Virtual Poster Session for Michigan Medicine Pediatric Research Symposium - 2022
Michigan Medicine - Department of Pediatrics

Michigan Medicine Pediatric Research Symposium - 2022

University of Michigan, Department of Pediatrics

Welcome to the MM Department of Pediatrics 'Research Day' highlighting research in pediatric/children's health medicine at the University of Michigan.   

Symposium (virtual) Activities:


8-9:00 AM  "Preparing for the next 50 years after the time of COVID"

Pediatric Research Symposium/The Annual Valerie Opipari Endowed Lecture

Leslie R. Walker-Harding, MD, FAAP, FSAHM
University of Washington, Seattle Children's Hospital


12-1:00pm VIRTUAL POSTER SESSION (you are here)

This virtual poster session, which begins at 12:00 Noon, features work by students, residents, fellows, staff, and faculty.  The posters/abstracts are numbered and categorized in tracks (basic science, clinical investigation, health services research, and quality improvement, medical education).  To attend a virtual poster discussion, click on the 'chat' button during the poster session (12-1pm, May 24).  A few posters feature a pre-recorded video presentation.

Abstract List by #                    Abstract List by author


1-3:00pm PLATFORM/ORAL PRESENTATIONS

 schedule of talks

Join Zoom Meeting:  https://umich.zoom.us/j/98914121266



More info: https://medicine.umich.edu/dept/pediatrics/research/annual-research-symposium

Filter displayed posters (69 tags)

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Show Posters:

Tracks

Basic Science Research (18)
Clinical Investigation/Research (31)
Health Services Research (12)
Quality Improvement & Education (16)

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01: Airway Bacterial Community Composition in Persons with Advanced Cystic Fibrosis Lung Disease

Christina S. Thornton1, Lisa A. Carmody1, Linda M. Kalikin1, Kristopher Opron2, Richard H. Simon2, Lindsay J. Caverly1 and John J. LiPuma1.

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Abstract
Background: Advanced lung disease in people with cystic fibrosis (pwCF) has been associated with airway bacterial communities that are dominated by a single pathogen, most often Pseudomonas, Staphylococcus, Burkholderia or Achromobacter. However, the degree to which such canonical pathogens dominate airway communities and how this relates to disease progression and clinical outcomes are unclear.

Objectives: We investigated the structure of airway bacterial communities in 190 pwCF with advanced lung disease with particular attention to the prevalence and relative abundance of bacteria that dominate airway communities and the associations these community structures may have with lung function.

Methods: We sequenced the bacterial 16S rRNA from sputum of 190 pwCF from the University of Michigan with advanced lung disease (percent predicted forced expiratory volume in 1 second (ppFEV1) <40%) to determine microbiome composition, prevalence, and relative abundance of dominant taxa (defined as the most abundant genus with at least twice the abundance of the second most abundant genus). Illumina MiSeq paired-end sequencing of the 16S rRNA V4 region was used to evaluate the airway microbiome. Statistical analyses were preformed using R v.4.1.1.

Results: Bacterial communities from 115 (60%) of 190 pwCF were characterized by low diversity and a dominant taxon. In most (90%), the dominant taxon was a canonical CF pathogen: Pseudomonas, Staphylococcus, Achromobacter, Stenotrophomonas or Burkholderia. Quantitative measures of bacterial load demonstrated no significant differences between advanced ppFEV1 groups dominant genera. Multivariable analysis (adjusted R2=0.282, F=28.9, p<0.0005) demonstrated increasing BMI, higher richness, highest relative abundance with MSSA or other taxon correlating with greater lung function. Conversely, higher dominance ratio, increasing number of antibiotics, higher relative abundance of the most abundant genera, and presence of exacerbation at time of sample collection was negatively correlated with lung function. PwCF with a low diversity community and dominant taxon had reduced lung transplant-free survival compared to those without (median survival of 1.6 yrs. vs 2.9 yrs.). Amongst dominant genera, those with Burkholderia had the lowest median lung transplant-free survival (0.95 years).

Conclusions: Although airway bacterial communities of most pwCF with advanced lung disease were characterized by the presence of a dominant taxon, a large minority (40%) were not. Most often, canonical CF pathogens dominated communities, but other genera were occasionally dominant. Higher relative abundance of dominant taxa was associated with adverse clinical outcomes. A better understanding of the antecedents of communities characterized by low diversity and the presence of a dominant species – and their impact on disease trajectory - may provide avenues to devise improved management strategies.
Presented by
Christina Thornton
Institution
1Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Hashtags
#microbiome #cysticfibrosis #AWARD #PlatformPresentation

02: ETV6 DEFICIENCY AND MICROSATELLITE ENHANCERS DRIVE TRANSCRIPTIONAL DYSREGULATION IN B-LYMPHOBLASTIC LEUKEMIA

Joshua W. Goldman1, Rohan Kodgule2, Alexander C. Monovich2, Travis Saari2, Cody N. Hall2, Niharika Rajesh2, Juhi Gupta2, Athalee R. Aguilar2, Noah Brown2, Mark Y. Chiang3, Marcin P. Cieslik2, Russell J. H. Ryan2

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Abstract
Background: Subtypes of B-lymphoblastic leukemia (B-ALL) are defined by unique genetic aberrations and gene expression programs. ETV6-RUNX1+ (E-R+) B-ALL, a common pediatric subtype, shares a gene activation signature with “ETV6-RUNX1-like” (E-R-like) B-ALL that lacks the E-R fusion gene. Both E-R+ and E-R-like B-ALL show frequent inactivating mutations or deletions of ETV6, which encodes an ETS family transcriptional repressor which has high affinity for the core binding motif GGAA/T. The mechanism by which ETV6 loss of function contributes to oncogenic gene expression programs has remained elusive.

