Pediatrics Commons^™

Diagnostic Accuracy Of Urinary N Terminal Pro-B Type Natriuretic Peptides For Hemodynamically Significant-Patent Ductus Arteriosus In Preterm Infants, Srirupa Hari Gopal, Ganga Gokulakrishnan, Madhulika Kulkarni, Caraciolo J Fernandes, Mohan Pammi

Faculty, Staff and Students Publications

Background: Echocardiography is the gold standard for the diagnosis hemodynamically significant-patent ductus arteriosus (hs-PDA). It requires trained personnel and is not readily available. Urinary biomarkers can be used as an adjunct.

Objective: The objective of this study was to systematically review the diagnostic accuracy of urinary N terminal pro-B type natriuretic peptides (NT-proBNP) for hs-PDA in preterm neonates.

Methods: We included studies that evaluated urinary NT-proBNP and urinary NT-proBNP/creatinine ratio (index tests) in preterm neonates with hs-PDA (participants) in comparison with echocardiogram (reference standard). Methodological quality and certainty of evidence were assessed using Quality Assessment of Diagnostic-Accuracy Studies (QUADAS-2) and …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Tanayott Thaweethai, Erika B Rosenzweig, James Chan, Lori B Chibnik, Mine S Cicek, Amy J Elliott, Valerie J Flaherman, Andrea S Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L Jernigan, Elizabeth W Karlson, Stuart D Katz, Patricia A Kinser, Lawrence C Kleinman, Michelle F Lamendola-Essel, Joshua D Milner, Sindhu Mohandas, Praveen C Mudumbi, Jane W Newburger, Kyung E Rhee, Amy L Salisbury, Jessica N Snowden, Cheryl R Stein, Melissa S Stockwell, Kelan G Tantisira, Moriah E Thomason, Dongngan T Truong, David Warburton, John C Wood, Shifa Ahmed, Almary Akerlundh, Akram N Alshawabkeh, Brett R Anderson, Judy L Aschner, Andrew M Atz, Robin L Aupperle, Fiona C Baker, Venkataraman Balaraman, Dithi Banerjee, Deanna M Barch, Arielle Baskin-Sommers, Sultana Bhuiyan, Marie-Abele C Bind, Amanda L Bogie, Tamara Bradford, Natalie C Buchbinder, Elliott Bueler, Hülya Bükülmez, B J Casey, Linda Chang, Maryanne Chrisant, Duncan B Clark, Rebecca G Clifton, Katharine N Clouser, Lesley Cottrell, Kelly Cowan, Viren D'Sa, Mirella Dapretto, Soham Dasgupta, Walter Dehority, Audrey Dionne, Kirsten B Dummer, Matthew D Elias, Shari Esquenazi-Karonika, Danielle N Evans, E Vincent S Faustino, Alexander G Fiks, Daniel Forsha, John J Foxe, Naomi P Friedman, Greta Fry, Sunanda Gaur, Dylan G Gee, Kevin M Gray, Stephanie Handler, Ashraf S Harahsheh, Keren Hasbani, Andrew C Heath, Camden Hebson, Mary M Heitzeg, Christina M Hester, Sophia Hill, Laura Hobart-Porter, Travis K F Hong, Carol R Horowitz, Daniel S Hsia, Matthew Huentelman, Kathy D Hummel, Katherine Irby, Joanna Jacobus, Vanessa L Jacoby, Pei-Ni Jone, David C Kaelber, Tyler J Kasmarcak, Matthew J Kluko, Jessica S Kosut, Angela R Laird, Jeremy Landeo-Gutierrez, Sean M Lang, Christine L Larson, Peter Paul C Lim, Krista M Lisdahl, Brian W Mccrindle, Russell J Mcculloh, Kimberly Mchugh, Alan L Mendelsohn, Torri D Metz, Julie Miller, Elizabeth C Mitchell, Lerraughn M Morgan, Eva M Müller-Oehring, Erica R Nahin, Michael C Neale, Manette Ness-Cochinwala, Sheila M Nolan, Carlos R Oliveira, Onyekachukwu Osakwe, Matthew E Oster, R Mark Payne, Michael A Portman, Hengameh Raissy, Isabelle G Randall, Suchitra Rao, Harrison T Reeder, Johana M Rosas, Mark W Russell, Arash A Sabati, Yamuna Sanil, Alice I Sato, Michael S Schechter, Rangaraj Selvarangan, S Kristen Sexson Tejtel, Divya Shakti, Kavita Sharma, Lindsay M Squeglia, Shubika Srivastava, Michelle D Stevenson, Jacqueline Szmuszkovicz, Maria M Talavera-Barber, Ronald J Teufel, Deepika Thacker, Felicia Trachtenberg, Mmekom M Udosen, Megan R Warner, Sara E Watson, Alan Werzberger, Jordan C Weyer, Marion J Wood, H Shonna Yin, William T Zempsky, Emily Zimmerman, Benard P Dreyer, Recover-Pediatric Consortium

