Pediatrics Commons^™

Reclassifying Pediatric Nafld Using The Steatotic Liver Disease Framework: A Multicenter Retrospective Study From The Nash Crn, Tin Bo Nicholas Lam, Katherine P Yates, Sheila L Noon, Kimberly P Newton, Mark H Fishbein, Jean P Molleston, Stavra A Xanthakos, Ajay K Jain, Miriam B Vos, Niviann M Blondet, Krupa R Mysore, Cynthia A Behling, Laura A Wilson, Jeffrey B Schwimmer

Faculty, Staff and Students Publications

Background and aims: The terminology for hepatic steatosis and NAFLD was revised under the umbrella of steatotic liver disease, with metabolic dysfunction-associated steatotic liver disease (MASLD) as the primary subtype. MASLD is defined by hepatic steatosis plus at least 1 cardiometabolic risk factor. A new category, Met-ALD, describes MASLD with alcohol consumption below the defined thresholds for alcohol-associated liver disease (ALD). While adult studies have demonstrated strong concordance between NAFLD and MASLD, the applicability of this framework in children remains unclear.

Approach and results: We assessed children clinically diagnosed with NAFLD and enrolled in the NASH CRN who had available …

Longitudinal And Cross-Sectional Evidence That Daily Resting And Activity Energy Expenditures Are Independent In Humans, Andrew K Yegian, Elizabeth Pachus, Leanne M Redman, Steven B Heymsfield, K Falkenhain, Alexandra R Harris, Shaji K Chacko, William W Wong, Daniel E Lieberman

Faculty, Staff and Students Publications

Total energy expenditure (TEE) is commonly modelled as the sum of resting energy expenditure (REE), activity energy expenditure (AEE), and diet-induced thermogenesis (DIT). This additive model has recently been challenged by the constrained energy balance model, which proposes that reductions in mass-adjusted REE compensate to some extent for increases in AEE, rendering mass-adjusted TEE effectively invariant. We tested these competing models using two complementary approaches. First, we conducted a short-term longitudinal, repeated-measures experiment in 12 adults who completed 10-day periods of high and low physical activity separated by a washout period. TEE was measured with doubly labelled water, AEE with …

Na-Gst-1 Adsorbed On Alhydrogel Co-Administered With Different Toll-Like Receptor Agonists In Hookworm-Naive Adults Using A Controlled Human Infection Model In The Usa: A Phase 2, Double-Blind, Randomised Controlled Trial, Caroline K Dirosato, Elissa M Malkin, Sean M Lee, Guacyara Erwin, Lara Hoeweler, Larissa Scholte, Maria Elena Bottazzi, David I Pritchard, Peter J Hotez, Jeffrey M Bethony, David J Diemert

Faculty, Staff and Students Publications

Background: Necator americanus glutathione S-transferase-1 (Na-GST-1) performs a crucial enzymatic step in hookworm blood feeding and is a leading target for vaccine development. Phase 1 trials in Brazil, Gabon, and the USA of recombinant Na-GST-1 adsorbed on Alhydrogel (Na-GST-1/Al), co-administered with or without AP 10-701 (Toll-like receptor [TLR] 4 agonist) or CpG 10104 (TLR9 agonist), showed the vaccine was well tolerated, safe, and immunogenic. A controlled human hookworm infection (CHHI) model was previously developed to evaluate the effect of candidate hookworm vaccines on infection. We aimed to assess the effect of vaccination with three different Na-GST-1 vaccine formulations on subsequent …

Helminth-Infected Mozambican Children With Malaria Have Increased Anaemia, Cytokines And Helminth-Specific Antibodies, Inocência Cuamba, Rebeca Santano, Berta Grau-Pujol, Marta Vidal, Anélsio Cossa, Chenjerai Jairoce, Rojelio Mejía, José Muñoz, Ruth Aguilar, Bin Zhan, Augusto Nhabomba, Gemma Moncunill, Carlota Dobaño

Faculty, Staff and Students Publications

Owing to their overlapping geographical distribution and the consequent occurrence of coinfections, several studies have evaluated the impact of helminth infections on malaria immune responses and clinical outcomes. However, little has been reported on how malaria coinfection affects anthelmintic responses in children harbouring worm infections. We therefore aimed to assess the impact of malaria coinfection on helminth-related clinical and immune outcomes in children. Here, we measured in plasma the levels of 30 cytokines, total IgE, and helminth-specific IgM, IgA, IgG, IgG1-4, and IgE antibodies to a panel of 11 helminth antigens by Luminex. Samples were obtained from 441 children aged …

