Pediatrics Commons^™

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 …

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 …

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 …

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, …

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 …

Pentoxifylline For Treatment Of Sepsis And Necrotising Enterocolitis In Neonates, Mohan Pammi, Khalid N Haque

Faculty, Staff and Students Publications

BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.

OBJECTIVES: To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We …

Irf7 And Unc93b1 Variants In An Infant With Recurrent Herpes Simplex Virus Infection., Megan H. Tucker, Wei Yu, Heather Menden, Sheng Xia, Carl F. Schreck, Margaret Gibson, Daniel A. Louiselle, T Pastinen, Nikita Raje, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Neonatal herpes simplex virus (HSV) infection is a devastating disease with substantial morbidity and mortality. The genetic basis of susceptibility to HSV in neonates remains undefined. We evaluated a male infant with neonatal skin/eye/mouth (SEM) HSV-1 disease, who had complete recovery after acyclovir but developed HSV-1 encephalitis at 1 year of age. An immune workup showed an anergic PBMC cytokine response to TLR3 stimulation but no other TLRs. Exome sequencing identified rare missense variants in IFN-regulatory factor 7 (IRF7) and UNC-93 homolog B1 (UNC93B1). PBMC single-cell RNA-Seq done during childhood revealed decreased expression of several innate immune genes and a …

Red Blood Cell Transfusion Thresholds For Anemia Of Prematurity, Lindsay F Holzapfel, Matthew A Rysavy, Edward F Bell

Faculty, Staff and Student Publications

Anemia of prematurity affects the majority of preterm infants, particularly extremely low birthweight infants. Anemia of prematurity arises from both innate and iatrogenic causes and results in more than 80% of extremely preterm infants receiving red blood cell transfusions during the first month after birth. Multiple randomized controlled trials were conducted to evaluate the effect of using lower versus higher transfusion thresholds based on hemoglobin levels. These trials showed no difference in the primary outcome of neurodevelopmental impairment at 2 years of age between lower and higher thresholds. However, some uncertainties about transfusion thresholds remain. This review elaborates the following: …

Association Between Early Prostacyclin Therapy And Extracorporeal Life Support Use In Patients With Congenital Diaphragmatic Hernia, Akila B Ramaraj, Samuel E Rice-Townsend, Carrie L Foster, Delphine Yung, Emma O Jackson, Ashley H Ebanks, Matthew T Harting, Rebecca A Stark, Congenital Diaphragmatic Hernia Study Group

Faculty, Staff and Student Publications

IMPORTANCE: Prostacyclin (PGI2) is a therapeutic option to treat congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension in neonates. Its use may decrease the need for extracorporeal life support (ECLS).

OBJECTIVE: To evaluate the association of early PGI2 therapy with ECLS use and outcomes among patients with CDH.

DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study from the CDH Study Group (CDHSG) registry of patients born from January 2007 to December 2019. Patients were from 88 different tertiary pediatric referral centers worldwide that contributed data to the CDHSG. Patients were included in the study if they were admitted within the first …

Preterm Birth Alters The Feeding-Induced Activation Of Akt Signaling In The Muscle Of Neonatal Piglets, Agus Suryawan, Marko Rudar, Jane K Naberhuis, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Postnatal lean mass accretion is commonly reduced in preterm infants. This study investigated mechanisms involved in the blunted feeding-induced activation of Akt in the skeletal muscle of preterm pigs that contributes to lower protein synthesis rates.

METHODS: On day 3 following cesarean section, preterm and term piglets were fasted or fed an enteral meal. Activation of Akt signaling pathways in skeletal muscle was determined.

RESULTS: Akt1 and Akt2, but not Akt3, phosphorylation were lower in the skeletal muscle of preterm than in term pigs (P < 0.05). Activation of Akt-positive regulators, PDK1 and mTORC2, but not FAK, were lower in preterm than in term (P < 0.05). The formation of Akt complexes with GAPDH and Hsp90 and the abundance of Ubl4A were lower in preterm than in term (P < 0.05). The abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN and IP6K1, were higher in preterm than in term pigs (P < 0.05). PP2A activation was inhibited by feeding in term but not in preterm pigs (P < 0.05).