Faculty, Staff and Students Publications

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Apixaban For Prevention Of Thromboembolism In Pediatric Heart Disease, R Mark Payne, Kristin M Burns, Andrew C Glatz, Christoph Male, Andrea Donti, Leonardo R Brandão, Gunter Balling, Christina J Vanderpluym, Frances Bu'lock, Lazaros K Kochilas, Brigitte Stiller, James F Cnota, Otto Rahkonen, Asra Khan, Rachele Adorisio, Serban Stoica, Lindsay May, Jane C Burns, Jose Francisco K Saraiva, Kimberly E Mchugh, John S Kim, Agustin Rubio, Nadia G Chía-Vazquez, Marcie R Meador, Joshua L Dyme, Alison M Reedy, Toni Ajavon-Hartmann, Praneeth Jarugula, Lauren E Carlson-Taneja, Donna Mills, Olivia Wheaton, Paul Monagle

Faculty, Staff and Students Publications

Background: Children with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages.

Objectives: The authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease.

Methods: Phase 2, open-label trial in children (ages, 28 days to < 18 years) with heart disease requiring thromboprophylaxis. Randomization 2:1 apixaban or SOC for 1 year with intention-to-treat analysis.

Primary endpoint: a composite of adjudicated major or clinically relevant nonmajor bleeding. Secondary endpoints: PK, pharmacodynamics, quality of life, and exploration of efficacy.

Results: From 2017 to 2021, 192 participants were randomized, 129 …

Neonatal Cholestasis In Children With Alpha-1-At Deficiency Is A Risk For Earlier Severe Liver Disease With Male Predominance, Jeffrey Teckman, Philip Rosenthal, Rosalinda V Ignacio, Cathie Spino, Lee M Bass, Simon Horslen, Kasper Wang, John C Magee, Saul Karpen, Akihiro Asai, Jean P Molleston, Robert H Squires, Binita M Kamath, Stephen L Guthery, Kathleen M Loomes, Benjamin L Shneider, Ronald J Sokol, Children (Childhood Liver Disease Research Network)

Faculty, Staff and Students Publications

BACKGROUND: Our objective was to better understand the natural history and disease modifiers of Alpha-1-antitrypsin deficiency (AATD), a common genetic liver disease causing hepatitis and cirrhosis in adults and children. The clinical course is highly variable. Some infants present with neonatal cholestasis, which can resolve spontaneously or progress to cirrhosis; others are well in infancy, only to develop portal hypertension later in childhood.

METHODS: The Childhood Liver Disease Research Network has been enrolling AATD participants into longitudinal, observational studies at North American tertiary centers since 2004. We examined the clinical courses of 2 subgroups of participants from the several hundred …

Nonsense Variant Prdm16-Q187x Causes Impaired Myocardial Development And Tgf-Β Signaling Resulting In Noncompaction Cardiomyopathy In Humans And Mice, Bo Sun, Omid M T Rouzbehani, Ryan J Kramer, Rajeshwary Ghosh, Robin M Perelli, Sage Atkins, Amir Nima Fatahian, Kathryn Davis, Marta W Szulik, Michael A Goodman, Marissa A Hathaway, Ellenor Chi, Tarah A Word, Hari Tunuguntla, Susan W Denfield, Xander H T Wehrens, Kevin J Whitehead, Hala Y Abdelnasser, Junco S Warren, Mingfu Wu, Sarah Franklin, Sihem Boudina, Andrew P Landstrom

Faculty, Staff and Students Publications

BACKGROUND: PRDM16 plays a role in myocardial development through TGF-β (transforming growth factor-beta) signaling. Recent evidence suggests that loss of PRDM16 expression is associated with cardiomyopathy development in mice, although its role in human cardiomyopathy development is unclear. This study aims to determine the impact of PRDM16 loss-of-function variants on cardiomyopathy in humans.