Asynchronous Transitions From High-Risk Hepatoblastoma To Carcinoma, Xinjian Yu, Stephen Sarabia, Martin Urbicain, Sonal Somvanshi, Roma Patel, Priyanka Rao, Tuan M Tran, Yen-Ping Yeh, Keng-Shih Chang, Yi-Tzu Lo, Jessica Epps, Kathleen A Scorsone, Hua-Sheng Chiu, Emporia Faith Hollingsworth, Cintia R Perez, Mohammad Javad Najaf Panah, Barry Zorman, Jordan Muscal, Milton J Finegold, John A Goss, Rita Alaggio, Angshumoy Roy, Kevin E Fisher, Andras Heczey, Sarah Woodfield, Sanjeev Vasudevan, Kalyani Patel, Ting-Wen Chen, Dolores Lopez-Terrada, Pavel Sumazin

Faculty, Staff and Students Publications

Background & aims: Most pediatric hepatocellular tumors are classified as hepatoblastoma (HB) or hepatocellular carcinoma (HCC), yet a subset exhibits mixed histological and molecular features. These hepatoblastomas with carcinoma features (HBCs) include cases provisionally designated as hepatocellular neoplasm-not otherwise specified (HCN-NOS). Their biology remains poorly understood, with unresolved questions about their cellular composition and outcomes. It is unclear whether HBCs comprise hybrid cells with combined HB and HCC characteristics (HBC cells) or admixtures of distinct HB and HCC cells. We characterized the biology, etiology, cellular composition, and evolutionary dynamics of HBCs.

Methods: We performed multi-omics profiling - including single-nucleus RNA …

Plasma Gdf15 Affects Long-Term Dementia Risk And Alters Neuroimmune Signaling, Cassandra O Blew, Michael R Duggan, Dimitrios Tsitsipatis, Gabriela T Gomez, Zulema Rodriguez-Hernandez, Luke C Pilling, Jingsha Chen, Eva Jacobsen, Heather E Dark, Yifei Lu, Shannon M Drouin, Cassandra M Joynes, Minhao Yao, Murat Bilgel, Abhay Moghekar, Qu Tian, Julián Candia, Mary Kaileh, Aditi Gupta, Krystyna Mazan-Mamczarz, Myriam Gorospe, Alexey Lyashkov, Yevgeniya Lukyanenko, Mika Kivimaki, Philipp Frank, Lori L Jennings, Valborg Gudmundsdottir, Vilmundur Gudnason, Lenore J Launer, Naoto Kaneko, Shintaro Kato, Makio Furuichi, Masaki Shibayama, Masahisa Katsuno, Keita Hiraga, Yukiko Nishita, Rei Otsuka, James R Pike, Mary R Rooney, Pascal Schlosser, Yuhan Cui, Guray Erus, Christos Davatzikos, Rebecca F Gottesman, Iwao Waga, Priya Palta, Christie Ballantyne, Michael Griswold, Zhonghua Liu, Luigi Ferrucci, Allison B Herman, Keenan A Walker

Faculty, Staff and Students Publications

Growth/differentiation factor-15 (GDF15) is a secreted cytokine strongly associated with dementia risk. However, the extent to which GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15- to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular, compared to Alzheimer's disease (AD), dementia. Two-sample Mendelian randomization supported plasma GDF15's mechanistic role in AD and related dementias, while cohort studies linked it to cerebral small vessel disease, neurodegeneration, phosphorylated tau, and a cerebrospinal fluid proteomic signature indicative of neuroimmune activation. …

Recent Antibiotic Exposure And Response To Treatment Of Juvenile Idiopathic Arthritis: A Retrospective Cohort Study, Daniel Horton, Charu Verma, Sanika Rege, Stephen Crystal, Tobias Gerhard, Alicia Iizuka, Matthew Iozzio, Dawn Koffman, Lauren Parlett, Julianne Varga, Carlos Rose, Brian Strom

Department of Medicine Faculty Papers

BACKGROUND: Juvenile idiopathic arthritis (JIA) has been tied to microbiome disruption and antibiotic exposure. Gut microbiota may affect how adults with rheumatoid arthritis respond to methotrexate. We tested if exposure to antibiotics was associated with response to methotrexate for JIA.

METHODS: We conducted a retrospective cohort study using national US public and private insurance claims data (2001-2023). We included children ages 1-17 continuously enrolled for ≥ 10 months and diagnosed with JIA who initiated methotrexate monotherapy or, for comparison, tumor necrosis factor inhibitor (TNFi) monotherapy without prior disease-modifying antirheumatic drug (DMARD) exposure. Antibiotic exposure during the 10-month baseline period was …

The Relationship Between Psychological Stress And Sars-Cov-2 Nucleocapsid-Antibody Response Following Natural Infection: Longitudinal Findings From The Aegis Study, Erika T Beidelman, Ashley Judge, David B Allison, Stephanie Dickinson, Lilian Golzarri Arroyo, Anna L M Macagno, Michael J Ricciardi, Jon Macy, Stanley Perlman, Christina Ludema, Kevin C Maki, Molly Rosenberg

