obesity epidemic is spreading to the most extremely preterm infants. Trial registration ClinicalTrials.gov NCT00063063 and NCT0000

Published
2018

40. Outcome of Preterm Infants with Transient Cystic Periventricular Leukomalacia on Serial Cranial Imaging Up to Term Equivalent Age

Author

Subrata Sarkar, Seetha Shankaran, John Barks, Barbara T. Do, Abbot R. Laptook, Abhik Das, Namasivayam Ambalavanan, Krisa P. Van Meurs, Edward F. Bell, Pablo J. Sanchez, Susan R. Hintz, Myra H. Wyckoff, Barbara J. Stoll, Waldemar A. Carlo, Alan H. Jobe, Michael S. Caplan, Richard A. Polin, Martin Keszler, William Oh, Betty R. Vohr, Angelita M. Hensman, Barbara Alksninis, Kristin M. Basso, Robert Burke, Melinda Caskey, Katharine Johnson, Mary Lenore Keszler, Andrea M. Knoll, Theresa M. Leach, Emilee Little, Elisabeth C. McGowan, Elisa Vieira, Victoria E. Watson, Suzy Ventura, Michele C. Walsh, Avroy A. Fanaroff, Anna Marie Hibbs, Deanne E. Wilson-Costello, Nancy S. Newman, Allison H. Payne, 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, Edward F. Donovan, Cathy Grisby, Kate Bridges, Barbara Alexander, Estelle E. Fischer, Holly L. Mincey, Jody Hessling, Teresa L. Gratton, Lenora Jackson, Kristin Kirker, Greg Muthig, Jean J. Steichen, Stacey Tepe, Marcia Worley Mersmann, Kimberly Yolton, Ronald N. Goldberg, C. Michael Cotten, Ricki F. Goldstein, Patricia L. Ashley, William F. Malcolm, Kathy J. Auten, Kimberley A. Fisher, Sandra Grimes, Kathryn E. Gustafson, Melody B. Lohmeyer, Joanne Finkle, Matthew M. Laughon, Carl L. Bose, Janice Bernhardt, Gennie Bose, Diane Warner, Janice Wereszczak, David P. Carlton, Ira Adams-Chapman, Ellen C. Hale, Yvonne Loggins, Ann M. Blackwelder, Diane I. Bottcher, Colleen Mackie, Rosemary D. Higgins, Stephanie Wilson Archer, Gregory M. Sokol, Brenda B. Poindexter, James A. Lemons, Anna M. Dusick, Lu-Ann Papile, Carolyn Lytle, Abbey C. Hines, Heike M. Minnich, Dianne E. Herron, Lucy Smiley, Susan Gunn, Leslie Dawn Wilson, Kathleen A. Kennedy, Jon E. Tyson, Georgia E. McDavid, Esther G. Akpa, Julie Arldt-McAlister, Nora I. Alaniz, Katrina Burson, Pamela J. Bradt, Susan Dieterich, Allison Dempsey, Andrea F. Duncan, Patricia W. Evans, Claudia I. Franco, Carmen Garcia, Charles Green, Beverly Foley Harris, Margarita Jiminez, Janice John, Patrick M. Jones, Layne M. Lillie, Anna E. Lis, Terri Major-Kincade, Karen Martin, Sara C. Martin, Brenda H. Morris, Patricia Ann Orekoya, Stacey Reddoch, Shawna Rodgers, Saba Siddiki, Maegan C. Simmons, Daniel Sperry, Patti L. Pierce Tate, Laura L. Whitely, Sharon L. Wright, Leif D. Nelin, Sudarshan R. Jadcherla, Patricia Luzader, Christine A. Fortney, Gail E. Besner, Nehal A. Parikh, Dennis Wallace, Marie G. Gantz, W. Kenneth Poole, Margaret M. Crawford, Jenna Gabrio, Betty K. Hastings, Jamie E. Newman, Jeanette O'Donnell Auman, Carolyn