Pediatrics Commons^™

Impact Of An Integrated Health, Nutrition, And Early Child Stimulation And Responsive Care Intervention Package Delivered To Preterm Or Term Small For Gestational Age Babies During Infancy On Growth And Neurodevelopment: Study Protocol Of An Individually Randomized Controlled Trial In India (Small Babies Trial), Ranadip Chowdhury, Rukman Manapurath, Ingvild Fossgard Sandøy, Ravi Prakash Upadhyay, Neeta Dhabhai, Saijuddin Shaikh, Harish Chellani, Tarun Shankar Choudhary, Abhinav Jain, Jose Martines, Nita Bhandari, Tor A Strand, Sunita Taneja

Faculty, Staff and Student Publications

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating.

METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata …

Implementation Of Rapid Genomic Sequencing In Safety-Net Neonatal Intensive Care Units: Protocol For The Virtual Genome Center (Vigor) Proof-Of-Concept Study., Alissa M. D'Gama, Sonia Hills, Jessica Douglas, Vanessa Young, Casie A. Genetti, Monica H. Wojcik, Henry A. Feldman, Timothy W. Yu, Margaret G. Parker, Pankaj B. Agrawal, T. Allcroft, Vineet Bhandari, L. Cantu, D. Honrubia, A. Kritzer, Q. Li, L. Rhein, R. Rothstein, O. Salinas, A. Santana, K. Schmitz-Abe, A. Serna, F. Shapiro, A. B. Shenoy, L. Simoncini, B. Sinha, A. S. Verran, A. Sousa, M. T. Newsam

Cooper Medical School of Rowan University Departmental Research

INTRODUCTION: Rapid genomic sequencing (rGS) in critically ill infants with suspected genetic disorders has high diagnostic and clinical utility. However, rGS has primarily been available at large referral centres with the resources and expertise to offer state-of-the-art genomic care. Critically ill infants from racial and ethnic minority and/or low-income populations disproportionately receive care in safety-net and/or community settings lacking access to state-of-the-art genomic care, contributing to unacceptable health equity gaps. VIrtual GenOme CenteR is a 'proof-of-concept' implementation science study of an innovative delivery model for genomic care in safety-net neonatal intensive care units (NICUs).

METHODS AND ANALYSIS: We developed a …

Neonatal Intensive Care Unit Resource Use For Infants At 22 Weeks' Gestation In The Us, 2008-2021, Matthew A Rysavy, Monica M Bennett, Kaashif A Ahmad, Ravi M Patel, Zubin S Shah, Dan L Ellsbury, Reese H Clark, Veeral N Tolia

Faculty, Staff and Student Publications

IMPORTANCE: During the past decade, clinical guidance about the provision of intensive care for infants born at 22 weeks' gestation has changed. The impact of these changes on neonatal intensive care unit (NICU) resource utilization is unknown.

OBJECTIVE: To characterize recent trends in NICU resource utilization for infants born at 22 weeks' gestation compared with other extremely preterm infants (≤28 weeks' gestation) and other NICU-admitted infants.

DESIGN, SETTING, AND PARTICIPANTS: This is a serial cross-sectional study of 137 continuously participating NICUs in 29 US states from January 1, 2008, through December 31, 2021. Participants included infants admitted to the NICU. …

Hospital-Level Nicu Capacity, Utilization, And 30-Day Outcomes In Texas, David C Goodman, Patrick Stuchlik, Cecilia Ganduglia-Cazaban, Jon E Tyson, Joanna Leyenaar, Elenir B C Avritscher, Mathew Rysavy, Kanekal S Gautham, David Lynch, Therese A Stukel

Faculty, Staff and Student Publications

IMPORTANCE: Risk-adjusted neonatal intensive care unit (NICU) utilization and outcomes vary markedly across regions and hospitals. The causes of this variation are poorly understood.

OBJECTIVE: To assess the association of hospital-level NICU bed capacity with utilization and outcomes in newborn cohorts with differing levels of health risk.

DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cohort study included all Medicaid-insured live births in Texas from 2010 to 2014 using linked vital records and maternal and newborn claims data. Participants were Medicaid-insured singleton live births (LBs) with birth weights of at least 400 g and gestational ages between 22 and 44 weeks. …

Increased Prevalence Of Clostridioides Difficile Infection Among Pediatric Oncology Patients: Risk Factors For Infection And Complications, Brianna R Murphy, Natalie J Dailey Garnes, Hyunsoo Hwang, Christine B Peterson, Kevin W Garey, Pablo Okhuysen

Faculty, Staff and Student Publications

Background: Pediatric oncology patients, who are typically immunosuppressed, exposed to medications associated with increased Clostridioides difficile infection (CDI) risk and hospitalized, are expected to be at substantial risk for infection and complications. Although certain C. difficile ribotypes have been associated with more severe infection in adults, such an association has not been described in children.

