Medicine and Health Sciences Commons^™

A Novel Approach To Triosephosphate Isomerase Deficiency, Kyra Mccarty

Research Days

Background: Triosephosphate isomerase deficiency (TPID) is a glycolytic pathway enzymopathy causing hemolytic anemia and neurologic dysfunction. TPID is caused by mutations in the TPI1 gene. These patients experience severe hemolytic anemia in infancy followed by progressive neurodegeneration. Diagnosis of TPID is made by measuring decreased TPI enzyme activity elevated dihydroxyacetone phosphate (DHAP) levels in the blood. The diagnosis is confirmed by molecular genetic testing. Neurological involvement typically manifests between 6 and 24 months of age, causing progressive motor dysfunction. Chronic axonal neuropathy is often present on nerve biopsy, and peripheral neuropathy is evident on electrophysiologic studies. Splenectomy and blood transfusions …

Sigirr Variants Identified In Nec Infants Exaggerate Toll-Like Receptor Mediated Inflammation, Jennie Godwin

Research Days

Background: A key event underlying uncontrolled inflammation in necrotizing enterocolitis (NEC) is pathologic activation of Toll-like receptors (TLR). TLR4 recognizes lipopolysaccharide (LPS), from Gramnegative bacteria, and TLR2 peptidoglycans (PAM3Csyk4, PAM), from Gram-positive bacteria. TLR4 and TLR2 signaling events induce an inflammatory cascade through NF-kB, a cytokine inducing transcription factor. Single-immunoglobulin interleukin-1-related receptor (SIGIRR) is a major negative regulator of TLR-mediated NF-kB activation. Previous work from our lab suggests that loss of function in SIGIRR may predispose to NEC. Our lab has identified four variants in NEC patients predicted to alter function of SIGIRR. We hypothesized that identified SIGIRR variants will …

Outcomes Of Infants With Severe Rop At Risk Of Treatment With Avastin Compared To Laser Surgery, Stephen Doxey

Research Days

Background: Retinopathy of prematurity (ROP) is a well-known complication occurring in the most premature infants leading to visual impairment and in the most severe cases associated with retinal detachment and childhood blindness. Factors contributing the development of ROP include chronic hypoxia and disordered vascular genesis primarily through the vascular endothelial growth factor (VEGF) signaling pathway. Infants at risk of developing ROP are screened with serial eye exam and treated with either laser surgery or intraocular injects of bevacizumab (Avastin) to prevent progression of ROP and preserve vision. Bevacizumab, an inhibitor of VEGF signaling, may have positive effects on preventing ROP …

Activation Of Aryl Hydrocarbon Receptor Signaling In Human Trophoblasts Alters Markers Of Growth And Differentiation, Asmaa Alsousi

Research Days

Background: It is estimated that 1.7% of pregnant women smoke during their pregnancy globally, with the highest levels observed in Europe at 8.1%, and lowest in Africa at 0.8. The association of maternal cigarette smoking with increased risk of poor birth outcomes such as preterm birth, congenital anomalies, and neonatal mortality is well-established. In addition, evidence suggests that intrauterine exposure to maternal smoking impacts the risk of developing diseases later in life; however, we still do not understand the exact mechanism(s) leading to these outcomes. Once components of cigarette smoke (CS) cross the placenta and enter the fetal compartment, several …

Tricuspid Atresia With Totally Anomalous Pulmonary Venous Connection: An Uncommon Finding, Anmol Goyal

Research Days

Background: Tricuspid atresia comprises 3-4% of all congenital heart disease (CHD). Anatomic findings are no true connection between the right atrium (RA) and right ventricle (RV) with concomitant findings of a ventricular septal defect (VSD), right ventricular hypoplasia, abnormalities of right ventricular outflow tract, pulmonary valve and pulmonary arteries. Common associated lesions have been described including transposition of great vessels, hypoplasia of aortic arch, double outlet ventricle or a common arterial trunk. Total anomalous pulmonary venous connection (TAPVC) is relatively rare and we present a case in addition to the six previously described cases in literature.