Faculty, Staff and Students Publications

Psychological stress can cause diminished immune response to infectious challenges. The extent this holds true during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the modifying effect of vaccination status is untested. We explored these relationships in a non-random sample standardized to the US adult population. Across 2178 participants in the Aegis study (2021-2022), we identified 507 eligible laboratory-confirmed SARS-CoV-2 infections. We estimated the natural log of nucleocapsid-binding antibody absorbance (N-antibody) at study visits up to 225 days following a positive SARS-CoV-2 test. Linear mixed effects models were fit to estimate the association of baseline perceived stress and, separately, …

Polygenic Risk Scores And Hla Class Ii Variants Are Biomarkers Of Corticosteroid Response In Childhood Nephrotic Syndrome., Tiffany Tu, Alejandro Ochoa, Amika Sood, Ashley Dabrik, Megan Chryst-Stangl, Brandon Lane, Guanghong Wu, Frank Donovan, Ursula Harper, Settara Chandrasekharappa, Christopher Esezobor, Adaobi Solarin, David Hooper, Christine Sethna, Sandra Amaral, Mahmoud Kallash, Michelle Rheault, Priya Verghese, Vikas Dharnidharka, Eloise Salmon, Patricia Weng, Tarak Srivastava, Michael E Seifert, Cozumel Pruette, David Selewski, Keisha Gibson, Tracy Hunley, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arvind Bagga, Aditi Sinha, Nicholas Webb, Larry Greenbaum, Ali Gharavi, Krzysztof Kiryluk, Matthias Kretzler, Lisa Guay-Woodford, Simone Sanna-Cherchi, Agnieszka Bierzynska, Ania Koziell, Gavin Welsh, Moin Saleem, Charles Rotimi, Eileen Chambers, Cliburn Chan, Curegn Consortium, Pnrc Glomerular Disease Group, Cibmtr/Nmdp Consortium, Annette Jackson, Adebowale Adeyemo, Rasheed Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Nephrotic syndrome (NS), a common glomerular disease in children, is classified based on response to corticosteroid therapy as either steroid-sensitive nephrotic syndrome (SSNS), or steroid-resistant nephrotic syndrome (SRNS). However, there are no current reliable predictors of therapy response at initial clinical presentation.

METHODS: To evaluate predictors, we conducted genome-wide association studies, developed polygenic risk scores (PRS) for therapy response and analyzed classical HLA alleles in 1,997 children (994 discovery and 1,003 replication/validation cohorts) previously unstudied children with NS and 3,558 ancestry-matched control individuals.

RESULTS: A significant association with HLA loci defined by variants in HLA-DQB1, HLA-DRB1, and HLA-DQA1 were …

Early Neurodevelopmental Outcomes In Children With Congenital Heart Disease., Mike Seed, Dawn Ilardi, Valerie Rofeberg, Cynthia Ortinau, Caren Goldberg, Garrett Reichle, Lauren Bush, Justin Elhoff, Amy Jo Lisanti, Jennifer Butcher, Caitlin Rollins, Andrew Van Bergen, Shabnam Peyvandi, Emily Bucholz, Stephanie Cox, Lyla Hampton, Jacqueline Sanz, Sonia Monteiro, Shruti Tewar, Kiona Allen, Caroline Lee, Kristi Glotzbach, Nneka Alexander, Laurel Bear, Corinne Anton, Renee Sananes, Linh Ly, Gina Boucher, Kelly Wolfe, Lindsay Edwards, Elizabeth J. Willen, Alexander Tan, Christina Ortega, Erica Sood, Anjali Sadhwani, Kari Crawford Plant, Lauren Quigley, Jessica Pliego, Elizabeth Valles, Abbey Hines, David Wypij, Thomas Miller

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Neurodevelopmental impairments are common in children with congenital heart disease.

OBJECTIVES: To compare neurodevelopmental outcomes by cardiac diagnosis and identify associations between medical and social factors and early neurodevelopmental outcomes among children with congenital heart disease.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used neurodevelopmental follow-up data obtained between May 1, 2019, and June 30, 2022, and entered into the Cardiac Neurodevelopmental Outcome Collaborative (CNOC) registry, with linkage to the Pediatric Cardiac Critical Care Consortium registry. Children younger than 30 months from 25 CNOC sites were studied. Data analysis was performed between January 2023 and December 2024.