Methods: To characterize CDI epidemiology, including risk factors and complications among pediatric oncology patients, we retrospectively reviewed charts of patients 1-18 years old treated at a designated cancer center during 2000-2017. We used fluorescence-based polymerase chain reaction to identify ribotypes causing disease at our institution. …

Association Of Socioeconomic Factors And Severity Of Bronchiolitis Hospitalizations, Raymond Parlar-Chun, Zoabe Hafeez

Faculty, Staff and Student Publications

It is unclear if socioeconomic status (SES) factors influence severity of illness of patients hospitalized with bronchiolitis. This study was conducted to identify SES factors including the Center for Disease Control and Prevention’s Social Vulnerability Composite Index (SVI), estimated income, proportion of minority, proportion of living below poverty, insurance status, and number of household members associated with length of stay (LOS) and intensive care unit admission. Infants hospitalized at a tertiary care urban center for bronchiolitis were identified using International Classification of Diseases codes. Federal information processing system codes were identified from home address and paired with SVI and 2018 …

Pulsatile Leucine Administration During Continuous Enteral Feeding Enhances Skeletal Muscle Mechanistic Target Of Rapamycin Complex 1 Signaling And Protein Synthesis In A Preterm Piglet Model, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 μmol Leu·kg–1·h–1 every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle.

OBJECTIVES: The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm.

METHODS: Pigs delivered 10 d preterm was advanced to full oral feeding >4 …

Maternal Vaccine Effectiveness Against Influenza-Associated Hospitalizations And Emergency Department Visits In Infants, Leila C Sahni, Samantha M Olson, Natasha B Halasa, Laura S Stewart, Marian G Michaels, John V Williams, Janet A Englund, Eileen J Klein, Mary A Staat, Elizabeth P Schlaudecker, Rangaraj Selvarangan, Jennifer E Schuster, Geoffrey A Weinberg, Peter G Szilagyi, Julie A Boom, Manish M Patel, Flor M Muñoz, New Vaccine Surveillance Network Collaborators

Faculty, Staff and Students Publications

IMPORTANCE: Influenza virus infection during pregnancy is associated with severe maternal disease and may be associated with adverse birth outcomes. Inactivated influenza vaccine during pregnancy is safe and effective and can protect young infants, but recent evidence, particularly after the 2009 novel influenza A (H1N1) pandemic, is limited.

OBJECTIVE: To evaluate the effectiveness of influenza vaccination during pregnancy against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits in infants younger than 6 months.

DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, test-negative case-control study using data from the New Vaccine Surveillance Network from the 2016 to 2017 through 2019 to …

Number Of Children In The Household Influences Respiratory Morbidities In Children With Bronchopulmonary Dysplasia In The Outpatient Setting, Joseph M Collaco, Katharine R Tsukahara, Michael C Tracy, Catherine A Sheils, Jessica L Rice, Lawrence M Rhein, Antonia P Popova, Leif Nelin, Audrey N Miller, Winston M Manimtim, Jonathan C Levin, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Manvi Bansal, Eric D Austin, Brianna Aoyama, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD.

METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations.

RESULTS: The mean gestational age of the study population was 26.5 …

Comprehensive Evaluation Of Smoking Exposures And Their Interactions On Dna Methylation, Thanh T Hoang, Yunsung Lee, Daniel L Mccartney, Elin T G Kersten, Christian M Page, Paige M Hulls, Mikyeong Lee, Rosie M Walker, Charles E Breeze, Brian D Bennett, Adam B Burkholder, James Ward, Anne Lise Brantsæter, Ida H Caspersen, Alison A Motsinger-Reif, Marie Richards, Julie D White, Shanshan Zhao, Rebecca C Richmond, Maria C Magnus, Bios Consortium, Gerard H Koppelman, Kathryn L Evans, Riccardo E Marioni, Siri E Håberg, Stephanie J London

Faculty, Staff and Students Publications

Background: Smoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (< 1 year), persistence of differential methylation from in utero smoking exposure, and effects of environmental tobacco smoke (ETS).