Case: A 33-year-old woman …

Early Impact Of The Covid-19 Pandemic On Congenital Heart Surgery Programs Across The World: Assessment By A Global Multi-Societal Consortium., Eleftherios M. Protopapas, Mauro Lo Rito, Vladimiro L. Vida, George E. Sarris, Christo I. Tchervenkov, Bohdan J. Maruszewski, Zdzislaw Tobota, Bistra Zheleva, Hao Zhang, Jeffery P. Jacobs, Joseph A. Dearani, Elizabeth H. Stephens, James S. Tweddell, Nestor F. Sandoval, Emile A. Bacha, Erle H. Austin, Kisaburo Sakamoto, Sachin Talwar, Hiromi Kurosawa, Zohair Y Al Halees, Marcello B. Jatene, Krishna S. Iyer, Cheul Lee, Rajesh Sharma, Yasutaka Hirata, Frank Edwin, Jorge L. Cervantes, James O'Brien, James D. St Louis, James K. Kirklin, Covid-19 International Congenital Heart Surgery Taskforce

Manuscripts, Articles, Book Chapters and Other Papers

The coronavirus disease 2019 (COVID-19) pandemic currently gripping the globe is impacting the entire health care system with rapidly escalating morbidities and mortality. Although the infectious risk to the pediatric population appears low, the effects on children with congenital heart disease (CHD) remain poorly understood. The closure of congenital heart surgery programs worldwide to address the growing number of infected individuals could have an unintended impact on future health for COVID-19-negative patients with CHD. Pediatric and congenital heart surgeons, given their small numbers and close relationships, are uniquely positioned to collectively assess the impact of the pandemic on surgical practice …

Identifying Genetic Factors That Contribute To The Increased Risk Of Congenital Heart Defects In Infants With Down Syndrome., Cristina E. Trevino, Aaron M. Holleman, Holly Corbitt, Cheryl L. Maslen, Tracie C. Rosser, David J. Cutler, H Richard Johnston, Benjamin L. Rambo-Martin, Jai Oberoi, Kenneth J. Dooley, George T. Capone, Roger H. Reeves, Heather J. Cordell, Bernard D. Keavney, A J Agopian, Elizabeth Goldmuntz, Peter J. Gruber, James O'Brien, Douglas C. Bittel, Lalita Wadhwa, Clifford L. Cua, Jennifer G. Mulle, Michael P. Epstein, Stephanie L. Sherman, Michael E. Zwick

Manuscripts, Articles, Book Chapters and Other Papers

Atrioventricular septal defects (AVSD) are a severe congenital heart defect present in individuals with Down syndrome (DS) at a > 2000-fold increased prevalence compared to the general population. This study aimed to identify risk-associated genes and pathways and to examine a potential polygenic contribution to AVSD in DS. We analyzed a total cohort of 702 individuals with DS with or without AVSD, with genomic data from whole exome sequencing, whole genome sequencing, and/or array-based imputation. We utilized sequence kernel association testing and polygenic risk score (PRS) methods to examine rare and common variants. Our findings suggest that the Notch pathway, particularly …

Serious Neonatal Morbidities Are Associated With Differences In Dna Methylation Among Very Preterm Infants., Todd M. Everson, T Michael O'Shea, Amber Burt, Karen Hermetz, Brian S. Carter, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Antoine Soliman, Sheri A. Dellagrotta, Lynne M. Dansereau, James F. Padbury, Barry M. Lester, Carmen J. Marsit

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Infants born very preterm are more likely to experience neonatal morbidities compared to their term peers. Variations in DNA methylation (DNAm) associated with these morbidities may yield novel information about the processes impacted by these morbidities.

METHODS: This study included 532 infants born < 30 weeks gestation, participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants study. We used a neonatal morbidity risk score, which was an additive index of the number of morbidities experienced during the NICU stay, including bronchopulmonary dysplasia (BPD), severe brain injury, serious neonatal infections, and severe retinopathy of prematurity. DNA was collected from buccal cells at discharge from the NICU, and DNAm was measured using the Illumina MethylationEPIC. We tested for differential methylation in association with the neonatal morbidity risk score then tested for differentially methylated regions (DMRs) and overrepresentation of biological pathways.

