Pediatrics Commons^™

Developmental Pharmacokinetics Of Indomethacin In Preterm Neonates: Severely Decreased Drug Clearance In The First Week Of Life., Wojciech Krzyzanski, Bradley Stockard, Andrea Gaedigk, Allison Scott, Whitney M. Nolte, Kim T. Gibson, J Steven Leeder, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Indomethacin is used commonly in preterm neonates for the prevention of intracranial hemorrhage and closure of an abnormally open cardiac vessel. Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently …

Feasibility Of And Experience Using A Portable Mri Scanner In The Neonatal Intensive Care Unit., Maura Sien, Amie L. Robinson, Houchun H. Hu, Christopher R. Nitkin, Ara Hall, Marcie G. Files, Nathan S. Artz, John T. Pitts, Sherwin S. Chan

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: A portable, low-field MRI system is now Food and Drug Administration cleared and has been shown to be safe and useful in adult intensive care unit settings. No neonatal studies have been performed. The objective is to assess our preliminary experience and assess feasibility of using the portable MRI system at the bedside in a neonatal intensive care unit (NICU) at a quaternary children's hospital.

STUDY DESIGN: This was a single-site prospective cohort study in neonates ≥2 kg conducted between October and December 2020. All parents provided informed consent. Neonates underwent portable MRI examination in the NICU with support …

Evaluating The Relationship Of In Utero Nicotine Exposure With Hypoglycemia After Delivery: An Observational Study, Mary G Johnson, Robert Suchting, Lisa M Scheid, Lindsay N Holzapfel, Aditi Chalise, Angela L Stotts, John C Chapman, Amir M Khan, Thomas F Northrup

Faculty, Staff and Student Publications

BACKGROUND: Hypoglycemia in neonates is common and contributes to 4.0-5.8% of neonatal intensive care unit (NICU) admissions. In utero nicotine exposure is underexplored as a potential contributor to neonatal hypoglycemia. Rat models have shown that in utero nicotine exposure can be associated with a reduction in pancreatic beta cell mass, leading to glucose dysregulation. The primary aim of this work is to study the risk of developing hypoglycemia after birth in a population of in utero nicotine-exposed neonates.

METHODS: We conducted a retrospective matched cohort study that augmented an existing dataset of neonates admitted to a level IV NICU with …

Growth And Differentiation Factor 15 (Gdf15) Levels Predict Adverse Respiratory Outcomes In Premature Neonates, Faeq Almudares, Joseph Hagan, Xinpu Chen, Sridevi Devaraj, Bhagavatula Moorthy, Krithika Lingappan

Faculty, Staff and Students Publications

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved …

Clostridioides Difficile Infection In Hospitalized Pediatric Patients: Comparisons Of Epidemiology, Testing, And Treatment From 2013 To 2019, Price T Edwards, Cary W Thurm, Matthew Hall, Jordan D Busing, Stacy A Kahn, Richard Kellermayer, Larry K Kociolek, Maria M Oliva-Hemker, Julia S Sammons, Madison Weatherly, Kathryn M Edwards, Maribeth R Nicholson

Faculty, Staff and Students Publications

OBJECTIVES: To compare the incidence, epidemiology, testing patterns, treatment, and outcomes of Clostridioides difficile infection (CDI) among hospitalized pediatric patients from 2013 to 2019.

STUDY DESIGN: The Pediatric Health Information System database was queried for patient admissions (age 0-17 years) with International Classification of Diseases, 9th and 10th edition, codes for diagnoses of CDI with a billing code for a CDI-related antibiotic treatment.

