Pediatrics Commons^™

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

Faculty, Staff and Students Publications

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

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

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

Faculty, Staff and Students Publications

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

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

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

Faculty, Staff and Students Publications

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

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

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …

World Allergy Organization (Wao) Diagnosis And Rationale For Action Against Cow's Milk Allergy (Dracma) Guidelines Update – X – Breastfeeding A Baby With Cow's Milk Allergy, Vicki Mcwilliam, Merryn Netting, Evelyn Volders, Debra Palmer, Ignacio Ansotegui, Stefania Arasi, Amal H. Assa'ad, Sami L. Bahna, Antonio Bognanni, Rose Kamenwa

Paediatrics and Child Health, East Africa

Cow’s milk allergy is rare in exclusively breastfed infants. To support the continuation of breastfeeding an infant after diagnosis with a cow’s milk allergy, it is critical to examine the evidence for and against any form of cow’s milk elimination diet for lactating mothers. In this narrative review, we highlight the lack of high-quality evidence, hence subsequent controversy, regarding whether the minuscule quantities of cow’s milk proteins detectable in human milk cause infant cow’s milk allergy symptoms. Current clinical practice recommendations advise a 2–4 week trial of maternal cow’s milk dietary elimination for: a) IgE-mediated cow’s milk allergy only if …

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

Faculty, Staff and Student Publications

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

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

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

Faculty, Staff and Student Publications

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

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

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

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

Faculty, Staff and Students Publications

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

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

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

The Development, Content And Response Process Validation Of A Caregiver-Reported Severity Measure For Cdkl5 Deficiency Disorder, Sonja I Ziniel, Alexandra Mackie, Jacinta Saldaris, Helen Leonard, Peter Jacoby, Eric D Marsh, Bernhard Suter, Elia Pestana-Knight, Heather E Olson, Dana Price, Judith Weisenberg, Rajsekar Rajaraman, Gina Vanderveen, Tim A Benke, Jenny Downs, Scott Demarest

Faculty, Staff and Students Publications

BACKGROUND: CDKL5 Deficiency Disorder (CDD) is a severe X-linked developmental and epileptic encephalopathy. Existing developmental outcome measures have floor effects and cannot capture incremental changes in symptoms. We modified the caregiver portion of a CDD clinical severity assessment (CCSA) and assessed content and response-process validity.

METHODS: We conducted cognitive interviews with 15 parent caregivers of 1-39-year-old children with CDD. Caregivers discussed their understanding and concerns regarding appropriateness of both questions and answer options. Item wording and questionnaire structure were adjusted iteratively to ensure questions were understood as intended.

RESULTS: The CCSA was refined during three rounds of cognitive interviews into …

Improving Outcomes For Infants After Cardiopulmonary Bypass Surgery For Congenital Heart Disease: A Commentary On Recent Randomized Controlled Trials, Luregn J Schlapbach, Kristen S Gibbons, Warwick Butt, Prince J Kannankeril, Jennifer S Li, Kevin D Hill

Faculty, Staff and Students Publications

The recent NITRIC and STRESS trials demonstrate opportunities to perform pragmatic large randomized trials in congenital heart disease. We discuss lessons learnt from these trials which can inform future trial design and conduct in the field of pediatric heart surgery.

Characteristics And Prognostic Impact Of Idh Mutations In Aml: A Cog, Swog, And Ecog Analysis., Sara Zarnegar-Lumley, Todd A. Alonzo, Robert B. Gerbing, Megan Othus, Zhuoxin Sun, Rhonda E. Ries, Jim Wang, Amanda Leonti, Matthew A. Kutny, Fabiana Ostronoff, Jerald P. Radich, Frederick R. Appelbaum, Era L. Pogosova-Agadjanyan, Kristen O'Dwyer, Martin S. Tallman, Mark Litzow, Ehab Atallah, Todd M. Cooper, Richard A. Aplenc, Omar Abdel-Wahab, Alan S. Gamis, Selina Luger, Harry Erba, Ross Levine, E Anders Kolb, Derek L. Stirewalt, Soheil Meshinchi, Katherine Tarlock