Objectives: We sought to identify and functionally characterize cancer-specific regulatory elements that contribute to leukemogenesis in ETV6-RUNX1+ B-ALL.

Methods: We performed k-means clustering and motif analysis on H3K27ac ChIP-Seq and ATAC-Seq data from 26 B-cell cancer cell lines. Lentiviral transgenes were used to re-express wild-type or mutant ETV6 in ETV6-deficient B-ALL. CRISPR-interference (CRISPRi) was used for epigenetic silencing of GGAA microsatellite enhancers and to repress ERG gene expression. ChIP-Seq was used to map genome-wide ERG and ETV6 binding sites. qPCR and RNA-Seq were used to profile transcriptional changes due to ERG, ETV6, and GGAA repeat perturbation.

Results: Motif analysis identified strong enrichment for tandem repeats of the sequence “GGAA” in enhancers that were exclusively acetylated in four E-R+ B-ALL cell lines and the E-R-like cell line MUTZ5. Repeats with ≥6 tandem copies of “GGAA” were selectively acetylated and accessible in H3K27ac ChIP-Seq and ATAC-Seq datasets from primary patient samples of E-R+ B-ALL but not from other genetic subtypes that lack ETV6 aberrations. Re-expression of ETV6 in ETV6-deficient, E-R+ B-ALL cells led to significant growth inhibition. Restored ETV6 bound extensively to GGAA repeats, repressed repeat enhancer acetylation, and repressed expression of adjacent E-R+ signature genes. CRISPRi targeting of six GGAA repeat enhancers led to significant downregulation of their associated E-R+ signature genes, including EPOR and PIK3C3. GGAA repeat enhancers are a known driver of Ewing sarcoma, where they are activated by oncogenic fusions of the ETS activators FLI1 or ERG. Use of CRISPRi to knock down ERG, but not FLI1, led to significant downregulation of E-R+ signature genes in B-ALL. ChIP-Seq showed that the ERG binds nearly all active GGAA repeat enhancers in three ETV6-deficient B-ALL cell lines, but not in ETV6-intact B-ALL.

Conclusions: GGAA repeat enhancers, sustained by ETV6 deficiency and strong ERG expression, regulate the unique gene expression program in E-R+ B-ALL and other ETV6-inactivated B-ALL. Our findings may have crucial implications for E-R+ B-ALL modeling, as most GGAA repeats are not conserved between mice and humans. Mechanisms that activate leukemia-specific repeat enhancers may represent appealing targets for future therapeutic development.
Presented by
Joshua Goldman
Institution
1Division of Pediatric Hematology/Oncology, 2Department of Pathology, 3Division of Hematology/Oncology
Hashtags
#AWARD #PlatformPresentation
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Available May 24 12-1pm

03: IMMUNOPROTEASOME ACTIVITY IS REQUIRED FOR HOST DEFENSE AGAINST MURINE CORONAVIRUS RESPIRATORY INFECTION

Xiaofeng Zhou,1 Jacob C. Steigmann,2 Bethany B. Moore,1 and Jason B. Weinberg1,2

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Abstract
Background: Exuberant inflammatory responses contribute to multi-organ damage and poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The immunoproteasome (IP) is an IFN--inducible component of the ubiquitin-proteasome system with increased efficiency in generating MHC class I (MHC-I) epitopes for recognition by CD8 T cells. This contributes to the breadth and diversity of viral epitopes generated during infection. IP activity also affects multiple other aspects of T and B cell, macrophage, and dendritic cell (DC) function, including production of antiviral and pro-inflammatory cytokines. While the IP influences multiple aspects of innate and adaptive immune function and inflammation, no information is available regarding specific contributions of IP activity to the pathogenesis of SARS-CoV-2 or other CoV.

Objective: We used murine hepatitis virus strain 1 (MHV-1), a murine coronavirus, to test the hypothesis that increased IP activity during coronavirus infection drives immunopathology and manifestations of disease.

Methods: We infected susceptible C3H.HeJ mice intranasally with MHV-1. Mice were treated with ONX-0914 (ONX), a specific inhibitor of the β5i IP subunit, or vehicle every other day beginning on the day of infection. We monitored weight loss and survival following infection and harvested lungs and livers at multiple time points. We used RT-qPCR and Western blot to evaluate IP subunit expression. RT-qPCR was used to assay viral load and virus-induced cytokine expression. Recruitment of immune cells to the lungs was evaluated by flow cytometry. Accumulation of ubiquitinated protein in organs was evaluated using Western blot.

Results: MHV-1 infection upregulated expression of IFN- and IP subunits in lungs and livers. Viral replication was slightly higher in lungs and livers of ONX-treated mice at early time points, but IP inhibition did not prevent clearance of virus. However, IP inhibition significantly enhanced virus-induced weight loss and mortality during late stages of infection. Pharmacologic inhibition of IP activity with ONX suppressed lung expression of pro-inflammatory cytokines such as IL 17A, TNF-, and IL-1β but had no effect on IFN-β expression. IP inhibition reduced recruitment to the lungs of CD4 T cells, CD8 T cells, monocyte-derived alveolar macrophages, and type 1 conventional dendritic cells. IP inhibition had mixed effects in the liver, suppressing IL-17A expression, enhancing TNF  expression, but not affecting IFN-β or IL-1β expression. Lastly, IP inhibition enhanced accumulation of ubiquitinated protein in infected mice, particularly in livers, at late times post infection.