METHODS: Individuals with PRDM16 variants were identified and consented. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from a proband hosting a Q187X nonsense variant as an in vitro model and underwent proliferative and transcriptional analyses. CRISPR-mediated knock-in mouse model hosting the Prdm16Q187X allele was generated …

Effectiveness Of A Community-Based Approach For The Investigation And Management Of Children With Household Tuberculosis Contact In Cameroon And Uganda: A Cluster-Randomised Trial, Maryline Bonnet, Anca Vasiliu, Boris K Tchounga, Benjamin Cuer, Katherine Fielding, Bob Ssekyanzi, Boris Tchakounte Youngui, Jennifer Cohn, Peter J Dodd, Georges Tiendrebeogo, Patrice Tchendjou, Leonie Simo, Richard F Okello, Albert Kuate Kuate, Stavia Turyahabwe, Daniel Atwine, Stephen M Graham, Martina Casenghi, Contact Study Group

Faculty, Staff and Students Publications

Background: Globally, the uptake of tuberculosis-preventive treatment (TPT) among children with household tuberculosis contact remains low, partly due to the necessity of bringing children to health facilities for investigations. This study aimed to evaluate the effect on TPT initiation and completion of community-based approaches to tuberculosis contact investigations in Cameroon and Uganda.

Methods: We did a parallel, cluster-randomised, controlled trial across 20 clusters (consisting of 25 district hospitals and primary health centres) in Cameroon and Uganda, which were randomised (1:1) to receive a community-based approach (intervention group) or standard-of-care facility-based approach to contact screening and management (control group). The community-based …

Generalizability Of The Necrotizing Enterocolitis Surgery Trial To The Target Population Of Eligible Infants, Matthew A Rysavy, Barry Eggleston, Issa J Dahabreh, Jon E Tyson, Ravi M Patel, Kristi L Watterberg, Rachel G Greenberg, Claudia Pedroza, Marissa Trotta, David K Stevenson, Barbara J Stoll, Kevin P Lally, Abhik Das, Martin L Blakely, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Faculty, Staff and Student Publications

Objective: The objective of this study was to evaluate whether infants randomized in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Necrotizing Enterocolitis Surgery Trial differed from eligible infants and whether differences affected the generalizability of trial results.

Study design: Secondary analysis of infants enrolled in Necrotizing Enterocolitis Surgery Trial (born 2010-2017, with follow-up through 2019) at 20 US academic medical centers and an observational data set of eligible infants through 2013. Infants born ≤1000 g and diagnosed with necrotizing enterocolitis or spontaneous intestinal perforation requiring surgical intervention at ≤8 weeks were eligible. …

Use Of Term Reference Infants In Assessing The Developmental Outcome Of Extremely Preterm Infants: Lessons Learned In A Multicenter Study, Charles E Green, Jon E Tyson, Roy J Heyne, Susan R Hintz, Betty R Vohr, Carla M Bann, Abhik Das, Edward F Bell, Sana Boral Debsareea, Emily Stephens, Marie G Gantz, Carolyn M Petrie Huitema, Karen J Johnson, Kristi L Watterberg, Ricardo Mosquera, Myriam Peralta-Carcelen, Deanne E Wilson-Costello, Tarah T Colaizy, Nathalie L Maitre, Stephanie L Merhar, Ira Adams-Chapman, Janell Fuller, Michelle E Hartley-Mcandrew, William F Malcolm, Sarah Winter, Andrea F Duncan, Gary J Myer, Stephen D Kicklighter, Myra H Wyckoff, Sara B Demauro, Anna Maria Hibbs, Barbara J Stoll, Waldemar A Carlo, Krisa P Van Meurs, Matthew A Rysavy, Ravi M Patel, Pablo J Sánchez, Abbot R Laptook, C Michael Cotten, Carl T D'Angio, Michele C Walsh, Human Development Neonatal Research Network

Faculty, Staff and Student Publications

OBJECTIVE: Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.