Methods: We meta-analysed data from up to 15,014 adults across 5 cohorts with DNA methylation measured in blood using Illumina's EPIC array for current smoking (2560 exposed), quit < 1 year (500 exposed), in utero (286 exposed), and ETS exposure (676 exposed). We also evaluated the interaction of current smoking with sex or diet (fibre, folate, and vitamin C).

Findings: Using false discovery rate (FDR < 0.05), 65,857 CpGs were differentially methylated in relation to current smoking, 4025 with recent quitting, 594 with in utero exposure, and 6 with ETS. Most current smoking CpGs attenuated within a year of quitting. CpGs related to in utero exposure in adults were enriched for those previously observed in newborns. Differential methylation by current smoking at 4-71 CpGs may be modified by sex or dietary intake. Nearly half (35-50%) of differentially methylated CpGs on the 450 K array were associated with blood gene expression. Current smoking and in utero smoking CpGs implicated 3049 and 1067 druggable targets, including chemotherapy drugs.

Interpretation: Many smoking-related methylation sites were identified with Illumina's EPIC array. Most signals revert to levels observed in never smokers within a year of cessation. Many in utero smoking CpGs persist into adulthood. Smoking-related druggable targets may provide insights into cancer treatment response and …

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …

Prenatal Cocaine Exposure And Its Influence On Pediatric Epigenetic Clocks And Epigenetic Scores In Humans, Thiago Wendt Viola, Christina Danzer, Victor Mardini, Claudia Szobot, João Henrique Chrusciel, Laura Stertz, Joy M Schmitz, Consuelo Walss-Bass, Gabriel R Fries, Rodrigo Grassi-Oliveira

Faculty, Staff and Student Publications

The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale …

Pearls & Oy-Sters: Cacna1a-Related Paroxysmal Tonic Upgaze With Ataxia Responsive To Acetazolamide, Steven M Lazar, Farida Abid

Faculty, Staff and Students Publications

A 9-month-old male infant was evaluated for sudden onset of paroxysmal episodes of forced, conjugate upward eye deviation. Extensive in-hospital evaluation including electrophysiology and neuroimaging studies were reassuring against seizures or a structural abnormality. Given the clinical presentation of sudden onset intermittent upward eye deviations, downbeating saccades, associated ataxia, and typical development, a clinical diagnosis of paroxysmal tonic upgaze (PTU) with ataxia was made. Targeted genetic testing of CACNA1A was performed, which revealed a variant of undetermined significance, which was later classified as a de novo pathogenic variant after protein modeling and parental testing performed. Off-label use of oral acetazolamide …

Multi-Dose Enteral L-Citrulline Administration In Premature Infants At Risk Of Developing Pulmonary Hypertension Associated With Bronchopulmonary Dysplasia, Candice D. Fike, Judy L. Aschner, Charul Avachat, Angela K. Birnbaum, Catherine M.T. Sherwin

Pediatrics Faculty Publications

Objective: Information is needed to guide the design of randomized controlled trials (RCTs) evaluating L-citrulline therapy for premature infants with pulmonary hypertension associated with bronchopulmonary dysplasia (BPD-PH). Based on our single-dose pharmacokinetic study, we evaluated the ability of a multi-dose enteral L-citrulline strategy to achieve a target trough steady-state L-citrulline plasma concentration and its tolerability in premature infants. Study design: Plasma L-citrulline concentrations were measured in six premature infants receiving 60 mg/kg L-citrulline every 6 h for 72 h before the first and last L-citrulline doses. L-citrulline concentrations were compared to concentration-time profiles from our previous study. Results: Target trough …

Hour Of Life At Enteral Feeding Initiation And Associated Clinical Morbidity In Extremely Low-Birth-Weight Infants, Melissa Thoene, Lauren Ridgway, Elizabeth Lyden, Ann Anderson-Berry

Journal Articles: Pediatrics

BACKGROUND/OBJECTIVES: Identifying nutritional interventions in extremely low-birth-weight (ELBW) infants (<1000 >g) that are associated with favorable clinical outcomes is important. Delayed enteral feeding initiation (>3 days) has been associated with increased odds of developing morbidity. Therefore, the aim of this study is to evaluate the relationship between hour of life at enteral feeding initiation and associated clinical outcomes.