Manuscripts, Articles, Book Chapters and Other Papers

Somatic mutations in isocitrate dehydrogenase (IDH) genes occur frequently in adult acute myeloid leukemia (AML) and less commonly in pediatric AML. The objective of this study was to describe the prevalence, mutational profile, and prognostic significance of IDH mutations in AML across age. Our cohort included 3141 patients aged betweenChildren's Cancer Group/Children's Oncology Group (n = 1872), Southwest Oncology Group (n = 359), Eastern Cooperative Oncology Group (n = 397) trials, and in Beat AML (n = 333) and The Cancer Genome Atlas (n = 180) genomic characterization cohorts. We retrospectively analyzed patients in 4 age groups (age range, n): …

3-Year Follow-Up Of A Prospective, Multicenter Study Of The Amplatzer Piccolo™ Occluder For Transcatheter Patent Ductus Arteriosus Closure In Children ≥ 700 Grams., Brian H. Morray, Shyam K. Sathanandam, Thomas Forbes, Matthew Gillespie, Darren Berman, Aimee K. Armstrong, Shabana Shahanavaz, Thomas Jones, Toby A. Rockefeller, Henri Justino, David Nykanen, Courtney Weiler, Dan Gutfinger, Evan M. Zahn

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: This study describes 3-year follow-up of 200 infants weighing ≥ 700 grams who underwent transcatheter patent ductus arteriosus (PDA) closure with the Amplatzer Piccolo™ Occluder.

STUDY DESIGN: Between June 2017 and February 2019, 200 children were enrolled in this U.S. study (NCT03055858). PDA closure, survival, and device- or procedure-related events were evaluated. A total of 156 of the available 182 patients (86%) completed the study.

RESULTS: The implant success rate was 95.5% (191/200). At 3 years, PDA closure was observed in 100% (33/33) of patients. Survival was >95% with 9 reported deaths. No deaths were adjudicated as device- or …

Can Craniosynostosis Be Diagnosed On Physical Examination? A Retrospective Review, Carmen A Zavala, Laura A Zima, Matthew R Greives, Stephen A Fletcher, Manish N Shah, Brandon A Miller, David I Sandberg, Phuong D Nguyen

Faculty, Staff and Student Publications

Craniosynostosis is a developmental craniofacial defect in which one or more sutures of the skull fuse together prematurely. Uncorrected craniosynostosis may have serious complications including elevated intracranial pressure, developmental delay, and blindness. Proper diagnosis of craniosynostosis requires a physical examination of the head with assessment for symmetry and palpation of sutures for prominence. Often, if craniosynostosis is suspected, computed tomography (CT) imaging will be obtained. Recent literature has posited that this is unnecessary. This study aims to address whether physical examination alone is sufficient for the diagnosis and treatment planning of single suture craniosynostosis. Between 2015 and 2022, the Divisions …

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

Faculty, Staff and Students Publications

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

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

Faculty, Staff and Students Publications

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

Effectiveness Of Maternal Mrna Covid-19 Vaccination During Pregnancy Against Covid-19-Associated Hospitalizations In Infants Aged <6 Months During Sars-Cov-2 Omicron Predominance - 20 States, March 9, 2022-May 31, 2023., Regina M. Simeone, Laura D. Zambrano, Natasha B. Halasa, Katherine E. Fleming-Dutra, Margaret M. Newhams, Michael J. Wu, Amber O. Orzel-Lockwood, Satoshi Kamidani, Pia S. Pannaraj, Katherine Irby, Aline B. Maddux, Charlotte V. Hobbs, Melissa A. Cameron, Julie A. Boom, Leila C. Sahni, Michele Kong, Ryan A. Nofziger, Jennifer E. Schuster, Hillary Crandall, Janet R. Hume, Mary A. Staat, Elizabeth H. Mack, Tamara T. Bradford, Sabrina M. Heidemann, Emily R. Levy, Shira J. Gertz, Samina S. Bhumbra, Tracie C. Walker, Katherine E. Bline, Kelly N. Michelson, Matt S. Zinter, Heidi R. Flori, Angela P. Campbell, Adrienne G. Randolph, Overcoming Covid-19 Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Infants aged < 6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19-related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022-May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19-related hospitalization in infants aged < 6 months and a subset of infants aged < 3 months. VE was calculated as (1 - adjusted odds ratio) x 100% among all infants aged < 6 months and < 3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19-like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19-related hospitalization was 35% (95% CI = 15%-51%) among infants aged < 6 months and 54% (95% CI = 32%-68%) among infants aged < 3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19-related hospitalizations among infants, particularly those aged < 3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19.