Conclusions: Our results indicate that the IP is vital for host defense against MHV-1 respiratory infection. IP activity contributed to appropriate leukocyte recruitment and expression of pro-inflammatory cytokines, consistent with our hypothesis. However, IP inhibition enhanced, rather than reduced, manifestations of disease without increasing virus replication. We surmise that inhibition of other IP functions, such as degradation of poly-ubiquitinated and oxidant-damaged proteins that accumulate during infection, enhances manifestations of disease caused by acute MHV-1 infection.
Presented by
Jason Weinberg
Institution
1Department of Microbiology & Immunology and 2Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Michigan, Ann Arbor, MI
Hashtags
#coronavirus #virology #inflammation #immunoproteasome #immunology
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Available May 24 12-1pm

04: CHD7, the causative gene for CHARGE syndrome, represses the transcription factor LHX1 to promote inner ear development

Jennifer M Skidmore, Anna M Graf, Jelka Cimerman, and Donna M Martin

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Abstract
Background: Loss of the chromatin remodeler CHD7 results in CHARGE syndrome, a multiple congenital anomaly disorder. Hallmark features of CHARGE syndrome include ocular coloboma, heart defects, atresia of the choanae, retardation of growth and development, genital abnormalities, and ear abnormalities including external ear malformations, deafness, and vestibular dysfunction. Mice that are heterozygous for Chd7 null alleles are an excellent model for CHARGE syndrome, as many of the same tissues are affected, including the ear. Chd7Gt/+ mice exhibit highly penetrant malformations of the lateral and posterior semicircular canals that can be detected as early as embryonic day 12.5. The mechanisms by which CHD7 promotes normal inner ear development are not well understood. Objective: Our goal is to understand the unique contributions of CHD7 to inner ear development. Design/Methods: Using a mouse model for CHARGE Syndrome (Chd7Gt/+), we utilized genetic crosses to identify specific contributions of Chd7 and Lhx1 to inner ear development. To identify targets of Chd7, we compared RNA-sequencing data from otocysts microdissected from Chd7+/+ and Chd7Gt/+ E10.5 embryos. We also performed immunohistochemistry and paint-fills on wild type and mutant embryonic inner ears. Results: We identified 164 downregulated genes and 43 upregulated genes in E10.5 Chd7Gt/+ otocysts compared to wild type controls. The gene Lhx1, encoding a LIM homeodomain transcription factor, was upregulated 4-fold in Chd7gt/+ E10.5 otocysts. Immunostaining showed LHX1 in the caudal E10.5 wild type otocyst and ectopic LHX1 in the Chd7Gt/Gt ventromedial otocyst. We next examined inner ears from E14.5 Chd7Gt/+;Lhx1+/TLZ embryos by paint-fill and found that Chd7Gt/+;Lhx1+/TLZ ears exhibited lateral semicircular canal defects similar to those in Chd7Gt/+ mice. Conclusions: Lhx1 is expressed in the caudal otocyst and is upregulated ventromedially with loss of Chd7. Despite this increased Lhx1 expression, loss of a single allele of Lhx1 is not sufficient to prevent the inner ear malformations in Chd7Gt/+ mice. Future experiments will examine whether two copy loss of Lhx1 in the inner ear is sufficient to rescue Chd7Gt/+ semicircular canal defects. These studies help establish molecular genetic regulatory networks critical for inner ear development in normal and disease states.
Presented by
Jennifer Skidmore
Institution
Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, MI
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Available May 24 12-1pm

05: Methods and Strategies to Modulate Expression of SCN1A for treatment of Dravet Syndrome

Jordan Safran*, Anna Loughman*, Grace Lin, Shivanshi Vaid, Louis T. Dang (*These authors contributed equally to this work.)

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Abstract
Background: Dravet Syndrome (DS) is a pediatric epilepsy primarily caused by a heterozygous loss-of-function mutation leading to haploinsufficiency of SCN1A, the gene that encodes for voltage-gated sodium channel NaV1.1. Individuals with DS have cognitive and motor impairment, severe seizures, and a high risk of sudden death. Anti-seizure medications can help alleviate seizures but often seizures persist despite treatment. An ideal therapy would target the underlying cause of DS in order to address the cognitive and motoric symptoms of the disease in addition to the seizures. One therapeutic strategy that addresses the underlying cause of DS is to boost expression from the non-mutated allele of SCN1A to compensate for the lack of expression from the mutated allele.

Objective: The SCN1A transcript has multiple upstream open reading frames (uORFs), which begin with “false” upstream AUG (uAUG) start codons that are 5’ of the primary AUG (pAUG) start codon. The presence of uAUGs can compete with the pAUGs for ribosomal translation, and this can result in decreased efficiency of translation from the pAUG. We hypothesize that targeting uORFs with antisense oligonucleotides (ASOs) in SCN1A will result in increased expression of NaV1.1.

Methods: We first constructed luciferase reporter plasmids that contained the uORFs and the initial coding sequence of SCN1A to quantify translation of the primary open reading frame (pORF). We disrupted the uORFs in our mutant plasmid by mutating the uAUGs of this reporter plasmid. The mutant and wild-type plasmids were used for luciferase enzyme assays after transfecting them into HEK293 cells or subjecting them to in vitro transcription and translation reactions. We designed ASOs to bind the three most proximal uORFs to the pORF and tested their effect on luciferase activity.

Results: When the four uAUGs most proximal to the pAUG were mutated, there was a 6.9-fold increase in luciferase expression in transfected HEK293 cells (p<0.0001). Individually mutating either of the two uAUGs most proximal to the pAUG increased luciferase activity by 1.5-fold (p<0.001). Treatment with individual and combinations of ASOs targeting the 4 uAUGs did not significantly increase luciferase activity in vitro.