RESULTS: We identified ten differentially methylated CpGs (α Bonferroni-adjusted for 706,278 tests) that were associated with increasing neonatal morbidity risk scores at three intergenic regions and at HPS4, SRRD, FGFR1OP, TNS3, TMEM266, LRRC3B, ZNF780A, and TENM2. These mostly followed dose-response patterns, for 8 CpGs increasing DNAm associated with increased numbers of morbidities, while for 2 CpGs …

Fosl1 Is A Novel Mediator Of Endotoxin/Lipopolysaccharide-Induced Pulmonary Angiogenic Signaling., Christopher R. Nitkin, Sheng Xia, Heather Menden, Wei Yu, Min Xiong, Daniel P. Heruth, Shui Qing Ye, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Systemic sepsis is a known risk factor for bronchopulmonary dysplasia (BPD) in premature infants, a disease characterized by dysregulated angiogenesis and impaired vascular and alveolar development. We have previoulsy reported that systemic endotoxin dysregulates pulmonary angiogenesis resulting in alveolar simplification mimicking BPD in neonatal mice, but the underlying mechanisms remain unclear. We undertook an unbiased discovery approach to identify novel signaling pathways programming sepsis-induced deviant lung angiogenesis. Pulmonary endothelial cells (EC) were isolated for RNA-Seq from newborn C57BL/6 mice treated with intraperitoneal lipopolysaccharide (LPS) to mimic systemic sepsis. LPS significantly differentially-regulated 269 genes after 6 h, and 1,934 genes after …

Atrioventricular Nodal Reentrant Tachycardia In Patients With Complex Congenital Heart Disease And Twin Atrioventricular Nodes., John Papagiannis, Christopher Mathis, Lindsey Malloy-Walton, Svjetlana Tisma-Dupanovic

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Similac Special Care And Elecare Cause Neonatal Gut Injury In Mice, Karishma Rao, Heather L. Menden, Wei Yu, Inamul Haque, Susana Chavez-Bueno, Alain C. Cuna, Shahid Umar, Venkatesh Sampath

Research Days

No abstract provided.

Clinical Validation And Diagnostic Rate/Outcomes Of A Dual Molecular Diagnostic Assay For Myotonic Dystrophy 1., Maxime Cadieux-Dion, Isabelle Thiffault, Midhat S. Farooqi, Joseph Alaimo

Research Days

No abstract provided.

Two Cases Of Severe Combined Immunodeficiency Disease With No Known Variants Identified In Genes Associated With Immunodeficiencies, Megan H. Tucker

Research Days

No abstract provided.

The Role Of Alternative Mrna Splicing In Heart Development, Douglas Bittel, Nataliya Kibiryeva, Naoya Kenmochi, Prakash Patil, Tamayo Uechi, Brenda Rongish, Mike Filla, Jennifer A. Marshall, Michael Artman, Rajasingh Johnson, James E. O'Brien

Manuscripts, Articles, Book Chapters and Other Papers

Research in the last 10 years has led to improved understanding of the genetic regulation of vertebrate heart development, but despite this effort, approximately 70% of all congenital heart defects (CHDs) still have an unknown etiology. Alternative splicing of mRNA has been documented to play roles in normal and abnormal development. Dysregulated splicing of mRNA has been shown to cause heart defects in mice, however a link between mRNA splicing and CHDs has not yet been shown in humans. We reported that more than 50% of genes associated with heart development were alternatively spliced in the right ventricle (RV) of …

Prevalence Of Sensorineural Hearing Loss In Children With Palliated Or Repaired Congenital Heart Disease., Lalitha Gopineti, Mane Paulpillai, Andrea Rosenquist, Andrew H. Van Bergen