A Comparative Study Of Postnatal Anthropometric Growth In Very Preterm Infants And Intrauterine Growth., Fu-Sheng Chou, Hung-Wen Yeh, Reese H. Clark

Manuscripts, Articles, Book Chapters and Other Papers

Most growth references for very preterm infants were developed using measurements taken at birth, and were thought to represent intrauterine growth. However, it remains unclear whether the goal of approximating an intrauterine growth rate as stated by the American Academy of Pediatrics is attainable by very preterm infants. Using real-world measurement data from very preterm infants born between 2010 through 2020, we develop models to characterize the patterns of postnatal growth, and compare them to intrauterine growth. By assessing the weight growth rate, we show three phases of postnatal growth not evident in intrauterine growth. Furthermore, postnatal length and head …

Fetal Echocardiographic Z Score Pilot Project: Study Design And Impact Of Gestational Age And Variable Type On Reproducibility Of Measurements Within And Across Investigators, Anita J Moon-Grady, Hyejung Lee, Leo Lopez, Oluwatosin Fatusin, Lindsay R Freud, Whitnee Hogan, Anita Krishnan, Carol Mcfarland, L Luann Minich, Shaine A Morris, Nelangi Pinto, Angela P Presson, Theresa A Tacy, Mary T Donofrio

Faculty, Staff and Students Publications

Background: Fetal echocardiography is widely available, but normative data are not robust. In this pilot study, the authors evaluated (1) the feasibility of prespecified measurements in a normal fetal echocardiogram to inform study design and (2) measurement variability to assign thresholds of clinical significance and guide analyses in larger fetal echocardiographic Z score initiatives.

Methods: Images from predefined gestational age groups (16-20, >20-24, >24-28, and >28-32 weeks) were retrospectively analyzed. Fetal echocardiography expert raters attended online group training and then independently analyzed 73 fetal studies (18 per age group) in a fully crossed design of 53 variables; each observer repeated …

Infants Admitted To Us Intensive Care Units For Rsv Infection During The 2022 Seasonal Peak., Natasha Halasa, Laura D. Zambrano, Justin Z. Amarin, Laura S. Stewart, Margaret M. Newhams, Emily R. Levy, Steven L. Shein, Christopher L. Carroll, Julie C. Fitzgerald, Marian G. Michaels, Katherine Bline, Melissa L. Cullimore, Laura Loftis, Vicki L. Montgomery, Asumthia S. Jeyapalan, Pia S. Pannaraj, Adam J. Schwarz, Natalie Z. Cvijanovich, Matt S. Zinter, Aline B. Maddux, Melania M. Bembea, Katherine Irby, Danielle M. Zerr, Joseph D. Kuebler, Christopher J. Babbitt, Mary Glas Gaspers, Ryan A. Nofziger, Michele Kong, Bria M. Coates, Jennifer E. Schuster, Shira J. Gertz, Elizabeth H. Mack, Benjamin R. White, Helen Harvey, Charlotte V. Hobbs, Heda Dapul, Andrew D. Butler, Tamara T. Bradford, Courtney M. Rowan, Kari Wellnitz, Mary Allen Staat, Cassyanne L. Aguiar, Saul R. Hymes, Adrienne G. Randolph, Angela P. Campbell, Rsv-Pic Investigators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide.

OBJECTIVE: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection.

EXPOSURE: Respiratory syncytial virus.

MAIN OUTCOMES AND MEASURES: Data were captured on demographics, …

A Previously Healthy Infant With Lemierre Syndrome In The Emergency Department: Case Report, Adeola Adekunbi Kosoko, Omoyeni O Clement

Faculty, Staff and Student Publications

INTRODUCTION: Lemierre syndrome (LS) is a rare condition with a high mortality risk. It is well described in older children and young adults involving bacteremia, thrombophlebitis, and metastatic abscess commonly due to Fusobacterium infections. Young, pre-verbal children are also susceptible to LS; thus, careful attention must be given to their pattern of symptoms and history to identify this condition in the emergency department (ED).