EXPOSURES: Patients …

Parent Perspectives On Neonatal Research Without Prior Consent: A Mixed-Methods Interview Study., Stephanie A. Kraft, Abigail Brickler, Abril Beretta, Rishabh Jain, Andrea Kelsh, Kaashif A. Ahmad, Justin T. Clapp, Neal W. Dickert, Rebecca A. Dorner, Katherine F. Guttmann, Anup C. Katheria, Stephanie Kukora, Benjamin A. Mooso, Elliott Mark Weiss, Fam-Connect Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Recruitment for clinical research in the neonatal intensive care unit (NICU) is difficult, which may lead to low enrollment rates, systematically skewed samples, and nongeneralizable results. Research without prior consent (RWPC), defined as obtaining consent only after infants have been randomized to a treatment arm, may improve enrollment but raises ethical challenges. There is a need to better understand how parents with lived experience of having an infant in the NICU consider RWPC’s impact on critical ethical values related to informed consent, including decision-making, respect, and trust. This mixed-methods study aimed to describe parental perceptions of the acceptability and …

Prognostic Value Of Stress Perfusion Cardiac Magnetic Resonance Imaging In Kawasaki Disease With Coronary Artery Aneurysms: A 10-Year Retrospective Cohort Study, Alexander J Kiener, S Kristen Sexson Tejtel, Aimee Liou, Carolyn A Altman, Tam T Doan

Faculty, Staff and Students Publications

Background: Kawasaki disease (KD) with coronary artery aneurysms (CAA) places patients at risk for myocardial ischemia and major cardiac events (MCE). While stress perfusion cardiac magnetic resonance imaging (spCMR) is used for surveillance, its prognostic value has not been established.

Methods: We conducted a retrospective cohort study of KD patients (AHA risk levels 3-5) who underwent clinically indicated vasodilator spCMR at a tertiary pediatric center between October 2014 and December 2024. We evaluated inducible perfusion defects, late gadolinium enhancement (LGE), ventricular function, and MCE (myocardial infarction, ventricular dysfunction, arrhythmia, revascularization, transplant, or death). We performed Cox regression and Kaplan-Meier analyses …

A Phase 4, Open-Label, Non-Randomized, Multicenter Study To Evaluate Efficacy (And Safety) Of Intravenous Administration Of Optison For Contrast-Enhanced Echocardiography In Pediatric Patients, Arash Sabati, Shuo Wang, Pushpa Shivaram, Joshua Hawley, David Thompson, Francine Erenberg, Shelby Kutty, Aparna Kulkarni, Tam T Doan, Joshua D Robinson

Faculty, Staff and Students Publications

Contrast-enhanced echocardiography (CE-echo) is commonly used in adult patients to optimize endocardial border delineation (EBD) but there is limited experience in children. A prospective, open-label, non-randomized, multicenter study was performed to evaluate the efficacy of intravenous Optison for CE-echo in pediatric patients and determine the optimal dose of Optison. Subjects ≥ 9 and <  18 years with suboptimal echocardiograms (defined as ≥ 2 contiguous segments that could not be adequately visualized) were enrolled. After a baseline non-contrast echocardiogram (NC-echo), CE-echo was performed with 2 dose levels of Optison based on patient weight. The primary endpoint was visualization of the LV wall segments (LVWS) in apical 2- and 4-chamber views. An EBD score was calculated by assigning a value from 0 (no visualization) to 3 (optimal visualization) for 12 LVWS. 37 subjects across 8 sites completed the study. 30 had complete echocardiograms at both dose levels. 2 patients had usable images at dose 2 only. Mean age was 13.4 years (± 2.6) with 23 males (62%). Mean weight was 73.9 kg (± 36.8) with wide distribution of weight (interquartile range of 42-102 kg). There were 8 patients under 40 kg. Most subjects had a prior medical/surgical history (n = 33, 89%). Both dose levels of Optison CE-echo improved the number of LVWS visualized from 3.7 ± 1.1 on NC-echo to 10.0 ± 0.1 with dose 1 (p <  0.001) and 10.5 ± 0.1 with dose 2 (p <  0.001). EBD score also improved at both dose levels from 11.9 ± 2.5 for NC-echo to 28.5 ± 1.7 for dose 1 (p <  0.001) and 30.2 ± 8.4 for dose 2 (p <  0.001). The number of suboptimal echocardiograms improved from 92.3% ± 10.7 in NC-echo to 26.2% ± 9 with dose 1 (p <  0.001) and 30.8% ± 4.5 with dose 2 (p <  0.001). CE-echo with intravenous Optison in pediatric patients improved the number of LVWS visualized, improved EBD score, and reduced the number of suboptimal echocardiograms at both dosages used in this study. Intravenous Optison can improve LV visualization in pediatric patients with suboptimal echocardiograms.

Myocardial T1 And T2 Values Are Associated With Patient Age In Healthy Pediatric Heart Transplant Recipients, Andrew A Lawson, Robyn G Lottes, Defne Magnetta, Andrada Popescu, Kae Watanabe, Cynthia K Rigsby, Michael Markl, Nazia Husain

Faculty, Staff and Students Publications

Background: In pediatric heart transplant recipients (PHTR), myocardial T1 and T2 values are elevated in the setting of acute rejection and with cardiac allograft vasculopathy. In normal, healthy children, T1 and T2 values vary with patient age. Our goal was to identify associations between T1, extracellular volume fraction (ECV), and T2 values and patient- and donor-characteristics in PHTR without history of significant graft pathology.