METHODS: An IRB-approved retrospective chart review evaluated ELBW infants. Birth acuity was evaluated using CRIB II scoring and incidence of various morbidities (bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and spontaneous intestinal perforation (SIP)) and mortality was assessed …

The Impact Of Iron Supplementation On The Preterm Neonatal Gut Microbiome: A Pilot Study, Matthew Van Ormer, Maranda Thompson, Melissa Thoene, Jean-Jack Riethoven, Sathish Kumar Natarajan, Corrine K. Hanson, Ann Anderson-Berry

Journal Articles: Pediatrics

OBJECTIVE: The gastrointestinal microbiome in preterm infants exhibits significant influence on optimal outcomes-with dysbiosis shown to substantially increase the risk of the life-threatening necrotizing enterocolitis. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurodevelopment. However, excess colonic iron exhibits potent oxidation capacity and alters the gut microbiome-potentially facilitating the proliferation of pathological bacterial strains. Breastfed preterm infants routinely receive iron supplementation starting 14 days after delivery and are highly vulnerable to morbidities associated with gastrointestinal dysbiosis. Therefore, we set out to determine if routine iron supplementation alters the preterm gut …

Streptococcus Pneumoniae Serotype 19a In Hospitalized Children With Invasive Pneumococcal Disease After The Introduction Of Conjugated Vaccines In Lima, Peru, Theresa J Ochoa, Olguita Del Águila, Isabel Reyes, Eduardo Chaparro, María E Castillo, Francisco Campos, Andrés Saenz, Roger Hernandez, Alessandra Luna-Muschi, Franco Castillo-Tokumori, Andrea E Montero, Brayan E Gonzales, Erik H Mercado

Faculty, Staff and Student Publications

BACKGROUND: The Pneumococcal conjugate vaccine (PCV) has decreased cases of invasive pneumococcal disease (IPD) worldwide. However, the impact of PCVs introduction may be affected by the serotype distribution in a specific context.

METHODS: Cross-sectional multicenter passive surveillance study of IPD cases in pediatric patients hospitalized in Lima, Peru between 2016 and 2019 (after PCV13 introduction) to determine the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae. Serotyping was performed by a sequential multiplex PCR and confirmed by whole genome sequencing.

RESULTS: Eighty-five S. pneumoniae isolates were recovered (4.07/100,000 among childrenage). Serotype 19A was the most common (49.4%). Children infected with …

Practical Quality Improvement Changes For A Low-Resourced Pediatric Unit, Phoebe H Yager, Kevin Mary Callans, Aubrey Samost-Williams, Jose A Bonilla, Luis J G Flores, Susana C A Hasbun, Angel E A Rodríguez, Alejandra B A Cárdenas, Alexia M L Núñez, Asitha D L Jayawardena, Evelyn J Zablah, Christopher J Hartnick

Faculty, Staff and Student Publications

Background: This work describes a sustainable and replicable initiative to optimize multi-disciplinary care and uptake of clinical best practices for patients in a pediatric intensive care unit in Low/Middle Income Countries and to understand the various factors that may play a role in the reduction in child mortality seen after implementation of the Quality Improvement Initiative.

Methods: This was a longitudinal assessment of a quality improvement program with the primary outcome of intubated pediatric patient mortality. The program was assessed 36 months following implementation of the quality improvement intervention using a t-test with linear regression to control for co-variates. …

Rising Prevalence Of Mild Chronic Gastritis In Children: A Single Center Experience, Rohit Josyabhatla, Mary Lauren Wood, Amber Gafur, Nina Tatevian, Amanda S Tchakarov, Syed Shahrukh Hashmi, Jon Marc Rhoads, Melissa Renee Van Arsdall

Faculty, Staff and Student Publications

OBJECTIVES AND METHODS: We analyzed upper endoscopic and histological findings in 3 cohorts of children undergoing upper gastrointestinal endoscopy over a 10-year period. Five hundred seventy-nine patients were identified, with 244 (42%), 199 (35%), and 136 (23%) in the 2011, 2015, and 2019 cohorts, respectively. The most common symptoms and signs were abdominal pain, vomiting, failure to thrive, and diarrhea.