STUDY DESIGN: Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.

RESULTS: We assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56-2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001). Difficulty recruiting …

Site-Specific Pathophysiology In A Neonatal Mouse Model Of Gastroparesis, Price T Edwards, Krishnakant G Soni, Margaret E Conner, Stephanie W Fowler, Jaime P P Foong, Rhian Stavely, Lily S Cheng, Geoffrey A Preidis

Faculty, Staff and Students Publications

BACKGROUND: Early-life events impact maturation of the gut microbiome, enteric nervous system, and gastrointestinal motility. We examined three regions of gastric tissue to determine how maternal separation and gut microbes influence the structure and motor function of specific regions of the neonatal mouse stomach.

METHODS: Germ-free and conventionally housed C57BL/6J mouse pups underwent timed maternal separation (TmSep) or nursed uninterrupted (controls) until 14 days of life. We assessed gastric emptying by quantifying the progression of gavaged fluorescein isothiocyanate (FITC)-dextran. With isolated rings of forestomach, corpus, and antrum, we measured tone and contractility by force transduction, gastric wall thickness by light …

Preterm Pigs Fed Donor Human Milk Have Greater Liver Β-Carotene Concentrations Than Pigs Fed Infant Formula, Nancy E Moran, Joshua Wade, Rachel Stroh, Barbara Stoll, Gregory Guthrie, Amy B Hair, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Milk carotenoids may support preterm infant health and neurodevelopment. Infants fed human milk often have higher blood and tissue carotenoid concentrations than infants fed carotenoid-containing infant formula (IF). Donor human milk (DHM) is a supplement to mother's own milk, used to support preterm infant nutrition.

OBJECTIVES: We tested whether tissue and plasma β-carotene concentrations would be higher in preterm pigs fed pasteurized DHM versus premature IF.

METHODS: This is a secondary analysis of samples collected from a study of the effects of enteral diet composition on necrotizing enterocolitis incidence. Preterm pigs received partial enteral feeding of either DHM (n …

Bronchopulmonary Dysplasia – Associated Pulmonary Hypertension: An Updated Review, Ahmed El-Saie, Nidhy P Varghese, Melissa K Webb, Natalie Villafranco, Bheru Gandhi, Milenka Cuevas Guaman, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) is the leading cause of chronic lung disease in infants and the commonest complication of prematurity. Advances in respiratory and overall neonatal care have increased the survival of extremely low gestational age newborns, leading to the continued high incidence of BPD. Pulmonary hypertension (PH) represents the severe form of the pulmonary vascular disease associated with BPD, and affects almost one-third of infants with moderate to severe BPD. PH responds suboptimally to pulmonary vasodilators and increases morbidity and mortality in BPD infants. An up-to-date knowledge of the pathogenesis, pathophysiology, diagnosis, treatment, and outcomes of BPD-PH can be helpful …

A Cross-Species Proteomic Map Reveals Neoteny Of Human Synapse Development, Li Wang, Kaifang Pang, Li Zhou, Arantxa Cebrián-Silla, Susana González-Granero, Shaohui Wang, Qiuli Bi, Matthew L White, Brandon Ho, Jiani Li, Tao Li, Yonatan Perez, Eric J Huang, Ethan A Winkler, Mercedes F Paredes, Rothem Kovner, Nenad Sestan, Alex A Pollen, Pengyuan Liu, Jingjing Li, Xianhua Piao, José Manuel García-Verdugo, Arturo Alvarez-Buylla, Zhandong Liu, Arnold R Kriegstein

Faculty, Staff and Students Publications

The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood1,2. Here we generate a cross-species proteomic map of synapse development in the human, macaque and mouse neocortex. By tracking the changes of more than 1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we find that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that human PSDs mature about two to three times slower than those of other species and contain higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the …