Methods: We performed a single-center, retrospective chart review of consecutive cardiac magnetic resonance (CMR) studies in PHTR from 2017 to 2023. Exclusion criteria were a prior CMR during the study period, history of any prior antibody-mediated …

Plasma Biomarkers Of Brain Injury In Critically Ill Children Receiving Extracorporeal Membrane Oxygenation, Matthew L Friedman, Michael J Bell, Bonnie A Brooks, Adam S Himebauch, Asavari Kamerkar, Kerri Larovere, Laura L Loftis, Jose A Pineda, Ahmed Said, Hitesh S Sandhu, Martin Stengelin, Catherine Demos, Mark S Wainwright, Alina N West, Allan Barnes, Allen D Everett, Ryan J Felling, Sue J Hong, Jennifer L Roem, Cynthia F Salorio, Derek K Ng, Melania M Bembea

Faculty, Staff and Students Publications

Importance: Timely identification of acute brain injury (ABI) in children receiving extracorporeal membrane oxygenation (ECMO) support is critical for early neuroprotective interventions.

Objectives: To determine if elevations in plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau levels in children receiving ECMO precede new ABI confirmed by neuroimaging, and if they are associated with mortality and functional outcomes.

Design, setting, and participants: This was a prospective observational cohort study conducted from 2019 to 2023, with 18-month follow-up completed in 2025. Children aged 2 days to younger than 18 years at ECMO cannulation were recruited from 11 US …

Coxfa4l2 Upregulation Preserves Residual Cytochrome C Oxidase Activity In Coxfa4-Related Leigh-Like Encephalopathy, Micol Falabella, Sandra Lopez Calcerrada, Jana Aref, Jiaze Gao, William L Macken, Chiara Pizzamiglio, Renata Kabiljo, Anna Lucia Francavilla, Pauline Gaignard, Antoine Pouzet, Jonathan Levy, Giulia Barcia, Jamie K Leighton, Efstathia Chronopoulou, Germaine Pierre, Riza Köksal Özgül, Ali Dursun, Rebecca Halligan, Helen Mundy, Javeria Raza Alvi, Tipu Sultan, William James Craigen, Lisa Emrick, Jill A Rosenfeld, Gehad Elmakkawy, Jihye Kim, Joseph J Gleeson, Aboulfazl Rad, Gabriela Oprea, Maqbool Hussain, Khalil Ur Rehman, Sadia Riaz, Robert W Taylor, Vincent Procaccio, Maha S Zaki, Erika Fernandez-Vizarra, Ciro Leonardo Pierri, Michael G Hanna, Henry Houlden, Reza Maroofian, Cristina Ugalde, Jan-Willem Taanman, Robert D S Pitceathly

Faculty, Staff and Students Publications

Primary mitochondrial diseases (PMDs) affect approximately 1 in 4300 individuals and cause early-onset neuromuscular and multisystem dysfunction with reduced lifespan. They result from pathogenic variants in mitochondrial or nuclear DNA that impair oxidative phosphorylation. Cytochrome c oxidase (COX; complex IV) deficiency is a well-established cause of PMD, leading to a broad spectrum of phenotypes. COXFA4 (cytochrome c oxidase subunit FA4), formerly NDUFA4, is a nuclear-encoded COX subunit, but its role in disease remains poorly defined. We report the largest genetically confirmed cohort of COXFA4-related PMD to date, comprising 13 individuals from 12 families with biallelic pathogenic COXFA4 variants. All present …

Smaller Right Ventricle Results In Poorer Exercise Performance In Young Patients With Repaired Tetralogy Of Fallot, Christiane Mhanna, Katerina Kourpas, Takeshi Tsuda

Department of Pediatrics Faculty Papers

BACKGROUND: Severe right ventricular (RV) dilatation and exercise intolerance are considered indications for pulmonary valve replacement in surgically repaired tetralogy of Fallot (rTOF).

METHODS AND RESULTS: Cardiopulmonary exercise testing (CPET) and cardiac magnetic resonance (CMR) were performed in rTOF patients with pulmonary insufficiency (PI). Oxygen pulse (OP), calculated as oxygen consumption (V̇O

CONCLUSIONS: A smaller RV was associated with worse exercise performance, indicating exercise intolerance is independent of RV dilatation in young rTOF with PI and represents a unique pathological entity responsible for reduced exercise performance.

Association Of Polygenic Risk Scores With Aortic Valve Calcium: The Multi-Ethnic Study Of Atherosclerosis, Seamus P Whelton, Jie Yao, Clary Clish, Alexis C Wood, Kent D Taylor, Michael J Blaha, Matthew Budoff, Natalie Marrero, George Thanassoulis, Wendy S Post, Xiuqing Guo, Jerome I Rotter

Faculty, Staff and Students Publications

Background: Aortic valve calcification (AVC) is the primary process leading to aortic stenosis. We examined whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors.