RESULTS: We identified 17 142 pediatric patients, representing 23 052 admissions, with CDI. The adjusted annual CDI incidence decreased over the study period from 7.09 cases per 10 000 patient-days (95% CI, 6.15-8.18) in 2013 to 4.89 …

A Systematic Review Of Associations Between Gut Microbiota Composition And Growth Failure In Preterm Neonates, Larissa L Neves, Amy B Hair, Geoffrey A Preidis

Faculty, Staff and Students Publications

Growth failure is among the most prevalent and devastating consequences of prematurity. Up to half of all extremely preterm neonates struggle to grow despite modern nutrition practices. Although elegant preclinical models suggest causal roles for the gut microbiome, these insights have not yet translated into biomarkers that identify at-risk neonates or therapies that prevent or treat growth failure. This systematic review aims to identify features of the neonatal gut microbiota that are positively or negatively associated with early postnatal growth. We identified 860 articles, of which 14 were eligible for inclusion. No two studies used the same definitions of growth, …

Multiomics, Artificial Intelligence, And Precision Medicine In Perinatology, Mohan Pammi, Nima Aghaeepour, Josef Neu

Faculty, Staff and Students Publications

Technological advances in omics evaluation, bioinformatics, and artificial intelligence have made us rethink ways to improve patient outcomes. Collective quantification and characterization of biological data including genomics, epigenomics, metabolomics, and proteomics is now feasible at low cost with rapid turnover. Significant advances in the integration methods of these multiomics data sets by machine learning promise us a holistic view of disease pathogenesis and yield biomarkers for disease diagnosis and prognosis. Using machine learning tools and algorithms, it is possible to integrate multiomics data with clinical information to develop predictive models that identify risk before the condition is clinically apparent, thus …

Cholestasis Impairs Gut Microbiota Development And Bile Salt Hydrolase Activity In Preterm Neonates, Lauren E Lynch, Amy B Hair, Krishnakant G Soni, Heeju Yang, Laura A Gollins, Monica Narvaez-Rivas, Kenneth D R Setchell, Geoffrey A Preidis

Faculty, Staff and Students Publications

Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops …

Assembling A Global Database Of Child Pneumonia Studies To Inform Who Pneumonia Management Algorithm: Methodology And Applications, Helena Martin, Jennifer Falconer, Emmanuel Addo-Yobo, Satinder Aneja, Luis Martinez Arroyo, Rai Asghar, Shally Awasthi, Salem Banajeh, Abdul Bari, Sudha Basnet, Ashish Bavdekar, Nita Bhandari, Shinjini Bhatnagar, Zulfiqar A Bhutta, Abdullah Brooks, Mandeep Chadha, Noel Chisaka, Monidarin Chou, Alexey W Clara, Tim Colbourn, Clare Cutland, Valérie D'Acremont, Marcela Echavarria, Angela Gentile, Brad Gessner, Christopher J Gregory, Tabish Hazir, Patricia L Hibberd, Siddhivinayak Hirve, Shubhada Hooli, Imran Iqbal, Prakash Jeena, Cissy B Kartasasmita, Carina King, Romina Libster, Rakesh Lodha, Juan M Lozano, Marilla Lucero, Norman Lufesi, William B Macleod, Shabir Ahmed Madhi, Joseph L Mathew, Irene Maulen-Radovan, Eric D Mccollum, Greta Mino, Charles Mwansambo, Mark I Neuman, Ngoc Tuong Vy Nguyen, Marta C Nunes, Pagbajabyn Nymadawa, Kerry-Ann F O'Grady, Jean-William Pape, Glaucia Paranhos-Baccala, Archana Patel, Valentina Sanchez Picot, Mala Rakoto-Andrianarivelo, Zeba Rasmussen, Vanessa Rouzier, Graciela Russomando, Raul O Ruvinsky, Salim Sadruddin, Samir K Saha, Mathuram Santosham, Sunit Singhi, Sajid Soofi, Tor A Strand, Mariam Sylla, Somsak Thamthitiwat, Donald M Thea, Claudia Turner, Philippe Vanhems, Nitya Wadhwa, Jianwei Wang, Syed Ma Zaman, Harry Campbell, Harish Nair, Shamim Ahmad Qazi, Yasir Bin Nisar, World Health Organization Pneumonia Research Partnership To Assess Who Recommendation (Prepare) Study Group

Faculty, Staff and Students Publications

BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines.

METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to …

Delayed-Interval Delivery In Multiple Gestation Pregnancies: Neonatal Mortality, Morbidity, And Development, Nicolas J Bouey, Shampa Saha, Deanne E Wilson-Costello, Matthew A Rysavy, Michele Walsh, Myra H Wyckoff, Anna Maria Hibbs

Faculty, Staff and Student Publications

OBJECTIVE: Delayed-interval delivery (DID) is the delivery of the first fetus in a multiple gestation pregnancy without prompt delivery of the remaining fetus(es). We aimed to assess infant outcomes of DID.

STUDY DESIGN: We performed a retrospective cohort study of infants born 22-28 weeks' gestation or weighing 401-1500 g. DID was defined as a passage of >24 h between the birth of firstborn and retained infants. Rates of mortality, morbidity, and developmental outcomes were compared within DID multiples, to other multiples not born by DID, and all infants in the Generic Database and follow-up datasets (excluding DID-born).

RESULTS: DID-born multiples …

Foxi3 Haploinsufficiency Contributes To Low T-Cell Receptor Excision Circles And T-Cell Lymphopenia, Rajarshi Ghosh, Marita Bosticardo, Sunita Singh, Morgan Similuk, Ottavia M Delmonte, Francesca Pala, Christine Peng, Colleen Jodarski, Michael D Keller, Ivan K Chinn, Andrew K Groves, Luigi D Notarangelo, Magdalena A Walkiewicz, Javier Chinen, Vanessa Bundy

Faculty, Staff and Students Publications

BACKGROUND: Newborn screening can identify neonatal T-cell lymphopenia through detection of a low number of copies of T-cell receptor excision circles in dried blood spots collected at birth. After a positive screening result, further diagnostic testing is required to determine whether the subject has severe combined immunodeficiency or other causes of T-cell lymphopenia. Even after thorough evaluation, approximately 15% of children with a positive result of newborn screening for T-cell receptor excision circles remain genetically undiagnosed. Identifying the underlying genetic etiology is necessary to guide subsequent clinical management and family planning.

OBJECTIVE: We sought to elucidate the genetic basis of …

Outcome Prediction In Newborn Infants: Past, Present, And Future, Vivek V Shukla, Matthew A Rysavy, Abhik Das, Jon E Tyson, Edward F Bell, Namasivayam Ambalavanan, Waldemar A Carlo

Faculty, Staff and Student Publications

The perinatal and neonatal periods are the periods of considerable organ development and maturation. Perinatal and neonatal illnesses can result in mortality and morbidities that burden families and the healthcare system. Outcome prediction is essential for informing perinatal and intensive care management, prognosis, and post-discharge interventions. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) research databases include hospital and neurodevelopment follow-up outcomes of infants with various underlying diseases and conditions receiving intensive care, providing a unique opportunity to assess outcome risk prediction. The NRN has developed outcome risk prediction tools for use …

Speech-Language Disorder Severity, Academic Success, And Socioemotional Functioning Among Multilingual And English Children In The United States: The National Survey Of Children’S Health, Martin L Blakely, Matthew A Rysavy, Kevin P Lally, Barry Eggleston, Claudia Pedroza, Jon E Tyson

Faculty, Staff and Student Publications

Randomized controlled trials (RCTs) are challenging, but are the studies most likely to change practice and benefit patients. RCTs investigating neonatal surgical therapies are rare. The Necrotizing Enterocolitis Surgery Trial (NEST) was the first surgical RCT conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN), and multiple lessons were learned. NEST was conducted over a 7.25-year enrollment period and the primary outcome was death or neurodevelopmental impairment (NDI) at 18-22 months corrected age. Surgical investigators designing clinical trials involving neonatal surgical treatments have many considerations to include, including how to …