Loss Of Growth Differentiation Factor 15 Exacerbates Lung Injury In Neonatal Mice, Faeq Al-Mudares, Manuel Cantu Gutierrez, Abiud Cantu, Weiwu Jiang, Lihua Wang, Xiaoyu Dong, Bhagavatula Moorthy, Eniko Sajti, Krithika Lingappan

Faculty, Staff and Students Publications

Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor-β (TGF-β) superfamily, and its expression increases under various stress conditions, including inflammation, hyperoxia, and senescence. GDF15 expression is increased in neonatal murine bronchopulmonary dysplasia (BPD) models, and GDF15 loss exacerbates oxidative stress and decreases cellular viability in vitro. Our overall hypothesis is that the loss of GDF15 will exacerbate hyperoxic lung injury in the neonatal lung in vivo. We exposed neonatal

Pragmatic, Randomized, Blinded Trial To Shorten Pharmacologic Treatment Of Newborns With Neonatal Opioid Withdrawal Syndrome (Nows), Adam Czynski, Abbot Laptook, Abhik Das, Brian Smith, Alan Simon, Rachel Greenberg, Robert Annett, Jeannette Lee, Jessica Snowden, Claudia Pedroza, Barry Lester, Barry Eggleston, Drew Bremer, Elisabeth Mcgowan

Faculty, Staff and Student Publications

BACKGROUND: The incidence of maternal opioid use in the USA has increased substantially since 2000. As a consequence of opioid use during pregnancy, the incidence of neonatal opioid withdrawal syndrome (NOWS) has increased fivefold between 2002 and 2012. Pharmacological therapy is indicated when signs of NOWS cannot be controlled, and the objective of pharmacological therapy is to control NOWS signs. Once pharmacologic therapy has started, there is great variability in strategies to wean infants. An important rationale for studying weaning of pharmacological treatment for NOWS is that weaning represents the longest time interval of drug treatment. Stopping medications too early …

Effect Of Reduced Versus Usual Lipid Emulsion Dosing On Bilirubin Neurotoxicity And Neurodevelopmental Impairment In Extremely Preterm Infants: Study Protocol For A Randomized Controlled Trial, Lindsay F Holzapfel, Cody Arnold, Jon E Tyson, Steven M Shapiro, Eric W Reynolds, Claudia Pedroza, Emily K Stephens, Alan Kleinfeld, Andrew H Huber, Matthew A Rysavy, Maria Del Mar Romero Lopez, Amir M Khan

Faculty, Staff and Student Publications

BACKGROUND: Bilirubin neurotoxicity (BN) occurs in premature infants at lower total serum bilirubin levels than term infants and causes neurodevelopmental impairment. Usual dose lipid infusions in preterm infants may increase free fatty acids sufficiently to cause bilirubin displacement from albumin, increasing passage of unbound bilirubin (UB) into the brain leading to BN and neurodevelopmental impairment not reliably identifiable in infancy. These risks may be influenced by whether cycled or continuous phototherapy is used to control bilirubin levels.

OBJECTIVE: To assess differences in wave V latency measured by brainstem auditory evoked responses (BAER) at 34-36 weeks gestational age in infants born …

Measuring The Effect Of Newborn Screening On Survival After Haematopoietic Cell Transplantation For Severe Combined Immunodeficiency: A 36-Year Longitudinal Study From The Primary Immune Deficiency Treatment Consortium, Monica S Thakar, Brent R Logan, Jennifer M Puck, Elizabeth A Dunn, Rebecca H Buckley, Morton J Cowan, Richard J O'Reilly, Neena Kapoor, Lisa Forbes Satter, Sung-Yun Pai, Jennifer Heimall, Sharat Chandra, Christen L Ebens, Deepak Chellapandian, Olatundun Williams, Lauri M Burroughs, Blachy Davila Saldana, Ahmad Rayes, Lisa M Madden, Shanmuganathan Chandrakasan, Jeffrey J Bednarski, Kenneth B Desantes, Geoffrey D E Cuvelier, Pierre Teira, Alfred P Gillio, Hesham Eissa, Alan P Knutsen, Frederick D Goldman, Victor M Aquino, Evan B Shereck, Theodore B Moore, Emi H Caywood, Mark T Vander Lugt, Jacob Rozmus, Larisa Broglie, Lolie C Yu, Ami J Shah, Jeffrey R Andolina, Xuerong Liu, Roberta E Parrott, Jasmeen Dara, Susan Prockop, Caridad A Martinez, Malika Kapadia, Soma C Jyonouchi, Kathleen E Sullivan, Jack J Bleesing, Sonali Chaudhury, Aleksandra Petrovic, Michael D Keller, Troy C Quigg, Suhag Parikh, Shalini Shenoy, Christine Seroogy, Tamar Rubin, Hélène Decaluwe, John M Routes, Troy R Torgerson, Jennifer W Leiding, Michael A Pulsipher, Donald B Kohn, Linda M Griffith, Elie Haddad, Christopher C Dvorak, Luigi D Notarangelo