M. Petrie Huitema, Kristin M. Zaterka-Baxter, David K. Stevenson, M. Bethany Ball, Marian M. Adams, Alexis S. Davis, Andrew W. Palmquist, Melinda S. Proud, Barbara Bentley, Elizabeth Bruno, Maria Elena DeAnda, Anne M. DeBattista, Beth Earhart, Lynne C. Huffman, Jean G. Kohn, Casey Krueger, Hali E. Weiss, Ivan D. Frantz, John M. Fiascone, Brenda L. MacKinnon, Anne Furey, Ellen Nylen, Myriam Peralta-Carcelen, Monica V. Collins, Shirley S. Cosby, Fred J. Biasini, Kristen C. Johnston, Kathleen G. Nelson, Cryshelle S. Patterson, Vivien A. Phillips, Sally Whitley, Uday Devaskar, Meena Garg, Isabell B. Purdy, Teresa Chanlaw, Rachel Geller, Neil N. Finer, David Kaegi, Maynard R. Rasmussen, Paul R. Wozniak, Kathy Arnell, Clarence Demetrio, Martha G. Fuller, Chris Henderson, Wade Rich, Yvonne E. Vaucher, Tarah T. Colaizy, Michael J. Acarregui, Jane E. Brumbaugh, Dan L. Ellsbury, John A. Widness, Karen J. Johnson, Donia B. Campbell, Diane L. Eastman, Nancy J. Krutzfield, 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, Jean R. Lowe, Tara Dupont, Janell F. Fuller, Robin K. Ohls, Conra Backstrom Lacy, Rebecca Montman, Barbara Schmidt, Haresh Kirpalani, Sara B. DeMauro, Aasma S. Chaudhary, Soraya Abbasi, Toni Mancini, Dara M. Cucinotta, Judy C. Bernbaum, Marsha Gerdes, Hallam Hurt, Noah Cook, Carl T. D'Angio, Dale L. Phelps, Ronnie Guillet, Satyan Lakshminrusimha, Julie Babish Johnson, Erica Burnell, Linda J. Reubens, Cassandra A. Horihan, Rosemary L. Jensen, Emily Kushner, Joan Merzbach, Gary J. Myers, Mary Rowan, Holly I.M. Wadkins, Anne Marie Scorsone, Melissa Bowman, Julianne Hunn, Stephanie Guilford, Deanna Maffett, Osman Farooq, Diane Prinzing, Anne Marie Reynolds, Michael G. Sacilowski, Ashley Williams, Karen Wynn, Kelley Yost, William Zorn, Lauren Zwetsch, Luc P. Brion, R. Sue Broyles, Roy J. Heyne, Merle Ipson, Walid A. Salhab, Charles R. Rosenfeld, Diana M. Vasil, Lijun Chen, Alicia Guzman, Gaynelle Hensley, Jackie F. Hickman, Melissa H. Leps, Susie Madison, Nancy A. Miller, Janet S. Morgan, Lara Pavageau, Sally S. Adams, Cristin Dooley, Elizabeth T. Heyne, Lizette E. Lee, Linda A. Madden, Catherine Twell Boatman, Roger G. Faix, Bradley A. Yoder, Karen A. Osborne, Cynthia Spencer, Kimberlee Weaver-Lewis, Shawna Baker, Karie Bird, Jill Burnett, Michael Steffen, Jennifer J. Jensen, Sarah Winter, Karen Zanetti, T. Michael O'Shea, Robert G. Dillard, Lisa K. Washburn, Barbara G. Jackson, Nancy J. 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, Athina Pappas, Rebecca Bara, Laura A. Goldston, Geraldine Muran, Girija Natarajan, Mary Christensen, Stephanie A. Wiggins, Diane White, Richard A. Ehrenkranz, Harris Jacobs, Christine G. Butler, Patricia Cervone, Patricia Gettner, Sheila Greisman, Monica Konstantino, JoAnn Poulsen, Elaine Romano, Janet Taft, and Joanne Williams