Genetic Testing To Inform Epilepsy Treatment Management From An International Study Of Clinical Practice, Dianalee Mcknight, Ana Morales, Kathryn E. Hatchell, Sara L. Bristow, Joshua L. Bonkowsky, Michael Scott Perry, Anne T. Berg, Felippe Borlot, Edward D. Esplin, Chad Moretz, Katie Angione, Loreto Ríos-Pohl, Robert L. Nussbaum, Swaroop Aradhya, Chad R. Haldeman-Englert, Rebecca J. Levy, Venu G. Parachuri, Guillermo Lay-Son, David J. Dávila-Ortiz De Montellano, Miguel Angel Ramirez-Garcia, Edmar O. Benítez Alonso, Julie Ziobro, Adela Chirita-Emandi, Temis M. Felix, Dianne Kulasa-Luke, Andre Megarbane, Shefali Karkare, Sarah L. Chagnon, Jennifer B. Humberson, Melissa J. Assaf, Sebastian Silva, Katherine Zarroli, Oksana Boyarchuk, Gary R. Nelson, Rachel Palmquist, Katherine C. Hammond, Sean T. Hwang, Susan B. Boutlier, Melinda Nolan, Kaitlin Y. Batley, Devraj Chavda, Carlos Alberto Reyes-Silva, Oleksandr Miroshnikov, Britton Zuccarelli, Louise Amlie-Wolf, James W. Wheless, Syndi Seinfeld, Manoj Kanhangad, Jeremy L. Freeman, Susana Monroy-Santoyo, Natalia Rodriguez-Vazquez, Monique M. Ryan, Michelle Machie, Patricio Guerra, Muhammad Jawad Hassan, Meghan S. Candee, Caleb P. Bupp, Kristen L. Park, Eric Muller, Pamela Lupo, Robert C. Pedersen, Amir M. Arain, Andrea Murphy, Krista Schatz, Weiyi Mu, Paige M. Kalika, Lautaro Plaza, Marissa A. Kellogg, Evelyn G. Lora, Robert P. Carson, Victoria Svystilnyk, Viviana Venegas, Rebecca R. Luke, Huiyuan Jiang, Tetiana Stetsenko, Milagros M. Dueñas-Roque, Joseph Trasmonte, Rebecca J. Burke, Anna C. E. Hurst, Douglas M. Smith, Lauren J. Massingham, Laura Pisani, Carrie E. Costin, Betsy Ostrander, Francis M. Filloux, Amitha L. Ananth, Ismail S. Mohamed, Alla Nechai, Jasmin M. Dao, Michael C. Fahey, Ermal Aliu, Stephen Falchek, Craig A. Press, Lauren Treat, Krista Eschbach, Angela Starks, Ryan Kammeyer, Joshua J. Bear, Mona Jacobson, Veronika Chernuha, Bailey Meibos, Kristen Wong, Matthew T. Sweney, A. Chris Espinoza, Colin B. Van Orman, Arie Weinstock, Ashutosh Kumar, Claudia Soler-Alfonso, Danielle A. Nolan, Muhammad Raza, Miguel David Rojas Carrion, Geetha Chari, Eric D. Marsh, Yael Shiloh-Malawsky, Sumit Parikh, Ernesto Gonzalez-Giraldo, Stephen Fulton, Yoshimi Sogawa, Kaitlyn Burns, Myroslava Malets, Johnny David Montiel Blanco, Christa W. Habela, Carey A. Wilson, Guillermo G. Guzmán, Mariia Pavliuk

Department of Pediatrics Faculty Papers

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.

OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a …

Infant Behavioral State And Stool Microbiome In Infants Receiving Lactocaseibacillus Rhamnosus Gg In Formula: Randomized Controlled Trial, Robert J Shulman, Maciej Chichlowski, Fabiola Gutierrez Orozco, Cheryl L Harris, Jennifer L Wampler, Nicholas A Bokulich, Carol Lynn Berseth

Faculty, Staff and Students Publications

BACKGROUND: Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG).