Conclusions: The presence of uORFs interferes with translation from the pORF in SCN1A, and mutating the uAUGs increased pORF translation efficiency. This suggests that targeting uORFs in SCN1A is a viable therapeutic strategy in DS. Treatment with ASOs targeted to the uAUGs did not increase luciferase activity, leaving room for design optimization. The next iteration of this experiment in our lab will utilize an induced pluripotent stem cell (iPSC) line with a tag on the NaV1.1 protein to rapidly determine the quantity of NaV1.1 produced using luciferase assays.
Presented by
Anna Loughman
Institution
Department of Pediatrics, Pediatric Neurology, Michigan Medicine
Hashtags
#HonorableMention #FeaturedPoster
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Available May 24 12-1pm

06: RHINOVIRUS-A1B DECREASES CORONAVIRUS NL63 REPLICATION AND INFLAMMATION IN HUMAN ACE2-EXPRESSING MICE.

J. Kelley Bentley, Haley A. Breckenridge, Jordan E. Kreger, Shilpi Singh, Adam M. Goldsmith, Carey N. Lumeng, and Marc B. Hershenson.

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Abstract
Introduction: SARS-CoV2 produces illness ranging from asymptomatic to acute respiratory failure. One disease factor is the host interferon response. Data suggest SARS-CoV2 pathology is modulated by previous respiratory viral infections. Objectives: We hypothesized rhinovirus-A1B infection modulates the response to coronavirus NL63 (HCoV-NL63), an α-coronavirus using the ACE2 receptor like SARS-CoV2. Methods: HCoV-NL63 (BEI Resources) was propagated in LLC-MK2 cells or HeLa cells stably expressing human ACE2. RV-A1B (ATCC) was grown in HeLa-H1 cells. Adult (6-8 week) wild-type (C57BL6/J) mice or hACE2-expressing (B6.Cg-Tg(K18-ACE2)2Prlmn/J) mice were infected intranasally with sham cell lysate or 1 x 106 PFU RV-A1B in 50 L PBS. Four days later, mice were infected with HCoV-NL63 (1 x 105 TCID50 units). At 3 or 5 days post-HCoV-NL63 infection, mouse lungs were assessed for HCoV-NL63 vRNA, nsp3 (a non-structural HCoV protein), bronchoalveolar lavage (BAL) cells, histology, and cytokine mRNA expression. Cultured primary human bronchial epithelial cells (HBEs, Lifeline Cell Technology) mucociliary-differentiated on Transwell membranes (Corning) at air-liquid interface for 3-12 wk in PneumaCult medium (StemCell Technologies)were infected with sham HeLa cell lysate or 1 multiplicity of infection (MOI) RV-A1B and treated 48 h later with sham or 0.1 MOI HCoV-NL63. Cells were harvested at 48 h post-NL63 infection and processed for RNA. Results: Three days after HCoV-NL63 infection, HCoV-NL63 copies were significantly higher in hACE2- mice than wild type mice (hACE2 mice, 2791±1593 copies/µg RNA; wild type mice, 16±13 copies/µg RNA (N=4, mean±SEM, p<0.0017, ANOVA). HCoV-NL63-infected hACE2 mice showed increasing levels of vRNA and nsp3 lung protein indicating a replicative infection. Compared to wild-type mice, infection of hACE2 mice with HCOV-NL63 caused perivascular and peribronchial inflammation and increased airway neutrophils and lymphocytes. Compared to sham-exposed hACE2 mice, inoculation of RV-A1B four days before HCoV-NL63 infection decreased HCoV-NL63 copy number. Prior RV-A1B infection significantly reduced BAL neutrophils and lymphocytes. In human bronchial epithelial cells, CoV-NL63 vRNA levels peaked 24-48 h after infection, and prior RV-A1B infection significantly decreased HCoV NL63 replication. Conclusion: HCoV-NL63 causes significant replicative infection in hACE2-expressing mice. Prior infection with RVA1B attenuates HCoV-NL63 viral copy number and inflammation in vivo. Future work will examine the mechanisms underlying this viral interaction.

Supported by National Institutes of Health grants AI120526 and AI155444.
Presented by
John Kelley Bentley
Institution
Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan
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Available May 24 12-1pm

07: HYPERMYELINATION OF CRANIAL NERVE VIII IN A MOUSE MODEL OF CHARGE SYNDROME

K. Elaine Ritter1, Sloane M. Lynch2, Ashley M. Gorris2, Lisa A. Beyer3, Lisa L. Kabara3, Yehoash Raphael3, Donna M. Martin1,4