RESULTS: The number of patients who had histological evidence of chronic gastritis increased from 2011 (n = 70, 29%) to 2015 (n = 106, 53%) and 2019 (n = 92, 68%;

CONCLUSIONS: There has been a significant rise in the …

Race, Ethnicity, Language, And The Treatment Of Low-Risk Febrile Infants, Colleen K Gutman, Paul L Aronson, Nidhi V Singh, Michelle L Pickett, Kamali Bouvay, Rebecca S Green, Britta Roach, Hannah Kotler, Jessica L Chow, Emily A Hartford, Mark Hincapie, Ryan St Pierre-Hetz, Jessica Kelly, Laura Sartori, Jennifer A Hoffmann, Jacqueline B Corboy, Kelly R Bergmann, Bolanle Akinsola, Vanessa Ford, Natalie J Tedford, Theresa T Tran, Sasha Gifford, Amy D Thompson, Andrew Krack, Mary Jane Piroutek, Samantha Lucrezia, Sunhee Chung, Nabila Chowdhury, Kathleen Jackson, Tabitha Cheng, Christian D Pulcini, Nirupama Kannikeswaran, Larissa L Truschel, Karen Lin, Jamie Chu, Neh D Molyneaux, Myto Duong, Leslie Dingeldein, Jerri A Rose, Carly Theiler, Sonali Bhalodkar, Emily Powers, Muhammad Waseem, Ahmed Lababidi, Xinyu Yan, Xiang-Yang Lou, Rosemarie Fernandez, K Casey Lion

Faculty, Staff and Students Publications

IMPORTANCE: Febrile infants at low risk of invasive bacterial infections are unlikely to benefit from lumbar puncture, antibiotics, or hospitalization, yet these are commonly performed. It is not known if there are differences in management by race, ethnicity, or language.

OBJECTIVE: To investigate associations between race, ethnicity, and language and additional interventions (lumbar puncture, empirical antibiotics, and hospitalization) in well-appearing febrile infants at low risk of invasive bacterial infection.

DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective cross-sectional analysis of infants receiving emergency department care between January 1, 2018, and December 31, 2019. Data were analyzed from December 2022 …

Population-Based Screening Strategies For Biliary Atresia In The Newborn: A Systematic Review And Meta-Analysis, Srirupa Hari Gopal, Rema Zebda, Arvind Mohan, Kristin Borovsky, Yemisi Takwoingi, Katie Scandrett, Mohan Pammi

Faculty, Staff and Students Publications

BACKGROUND: Newborn screening for biliary atresia (BA) may facilitate earlier diagnosis and intervention for improved clinical outcomes.

METHODS: We systematically reviewed the accuracy of population-based screening strategies for BA in the newborn using PRISMA-DTA guidelines. We included cohort or cross-sectional studies. The screening (index) tests included stool color card (SCC) and direct/conjugated bilirubin (DB/CB) and the reference standard was intraoperative cholangiogram. Meta-analysis was performed using random-effects logistic regression models.

RESULTS: We included 15 studies (1,816,722 participants) that assessed 5 different population-based screening strategies. QUADAS-2 assessment revealed high risk of bias for patient selection in one study and uncertain risks for …

Systemic Complications Of Aicardi Goutières Syndrome Using Real-World Data, Isabella Peixoto De Barcelos, Amanda K Jan, Nicholson Modesti, Sarah Woidill, Francesco Gavazzi, David Isaacs, Russell D'Aiello, Anjana Sevagamoorthy, Lauren Charlton, Amy Pizzino, Johanna Schmidt, Keith Van Haren, Stephanie Keller, Florian Eichler, Lisa T Emrick, Jamie L Fraser, Justine Shults, Adeline Vanderver, Laura A Adang

Faculty, Staff and Students Publications

Objective: Aicardi Goutières Syndrome (AGS) is a rare genetic interferonopathy associated with diverse multisystemic complications. A critical gap exists in our understanding of its longitudinal, systemic disease burden, complicated by delayed diagnosis. To address this need, real-world data extracted from existing medical records were used to characterize the longitudinal disease burden.

Methods: All subjects (n = 167) with genetically confirmed AGS enrolled in the Myelin Disorders Biorepository Project (MDBP) were included. As available in medical records, information was collected on subject demographics, age of onset, and disease complications. Information from published cases of AGS (2007-2022; n = 129) with individual-level …

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 …

Evaluating One-Week Post-Casting Alignment Checks And Surgical Intervention Rates In Pediatric Type Iia Supracondylar Humeral Fractures, Jason Z Amaral, Rebecca J Schultz, Benjamin M Martin, Jacob P Scioscia, Basel Touban, Barkha N Chhabra, Kelly Cline, Scott D Mckay

Faculty, Staff and Students Publications

BACKGROUND: This study aims to determine the rate of surgical intervention in children with type IIA supracondylar humerus fractures (SCHF) following routine post-casting radiographic assessment. We hypothesized that no cases would convert to operative management following one-week post-casting alignment assessments.