Subjects
Male, congenital, hereditary, and neonatal diseases and abnormalities, Pediatrics, medicine.medical_specialty, Adverse outcomes, Developmental Disabilities, Leukomalacia, Periventricular, Gestational Age, Article, 03 medical and health sciences, Neonatal Screening, 0302 clinical medicine, Risk Factors, 030225 pediatrics, medicine, Humans, Prospective Studies, cardiovascular diseases, reproductive and urinary physiology, Ultrasonography, business.industry, Term equivalent age, Infant, Newborn, Brain, Infant, Cystic Periventricular Leukomalacia, nervous system diseases, Logistic Models, Increased risk, nervous system, Case-Control Studies, Infant, Extremely Premature, Pediatrics, Perinatology and Child Health, Gestation, Female, business, 030217 neurology & neurosurgery
Abstract

OBJECTIVE: To determine the outcome of preterm infants whose cystic periventricular leukomalacia “disappeared” on serial screening cranial imaging studies. STUDY DESIGN: Infants ≤26 weeks of gestation born between 2002 and 2012 who had cranial imaging studies at least twice, the most abnormal study at

Published
2018

41. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial

Author

Susan Gunn, Stephanie Guilford, Lisa Sulkowski, Shannon E. G. Hamrick, David P. Carlton, Cathy Grisby, Sara B. De Mauro, Scott A. McDonald, Amir M. Khan, Christine A. Gleason, Jeffrey L. Segar, Sandra Grimes, William E. Truog, Lenora Jackson, Conra Backstrom Lacy, Cheri Gauldin, Kimberley A. Fisher, Carmen Garcia, Jacky R. Walker, Nancy S. Newman, Brenda B. Poindexter, Nirupama Laroia, Monica V. Collins, Jonathan M. Klein, Ellen C. Hale, Jeffrey R. Parker, Emilee Little, Tracy L. Nolen, Carol K. Redmond, Sandra Sundquist Beauman, Namasivayam Ambalavanan, Toni Mancini, Richard A. Polin, Aasma S. Chaudhary, Janice Bernhardt, Athina Pappas, Alexis S. Davis, Emma Ramon, Kathleen Weingarden, Laura Sumner, Edward F. Bell, Edward G. Shepherd, Karen J. Johnson, Beena G. Sood, Holly I.M. Wadkins, Robert D. Roghair, Patrick J. Conway, Julie Arldt-McAlister, Mary E. Johnson, Kevin Dysart, Myra H. Wyckoff, Lina F. Chalak, Ann Marie Scorsone, Donia B. Campbell, Rebecca Bara, Howard W. Kilbride, Anne Marie Reynolds, Dennis Wallace, Soraya Abbasi, Satyanarayana Lakshminrusimha, Carl L. Bose, Jon E. Tyson, Kathy Johnson, Ronnie Guillet, Robert T. Burke, Sharon L. Wright, Jeanette O'Donnell Auman, Teresa Chanlaw, Glenda K. Rabe, Suhas G. Kallapur, Ashley Williams, Gail E. Besner, Elisa Vierira, Stephanie Wilson Archer, Waldemar A. Carlo, Greg Muthig, Leslie T. McKinley, Sandra Wuertz, Shirley S. Cosby, Kristin Kirker, Melinda S. Proud, Melinda Caskey, Angelita M. Hensman, Kimberly Hayes-Hart, Karen Martin, Claudia Pedroza, Eugenia K. Pallotto, Carolyn M. Petrie Huitema, Lauritz R. Meyer, Jane E. Brumbaugh, Patricia Luzader, Jamie E. Newman, Georgia E. McDavid, Joanne Finkle, Meena Garg, Carl T. D'Angio, Vipinchandra Bhavsar, Krisa P. Van Meurs, Anne Holmes, Sudarshan R. Jadcherla, Ross Sommers, John D.E. Barks, Rosemary D. Higgins, Traci E Clemons, Leslie Dawn Wilson, Michael G. Sacilowski, Karen A. Wynn, Martin Keszler, Kristi L. Watterberg, Nicole Walker, Christine A. Fortney, Stephanie A. Wiggins, Cary R. Murphy, Marian Willinger, Michael S. Caplan, Betty R. Vohr, Rachel Geller, Ronald N. Goldberg, Margaret M. Crawford, Lucy Smiley, Steven J. Weiner, Dara M. Cucinotta, Barbara Schmidt, Mary E. D'Alton, Tarah T. Colaizy, John M. Dagle, Robin K. Ohls, Gregory M Sokol, Yvonne Loggins, Katrina Burson, Luc P. Brion, Kathleen A. Kennedy, Pablo J. Sánchez, Abbot R. Laptook, Ronald J. Wong, Roy J. Heyne, Anna Maria Hibbs, Haresh Kirpalani, Andrea Halbrook, Carol Kibler, Seetha Shankaran, Patti L. Pierce Tate, Carol H. Hartenberger, Steven J. McElroy, Dan L. Ellsbury, Diana M. Vasil, Teresa L. Gratton, Kurt Schibler, M. Bethany Ball, Michele C. Walsh, Nehal A. Parikh, Maria Batts, Abhik Das, Richard A. Ehrenkranz, Dianne E. Herron, Birju A. Shah, Marian M. Adams, Jenna Gabrio, Jennifer Jennings, Cindy Clark, Barbara J. Stoll, Robert J. Boyle, Matthew M. Laughon, Marie Gantz, Lilia C. De Jesus, Julie B. Lindower, U. Devaskar, Shawna Rodgers, Estelle E. Fischer, Kristin M. Zaterka-Baxter, Mary Christensen, David K. Stevenson, Lijun Chen, Michael G. Ross, Girija Natarajan, Nicholas Guerina, and Barbara D. Alexander