Faculty, Staff and Students Publications

Background: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18.

Methods: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by …

Prematurity Blunts Protein Synthesis In Skeletal Muscle Independently Of Body Weight In Neonatal Pigs, Marko Rudar, Jane K Naberhuis, Agus Suryawan, Hanh V Nguyen, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Background

Postnatal growth failure in premature infants is associated with reduced lean mass accretion. Prematurity impairs the feeding-induced stimulation of translation initiation and protein synthesis in the skeletal muscle of neonatal pigs. The objective was to determine whether body weight independently contributes to the blunted postprandial protein synthesis.

Methods

Preterm and term pigs that were either fasted or fed were stratified into quartiles according to birth weight to yield preterm and term groups of similar body weight; first and second quartiles of preterm pigs and third and fourth quartiles of term pigs were compared (preterm-fasted, n = 23; preterm-fed, n …

Realizing The Promise Of Dolutegravir In Effectively Treating Children And Adolescents Living With Hiv In Real-World Settings In 6 Countries In Eastern And Southern Africa, Jason Michael Bacha, Sandile Dlamini, Florence Anabwani, Judith Gwimile, Jacqueline Balungi Kanywa, John Farirai, Menard Bvumbwe, Mabene Tsotako, Teresa Steffy, Diane Nguyen, Jose Euberto Mendez-Reyes, Peter Elyanu, Heather Haq

Faculty, Staff and Students Publications

BACKGROUND: Despite encouraging results from clinical trials and in high-income countries, large-scale data on the effectiveness and safety of dolutegravir (DTG) in children and adolescents living with HIV (CALHIV) are lacking in low- and middle-income countries (LMICs).

METHODS: Retrospective analysis was performed among CALHIV 0-19 years old and weighing greater than or equal to 20 kg who received DTG from 2017 to 2020 at sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania and Uganda to determine effectiveness, safety and predictors of viral load suppression (VLS) among CALHIV using DTG, including through single drug substitutions (SDS).

RESULTS: Among 9419 CALHIV using DTG, …

Transpyloric Feed In Reflux-Associated Apnea In Preterm Newborns: A Prospective Study, Tamoghna Biswas, Tapas K. Sabui, Somosri Roy, Rakesh Mondal, Shubhabrata Majumdar, Sudipta Misra

HCA Healthcare Journal of Medicine

Background

The etiological correlation between gastroesophageal reflux (GER) and apnea is controversial. We conducted a prospective interventional study designed to address the controversy.

Methods

Preterm neonates with apnea at a tertiary care center, who had clinical features of GER without any other comorbidities likely to cause apnea, were included in the study. The enrolled neonates underwent continuous transpyloric tube feeding for 72 hours. The primary outcome measure was the difference in the number of apneic episodes pre- and post-initiation of nasoduodenal (ND) feeding. Secondary outcome measures included the incidence of necrotizing enterocolitis, other gastrointestinal disturbances, and mortality.