CONCLUSIONS: Our results suggest that preterm birth impairs regulatory components involved in Akt activation, …

Videolaryngoscopy Versus Direct Laryngoscopy For Tracheal Intubation In Neonates, Krithika Lingappan, Nicole Neveln, Jennifer L Arnold, Caraciolo J Fernandes, Mohan Pammi

Faculty, Staff and Students Publications

BACKGROUND: Establishment of a secure airway is a critical part of neonatal resuscitation in the delivery room and the neonatal intensive care unit. Videolaryngoscopy has the potential to facilitate successful endotracheal intubation, and decrease adverse consequences of a delay in airway stabilization. Videolaryngoscopy may enhance visualization of the glottis and intubation success in neonates. This is an update of a review first published in 2015, and updated in 2018.

OBJECTIVES: To determine the effectiveness and safety of videolaryngoscopy compared to direct laryngoscopy in decreasing the time and attempts required for endotracheal intubation and increasing the success rate on first intubation …

Heterogeneity Of Treatment Effects Of Hydrocortisone By Risk Of Bronchopulmonary Dysplasia Or Death Among Extremely Preterm Infants In The National Institute Of Child Health And Human Development Neonatal Research Network Trial: A Secondary Analysis Of A Randomized Clinical Trial, Samuel J Gentle, Matthew A Rysavy, Lei Li, Matthew M Laughon, Ravi M Patel, Erik A Jensen, Susan Hintz, Namasivayam Ambalavanan, Waldemar A Carlo, Kristi Watterberg, National Institute Of Child Health And Human Development Neonatal Research Network

Faculty, Staff and Student Publications

IMPORTANCE: Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death.

OBJECTIVE: To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death.

DESIGN, SETTING, AND PARTICIPANTS: …

Assessment Of Corticosteroid Therapy And Death Or Disability According To Pretreatment Risk Of Death Or Bronchopulmonary Dysplasia In Extremely Preterm Infants, Erik A Jensen, Laura Elizabeth Wiener, Matthew A Rysavy, Kevin C Dysart, Marie G Gantz, Eric C Eichenwald, Rachel G Greenberg, Heidi M Harmon, Matthew M Laughon, Kristi L Watterberg, Michele C Walsh, Bradley A Yoder, Scott A Lorch, Sara B Demauro

Faculty, Staff and Student Publications

IMPORTANCE: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended.

OBJECTIVE: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants.

DESIGN, SETTING, AND …

Assessment Of Psychosocial And Neonatal Risk Factors For Trajectories Of Behavioral Dysregulation Among Young Children From 18 To 72 Months Of Age., Julie A. Hofheimer, Monica Mcgrath, Rashelle Musci, Guojing Wu, Sarah Polk, Courtney K. Blackwell, Annemarie Stroustrup, Robert D. Annett, Judy Aschner, Brian S. Carter, Jennifer Check, Elisabeth Conradt, Lisa A. Croen, Anne L. Dunlop, Amy J. Elliott, Andrew Law, Leslie D. Leve, Jenae M. Neiderhiser, T Michael O'Shea, Amy L. Salisbury, Sheela Sathyanarayana, Rachana Singh, Lynne M. Smith, Andréa Aguiar, Jyoti Angal, Hannah Carliner, Cindy Mcevoy, Steven J. Ondersma, Barry Lester, Program Collaborators For Environmental Influences On Child Health Outcomes

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Emotional and behavioral dysregulation during early childhood are associated with severe psychiatric, behavioral, and cognitive disorders through adulthood. Identifying the earliest antecedents of persisting emotional and behavioral dysregulation can inform risk detection practices and targeted interventions to promote adaptive developmental trajectories among at-risk children.

OBJECTIVE: To characterize children's emotional and behavioral regulation trajectories and examine risk factors associated with persisting dysregulation across early childhood.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined data from 20 United States cohorts participating in Environmental influences on Child Health Outcomes, which included 3934 mother-child pairs (singleton births) from 1990 to 2019. Statistical analysis …

Necrotizing Enterocolitis In Premature Infants-A Defect In The Brakes? Evidence From Clinical And Animal Studies., Venkatesh Sampath, Maribel Martinez, Michael Caplan, Mark A. Underwood, Alain Cuna

Manuscripts, Articles, Book Chapters and Other Papers

A key aspect of postnatal intestinal adaptation is the establishment of symbiotic relationships with co-evolved gut microbiota. Necrotizing enterocolitis (NEC) is the most severe disease arising from failure in postnatal gut adaptation in premature infants. Although pathological activation of intestinal Toll-like receptors (TLRs) is believed to underpin NEC pathogenesis, the mechanisms are incompletely understood. We postulate that unregulated aberrant TLR activation in NEC arises from a failure in intestinal-specific mechanisms that tamponade TLR signaling (the brakes). In this review, we discussed the human and animal studies that elucidate the developmental mechanisms inhibiting TLR signaling in the postnatal intestine (establishing the …

Incidence Rates Of Medically Attended Covid-19 In Infants Less Than 6 Months Of Age, Isabel Griffin, Stephanie A Irving, Carmen Sofia Arriola, Angela P Campbell, De-Kun Li, Fatimah S Dawood, Caroline Doughty-Skierski, Jeannette R Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Mary Juergens, Venkatesh Kancharla, Allison L Naleway, Gabriella Newes-Adeyi, Erin Nicholson, Roxana Odouli, Lawrence Reichle, Mo Sanyang, Kate Woodworth, Flor M Munoz

Faculty, Staff and Students Publications

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age.

METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test …

Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation In Preterm Pigs, Line I Christiansen, Bo Holmqvist, Xiaoyu Pan, Kristine Holgersen, Sandy E H Lindholm, Nicole L Henriksen, Douglas G Burrin, David Ley, Thomas Thymann, Per Torp Sangild, Stanislava Pankratova

Faculty, Staff and Students Publications

Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was …

A National, Electronic Health Record-Based Study Of Perinatal Hemorrhagic And Ischemic Stroke, Stuart Fraser, Samantha M Levy, Yashar Talebi, Sean I Savitz, Alicia Zha, Gen Zhu, Hulin Wu

Faculty, Staff and Student Publications

BACKGROUND: Perinatal stroke occurs in approximately 1 in 1100 live births. Large electronic health record (EHR) data can provide information on exposures associated with perinatal stroke in a larger number of patients than is achievable through traditional clinical studies. The objective of this study is to assess prevalence and odds ratios of known and theorized comorbidities with perinatal ischemic and hemorrhagic stroke.

METHODS: The data for patients aged 0-28 days with a diagnosis of either ischemic or hemorrhagic stroke were extracted from the Cerner Health Facts Electronic Medical Record (EMR) database. Incidence of birth demographics and perinatal complications were recorded. …

Fibroblast Growth Factor 19 Secretion And Function In Perinatal Development, Caitlin Vonderohe, Gregory Guthrie, Douglas G Burrin

Faculty, Staff and Students Publications

Limited work has focused on fibroblast growth factor-19 (FGF19) secretion and function in the perinatal period. FGF19 is a potent growth factor that coordinates development of the brain, eye, inner ear, and skeletal system in the embryo, but after birth, FGF19 transitions to be an endocrine regulator of the classic pathway of hepatic bile acid synthesis. FGF19 has emerged as a mediator of metabolism and bile acid synthesis in aged animals and adults in the context of liver disease and metabolic dysfunction. FGF19 has also been shown to have systemic insulin-sensitizing and skeletal muscle hypertrophic effects when induced or supplemented …

Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Testing And Detection During Peripartum Hospitalizations Among A Multicenter Cohort Of Pregnant Persons: March 2020-February 2021, Miranda J Delahoy, Flor Munoz, De-Kun Li, Carmen Sofia Arriola, Nanette Lee Bond, Michael Daugherty, Jeannette Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Stephanie A Irving, Mary Juergens, Venkatesh Kancharla, Mara Greenberg, Roxana Odouli, Gabriella Newes-Adeyi, Erin G Nicholson, Lawrence Reichle, Momodou Sanyang, Margaret Snead, Fatimah S Dawood, Allison L Naleway

Faculty, Staff and Students Publications

BACKGROUND: Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden.

METHODS: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing …

Acoustic Cry Characteristics In Preterm Infants And Developmental And Behavioral Outcomes At 2 Years Of Age., Andrew W. Manigault, Stephen J. Sheinkopf, Brian S. Carter, Jennifer Check, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Michael O'Shea, Steven Pastyrnak, Lynne M. Smith, Todd M. Everson, Carmen J. Marsit, Lynne M. Dansereau, Sheri A. Dellagrotta, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Acoustic cry characteristics have been associated with severe medical problems in newborns. However, little is known about the utility of neonatal acoustic cry characteristics in the prediction of long-term outcomes of very preterm infants.

OBJECTIVES: To evaluate whether acoustic characteristics of infant cry at neonatal intensive care unit (NICU) discharge are associated with behavioral and developmental outcomes at age 2 years in infants born very preterm.