Methods: We included 6812 participants in MESA (Multi-Ethnic Study of Atherosclerosis) with computed tomography-measured AVC at Visit 1. Using previously published PRS we calculated weighted PRS, standardized within each ancestry group. The cross-sectional association per 1 SD higher PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction. The mean age was 62 years old, 53% were female, and 913 (13.4%) had AVC >0 at …

Natural History Of Ngly1 Deficiency: Motor Function & Clinical Features, Grace Morrison, Selina Dwight, Hal Landy, William F Mueller, Pam Ventola, Regina Deck, Becky Schweighardt, Matt Wilsey, Kevin J Lee, Bernhard Suter

Faculty, Staff and Students Publications

N-glycanase 1 (NGLY1) Deficiency is an ultra-rare neurodevelopmental disorder caused by biallelic loss-of-function mutations in the NGLY1 gene, leading to severe impairments in neurocognitive and motor function abilities in the affected patient population. Its core clinical features include global developmental delay, hyperkinetic movement disorders, elevation of liver transaminases, (hypo)alacrima, and progressive sensorimotor neuropathy. Due to the range of phenotypes and severity within the confirmed patient population, ongoing characterization of the disease is critical. A prospective natural history study (NHS) was conducted to further elucidate disease phenotypes and examine any changes in neurocognitive or motor function over a one-year period. Fifteen …

Regional Variation Of Underlying Kidney Diseases In Children Undergoing Chronic Kidney Replacement Therapy Around The Globe., Dagmara Borzych-Dużałka, Marjolein Bonthuis, Uma Ali, Yok-Chin Yap, Michael Manno, Yihui Zhai, Reyner Loza, Seema Hashmi, Naye Choi, Kenza Soulami, Judith Exantus, Mohamed S. Al Riyami, Sameh Mabrouk, Marbella Ma Angeles, Cristina Zelaya-Camacho, Henny Adriani Puspitasari, Syed Saimul Huque, Francisco Cano, Kar Hui Ng, Sevcan A. Bakkaloğlu, Jerome Harambat, Kitty J. Jager, Bradley A. Warady, Franz Schaefer

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: There is a scarcity of information regarding the distribution of the diseases leading to kidney failure (KF) in children living in the emerging world. We used registry data to provide a global overview of the underlying disease spectrum in children commencing kidney replacement therapy (KRT).

METHODS: We analyzed KF causes among 23,620 children and adolescents commencing maintenance KRT in 80 countries, using data from the IPNA Global KRT Registry (including ESPN/ERA Registry), the International Pediatric Dialysis Network (IPDN), the United States Renal Data System (USRDS), and the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). The analysis considered …

Accelerated Weaning Of Opioids To Reduce Pharmacologic Exposure For Neonatal Opioid Withdrawal Syndrome: A Randomized Clinical Trial., Abbot R. Laptook, Adam Czynski, Rouba Chahine, Rachel G. Greenberg, P Brian Smith, Erica Oliveira, Jenna Gabrio, Barry Eggleston, Abhik Das, Jeannette Lee, Barry Lester, Dave Clark, Michele Walsh, Helen Ko, Clare Campbell Asher, Hayley Friedman, Samuel Gentle, Karishma Rao, Anup Katheria, Kristen Benninger, Sanket Jani, Mark Cody Smith, Akram Khan, Ajay Talati, Shaina Lodhi, Fernando Mena, Amanda England, Prabhu Parimi, Ranjit Kylat, Heidi Harmon, Javed Mannan, Meghan P. Howell, Tanner Wright, Jessica Snowden, Act Now Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To determine if newborns receiving morphine or methadone as the primary pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS) tolerate and receive fewer days of opioid using an accelerated wean protocol (15% decrements) compared with using a slower wean protocol (10% decrements).

STUDY DESIGN: Newborns ≥36 weeks of gestation receiving morphine or methadone for NOWS were enrolled in a pragmatic blinded, randomized multicenter trial. Newborns underwent protocol-driven weaning with decreasing opioid doses of either 15% or 10% decrements. Weaning was encouraged every 24 hours, and if signs of NOWS worsened, the preceding dose was resumed. To maintain blinding, the …

Natural Maternal Immunity Protects Neonates From Escherichia Coli Sepsis., Raymond E. Diep, Ujjwal Adhikari, Kubra Gokce Tezel, Giang Pham, Allison R. Burrell, Mary A. Staat, Nguyen Thi Khanh Nhu, Minh-Duy Phan, Kate M. Peters, Mark A. Schembri, Scott H. Saunders, David B. Haslam, John J. Erickson, Susana Chavez-Bueno, Sing Sing Way