Manuscripts, Articles, Book Chapters and Other Papers

Background Children with congenital heart disease (CHD) are at increased risk of neurodevelopmental deficits, and the presence of sensorineural hearing loss (SNHL) may further lead to poor language skills acquisition and speech delays. Prevalence of SNHL in the general pediatric population is estimated to be 0.2% at birth to 0.35% during adolescence. Very few studies have attempted to estimate SNHL prevalence in children who have undergone congenital heart surgery. Methods This retrospective study aimed to estimate SNHL prevalence in children who underwent congenital heart surgery in our institution and were followed up in our high-risk pediatric cardiology clinics for four …

Hypomorphic Si Genetic Variants Are Associated With Childhood Chronic Loose Stools., Bruno P Chumpitazi, Jeffery Lewis, Derick Cooper, Mauro D'Amato, Joel Lim, Sandeep Gupta, Adrian Miranda, Natalie Terry, Devendra Mehta, Ann Scheimann, Molly O'Gorman, Neelesh Tipnis, Yinka Davies, Joel Friedlander, Heather Smith, Jaya Punati, Julie Khlevner, Mala Setty, Carlo Di Lorenzo

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The SI gene encodes the sucrase-isomaltase enzyme, a disaccharidase expressed in the intestinal brush border. Hypomorphic SI variants cause recessive congenital sucrase-isomaltase deficiency (CSID) and related gastrointestinal (GI) symptoms. Among children presenting with chronic, idiopathic loose stools, we assessed the prevalence of CSID-associated SI variants relative to the general population and the relative GI symptom burden associated with SI genotype within the study population.

METHODS: A prospective study conducted at 18 centers enrolled 308 non-Hispanic white children ≤18 years old who were experiencing chronic, idiopathic, loose stools at least once per week for >4 weeks. Data on demographics, GI …

Morgagni Hernia, Wendy Jo Svetanoff, Rebecca M. Rentea

Manuscripts, Articles, Book Chapters and Other Papers

A Morgagni hernia is one of four types of diaphragmatic hernias; the other types include a Bochdalek hernia, where the defect is posterolateral, a hiatal hernia, where the defect is at the esophageal hiatus, and a paraesophageal hernia, where the defect is located adjacent to the esophageal hiatus. The Morgagni hernia, in which the defect is found in an anterior and retrosternal location, was first described by Morgagni in 1769. It is rarer than the other type of congenital diaphragmatic hernia (Bochdalek hernia) and comprises only 2% to 5% of all congenital diaphragmatic hernias. Morgagni hernias tend to be less …

Gastroschisis, Rebecca M. Rentea, Vikas Gupta

Manuscripts, Articles, Book Chapters and Other Papers

Gastroschisis is a paraumbilical, full-thickness abdominal wall defect associated with protrusion of the bowel through the defect. It is rarely associated with genetic conditions. A membrane does not cover the bowel exposed in utero and, as a result, may be matted, dilated, and covered with a fibrinous inflammatory rind. Infants have a high proportion of intrauterine growth restriction. Diagnosis is often made on the 20-week ultrasound with free-floating bowel loops in the uterine cavity. Maternal serum alpha-fetoprotein (AFP) is elevated in pregnancies with gastroschisis. Compared with other abdominal wall defects diagnosed prenatally such as omphalocele, only 10 percent of cases …

Patent Urachus, Kayla B. Briggs, Rebecca M. Rentea

Manuscripts, Articles, Book Chapters and Other Papers

atent urachus refers to one condition in a rare spectrum of disorders referred to as urachal anomalies. These conditions result from the failure of the involution of normal embryologic tissues that serve to empty the fetal bladder. The location and amount of persistent tissue dictate the presenting symptoms. Some of these urachal anomalies are obvious at birth, while others are more subtle and not diagnosed until adulthood or only incidentally discovered after imaging is obtained for other reasons. Historically, surgical resection of urachal anomalies was routinely undertaken, given the potential for malignancy in retained ectopic tissue. Early surgical resection has …