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Abstract
Background & Objectives: CHARGE syndrome is a multiple anomaly developmental disorder characterized by a variety of sensory deficits, including sensorineural hearing loss. The majority of cases of CHARGE are caused by pathogenic variants in Chromodomain DNA-binding Protein 7 (CHD7), a chromatin remodeler important for the development of neurons and glial cells. The structural substrate for hearing loss is not well understood. Using the Chd7Gt/+ mouse model of CHARGE syndrome, we sought to determine how Chd7 haploinsufficiency affects mature neurons, myelinating Schwann cells, and inner hair cell innervation in the cochlea. Methods: Auditory Brainstem Responses (ABRs) were recorded in adult Chd7+/+ and Chd7Gt/+ animals. Cochleae were sub-dissected and processed for transmission electron microscopy (TEM). TEM images were captured in the apical and basal regions of the spiral ganglion. Myelin thickness and axon diameter were measured using ImageJ. Semi-thin sections of spiral ganglia were imaged for further histological analysis, cell counting, and nerve density quantification. Immunohistochemical staining for hair cell synaptic markers CtBP2 and GluA2 was conducted on 4-week old wild-type and Chd7Gt/+ cochleae, which were imaged by confocal microscopy. Results: Analysis of ABR recordings in Chd7Gt/+ adult animals show elevated ABR thresholds at 4 kHz and 16 kHz, but not at 32 kHz. ABR Wave I peak latency and amplitude in Chd7Gt/+ mice are not significantly different from wild-type controls. Proportions of neurons and glial cells in the spiral ganglion are not significantly different, nor are densities of nerve projections from the spiral ganglion to the organ of Corti. Staining for CtBP2 and GluA2 showed no differences in hair cell synapse formation in Chd7Gt/+ mutant cochleae. However, G-ratio analysis of myelin thickness in peripheral spiral ganglion Type I neuronal projections indicates subtle but statistically significant hypermyelination in Chd7Gt/+ mice. Conclusions: Collectively these results suggest that in the mouse, the inner ear is largely resilient to haploinsufficiency of CHD7, with the exception of myelin sheaths produced by Schwann cells encasing the peripheral aspect of the auditory nerve. Previous studies in Chd7Gt/+ embryos showed substantial neuronal loss in the developing spiral ganglion, and here we found that the inner ear is able to compensate for Chd7 loss by adulthood. There may be other peripheral or central auditory components contributing to sensorineural hearing loss in Chd7Gt/+ mice, and middle ear defects may be the primary source of increased ABR thresholds in this mouse model of CHARGE syndrome. Our work was supported by NIH Grants R01 DC014456 (DM, YR), R01 DC018404 (DM) and T32 DC000011 (KER).
Presented by
Elaine Ritter
Institution
1Division of Genetics, Metabolism, & Genomics Medicine, Department of Pediatrics, University of Michigan Medical School; 2College of Literature, Science and Art, University of Michigan; 3Department of Otolaryngology, Kresge Hearing Research Institute, University of Michigan Medical School; 4Department of Human Genetics, University of Michigan Medical School
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Available May 24 12:00-1:00pm

08: IDENTIFICATION OF SINGLE NUCLEUS RNA TRANSCRIPTS IN BRAIN REGIONS CRITICAL FOR ENERGY HOMEOSTASIS

AG Diamant1, A Rupp2, DP Olson1

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Abstract
Background: One in six children in the USA is obese and the prevalence is increasing. This trend is fueled by myriad societal, economic and environmental factors and is exacerbated by a dearth of effective interventions. The paraventricular nucleus of the hypothalamus (PVH) and the parabrachial nuclei (PBN) in the dorsolateral pons are heterogenous brain regions that contribute to energy homeostasis. Characterizing the molecular signatures of neuronal cell types within the PVH and PBN may suggest important cellular functions and provide new therapeutic targets for obesity. Objective: To identify neuronal subpopulations within the PVH and PBN and to characterize their gene expression. Methods: Bilateral PVH (n=8) and bilateral PBN (n=7) were dissected from mice and the nuclei were isolated from homogenized tissue and purified by flow cytometry. Purified nuclei were submitted to the Advanced Genomics Core for single nucleus RNA sequencing (snRNA-seq). The resulting data were analyzed and visualized using Seurat, an R-based toolkit. Results: ~52,000 PVH nuclei were initially sequenced and ~46,000 remained after quality control. ~32,000 PBN nuclei were initially sequenced and ~30,000 remained after quality control. In both datasets, neurons were successfully identified using well-established neuronal markers. In the PVH dataset, ~27,000 neurons were resolved into 21 subpopulations, two of which strongly expressed Sim1, a well-known marker of the PVH. These two subpopulations were further resolved into distinct cell types, 5 of which had expression patterns consistent with previously known PVH subpopulations. These 5 PVH subpopulations were each characterized by expression of arginine vasopressin, oxytocin, somatostatin, thyrotropin releasing hormone or urocortin-3 (a member of the corticotropin releasing hormone family). In the PBN dataset, ~22,000 neurons were initially resolved into 7 groups of neurons, many of which were enriched with cerebellar markers. After exclusion of the cerebellar neurons, ~6,000 PBN neurons remained and were further resolved into 16 subpopulations. Two of these subpopulations had expression patterns consistent with previously known PBN populations characterized by expression of Calca (the gene encoding calcitonin gene-related peptide) or somatostatin. The remaining 16 PVH subpopulations and 14 PBN subpopulations may represent previously undescribed and functionally distinct groups of neurons. Conclusions: We used snRNA-seq to identify subpopulations of neurons within the PVH and PBN and characterize their gene expression patterns. Our analysis provides potential novel genetic targets for manipulating subgroups of neurons within brain areas already known to be important in energy homeostasis. Characterization of transcripts within these novel neuronal subpopulations may provide additional therapeutic targets for obesity in the future.
Presented by
Aristides Diamant
Institution
1 Department of Pediatrics, University of Michigan, Ann Arbor, MI; 2 Department of Internal Medicine, University of Michigan, Ann Arbor.
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Available May 24 12-1pm

10: SOX2 AND CHD7 COOPERATE TO REGULATE DEVELOPMENT OF THE INNER EAR

Jingxia Gao, Jelka Cimerman, K. Elaine Ritter, Jennifer M. Skidmore, Donna M. Martin