Manuscripts, Articles, Book Chapters and Other Papers

Escherichia coli is a leading cause of neonatal sepsis, with infection occurring in approximately one in every 1,000 live births. However, with E. coli colonization beginning soon after birth and defects in neonatal host defence maturation, an alternative consideration is why infection does not occur even more frequently. Here we show that newborn babies with E. coli sepsis have selectively reduced vertically transferred natural antibodies that recognize E. coli, mechanistically explaining their susceptibility to infection. Complementary preclinical studies show that preconceptual intestinal colonization with probiotic E. coli Nissle 1917 (EcN) primes anti-E. coli immunoglobulin G (IgG) antibodies with broad cross-reactivity …

Population Pharmacokinetics And Dosing Simulations Of Pentobarbital In The Pediatric Population, Victoria Etges Helfer, Lorena Medina-Aymerich, William J. Muller, Marisa Meyer, Amira Al-Uzri, Russell Mcculloh, Chi D. Hornik, Stephen J. Balevic, Rachel G. Greenberg, Daniel K. Benjamin, Sarah G. Anderson, Daniel Gonzalez

Department of Pediatrics Faculty Papers

Pentobarbital is a barbiturate with sedative and anticonvulsant properties, occasionally used in pediatric patients for preoperative sedation, deep sedation during mechanical ventilation, and seizure control. Despite its long-standing clinical use, age-appropriate dosing remains challenging due to variability across studies and limited pediatric pharmacokinetic (PK) data. This study (NCT01431326) aimed to characterize the population pharmacokinetics of pentobarbital in pediatric patients (birth to 21 years) and evaluate dosing strategies using model-based simulations. A two-compartment population PK model, allometrically scaled to total body weight, adequately described pentobarbital plasma concentrations, with no additional covariates identified as significant. Simulations were conducted across four age groups: …

Derivation And Validation Of The Pediatric Community-Acquired Pneumonia Severity (Pedcaps) Score: A Prospective Cohort Study, Todd A Florin, Ron Reeder, Lilliam Ambroggio, Richard M Ruddy, Samir S Shah, Allison Cator, Matthew J Lipshaw, Geoffrey A Capraro, Laura F Sartori, Amy Y Cheng, Leah Tzimenatos, Patrick S Walsh, Claudia R Morris, Chris A Rees, Son H Mclaren, Tamar R Lubell, Chari D Larsen, Justin Moher, Eileen J Klein, Shubhada Hooli, Nathan Kuppermann

Faculty, Staff and Students Publications

Introduction: Community-acquired pneumonia (CAP) is a frequent and costly cause of pediatric emergency department (ED) visits and hospitalizations. Previous prognostic tools for CAP are limited by small samples, single-center or retrospective designs, lack of generalizability to ED settings, lack of biomarkers, or limited objective data. To overcome these limitations, we will derive and externally validate a prediction rule for pediatric CAP severity in a large, multicenter prospective cohort.

Methods: This is a prospective cohort study of children 3 months to 18 years old with CAP who present to EDs within the Pediatric Emergency Care Applied Research Network. Enrollment began 8/2023 …

The Impact Of Tracheal Intubation Attempts On Chest Compression Fraction During Pediatric Cpr: A Report From The Videography In Pediatric Resuscitation (Viper) Collaborative, Theerapon Jariyasakoolroj, Karen O'Connell, Thomas Macdonald, John Breslin, Jennifer Murphy, Crystal Macdonald, Tara Neubrand, Laura Rochford, Sage Myers, Benjamin Kerrey, Aaron Donoghue

Faculty, Staff and Students Publications

Aim: To examine the association between tracheal intubation (TI) attempts and chest compression (CC) pauses on chest compression fraction (CCF) during pediatric CPR across a network of emergency departments.

Methods: Prospective observational cohort by the Videography in Pediatric Resuscitation (VIPER) Collaborative. Videorecorded CPR events were reviewed to measure CC pauses and characterize TI attempts. CCF was calculated as the proportion of time compressions were delivered during each event. Events were categorized based on whether TI-associated pauses occurred, and CCF was compared using Wilcoxon rank-sum testing.

Results: A total of 183 CPR events were included. The median event duration was 971 …

Plasma Proteins Associated With Psychosocial Factors And Heart Disease: The Jackson Heart Study, Sara N O'Brien, Madeline G Gillman, Michael D Green, Daniel E Cruz, James S Floyd, Susan Hankinson, Daniel H Katz, Xiaojuan Liu, Michelle C Odden, Bruce M Psaty, Alexander P Reiner, Jerome I Rotter, Stephen S Rich, Robert E Gerszten, Amil Shah, Mario Sims, Usman A Tahir, Lesley F Tinker, Alexis C Wood, Bing Yu, Anthony S Zannas, Laura M Raffield, Láshauntá M Glover

Faculty, Staff and Students Publications

Background: Knowledge of proteomic mechanisms explaining the link between psychosocial stress and cardiovascular disease is limited. This study aimed to (1) identify plasma proteins associated with psychosocial factors and (2) assess associational pathways between psychosocial factors, identified proteins, and incident cardiovascular disease events in a discovery cohort, JHS (Jackson Heart Study), and 2 replication cohorts, the CHS (Cardiovascular Health Study), and the MESA (Multi-Ethnic Study of Atherosclerosis).