Subjects
Male, Neonatal intensive care unit, Time Factors, Developmental Disabilities, Hypothermia, Reproductive health and childbirth, Arrhythmias, Medical and Health Sciences, Hypoxic Ischemic Encephalopathy, law.invention, Randomized controlled trial, law, Hypothermia, Induced, Neonatal, Infant Mortality, Medicine, Duration (project management), Pediatric, Mortality rate, Temperature, Brain, Obstetrics and Gynecology, General Medicine, Intensive Care Units, Anesthesia, Hypoxia-Ischemia, Brain, Female, medicine.symptom, Acidosis, Cardiac, medicine.medical_specialty, Clinical Trials and Supportive Activities, Hemorrhage, Article, Clinical Research, General & Internal Medicine, Intensive Care Units, Neonatal, Hypoxia-Ischemia, Humans, Survival analysis, business.industry, Induced, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Infant, Newborn, Infant, Arrhythmias, Cardiac, Thrombosis, Perinatal Period - Conditions Originating in Perinatal Period, Newborn, Survival Analysis, Surgery, Clinical trial, Relative risk, business
Abstract

Importance Hypothermia at 33.5°C for 72 hours for neonatal hypoxic ischemic encephalopathy reduces death or disability to 44% to 55%; longer cooling and deeper cooling are neuroprotective in animal models. Objective To determine if longer duration cooling (120 hours), deeper cooling (32.0°C), or both are superior to cooling at 33.5°C for 72 hours in neonates who are full-term with moderate or severe hypoxic ischemic encephalopathy. Design, Setting, and Participants A randomized, 2 × 2 factorial design clinical trial performed in 18 US centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network between October 2010 and November 2013. Interventions Neonates were assigned to 4 hypothermia groups; 33.5°C for 72 hours, 32.0°C for 72 hours, 33.5°C for 120 hours, and 32.0°C for 120 hours. Main Outcomes and Measures The primary outcome of death or disability at 18 to 22 months is ongoing. The independent data and safety monitoring committee paused the trial to evaluate safety (cardiac arrhythmia, persistent acidosis, major vessel thrombosis and bleeding, and death in the neonatal intensive care unit [NICU]) after the first 50 neonates were enrolled, then after every subsequent 25 neonates. The trial was closed for emerging safety profile and futility analysis after the eighth review with 364 neonates enrolled (of 726 planned). This report focuses on safety and NICU deaths by marginal comparisons of 72 hours’ vs 120 hours’ duration and 33.5°C depth vs 32.0°C depth (predefined secondary outcomes). Results The NICU death rates were 7 of 95 neonates (7%) for the 33.5°C for 72 hours group, 13 of 90 neonates (14%) for the 32.0°C for 72 hours group, 15 of 96 neonates (16%) for the 33.5°C for 120 hours group, and 14 of 83 neonates (17%) for the 32.0°C for 120 hours group. The adjusted risk ratio (RR) for NICU deaths for the 120 hours group vs 72 hours group was 1.37 (95% CI, 0.92-2.04) and for the 32.0°C group vs 33.5°C group was 1.24 (95% CI, 0.69-2.25). Safety outcomes were similar between the 120 hours group vs 72 hours group and the 32.0°C group vs 33.5°C group, except major bleeding occurred among 1% in the 120 hours group vs 3% in the 72 hours group (RR, 0.25 [95% CI, 0.07-0.91]). Futility analysis determined that the probability of detecting a statistically significant benefit for longer cooling, deeper cooling, or both for NICU death was less than 2%. Conclusions and Relevance Among neonates who were full-term with moderate or severe hypoxic ischemic encephalopathy, longer cooling, deeper cooling, or both compared with hypothermia at 33.5°C for 72 hours did not reduce NICU death. These results have implications for patient care and design of future trials. Trial Registration clinicaltrials.gov Identifier:NCT01192776