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Abstract
Background: CHD7, encoding Chromodomain-containing Helicase DNA binding protein 7, is highly expressed in the developing ear. Pathogenic variants in CHD7 cause CHARGE (Coloboma, Heart defects, Atresia Choanae, Growth retardation, Genital abnormalities, and Ear abnormalities) syndrome, which features ear malformations. SOX2 (Sex determining region Y-box 2) is one of the earliest genes expressed in neurosensory progenitors within the otic epithelium and continues to be expressed through postnatal stages. SOX2 regulates both sensory and non-sensory development of the inner ear. SOX2 and CHD7 have been shown to physically interact in neural stem cells, but whether Chd7 and Sox2 genes interact functionally, and the consequences of this interaction, remain elusive. Objective: Our goal is to examine inner ear phenotypes in mice with heterozygous deletion of both Sox2 and Chd7 and to determine the underlying mechanisms leading to these phenotypes. Design/Methods: We examined postnatal survival of doubly heterozygous Sox2CreER/+;Chd7Gt/+ mice in comparison to wild type (Sox2+/+;Chd7+/+) and single heterozygous (Sox2CreER/+ or Chd7Gt/+) littermates. To characterize inner ear phenotypes, we measured cochlear length, paint-filled the inner ear labyrinth structure and stained whole-mounted cochlear sensory epithelia with Phalloidin (Actin) or antibodies to MYO7A, Neurofilament, or Prox1. To identify downstream genetic targets of Chd7 and Sox2, we performed bulk RNA sequencing on otocysts microdissected from Sox2+/+;Chd7+/+ , Chd7Gt/+ , Sox2CreER/+ and Sox2CreER/+;Chd7Gt/+ E10.5 embryos. Results: Sox2CreER/+;Chd7Gt/+ mice exhibited earlier postnatal death compared to wild type or single heterozygous mutant littermates. The vestibular system of Sox2CreER/+;Chd7Gt/+ mice showed severe anterior, posterior, and lateral semicircular canal dysplasia along with malformed endolymphatic duct and absent ampullae and utricles. Cochleae from Sox2CreER/+;Chd7Gt/+ mice were significantly shortened and exhibited supernumerary outer hair cells with corresponding supporting cells. Sox2CreER/+ mice also exhibited supernumerary inner hair cells but normal cochlear length. Neither hair cell stereociliary bundle orientation nor cochlear innervation were affected by single or double heterozygous deletion of Sox2 and Chd7. Differential gene expression analysis via RNA sequencing revealed additive effects of CHD7 and SOX2 on gene expression in the E10.5 otocyst. Notably, Dlx1 and Dlx2 expression was significantly down-regulated in doubly heterozygous (Sox2CreER/+;Chd7Gt/+) otocysts. Conclusions: SOX2 and CHD7 functionally interact to regulate development of the inner ear, likely through changes in target gene expression. Ongoing experiments are aimed at determining whether changes in convergent extension, cell proliferation, cell death, or a combination of these mechanisms contribute to the cochlear defects observed with heterozygous deletion of both Sox2 and Chd7.
Presented by
Jingxia Gao
Institution
Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, MI
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Available May 24 12-1pm

11: ZERO-WASTE MOLECULAR DIAGNOSTICS FROM BIOPSY NEEDLE WASH WATER

Jack Wadden1, Vishal John1, Kait Verbal2, Amy Bruzek2, Wajd-Al-Holou2, Jason Heth2, Hugh Garton2 and Carl Koschmann1.

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Abstract
Background: Brain tumors make up a significant proportion of pediatric cancers. Due to their sensitive location, many difficulties exist in providing effective diagnostics and treatments for these patients. In particular, biopsy tissue is precious due to morbidity associated with repeat biopsies, and usually earmarked for clinical diagnostics. We have identified that the water used to wash biopsy needles in-between cores contains excess tumor DNA and cells that can be diagnostically useful. Additional research of tumor DNA and tumor cells recovered from biopsy needle washes provides a potential opportunity for improvement in the diagnosis and treatment for brain tumor patients. Methods: In two cases, surgeons were instructed to save 5-15ml of fluid used to wash biopsy needles. In both cases, small tissue pellets were identified after centrifugation. Isothermal targeted amplification assays targeting the H3K27M histone mutation were applied to both raw wash fluid as well as DNA extracted from the tissue pellet and wash fluid (Qiagen). Resulting amplicons were sequenced using an Oxford Nanopore MinION device and rapid library preparation. Resulting reads were analyzed to identify histone mutations. Results: For both cases, raw wash water as well as a small tissue pellet were recovered from the needle wash. For case 1, 5ul of raw wash water as well as DNA extracted from the pellet was used as input for Loop-mediated Isothermal Amplification (LAMP) assays targeting the H3.1 and H3.3 K27M histone mutations. Sequencing revealed a H3.3 histone mutation present in both tissue pellet and wash water at 28% and 12% variant allele fractions respectively. Variant calls (99.99% CI) were available 1hr5mins after acquisition of material. For case 2, 5ml of wash water was processed using a cell-free DNA extraction kit resulting in ~250ng of DNA. A LAMP assay targeting the H3.3 K27M mutation was performed on extracted DNA from wash water and tissue pellet. Sequencing revealed an H3.3 K27M histone mutation present at 55% (wash water) and 56% (tissue peelet) respectively. These results were corroborated using digital droplet PCR. Ongoing accrual is currently expanding this cohort with multiple monthly procedures. Conclusions: Our results indicate that large amounts of diagnostically useful material is present in biopsy needle wash water, which is usually discarded. We also found that isothermal assays coupled with MinION sequencing can rapidly identify clinically relevant mutations identifying biopsy needle wash water as a first-class diagnostic resource in any cancer.
Presented by
Jack Wadden
Institution
1Department of Pediatrics, 2Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
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#cancer #diagnostics #liquidbiopsy #moleculardiagnostics #biopsy #braintumor #sequencing #nanopore
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Available May 24 12-1pm

12: Epidemiology and clinical outcomes of airway infection with Pseudomonas species other than P. aeruginosa in cystic fibrosis