Methods: JHS participants from exam 1 (2000-2004) with SomaScan 1.3k platform proteomics data were included (n=2143, mean age=55.3). Depressive symptoms and perceived stress scores were measured via the 20-item Center for Epidemiological Studies …

Ixodid And Flea Infestations And Associated Bacteria On Two Sympatric Felid Species In South Texas, Allan T Showler, Hilary Swarts, Maya Murry, Alisa Nelson, Alexander R Kneubehl, Sarah M Gunter

Faculty, Staff and Students Publications

Ixodid ticks and fleas parasitize wild felids and can transmit pathogens of veterinary and public health concern. We identified ixodid and flea species collected from sympatric South Texas bobcats, L. rufus, and ocelots, L. pardalis. Greater diversities of ixodids were found on both felids than in previous reports, with seven species in three genera on L. rufus and six species in three genera on L. pardalis. We report first findings of tropical horse tick, Dermacentor nitens, on L. rufus in Texas, and Ixodes keiransi on both felids in Texas. Although false cayenne tick, Amblyomma tenellum, nymphs were the most abundant …

High-Precision Automated Bone Age: A Clinically Useful Tool In Monitoring Of Treatment Effects In Children And Adolescents, Hans Henrik Thodberg, Lise Aksglaede, Anders Juul, Shanlee M. Davis, Judith L. Ross

Department of Pediatrics Faculty Papers

The clinical value of serial bone age (BA) determinations in children during growth is limited by the manual rater variability (precision 0.63 years). The objective of this work was to determine the precision of automated bone age and bone health index (BHI) measurements by BoneXpert and to establish the time interval at which the automated method can detect a significant treatment effect. The data were from a case-control trial (oxandrolone/placebo) following 90 boys with Klinefelter syndrome (KS) with five visits over 2 years, recording X-rays of both hands. The precision of BA was 0.08 years [0.07; 0.09] 95% CI, leading …

A Digital Diabetes Prevention Program For Hispanic Adolescents (Fit24+): Protocol For A Feasibility Randomized Controlled Trial, Erica G Soltero, Marbelly Partida, Sandra Mihail, Lizette Villanueva, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Maria J Redondo, Matthew Buman, Debbe Thompson

Faculty, Staff and Students Publications

Background: Hispanic youth are disproportionately impacted by obesity and subsequent type 2 diabetes (T2D) yet remain underrepresented in diabetes prevention research. Digital health interventions hold promise for increasing the accessibility to and engagement in disease prevention programming, particularly among high-risk populations. However, there is a significant gap in the literature regarding digital T2D prevention programs for adolescents or Hispanic youth.

Objective: The objective of this article is to describe the protocol for examining the feasibility of a 12-week digital diabetes prevention program among Hispanic adolescents with obesity.

Methods: Participants (N=40; aged 12-16 years) will be randomized (1:1) to a 12-week …

Factors Associated With Child Protective Services Referrals In Young Children With Isolated Skull Fractures., Karli Breeden-Carino, Joanne N. Wood, Cindy W. Christian, Tagrid M. Ruiz-Maldonado, Daniel M. Lindberg, Angela Bachim, Lori Frasier, Terra N. Frazier, Nancy S. Harper, Sara E. Kruczek, Farah Brink, Jennifer E. Wolford, Jan Leonard, M Katherine Henry

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Many young children with isolated skull fractures are referred to child protective services (CPS) despite being assessed to have a low likelihood of abuse. We sought to identify factors associated with CPS referrals in this population and to quantify hospital-level variation.

METHODS: We performed a multicenter retrospective cross-sectional study of children < 2 years with skull fractures with or without a small underlying intracranial hemorrhage (ICH) and no additional injuries undergoing a child abuse pediatrics (CAP) subspecialty evaluation. We explored associations between demographic factors, clinical characteristics, psychosocial risk factors, and hospital site with CPS referral status. We performed multivariable logistic regression, adjusting for transfer status and all significant covariates from unadjusted analyses. We utilized marginal standardization to calculate the estimated probability of CPS referrals at each site, adjusting for all factors in the final model.

RESULTS: Of 528 children, 303 (57.4%) were referred to CPS, with 86.5% referred before CAP consultation. In multivariable logistic regression, presence of psychosocial risk factors (OR 4.00; 95% CI 2.25, 7.11), in-person CAP consult (OR 3.93; 1.61, 9.62), inflicted or no trauma history provided (OR 6.15; 3.30, 11.45), …