METHODS: In this single-center, double-blind, controlled, parallel, prospective study, term infants (14-28 days of age) identified with colic (using modified Wessel's criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow's milk-based infant formula (PHF, n = 35) or a similar formula with …

Association Of Cerebrovascular Stability Index And Head Circumference Between Infants With And Without Congenital Heart Disease, Nhu N Tran, Michelle Tran, Ashok Panigrahy, Ken M Brady, Jodie K Votava-Smith

Faculty, Staff and Student Publications

Congenital heart disease (CHD) is a common birth defect in the United States. CHD infants are more likely to have smaller head circumference and neurodevelopmental delays; however, the cause is unknown. Altered cerebrovascular hemodynamics may contribute to neurologic abnormalities, such as smaller head circumference, thus we created a novel Cerebrovascular Stability Index (CSI), as a surrogate for cerebral autoregulation. We hypothesized that CHD infants would have an association between CSI and head circumference. We performed a prospective, longitudinal study in CHD infants and healthy controls. We measured CSI and head circumference at 4 time points (newborn, 3, 6, 9 months). …

A Hydrogen-Sulfide Derivative Of Mesalamine Reduces The Severity Of Intestinal And Lung Injury In Necrotizing Enterocolitis Through Endothelial Nitric Oxide Synthase, Brian D Hosfield, Chelsea E Hunter, Hongge Li, Natalie A Drucker, Anthony R Pecoraro, Krishna Manohar, W Christopher Shelley, Troy A Markel

Faculty, Staff and Student Publications

Necrotizing enterocolitis (NEC) remains a devastating disease that affects preterm infants. Hydrogen sulfide (H2S) donors have been shown to reduce the severity of NEC, but the optimal compound has yet to be identified. We hypothesized that oral H2S-Mesalamine (ATB-429) would improve outcomes in experimental NEC, and its benefits would be dependent on endothelial nitric oxide synthase (eNOS) pathways. NEC was induced in 5-day-old wild-type (WT) and eNOS knockout (eNOSKO) pups by formula feeding and stress. Four groups were studied in both WT and eNOSKO mice: 1) breastfed controls, 2) NEC, 3) NEC + 50 mg/kg mesalamine, and …

Microrna Expression Levels Change In Neonatal Patients During And After Exposure To Cardiopulmonary Bypass., Lance Hsieh, Lan N. Tu, Alison Paquette, Quanhu Sheng, Shilin Zhao, Douglas C. Bittel, James O'Brien, Kasey Vickers, Peter Pastuszko, Vishal Nigam

Manuscripts, Articles, Book Chapters and Other Papers

Background The systemic inflammation that occurs after exposure to cardiopulmonary bypass (CPB), which is especially severe in neonatal patients, is associated with poorer outcomes and is not well understood. In order to gain deeper insight into how exposure to bypass activates inflammatory responses in circulating leukocytes, we studied changes in microRNA (miRNA) expression during and after exposure to bypass. miRNAs are small noncoding RNAs that have important roles in modulating protein levels and function of cells. Methods and Results We performed miRNA-sequencing on leukocytes isolated from neonatal patients with CPB (n=5) at 7 time points during the process of CPB, …

Rolling Stones: An Instructive Case Of Neonatal Cholestasis, Paige Killelea, Shruti Sakhuja, Jose Hernandez, M John Hicks, Sanjiv Harpavat

Faculty, Staff and Students Publications

BACKGROUND: Jaundice within the first 1-2 weeks of a neonate's life will generally self-resolve; however, if it lasts longer than this time frame it warrants further work up. Direct or conjugated hyperbilirubinemia can suggest neonatal cholestasis, which in turn reflects marked reduction in bile secretion and flow. The differential diagnosis for neonatal cholestasis is broad. Neonatal choledocholithiasis is a rare cause of neonatal cholestasis, but should be considered on the differential diagnosis for patients presenting with elevated conjugated bilirubin.