Nada H Youssef1, MD, Madsen Zimbric1, Lindsay J. Caverly1

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Background: Chronic airway infections with Pseudomonas aeruginosa are significant contributors to morbidity and mortality in people with cystic fibrosis (pwCF). The understanding of epidemiology and clinical outcomes of P. aeruginosa infection has led to recommendations for P. aeruginosa eradication for early infection, and management strategies for chronic infection. These interventions have led to reduced rates of chronic P. aeruginosa infection, and improved outcomes for pwCF. Much less is known about the clinical impact of other Pseudomonas spp. in pwCF, and it is unclear if these infections should be managed similarly to P. aeruginosa. The objective of this study was to determine the epidemiology and outcomes of Pseudomonas spp. other than P. aeruginosa in pwCF. Methods: This was a single center, retrospective study of pwCF with one or more airway cultures positive for a Pseudomonas spp. (other than P. aeruginosa) from 2014-2021. Medical records were reviewed for demographic and clinical data, and descriptive statistics were used. Clinical outcomes over the two-year period following incident Pseudomonas spp. infection were evaluated and included microbiological culture results, changes in lung function, and number of pulmonary exacerbations. Results: We identified 194 airway cultures positive for Pseudomonas spp. other than P. aeruginosa from 135 pwCF. Prevalence of Pseudomonas spp. at our CF center was ~4% of pwCF annually. The median age of incident infection with Pseudomonas spp. was 13.1 years (range 0.2¬–78.6 years). The majority (56%) of the patients were female. 41% were homozygous for F508del, and 41% were heterozygous for F508del. The majority (63%) of cultures positive for Pseudomonas spp. were from oropharyngeal swabs, 36% were from sputum samples, and 1% from bronchoalveolar lavage. P. fluorescens was the most prevalent identified species (36% of cultures), followed by P. putida (24%), P. koreensis (4%), and P. oryzihabitans (4%). 32% of cultures were Pseudomonas spp, not further identified. 18% of patients had multiple positive cultures of at least one Pseudomonas spp, with a median of 2 positive cultures (range 2–8). 29% of patients had cultures positive for more than one Pseudomonas spp. Conclusions: In this single center, retrospective study, Pseudomonas spp. other than P. aeruginosa were low in prevalence rate in pwCF, and P. fluorescens was the species most often identified. Most positive cultures were transient, and did not lead to chronic Pseudomonas spp. infection. Ongoing work in this cohort is evaluating associations between Pseudomonas spp. and other CF pathogens including P. aeruginosa, clinical outcomes including changes in lung function and pulmonary exacerbation rate following Pseudomonas spp. infection, and the potential impact on anti-pseudomonal treatment.
Presented by
Nada Youssef
Institution
1 University of Michigan Medical School, Ann Arbor, MI 48109, USA
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13: THE ACTIVATING NKG2D RECEPTOR MEDIATES NEONATAL LUNG INJURY INDUCED BY CHRONIC EXPOSURE TO BACTERIAL ENDOTOXIN: IMPLICATIONS FOR BRONCHOPULMONARY DYSPLASIA

Cui TX, Zhang YJ, Anderson C, Popova AP,

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Background: In premature infants, airway colonization with gram-negative bacteria is associated with development of bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by impaired alveolarization and dysmorphic vasculature. Inflammation precedes BPD development and persists later during disease progression. We have shown that in immature mice chronic airway exposure to lipopolysaccharide (LPS) increases inflammation and results in hypoalveolarization, reminiscent of human BPD. We also demonstrated LPS increased the IL-17a-producing gamma-delta (γδ) T cells (AJRCCM 2020). The natural-killer group 2, member D (NKG2D) receptor mediates activation and IL-17a production in γδ T cells and other immune cells by binding to cell stress molecules. LPS induces cell stress, DNA damage and increases the expression of NKG2D ligands, including retinoic acid early inducible-1 (Rae-1), murine ULBP-like transcript 1 (MULT-1), and others. We hypothesized that NKG2D mediates neonatal LPS exposure-induced pulmonary immunopathology. Methods: Immature C57BL/6J mice were inoculated with 3ug/10ul LPS from E. coli O26:B6 or 10ul PBS intranasally on day of life 3, 5, 7, and 10. Selected mice were treated with neutralizing antibody against NKG2D or control IgG intraperitoneally. Lung immune cells were assessed by flow cytometry. Whole lung gene expression was analyzed by qPCR. Alveolar growth was assessed by lung morphometry. Results: LPS induced whole lung NKG2D mRNA expression, the mRNA of NKG2D ligands and downstream effectors, including Rae-1, MULT-1, β2-microglobulin, p53, Granzyme B, as well as pro-inflammatory cytokines Il-17a, IFN-γ, IL-1β and Ccl2. NKG2D+ γδ T cells, NK cells, and CD8+ T cells were present in the lungs after LPS. LPS increased per cell NKG2D expression in γδ T cells and NK cells. After repeated LPS exposure, NKG2D+ γδ T cells were the most expanded NKG2D+ population (10 times more than control). LPS stimulated IL-17a and Granzyme B expression in NKG2D+ γδ T while LPS only stimulated Granzyme B but not IL-17a in NKG2D+ NK cells. Anti-NKG2D treatment attenuated the effect of LPS on total γδ T cells, as well as IL-17a+ and Granzyme B+ NKG2D+ γδ T cell numbers. Anti-NKG2D treatment also blocked the effect of LPS on β2-microglobulin, Granzyme B, Il-17a, IFN-γ, IL-1β and Ccl2 mRNA expression. Anti-NKG2D treatment reduced immune cell infiltration and attenuated hypoalveolarization induced by LPS. Finally, tracheal aspirates of premature infants mechanically ventilated for RDS contain Granzyme B+ NKG2D+ cells, mRNA of NKG2D its ligands MHC class-I-related protein A (MICA) and MICB. MICA positively correlates with median FiO2. Conclusions: Our findings demonstrate a central role for activated NKG2D signaling in neonatal LPS-induced lung injury. Future studies will determine the role of individual NKG2D+ cells, NKG2D ligands and effectors in early-life endotoxin-induced pulmonary immunopathology and in BPD. Supported by NIH grant R01 HL140572.
Presented by
Tracy Cui
Institution
Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI.
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Available May 24th 12pm-1pm