CASE REPORT: A 12-month-old previously healthy boy with a recent diagnosis of acute otitis media and viral illness presented to the ED with a complaint of fever. Additional symptoms developed at the head and neck and …

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

Faculty, Staff and Student Publications

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

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

Faculty, Staff and Student Publications

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

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

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

Faculty, Staff and Students Publications

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

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

Epilepsy Severity Is Associated With Head Circumference And Growth Rate In Infants With Tuberous Sclerosis Complex, Alexis Levine, Peter Davis, Bo Zhang, Jurriaan Peters, Rajna Filip-Dhima, Simon K Warfield, Anna Prohl, Jamie Capal, Darcy Krueger, E Martina Bebin, Hope Northrup, Joyce Y Wu, Mustafa Sahin

Faculty, Staff and Student Publications

BACKGROUND: Abnormal brain growth in tuberous sclerosis complex (TSC) reflects abnormalities in cellular proliferation and differentiation and results in epilepsy and other neurological manifestations. Head circumference (HC) as a proxy for brain volume may provide an easily tracked clinical measure of brain overgrowth and neurological disease burden. This study investigated the relationship between HC and epilepsy severity in infants with TSC.

METHODS: Prospective multicenter observational study of children from birth to three years with TSC. Epilepsy data were collected from clinical history, and HC was collected at study visits at age three, six, nine, 12, 18, 24, and 36 months. …

Difficult Or Impossible Facemask Ventilation In Children With Difficult Tracheal Intubation: A Retrospective Analysis Of The Pedi Registry, Annery G Garcia-Marcinkiewicz, Lisa K Lee, Bishr Haydar, John E Fiadjoe, Clyde T Matava, Pete G Kovatsis, James Peyton, Mary L Stein, Raymond Park, Brad M Taicher, Thomas W Templeton

Faculty, Staff and Student Publications

BACKGROUND: Difficult facemask ventilation is perilous in children whose tracheas are difficult to intubate. We hypothesised that certain physical characteristics and anaesthetic factors are associated with difficult mask ventilation in paediatric patients who also had difficult tracheal intubation.

METHODS: We queried a multicentre registry for children who experienced "difficult" or "impossible" facemask ventilation. Patient and case factors known before mask ventilation attempt were included for consideration in this regularised multivariable regression analysis. Incidence of complications, and frequency and efficacy of rescue placement of a supraglottic airway device were also tabulated. Changes in quality of mask ventilation after injection of a …

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

Faculty, Staff and Students Publications

Background

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

Methods

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

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

Faculty, Staff and Students Publications

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

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

RESULTS: Among 9419 CALHIV using DTG, …

Epileptic Spasms In Cdkl5 Deficiency Disorder: Delayed Treatment And Poor Response To First-Line Therapies, Heather E Olson, Scott Demarest, Elia Pestana-Knight, Ahsan N Moosa, Xiaoming Zhang, José R Pérez-Pérez, Judy Weisenberg, Erin O'Connor Prange, Eric D Marsh, Rajsekar R Rajaraman, Bernhard Suter, Akshat Katyayan, Isabel Haviland, Carolyn Daniels, Bo Zhang, Caitlin Greene, Michelle Deleo, Lindsay Swanson, Jamie Love-Nichols, Timothy Benke, Chellamani Harini, Annapurna Poduri

Faculty, Staff and Students Publications

OBJECTIVE: We aimed to assess the treatment response of infantile-onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) vs other etiologies.

METHODS: We evaluated patients with ES from the CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC), with onset from 2 months to 2 years, treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, vigabatrin, and/or the ketogenic diet. We excluded children with tuberous sclerosis complex, trisomy 21, or unknown etiology with normal development because of known differential treatment responses. We compared the two cohorts for time to treatment and ES remission at 14 days and 3 months.

RESULTS: …

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

Faculty, Staff and Students Publications

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

Achondroplasia Natural History Study (Clarity): 60-Year Experience In Orthopedic Surgery From Four Skeletal Dysplasia Centers, Nickolas J Nahm, W G Stuart Mackenzie, William G Mackenzie, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria Elena Serna, Cory J Smid, Julie Hoover-Fong, Michael B Bober

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database.

RESULTS: Information from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. …