Published
2014

42. Inhaled Nitric Oxide for Premature Infants with Severe Respiratory Failure

Author

David K. Stevenson, Gregory M Sokol, Barbara J. Stoll, William Oh, Jon H. Fridriksson, Girija G. Konduri, Seetha Shankaran, Kathleen A. Kennedy, M. Bethany Ball, Carl T. D'Angio, James A. Lemons, Robin H. Steinhorn, Linda L. Wright, Abbot R. Laptook, Rebecca Perritt, Judy L. Aschner, Richard A. Ehrenkranz, Neil N. Finer, Rosemary D. Higgins, Krisa P. Van Meurs, Mark L. Hudak, Waldemar A. Carlo, and W. Kenneth Poole

Subjects
Periventricular leukomalacia, business.industry, Birth weight, Respiratory disease, General Medicine, medicine.disease, Placebo, Nitric oxide, chemistry.chemical_compound, chemistry, Respiratory failure, Bronchopulmonary dysplasia, Anesthesia, medicine, Gestation, business
Abstract

background Inhaled nitric oxide is a controversial treatment for premature infants with severe respiratory failure. We conducted a multicenter, randomized, blinded, controlled trial to determine whether inhaled nitric oxide reduced the rate of death or bronchopulmonary dysplasia in such infants. methods We randomly assigned 420 neonates, born at less than 34 weeks of gestation, with a birth weight of 401 to 1500 g, and with respiratory failure more than four hours after treatment with surfactant to receive placebo (simulated flow) or inhaled nitric oxide (5 to 10 ppm). Infants with a response (an increase in the partial pressure of arterial oxygen of more than 10 mm Hg) were weaned according to protocol. Treatment with study gas was discontinued in infants who did not have a response. results The rate of death or bronchopulmonary dysplasia was 80 percent in the nitric oxide group, as compared with 82 percent in the placebo group (relative risk, 0.97; 95 percent confidence interval, 0.86 to 1.06; P=0.52), and the rate of bronchopulmonary dysplasia was 60 percent versus 68 percent (relative risk, 0.90; 95 percent confidence interval, 0.75 to 1.08; P=0.26). There were no significant differences in the rates of severe intracranial hemorrhage or periventricular leukomalacia. Post hoc analyses suggest that rates of death and bronchopulmonary dysplasia are reduced for infants with a birth weight greater than 1000 g, whereas infants weighing 1000 g or less who are treated with inhaled nitric oxide have higher mortality and increased rates of severe intracranial hemorrhage. conclusions The use of inhaled nitric oxide in critically ill premature infants weighing less than 1500 g does not decrease the rates of death or bronchopulmonary dysplasia. Further trials are required to determine whether inhaled nitric oxide benefits infants with a birth weight of 1000 g or more.

Published
2005

43. A Randomized Trial of Early Versus Standard Inhaled Nitric Oxide Therapy in Term and Near-Term Newborn Infants With Hypoxic Respiratory Failure

Author

Nalini Singhal, Girija G. Konduri, Joel Singer, Haresh Kirpalani, Eileen K. Stork, Alfonso Solimano, Krisa P. Van Meurs, Gregory M. Sokol, Linda L. Wright, Abraham Peliowski, and Richard A. Ehrenkranz

Subjects
Male, Oxygenation index, medicine.medical_treatment, Nitric Oxide, law.invention, Extracorporeal Membrane Oxygenation, Double-Blind Method, Randomized controlled trial, law, Multicenter trial, Administration, Inhalation, Extracorporeal membrane oxygenation, medicine, Humans, Hypoxia, business.industry, Respiratory disease, Infant, Newborn, Oxygenation, medicine.disease, Respiration, Artificial, Survival Analysis, Pulmonary hypertension, Respiratory failure, Anesthesia, Pediatrics, Perinatology and Child Health, Female, Blood Gas Analysis, Respiratory Insufficiency, business
Abstract