Results

Sixteen preterm …

Infant Isolation And Cohorting For Preventing Or Reducing Transmission Of Healthcare-Associated Infections In Neonatal Units, Morcos Hanna, Rita Shah, Lucila Marquez, Rebecca Barzegar, Adrienne Gordon, Mohan Pammi

Faculty, Staff and Students Publications

BACKGROUND: Neonatal healthcare-associated infections (HAIs) result in increased morbidity and mortality, as well as increased healthcare costs. Patient isolation measures, i.e. single-room isolation or the cohorting of patients with similar infections, remain a recommended and commonly used practice for preventing horizontal spread of infections in the neonatal intensive care unit (NICU). OBJECTIVES: Our primary objective was to assess the effect of single-room isolation or cohorting, or both for preventing transmission of HAIs or colonization with HAI-causing pathogens in newborn infants less than six months of age admitted to the neonatal intensive care unit (NICU). Our secondary objective was to assess …

Red Blood Cell Transfusion Thresholds For Anemia Of Prematurity, Lindsay F Holzapfel, Matthew A Rysavy, Edward F Bell

Faculty, Staff and Student Publications

Anemia of prematurity affects the majority of preterm infants, particularly extremely low birthweight infants. Anemia of prematurity arises from both innate and iatrogenic causes and results in more than 80% of extremely preterm infants receiving red blood cell transfusions during the first month after birth. Multiple randomized controlled trials were conducted to evaluate the effect of using lower versus higher transfusion thresholds based on hemoglobin levels. These trials showed no difference in the primary outcome of neurodevelopmental impairment at 2 years of age between lower and higher thresholds. However, some uncertainties about transfusion thresholds remain. This review elaborates the following: …

Association Between Early Prostacyclin Therapy And Extracorporeal Life Support Use In Patients With Congenital Diaphragmatic Hernia, Akila B Ramaraj, Samuel E Rice-Townsend, Carrie L Foster, Delphine Yung, Emma O Jackson, Ashley H Ebanks, Matthew T Harting, Rebecca A Stark, Congenital Diaphragmatic Hernia Study Group

Faculty, Staff and Student Publications

IMPORTANCE: Prostacyclin (PGI2) is a therapeutic option to treat congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension in neonates. Its use may decrease the need for extracorporeal life support (ECLS).

OBJECTIVE: To evaluate the association of early PGI2 therapy with ECLS use and outcomes among patients with CDH.

DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study from the CDH Study Group (CDHSG) registry of patients born from January 2007 to December 2019. Patients were from 88 different tertiary pediatric referral centers worldwide that contributed data to the CDHSG. Patients were included in the study if they were admitted within the first …

Preterm Birth Alters The Feeding-Induced Activation Of Akt Signaling In The Muscle Of Neonatal Piglets, Agus Suryawan, Marko Rudar, Jane K Naberhuis, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Postnatal lean mass accretion is commonly reduced in preterm infants. This study investigated mechanisms involved in the blunted feeding-induced activation of Akt in the skeletal muscle of preterm pigs that contributes to lower protein synthesis rates.

METHODS: On day 3 following cesarean section, preterm and term piglets were fasted or fed an enteral meal. Activation of Akt signaling pathways in skeletal muscle was determined.

RESULTS: Akt1 and Akt2, but not Akt3, phosphorylation were lower in the skeletal muscle of preterm than in term pigs (P < 0.05). Activation of Akt-positive regulators, PDK1 and mTORC2, but not FAK, were lower in preterm than in term (P < 0.05). The formation of Akt complexes with GAPDH and Hsp90 and the abundance of Ubl4A were lower in preterm than in term (P < 0.05). The abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN and IP6K1, were higher in preterm than in term pigs (P < 0.05). PP2A activation was inhibited by feeding in term but not in preterm pigs (P < 0.05).

CONCLUSIONS: Our results suggest that preterm birth impairs regulatory components involved in Akt activation, …

Surgeons’ Knowledge Regarding Perioperative Pain Management In Patients With Opioid Use Disorder: A Survey Among 260 Members Of The American College Of Surgeons, Caroline E Crocker, Romana Sharmeen, Thu T Tran, Amir M Khan, Wen Li, Joseph L Alcorn

Faculty, Staff and Student Publications

Surfactant protein A (SP-A) has important roles in innate immunity and modulation of pulmonary and extrapulmonary inflammation. Given SP-A has been detected in rat and human brain, we sought to determine if SP-A has a role in modulating inflammation in the neonatal mouse brain. Neonatal wildtype (WT) and SP-A-deficient (SP-A