CASE PRESENTATION: We describe an infant who presented with neonatal cholestasis. He subsequently underwent work up for biliary atresia, as this …

Association Of Antenatal Steroid Exposure At 21 To 22 Weeks Of Gestation With Neonatal Survival And Survival Without Morbidities, Sanjay Chawla, Myra H Wyckoff, Matthew A Rysavy, Ravi Mangal Patel, Dhuly Chowdhury, Girija Natarajan, Abbot R Laptook, Satyan Lakshminrusimha, Edward F Bell, Seetha Shankaran, Krisa P Van Meurs, Namasivayam Ambalavanan, Rachel G Greenberg, Noelle Younge, Erika F Werner, Abhik Das, Waldemar A Carlo, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Faculty, Staff and Student Publications

IMPORTANCE: The provision of antenatal corticosteroids to pregnant patients at gestational age (GA) 22 6/7 weeks or less remains controversial and lacks support from randomized clinical trials.

OBJECTIVE: To compare rates of survival and survival without major morbidities among infants born at GA 22 0/7 to 23 6/7 weeks after exposure to antenatal steroids at 22 6/7 weeks' gestation or less vs no exposure to antenatal steroids.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study enrolled infants born at GA 22 0/7 to 23 6/7 weeks between January 1, 2016, and December 31, 2019, at centers in the National Institute of …

Rates Of Laboratory Adverse Events By Course In Paediatric Leukaemia Ascertained With Automated Electronic Health Record Extraction: A Retrospective Cohort Study From The Children’S Oncology Group, Tamara P Miller, Kelly D Getz, Yimei Li, Biniyam G Demissei, Peter C Adamson, Todd A Alonzo, Evanette Burrows, Lusha Cao, Sharon M Castellino, Marla H Daves, Brian T Fisher, Robert Gerbing, Robert W Grundmeier, Edward M Krause, Judy Lee, Philip J Lupo, Karen R Rabin, Mark Ramos, Michael E Scheurer, Jennifer J Wilkes, Lena E Winestone, Douglas S Hawkins, M Monica Gramatges, Richard Aplenc

Center for Medical Ethics and Health Policy Staff Publications

Background: Adverse events are often misreported in clinical trials, leading to an incomplete understanding of toxicities. We aimed to test automated laboratory adverse event ascertainment and grading (via the ExtractEHR automated package) to assess its scalability and define adverse event rates for children with acute myeloid leukaemia and acute lymphoblastic leukaemia.

Methods: For this retrospective cohort study from the Children's Oncology Group (COG), we included patients aged 0-22 years treated for acute myeloid leukaemia or acute lymphoblastic leukaemia at Children's Healthcare of Atlanta (Atlanta, GA, USA) from Jan 1, 2010, to Nov 1, 2018, at the Children's Hospital of Philadelphia …

Analysis Of Neonatal Neurobehavior And Developmental Outcomes Among Preterm Infants., Elisabeth C. Mcgowan, Julie A. Hofheimer, T Michael O'Shea, Howard Kilbride, Brian S. Carter, Jennifer Check, Jennifer Helderman, Charles R. Neal, Steve Pastyrnak, Lynne M. Smith, Marie Camerota, Lynne M. Dansereau, Sheri A. Della Grotta, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

Importance: The ability to identify poor outcomes and treatable risk factors among very preterm infants remains challenging; improving early risk detection and intervention targets to potentially address developmental and behavioral delays is needed.

Objective: To determine associations between neonatal neurobehavior using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS), neonatal medical risk, and 2-year outcomes.

Design, Setting, and Participants: This multicenter cohort enrolled infants born at less than 30 weeks' gestation at 9 US university-affiliated NICUs. Enrollment was conducted from April 2014 to June 2016 with 2-year adjusted age follow-up assessment. Data were analyzed from December 2019 to …