Objective. Inhaled nitric oxide (iNO) reduces the use of extracorporeal membrane oxygenation (ECMO)/incidence of death in term and near-term neonates with severe hypoxic respiratory failure. We conducted a randomized, double masked, multicenter trial to determine whether administration of iNO earlier in respiratory failure results in additional reduction in the incidence of these outcomes. Methods. Neonates who were born at ≥34 weeks’ gestation were enrolled when they required assisted ventilation and had an oxygenation index (OI) ≥15 and Results. The trial enrollment was halted after 75% of target sample size was reached because of decreasing availability of eligible patients. The 150 infants who were given early iNO and 149 control infants had similar baseline characteristics. Arterial oxygen tension increased by >20 mm Hg in 73% of early iNO and 37% of control infants after study gas initiation. Control infants received standard iNO and deteriorated to OI >40 more often than infants who were given early iNO. The incidence of death (early iNO, 6.7% vs control, 9.4%), ECMO (10.7% vs 12.1%), and their combined incidence (16.7% vs 19.5%) were similar in both groups. Conclusion. iNO improves oxygenation but does not reduce the incidence of ECMO/mortality when initiated at an OI of 15 to 25 compared with initiation at >25 in term and near-term neonates with respiratory failure.

Published
2004

44. Nitrogen Dioxide Formation during Inhaled Nitric Oxide Therapy

Author

Gregory M. Sokol, Robert L. Sams, Linda L. Wright, Krisa P. Van Meurs, Oswaldo Rivera, William J Thorn, and Pamela M. Chu

Subjects
Tunable diode laser absorption spectroscopy, Inhalation, Chemistry, Biochemistry (medical), Clinical Biochemistry, Radiochemistry, Oxygene, Mineralogy, chemistry.chemical_element, Oxygen, Nitric oxide, Matrix (chemical analysis), chemistry.chemical_compound, Reaction rate constant, Nitrogen dioxide, computer, computer.programming_language
Abstract

Background: Nitrogen dioxide (NO2) is a toxic by-product of inhalation therapy with nitric oxide (NO). The rate of NO2 formation during NO therapy is controversial. Methods: The formation of NO2 was studied under dynamic flows emulating a base case NO ventilator mixture containing 80 ppm NO in a 90% oxygen matrix. The difficulty in measuring NO2 concentrations below 2 ppm accurately was overcome by the use of tunable diode laser absorption spectroscopy. Results: Using a second-order model, the rate constant, k, for NO2 formation was determined to be (1.19 ± 0.11) × 10−11 ppm−2s−1, which is in basic agreement with evaluated data from atmospheric literature. Conclusions: Inhaled NO can be delivered safely in a well-designed, continuous flow neonatal ventilatory circuit, and NO2 formation can be calculated reliably using the rate constant and circuit dwell time.

Published
1999

45. Impact of early surfactant and inhaled nitric oxide therapies on outcomes in term/late preterm neonates with moderate hypoxic respiratory failure

Author

Namasivayam Ambalavanan, Gregory M Sokol, Joel Singer, A Solimano, Girija G. Konduri, K. P. Van Meurs, and Terry Lee

Subjects
Male, medicine.medical_treatment, Infant, Premature, Diseases, Nitric Oxide, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Extracorporeal Membrane Oxygenation, Pulmonary surfactant, Risk Factors, 030225 pediatrics, Administration, Inhalation, medicine, Extracorporeal membrane oxygenation, Late preterm, Humans, 030212 general & internal medicine, Hypoxia, Respiratory Distress Syndrome, Newborn, Inhalation, business.industry, Infant, Newborn, Obstetrics and Gynecology, Drug Synergism, Pulmonary Surfactants, Pneumonia, Hypoxia (medical), Combined Modality Therapy, 3. Good health, Oxygen, Logistic Models, Respiratory failure, chemistry, Anesthesia, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, RESPIRATORY DISTRESS SYNDROME NEWBORN, business, Infant, Premature
Abstract

We conducted a post-hoc analysis of early inhaled nitric oxide (iNO)-randomized controlled trial data to identify associations pertinent to the management of moderate hypoxic respiratory failure in term/late preterm infants.Univariate and multivariate logistic regression analyses were used to determine risk factors for the progression of respiratory failure and extracorporeal membrane oxygenation (ECMO)/death.Among the 299 enrolled infants, oxygenation index (OI)20 at enrollment (odds ratio 0.52, confidence interval (CI) 0.27 to 0.97) and surfactant use before randomization (odds ratio 0.47, CI 0.24 to 0.91) were associated with decreased ECMO/death rates. Early surfactant use for respiratory distress syndrome, perinatal aspiration syndrome and pneumonia/sepsis was associated with lower risk of ECMO/death (P0.001). Early iNO (OI 15 to 25) decreased the progression of respiratory failure to OI30 (P=0.002) and to composite outcome of OI30 or ECMO/death (P=0.02).This post-hoc analysis suggests that early use of surfactant and iNO in moderate respiratory failure is associated with improved outcomes.