Videolaryngoscopy Versus Direct Laryngoscopy For Tracheal Intubation In Neonates, Krithika Lingappan, Nicole Neveln, Jennifer L Arnold, Caraciolo J Fernandes, Mohan Pammi

Faculty, Staff and Students Publications

BACKGROUND: Establishment of a secure airway is a critical part of neonatal resuscitation in the delivery room and the neonatal intensive care unit. Videolaryngoscopy has the potential to facilitate successful endotracheal intubation, and decrease adverse consequences of a delay in airway stabilization. Videolaryngoscopy may enhance visualization of the glottis and intubation success in neonates. This is an update of a review first published in 2015, and updated in 2018.

OBJECTIVES: To determine the effectiveness and safety of videolaryngoscopy compared to direct laryngoscopy in decreasing the time and attempts required for endotracheal intubation and increasing the success rate on first intubation …

Heterogeneity Of Treatment Effects Of Hydrocortisone By Risk Of Bronchopulmonary Dysplasia Or Death Among Extremely Preterm Infants In The National Institute Of Child Health And Human Development Neonatal Research Network Trial: A Secondary Analysis Of A Randomized Clinical Trial, Samuel J Gentle, Matthew A Rysavy, Lei Li, Matthew M Laughon, Ravi M Patel, Erik A Jensen, Susan Hintz, Namasivayam Ambalavanan, Waldemar A Carlo, Kristi Watterberg, National Institute Of Child Health And Human Development Neonatal Research Network

Faculty, Staff and Student Publications

IMPORTANCE: Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death.

OBJECTIVE: To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death.

DESIGN, SETTING, AND PARTICIPANTS: …

Assessment Of Corticosteroid Therapy And Death Or Disability According To Pretreatment Risk Of Death Or Bronchopulmonary Dysplasia In Extremely Preterm Infants, Erik A Jensen, Laura Elizabeth Wiener, Matthew A Rysavy, Kevin C Dysart, Marie G Gantz, Eric C Eichenwald, Rachel G Greenberg, Heidi M Harmon, Matthew M Laughon, Kristi L Watterberg, Michele C Walsh, Bradley A Yoder, Scott A Lorch, Sara B Demauro

Faculty, Staff and Student Publications

IMPORTANCE: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended.

OBJECTIVE: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants.

DESIGN, SETTING, AND …

Incidence Rates Of Medically Attended Covid-19 In Infants Less Than 6 Months Of Age, Isabel Griffin, Stephanie A Irving, Carmen Sofia Arriola, Angela P Campbell, De-Kun Li, Fatimah S Dawood, Caroline Doughty-Skierski, Jeannette R Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Mary Juergens, Venkatesh Kancharla, Allison L Naleway, Gabriella Newes-Adeyi, Erin Nicholson, Roxana Odouli, Lawrence Reichle, Mo Sanyang, Kate Woodworth, Flor M Munoz

Faculty, Staff and Students Publications

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age.

METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test …

Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation In Preterm Pigs, Line I Christiansen, Bo Holmqvist, Xiaoyu Pan, Kristine Holgersen, Sandy E H Lindholm, Nicole L Henriksen, Douglas G Burrin, David Ley, Thomas Thymann, Per Torp Sangild, Stanislava Pankratova

Faculty, Staff and Students Publications

Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was …

A National, Electronic Health Record-Based Study Of Perinatal Hemorrhagic And Ischemic Stroke, Stuart Fraser, Samantha M Levy, Yashar Talebi, Sean I Savitz, Alicia Zha, Gen Zhu, Hulin Wu

Faculty, Staff and Student Publications

BACKGROUND: Perinatal stroke occurs in approximately 1 in 1100 live births. Large electronic health record (EHR) data can provide information on exposures associated with perinatal stroke in a larger number of patients than is achievable through traditional clinical studies. The objective of this study is to assess prevalence and odds ratios of known and theorized comorbidities with perinatal ischemic and hemorrhagic stroke.

METHODS: The data for patients aged 0-28 days with a diagnosis of either ischemic or hemorrhagic stroke were extracted from the Cerner Health Facts Electronic Medical Record (EMR) database. Incidence of birth demographics and perinatal complications were recorded. …