Insurance Coverage And Respiratory Morbidities In Bronchopulmonary Dysplasia., Joseph M. Collaco, Michael C. Tracy, Catherine A. Sheils, Jessica L. Rice, Lawrence M. Rhein, Leif D. Nelin, Paul E. Moore, Winston M. Manimtim, Jonathan C. Levin, Khanh Lai, Lystra P. Hayden, Julie L. Fierro, Eric D. Austin, Stamatia Alexiou, Amit Agarwal, Natalie Villafranco, Roopa Siddaiah, Antonia P. Popova, Ioana A. Cristea, Christopher D. Baker, Manvi Bansal, Sharon A. Mcgrath-Morrow

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Preterm infants and young children with bronchopulmonary dysplasia (BPD) are at increased risk for acute care utilization and chronic respiratory symptoms during early life. Identifying risk factors for respiratory morbidities in the outpatient setting could decrease the burden of care. We hypothesized that public insurance coverage was associated with higher acute care usage and respiratory symptoms in preterm infants and children with BPD after initial neonatal intensive care unit (NICU) discharge.

METHODS: Subjects were recruited from BPD clinics at 10 tertiary care centers in the United States between 2018 and 2021. Demographics and clinical characteristics were obtained through chart …

A Pilot Study To Determine The Incidence, Type, And Severity Of Non-Routine Events In Neonates Undergoing Gastrostomy Tube Placement, Daniel J France, Emma Schremp, Evan B Rhodes, Jason Slagle, Sarah Moroz, Peter H Grubb, Leon D Hatch, Matthew Shotwell, Amanda Lorinc, Jamie Robinson, Marlee Crankshaw, Timothy Newman, Matthew B Weinger, Martin L Blakely

Faculty, Staff and Student Publications

BACKGROUND: Non-routine events (NRE) are defined as any suboptimal occurrences in a process being measured in the opinion of the reporter and comes from the field of human factors engineering. These typically occur well up-stream of an adverse event and NRE measurement has not been applied to the complex context of neonatal surgery. We sought to apply this novel safety event measurement methodology to neonates in the NICU undergoing gastrostomy tube placement.

METHODS: A prospective pilot study was conducted between November 2016 and August 2020 in the Level IV NICU and the pediatric operating rooms of an urban academic children's …

The Epidemiology Of Biliary Atresia: Exploring The Role Of Developmental Factors On Birth Prevalence, Laurel Cavallo, Erin M Kovar, Amal Aqul, Lucille Mcloughlin, Naveen K Mittal, Norberto Rodriguez-Baez, Benjamin L Shneider, Robert J Zwiener, Tiffany M Chambers, Peter H Langlois, Mark A Canfield, A J Agopian, Philip J Lupo, Sanjiv Harpavat

Faculty, Staff and Students Publications

OBJECTIVE: To identify key epidemiologic factors relevant to fetal development that are associated with biliary atresia.

STUDY DESIGN: This population-based registry study examined infants born in Texas between 1999 and 2014. Epidemiologic data relevant to fetal development were compared between cases of biliary atresia identified in the Texas Birth Defects Registry (n = 305) vs all live births (n = 4 689 920), and Poisson regression was used to calculate prevalence ratios (PRs) and 95% CIs.

RESULTS: The prevalence of biliary atresia over the study period was 0.65 per 10 000 live births. Biliary atresia was positively associated with female …

Pathogenesis Of Tuberculosis: The 1930 Lübeck Disaster Revisited, Peter Donald, Stefan Kaufmann, Stephanie Thee, Anna Maria Mandalakas, Christoph Lange

Faculty, Staff and Students Publications

During the 1930 Lübeck Mycobacterium bovis bacille Calmette–Guérin (BCG) disaster, 251 neonates received three oral BCG doses accidentally contaminated by virulent Mycobacterium tuberculosis; 67 (26.7%) infants died of tuberculosis. BCG reversion to pathogenicity did not occur. Detailed post mortem examinations clarified contested aspects of tuberculosis pathogenesis. Gastrointestinal infection was seldom “silent” and did not cause typical primary pulmonary lesions. In 15 infants, primary pulmonary foci were found but these resulted from vaccine ingestion and aspiration and were not caused by gastrointestinal infection spreading to the lungs without trace of its journey, as claimed by prominent researchers such as Calmette …