Ileal Atresia, Obiyo O. Osuchukwu, Rebecca M. Rentea

Manuscripts, Articles, Book Chapters and Other Papers

Ileal and jejunal atresias are usually described together as jejunoileal atresia (JIA). JIA is a common cause of intestinal obstruction in neonates. It is seen in 1 in 5000 to 1 in 14000 live births. Intestinal atresia can occur in any location on the small bowel as a solitary or even multiple lesions. Distally located atresia usually presents with delayed symptoms compared to proximal ones. Occasionally, JIA is associated with other malformations such as cardiac anomalies, gastroschisis, and cystic fibrosis. Evaluation can be initiated before birth with prenatal diagnosis using ultrasound findings of evidence of intestinal obstruction reported in 29% …

Pentalogy Of Cantrell, Muhammad Khawar Sana, Rebecca M. Rentea

Manuscripts, Articles, Book Chapters and Other Papers

Pentalogy of Cantrell (POC) is a collection of five congenital midline birth anomalies that present a distinctive challenge for clinicians and surgeons. Those five defects are of the heart, pericardium, diaphragm, sternum, and abdominal wall. This condition has been divided into two categories, complete or partial. Complete, as the name indicates, refers to the presence of all five defects, while others may present with only partial defects. It is also referred to as thoracoabdominal ectopia cordis, a condition where the heart is covered by an omphalocele-like membrane. Ectopia cordis (EC) is often found in fetuses with POC. Infants usually have …

Anticipation, Accompaniment, And A Good Death In Perinatal Care., Bryanna S. Moore, Brian S. Carter, Bryan Beaven, Katie House, Joel House

Manuscripts, Articles, Book Chapters and Other Papers

The ethics of perinatal care, and the experiences of families who receive such care, remains a nascent area of inquiry. It can be hard to see how existing "good death" constructs apply to the experiences of fetal patients and their families. In this paper, we explore two themes raised by a case at our fetal health center: anticipation and accompaniment. In this case, a mother presented to our fetal health center; her unborn son, our fetal patient, was diagnosed with life-threatening hypoplastic left heart syndrome and endocardial fibroelastosis. The parents were told that their son's life expectancy, upon birth, was …

Pharmacometabolomics Of Respiratory Phenotypic Response To Dexamethasone In Preterm Infants At Risk For Bronchopulmonary Dysplasia., Tamorah R. Lewis Md Phd, Prabhakar Chalise, Cheri Gauldin, William E. Truog

Manuscripts, Articles, Book Chapters and Other Papers

A prospective cohort study was performed in preterm infants less than 32 weeks gestation at birth who were treated with dexamethasone for developing or established bronchopulmonary dysplasia (BPD). Respiratory phenotype (Respiratory Severity Score (RSS)), serum, and urine metabolomics were assessed before and after treatment. Ten infants provided nine matched serum and nine matched urine samples. There was a significant decrease in RSS with steroid treatment. Serum gluconic acid had the largest median fold change (140 times decreased, P = 0.008). In metabolite set enrichment analysis, in both serum and urine, the urea cycle, ammonia recycling, and malate-aspartate shuttle pathways were …

Lighting The Way To Ensure Safe Transition Home, Barb Haney, Ashley Mirabile, Dianne Wilderson, Beckie Palmer, Ashley Lewis, Cris Mills, Eugenia K. Pallotto

Posters

All aspects of discharge (education, screenings, appointments, plans and home services" must be completed and appropriately communicated prior to discharge to ensure safe transition to home.

Goal: Standardize all aspects of discharge in a large, busy 84-bed Level IV NICU with >1000 admissions/year and >300 nurses, >60 NNPs, and >25 neonatologists.

• 95% of patients with lengths of stay >3 days have all discharge planning completed prior to discharge/Parent Care Unit overnight stay

Safe Sleep In The Nicu, Ashley Mirabile, Barb Haney, Dianne Wilderson, Beckie Palmer, Ashley Domsch, Eugenia K. Pallotto

Posters

Goal: To evaluate a staff education program on approach to improve in the rate of eligible NICU infants in safe sleep in a busy 84-bed level IV NICU.