Published
2013

46. Inhaled nitric oxide therapy in neonatal hypoxic respiratory failure: insights beyond primary outcomes

Author

Gregory M Sokol and Richard A. Ehrenkranz

Subjects
Male, medicine.medical_specialty, Canada, business.industry, Infant, Newborn, Obstetrics and Gynecology, Nitric Oxide, Persistent Fetal Circulation Syndrome, United States, Bronchodilator Agents, Clinical trial, Respiratory failure, National Institutes of Health (U.S.), Pediatrics, Perinatology and Child Health, Administration, Inhalation, medicine, Humans, Multicenter Studies as Topic, Observational study, Female, Nitric oxide therapy, Clinical care, Intensive care medicine, business, Randomized Controlled Trials as Topic
Abstract

The Neonatal Research Network developed and initiated 3 multicenter randomized controlled clinical trials evaluating inhaled nitric oxide therapy. Additional projects evolved from these efforts including basic science research and observational investigations. This article provides a historical prospective of the Network's investigations related to the diagnosis and management of neonatal hypoxic respiratory failure, especially those related to inhaled nitric oxide therapy. It will review the Network's contributions toward advancing the clinical care of the newborn with severe hypoxic respiratory failure.

Published
2003

48. Changes in arterial oxygen tension when weaning neonates from inhaled nitric oxide

Author

Gregory M. Sokol, Naomi S. Fineberg, Richard A. Ehrenkranz, and Linda L. Wright

Subjects
Pulmonary and Respiratory Medicine, congenital, hereditary, and neonatal diseases and abnormalities, Pulmonary Circulation, Surfactant therapy, Nitric Oxide, Nitric oxide, chemistry.chemical_compound, Double-Blind Method, Administration, Inhalation, Medicine, Weaning, Humans, Prospective Studies, Hypoxia, Inhalation, Dose-Response Relationship, Drug, business.industry, Infant, Newborn, Oxygenation, respiratory system, medicine.disease, Pulmonary hypertension, respiratory tract diseases, Oxygen, Dose–response relationship, Treatment Outcome, chemistry, Respiratory failure, Anesthesia, Pediatrics, Perinatology and Child Health, bacteria, Regression Analysis, business, Respiratory Insufficiency, Blood Gas Monitoring, Transcutaneous, Ventilator Weaning
Abstract

We set out to evaluate changes in arterial oxygen tension (PaO(2)) when weaning neonates from inhaled nitric oxide (INO). We reviewed the records of 505 prospectively collected INO weaning attempts on 84 neonates with hypoxic respiratory failure. PaO(2) values before and 30 min after weaning attempts were recorded. Relationships between change in PaO(2) and decreases in INO concentrations were investigated using regression analysis and ANOVA. PaO(2) decreased (-18.7 +/- 1.8 torr; P < 0.001); when weaning INO. A stepwise decline in PaO(2) was observed weaning INO from 40 ppm. The greatest decline occurred when INO was discontinued (-42.1 +/- 4.1 torr). Forward stepwise multiple regression using variables with significant relationships to the decline in PaO(2) identified the specific dose reduction 7(P < 0.001), the prewean PaO(2) (P < 0.001), and surfactant therapy (P = 0.018) as the variables best describing the change in PaO(2)(P = 0.004, r = 0.51). In conclusion, a graded decline in PaO(2) occurs when reducing INO. INO should be weaned to less than 1 ppm before discontinuing its use. Prior surfactant treatment appears to enhance the oxygenation reserve when weaning INO.