Neurovascular Abnormalities In Retinopathy Of Prematurity And Emerging Therapies, Chang Dai, Jun Xiao, Chenguang Wang, Wei Li, Guanfang Su

Faculty, Staff and Students Publications

Blood vessels in the developing retina are formed in concert with neural growth, resulting in functional neurovascular network. Disruption of the neurovascular coordination contributes to the pathogenesis of retinopathy of prematurity (ROP), a potentially blinding retinal neovascular disease in preterm infants that currently lacks an approved drug therapy in the USA. Despite vasculopathy as predominant clinical manifestations, an increasing number of studies revealed complex neurovascular interplays among neurons, glial cells and blood vessels during ROP. Coordinated expression of glia-derived vascular endothelial growth factor (VEGF) in spatio-temporal gradients is pivotal to the formation of well-organized vascular plexuses in the healthy retina, …

Lmod2-Related Dilated Cardiomyopathy Presenting In Late Infancy, Erica Lay, Mahshid S Azamian, Susan W Denfield, William Dreyer, Joseph A Spinner, Debra Kearney, Lilei Zhang, Kim C Worley, Weimin Bi, Seema R Lalani

Faculty, Staff and Students Publications

Leiomodin-2 (LMOD2) is an important regulator of the thin filament length, known to promote elongation of actin through polymerization at pointed ends. Mice with Lmod2 deficiency die around 3 weeks of age due to severe dilated cardiomyopathy (DCM), resulting from decreased heart contractility due to shorter thin filaments. To date, there have been three infants from two families reported with biallelic variants in LMOD2, presenting with perinatal onset DCM. Here, we describe a third family with a child harboring a previously described homozygous frameshift variant, c.1243_1244delCT (p.L415Vfs*108) with DCM, presenting later in infancy at 9 months of age. Family history …

Sex-Specific Alterations In Hepatic Cholesterol Metabolism In Low Birth Weight Adult Guinea Pigs., Ousseynou Sarr, Katherine E Mathers, Christina Vanderboor, Kristina Wiggers, Aditya Devgan, Daniel B Hardy, Lin Zhao, Timothy Regnault

Paediatrics Publications

BACKGROUND: Intrauterine growth restriction and low birth weight (LBW) have been widely reported as an independent risk factor for adult hypercholesterolaemia and increased hepatic cholesterol in a sex-specific manner. However, the specific impact of uteroplacental insufficiency (UPI), a leading cause of LBW in developed world, on hepatic cholesterol metabolism in later life, is ill defined and is clinically relevant in understanding later life liver metabolic health trajectories.

METHODS: Hepatic cholesterol, transcriptome, cholesterol homoeostasis regulatory proteins, and antioxidant markers were studied in UPI-induced LBW and normal birth weight (NBW) male and female guinea pigs at 150 days.

RESULTS: Hepatic free and …

Association Of Abnormal Findings On Neonatal Cranial Ultrasound With Neurobehavior At Neonatal Intensive Care Unit Discharge In Infants Born Before 30 Weeks' Gestation., Jennifer Helderman, T Michael O'Shea, Lynne Dansereau, Jennifer Check, Julie A. Hofheimer, Lynne M. Smith, Elisabeth Mcgowan, Charles R. Neal, Brian S. Carter, Steven L. Pastyrnak, Bradford Betz, Joseph Junewick, Heather L. Borders, Sheri A. Dellagrotta, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

Importance: Cranial ultrasound (CUS) findings are routinely used to identify preterm infants at risk for impaired neurodevelopment, and neurobehavioral examinations provide information about early brain function. The associations of abnormal findings on early and late CUS with neurobehavior at neonatal intensive care unit (NICU) discharge have not been reported.

Objective: To examine the associations between early and late CUS findings and infant neurobehavior at NICU discharge.

Design, Setting, and Participants: This prospective cohort study included infants enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants Study between April 2014 and June 2016. Infants born before 30 weeks' gestational …