METHODS: This single-center retrospective study focused on pediatric patients diagnosed with type IIA SCHF from 2019 to 2022. Patients were treated with initial long arm cast immobilization, followed by a one-week post-casting radiographic alignment check in cast. Fractures were graded in consensus using the Wilkins-Modified Gartland classification system by three fellowship-trained pediatric orthopaedic surgeons. Demographics, casting details, follow-up dates, 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 …

Association Between Remote Monitoring And Interstage Morbidity And Death In Patients With Single-Ventricle Heart Disease Across Socioeconomic Groups., Bianca Cherestal, Lori A. Erickson, Janelle R. Noel-Macdonnell Phd, Girish S. Shirali, Hayley S. Hancock, Doaa Aly, Matthew Files, Sarah Clauss, Natalie Jayaram

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improvements in survival over time, the mortality rate for infants with single-ventricle heart disease remains high. Infants of low socioeconomic status (SES) are particularly vulnerable. We sought to determine whether use of a novel remote monitoring program, the Cardiac High Acuity Monitoring Program, mitigates differences in outcomes by SES.

METHODS AND RESULTS: Within the Cardiac High Acuity Monitoring Program, we identified 610 infants across 11 centers from 2014 to 2021. All enrolled families had access to a mobile application allowing for near-instantaneous transfer of patient information to the care team. Patients were divided into SES tertiles on the …

Sars-Cov-2 Epidemiology And Covid-19 Mrna Vaccine Effectiveness Among Infants And Children Aged 6 Months-4 Years - New Vaccine Surveillance Network, United States, July 2022-September 2023., Ayzsa Tannis, Janet A. Englund, Ariana Perez, Elizabeth J. Harker, Mary Allen Staat, Elizabeth P. Schlaudecker, Natasha B. Halasa, Laura S. Stewart, John V. Williams, Marian G. Michaels, Rangaraj Selvarangan, Jennifer E. Schuster, Leila C. Sahni, Julie A. Boom, Geoffrey A. Weinberg, Peter G. Szilagyi, Benjamin R. Clopper, Yingtao Zhou, Meredith L. Mcmorrow, Eileen J. Klein, Heidi L. Moline

Manuscripts, Articles, Book Chapters and Other Papers

SARS-CoV-2 infection in young children is often mild or asymptomatic; however, some children are at risk for severe disease. Data describing the protective effectiveness of COVID-19 mRNA vaccines against COVID-19-associated emergency department (ED) visits and hospitalization in this population are limited. Data from the New Vaccine Surveillance Network, a prospective population-based surveillance system, were used to estimate vaccine effectiveness using a test-negative, case-control design and describe the epidemiology of SARS-CoV-2 in infants and children aged 6 months-4 years during July 1, 2022-September 30, 2023. Among 7,434 children included, 5% received a positive SARS-CoV-2 test result, and 95% received a negative …

Human Parechovirus Central Nervous System Infection In A Young Infant Cohort, Aspasia Katragkou, Avni Sheth, Christina Gagliardo, Jessica Aquino, Niva Shah, Eberechi Nwaobasi-Iwuh, Christina Melchionne, Paige Black, Stephanie Chiu, Cecilia Di Pentima

Department of Pediatrics Faculty Papers

In 2022, a surge in cases of pediatric human parechovirus (HPeV) central nervous system infections in young infants was seen at our institution. Despite the dramatic increase in the number of cases seen that year, the clinical features of the illness were similar to prior years. The recent pediatric HPeV surge highlights the need to evaluate treatment options and standardize follow-up to better understand the long-term prognosis of infants with HPeV infection.

Epigenetic Age Acceleration, Neonatal Morbidities, And Neurobehavioral Profiles In Infants Born Very Preterm., Uriel Paniagua, Barry M. Lester, Carmen J Marsit, Marie Camerota, Brian S. Carter, Jennifer F. Check, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Sheri A. Dellagrotta, Lynne M. Dansereau, T Michael O'Shea, Todd M. Everson

Manuscripts, Articles, Book Chapters and Other Papers

Epigenetic age acceleration is a risk factor for chronic diseases of ageing and may reflect aspects of biological ageing. However, few studies have examined epigenetic ageing during the early neonatal period in preterm infants, who are at heightened risk of developmental problems. We examined relationships between neonatal age acceleration, neonatal morbidities, and neurobehavioral domains among very preterm (gestation) infants to characterize whether infants with early morbidities or different neurobehavioral characteristics had accelerated or decelerated epigenetic ageing. This study uses data from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, restricted to infants with data on variables assessed …