DESIGN, SETTING, AND PARTICIPANTS: Infants born less than 30 weeks postmenstrual age (PMA) were enrolled from April 2014 through June 2016 as part of a multicenter (9 US university affiliated NICUs) cohort study …

Risk Stratification By Percent Liver Herniation In Congenital Diaphragmatic Hernia, Oluyinka O Olutoye, Steven C Mehl, Anoosha Moturu, Rowland W Pettit, Ryan D Coleman, Adam M Vogel, Timothy C Lee, Sundeep G Keswani, Alice King

Faculty, Staff and Students Publications

INTRODUCTION: Congenital diaphragmatic hernia is associated with pulmonary hypoplasia, pulmonary hypertension, and significant neonatal morbidity. Although intrathoracic liver herniation (LH) >20% is associated with adverse outcomes, the relationship between LH

METHODS: A single-center retrospective cohort study was performed from 2011 to 2020 of 80 fetuses with left-sided congenital diaphragmatic hernia that were delivered and repaired at our institution. Perinatal, perioperative, and postoperative data were collected. We evaluated the association of %LH with outcomes as a stratified ordinal variable (0%-10% LH, 10%-19% LH, and >20% LH) and as a continuous variable. Data were analyzed by analysis of variance with Bonferroni post …

Lumasiran For Advanced Primary Hyperoxaluria Type 1: Phase 3 Illuminate-C Trial, Mini Michael, Jaap W Groothoff, Hadas Shasha-Lavsky, John C Lieske, Yaacov Frishberg, Eva Simkova, Anne-Laure Sellier-Leclerc, Arnaud Devresse, Fitsum Guebre-Egziabher, Sevcan A Bakkaloglu, Chebl Mourani, Rola Saqan, Richard Singer, Richard Willey, Bahru Habtemariam, John M Gansner, Ishir Bhan, Tracy Mcgregor, Daniella Magen

Faculty, Staff and Students Publications

Rationale & objective: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease.

Study design: Phase 3, open-label, single-arm trial.

Setting & participants: Multinational study; enrolled patients with PH1 of all ages, estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (if age ≥12 months) or increased serum creatinine level (if age < 12 months), and POx ≥20 μmol/L at screening, including patients with or without systemic oxalosis.

Intervention: Lumasiran administered subcutaneously; 3 monthly doses followed by monthly or quarterly weight-based dosing.

Outcome: Primary end point: percent change in POx …

Regulation Of Skeletal Muscle Protein Synthesis In The Preterm Pig By Intermittent Leucine Pulses During Continuous Parenteral Feeding, 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: Extrauterine growth restriction is a common complication of preterm birth. Leucine (Leu) is an agonist for the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway that regulates translation initiation and protein synthesis in skeletal muscle. Previously, we showed that intermittent intravenous pulses of Leu to neonatal pigs born at term receiving continuous enteral nutrition increases muscle protein synthesis and lean mass accretion. Our objective was to determine the impact of intermittent intravenous pulses of Leu on muscle protein anabolism in preterm neonatal pigs administered continuous parenteral nutrition.

METHODS: Following preterm delivery (on day 105 of 115 gestation), …

Fecal Elastase In Preterm Infants To Predict Growth Outcomes, Lindsay F Holzapfel, Amy B Hair, Geoffrey A Preidis, Tripti Halder, Heeju Yang, Jana P Unger, Steven Freedman, Camilia R Martin

Faculty, Staff and Student Publications

OBJECTIVES: Preterm infants are born functionally pancreatic insufficient with decreased pancreatic production of lipase and proteases. Developmental pancreatic insufficiency (PI) may contribute to reduced nutrient absorption and growth failure. We sought to determine longitudinal fecal elastase (ELA1) levels in a cohort of preterm infants and whether levels are associated with growth outcomes.

METHODS: Prospective observational study of 30 infants 24-34 weeks gestational age and birth weight ≤1250 g fed the exclusive human milk diet, consisting of human milk with human milk-based fortifier. ELA1 was quantified by ELISA during the first 2 weeks of life [Early; 7.5 ± 1.8 days of …

Oxygenation Index In The First Three Weeks Of Life Is A Predictor Of Bronchopulmonary Dysplasia Grade In Very Preterm Infants., Fu-Sheng Chou, Rebekah M. Leigh, Srinandini S. Rao, Arvind Narang, Hung-Wen Yeh

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The new bronchopulmonary dysplasia (BPD) grading system was developed based on its correlation with long-term respiratory and neurodevelopmental outcomes and may provide better personalized prognostication. Identifying early-life predictors for accurate BPD grade prediction may allow interventions to be tailored to individual needs. This study aimed to assess whether oxygenation index (OI) dynamics in the first three weeks of life are a predictor of BPD grade.

METHODS: A single-center retrospective study was performed. Generalized additive mixed modeling was used to model OI trajectories for each BPD grade subgroup. A multinomial regression model was then developed to quantify the association between …