Outcome Measures; Improve safe sleep compliance for eligible patients to 90% or greater by December 2019.

Process Measures: Audits from bedside RNs showing compliance with safe sleep.

Planned Intervention: In December of 2018 a multidisciplinary work group brainstormed and implemented best practice safe sleep education for staff and parents. September 2019 a Safe Sleep Educational Toolkit was made available for staff.

Results: Safe Sleep compliance has gone from 53% to 90% in …

Comparison Of Echocardiographic Measurements To Invasive Measurements Of Diastolic Function In Infants With Single Ventricle Physiology: A Report From The Pediatric Heart Network Infant Single Ventricle Trial., Suma P. Goudar, Victor Zak, Andrew M. Atz, Karen Altmann, Steven D. Colan, Christine B. Falkensammer, Mark K. Friedberg, Michele Frommelt, Kevin D. Hill, Daphne T. Hsu, Jami C. Levine, Renee Margossian, Christopher R. Mart, Joshua Sticka, Peter Shrader, Girish S. Shirali, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.

METHODS: Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to …

A Multifaceted Approach To Improve Quarterly Visit Rates At A Pediatric Cystic Fibrosis Care Center, Paula Capel, Jessica Banks, Micaela Mckenna, Ashley Andrews, Christopher M. Oermann

Posters

Standard quality improvement methodology was used to improve quarterly visit rates among cystic fibrosis patients at Children's Mercy Kansas City Cystic Fibrosis Center.

• A family-centered, team-based approach was adopted
• A change in culture led to sustained improvement

Improved quarterly visit rates should drive improvement in outcomes including pulmonary function and nutritional status.

Safe To Sleep In The Icn, Megan Kelly, Alexandra (Lexi) Van Noy, Molly Kruse, Megan English, Hannah Culbertson, Brianne Truitt, Ziryan Salihparkhy, Jenny Mckee, Brecklyn Findley

Posters

The CDC states that 1,545 infants passed away from SIDS in 2014. Safe sleep includes supine, in a crib, head of bed flat, firm sleep surface, tightly fitted sheet, no loose blankets, no toys or supplies in crib with infant. It is important for nurses to model safe sleep practices in the hospital setting. Current compliance with safe sleep in the Intensive Care Nursery is 50%.

AIM Statement:

By August 1, 2019 we want to increase the compliance of modeling safe sleep behaviors for patients who qualify for safe sleep from 50% to 90% in the Intensive Care Nursery.

Increasing Rates Of Breastmilk Use At Time Of Neonatal Intensive Care Unit (Nicu) Discharge: An Improvement Project In A Midwest Level Iv Nicu, Kathleen Hortenstine, Teresa Fulk, Stephanie Callis, Kyla Galate, Beckie Palmer

Posters

• Breast milk is the preferred food for all infants.
• The rate of breast milk use at time of discharge was below the goal of the institution.
• A gap was identified in bedside nursing education, limiting their ability to provide resources and education to mothers. Nursing involvement ensures skilled, comprehensive, and accessible breastfeeding support.
• The aim of this project is to increase breast milk rates at time of NICU discharge to 95% of eligible patients by December of 2019.

Improving Care Of The Small Baby, Beckie Palmer, Abdebayo Oshodi, Brandy Huitt, Kaylee Hurt, Pamela Kliethermes, Trudy Koons, Patricia Lanzer, Ashley Mirabile, Allyson Owen, Christian Anthony Schneider, Betsi Anderson, Steven Olsen

Posters

Hierarchy of Aims:

• Global Aim: Create a Small Baby Unit for infants admitted to our NICU that arebirth, in which 90% of our patients are admitted to F pod on day of admission, by March 2019
• Interim Aim: Staff 80% of our micropremie patients with a Small Baby Team nurse from admission until >32 weeks by May 2019.
• Sub Aim: Increase rates of developmentally appropriate care (2 person cares, kangaroo care compliance) by 50% by August 2019.