Published
2001

49. Comparison of steady-state diffusion and transit time ultrasonic measurements of umbilical blood flow in the chronic fetal sheep preparation

Author

David W. Boyle, Edward A. Liechty, and Gregory M. Sokol

Subjects
medicine.medical_specialty, Time Factors, Coefficient of variation, Umbilical cord, Ultrasonography, Prenatal, Diffusion, Fetus, Oxygen Consumption, Pregnancy, medicine.artery, medicine, Animals, Homeostasis, Sheep, business.industry, Obstetrics and Gynecology, Umbilical artery, Blood flow, Fetal Blood, Surgery, medicine.anatomical_structure, Transducer, Flow (mathematics), Regional Blood Flow, Ultrasonic sensor, Female, business, Rheology, Biomedical engineering
Abstract

OBJECTIVE: Our purpose was to measure umbilical blood flow continuously by use of a transit time ultrasonic flow transducer and to compare the blood flow measurements with the steady-state diffusion method in the chronic fetal sheep preparation. STUDY DESIGN: We compared umbilical blood flow measurements calculated by the steady-state diffusion method with ethanol as the diffusing substance and with the transit time ultrasonic flow transducer placed on the common umbilical artery in five chronically prepared fetal sheep. RESULTS: There was no statistical difference between measurements of umbilical blood flow measured by the flow transducer versus the steady-state diffusion method, 600 ± 22 versus 664 ± 56 ml per minute (mean ± SEM) ( p = 0.23). The mean coefficient of variation within each study was 13.6% for the steady-state diffusion method versus 4.1% for the transit time flow transducer. Umbilical blood flow variance was significantly lower as measured by the flow transducer compared with the diffusion method ( p < 0.0001). There were no differences in umbilical blood flow per kilogram or fetal oxygen uptake between the two methods. CONCLUSION: We conclude that umbilical blood flow can be measured continuously under steady-state conditions by use of a transit time flow transducer. Because of the lower variability in the flow transducer–obtained measurements, we speculate that the flow transducer may differentiate alterations in umbilical blood flow with greater precision in chronic preparations. This may be advantageous for measuring absolute changes in fetal substrate uptake, especially under non-steady-state conditions. (AM J OBSTET GYNECOL 1996;174:1456-60.)

Published
1996

50. Early Inhaled Nitric Oxide Therapy for Term and Near-Term Newborn Infants with Hypoxic Respiratory Failure: Neurodevelopmental Follow-Up

Author

Abraham Peliowski, Gregory M. Sokol, Eileen K. Stork, Charlene M.T. Robertson, Yvette R. Johnson, Krisa P. Van Meurs, Haresh Kirpalani, Nalini Singhal, Betty R. Vohr, Linda L. Wright, Girija G. Konduri, Joel Singer, Alfonso Solimano, and Richard A. Ehrenkranz

Subjects
Pediatrics, medicine.medical_specialty, Oxygenation index, business.industry, medicine.medical_treatment, Respiratory disease, Gestational age, medicine.disease, Respiratory failure, Anesthesia, Pediatrics, Perinatology and Child Health, Severity of illness, medicine, Extracorporeal membrane oxygenation, Prospective cohort study, business, Survival rate
Abstract

Inhaled nitric oxide (iNO) therapy reduces the use of extracorporeal membrane oxygenation (ECMO) in term and near term infants with hypoxic respiratory failure (1–4). Based on the initial randomized clinical trials, iNO therapy is commonly used for treating moderate to severe neonatal respiratory failure with an oxygenation index (OI) ≥25 (5). A review of the previous randomized trials (1–4) indicated that initiation of iNO therapy at a lower oxygenation index was associated with lower ECMO use/mortality. Therefore, we conducted a randomized, multi-center clinical trial of early initiation of iNO therapy for babies presenting with respiratory failure at an oxygenation index of 15–25 over a three-year period from July 1998 – May 2001. The primary hypothesis for this study was that initiation of iNO at an oxygenation index of 15–25 compared to use of standard iNO therapy at an oxygenation index ≥25 would decrease the rate of ECMO/mortality from 35% to 20%. A secondary hypothesis for this study was that early iNO therapy would not increase neurodevelopmental impairment or hearing loss rates among surviving infants at 18–24 months of age compared to use of standard iNO therapy. Analysis of the outcomes observed prior to discharge from the hospital indicated that early iNO therapy did not reduce the combined incidence of ECMO/mortality and the rates of ECMO and mortality individually were similar between the groups. Early iNO therapy decreased the progression of respiratory failure to an oxygenation index >25 and to an oxygenation index >40. Here we report the results of the neurodevelopmental follow-up of the surviving infants at 18–24 months of postnatal age.

Published
2007

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