14: EXPOSURE TO A REAL-LIFE ENVIRONMENTAL CHEMICAL MIXTURE ALTERS THE METABOLITE PROFILE IN THE PLASMA OF SHEEP: AN UNTARGETED METABOLOMICS STUDY

Thangaraj SV1, Kachman M2, Bellingham M3, Sinclair KD4, Lea R4, Evans NP3 and Padmanabhan V1.

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Background: Everyday humans are exposed to a mixture of endocrine disrupting chemicals (EDCs) believed to promote non-communicable diseases. Adverse health impacts of exposure to individual EDCs is well known but studies on effects of real-world exposures characterized by chronic low doses of a mixture of chemicals are only recently emerging. Biosolids derived from human wastes exemplify both the array and dosage of chemicals humans are exposed to in real life and represents a novel model to investigate the risk posed by EDCs. Prior studies in sheep have shown aberrant reproductive and metabolic phenotypic effects in offsprings, as a result of maternal biosolid exposure. Objective: We hypothesize that EDC-mediated disruption in the maternal metabolic milieu is a potential mediator of aberrant phenotypic outcomes in offsprings in the biosolid-exposure model. Untargeted metabolomics could unravel biomarkers of both exposure and effect by identifying the disrupted endogenous metabolite profile and xenobiotic mixture, respectively. In this study, we aim to identify biosolid exposure-induced maternal metabolic fingerprints that could influence fetal programming. Method: Ewes were grazed on organic fertilizer or biosolid-treated pastures from before mating until parturition. Plasma from blood samples collected on day 90 of the 147-day gestation period, from ewes with singleton pregnancies (Control n=15, Treatment n=15) were analysed by untargeted metabolomics using liquid chromatography-quadrupole time-of-flight mass spectrometry. Metabolites were identified by matching the retention time, mass and isotope profile to authentic standards or metabolome databases using Agilent MassHunter. Results: Principal component analysis and orthogonal projections to latent structure discriminant analysis of the 2301 annotated metabolic features discriminated the metabolomes of control sheep and sheep grazed in biosolid-treated pasture. The key differentially expressed metabolites (DM) identified by variable importance in projection score primarily belonged to the super-class organic acids, fatty acids, benzenoids, glycerophospholipids and organoheterocyclic compounds. These DM are implicated in metabolic pathways including carnitine synthesis, alanine metabolism, glucose alanine cycle, phosphatidyl choline biosynthesis and glutathione metabolism. Some of the top DM are implicated in fetal development - oleamide has growth inhibitory properties and 15-HETrE modulates arachidonic acid metabolism and upregulate PPARγ expression. Conclusion: Our results indicate that biosolid exposure effects alterations in the maternal metabolome which likely contributes to the aberrant phenotypic outcomes reported in offspring of biosolid-exposed mothers. This is the first study to apply metabolomics to validate the effect of real-life EDC exposure in sheep, a translationally relevant precocial model with a developmental trajectory similar to humans.

Presented by
Soundara Viveka, Thangaraj
Institution
1 -Department of Pediatric-Endocrinology, University of Michigan, USA. 2- Metabolomics Core, University of Michigan, USA.
Other Affiliations
3- Institute of Biodiversity Animal Health & Comparative Medicine, University of Glasgow, UK. 4-Schools of Veterinary Medicine and Biosciences, University of Nottingham, UK.
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Available May 24, 12 to 1 p.m.

15: SOX11 AND CHD7 ACT IN THE SAME GENE REGULATORY NETWORK TO PROMOTE INNER EAR DEVELOPMENT

Jelka Cimerman1, Ethan D. Sperry2,5, Ronus Hojjati3, Donald L. Swiderski4, Yehoash Raphael4, and Donna M. Martin1,2,4

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Background: Development of the inner ear depends on a precise spatiotemporal orchestration of gene expression via transcriptional networks in the cell nucleus. SOX11, a SoxC transcription factor of the SRY-related high-mobility-group (HMG) box family, has been implicated in inner ear morphogenesis. In neural stem cells, SOX11 is a genetic target of CHD7, an ATP-dependent chromatin remodeler in which regulates nucleosomes and transcription. Haploinsufficiency of CHD7 results in CHARGE syndrome which presents with hearing loss and balance impairment due to inner ear dysplasia. The specific mechanisms by which loss of CHD7 results in inner ear malformation are not well understood. Since pathogenic variants in either CHD7 or SOX11 have been shown to cause phenotypically similar developmental malformations, we asked whether SOX11 and CHD7 function together in a common genetic regulatory network in the developing otocyst. Objective: We aimed to explore potential molecular genetic pathways of Sox11 and Chd7 in the developing mouse inner ear. Design/Methods: We analyzed Sox11+/+ and Sox11-/- mice for (1) morphological abnormalities using histological studies and paintfill of inner ears from embryonic ages E11.5-E14.5, (2) changes in inner ear gene expression using immunofluorescence in situ hybridization assays and qRT-PCR assay and, (3) cell proliferation and apoptosis using BrdU incorporation and anti-Caspase3, respectively. Results: We observed abnormalities in the lateral and posterior semicircular canals in Sox11-/-, Pax2Cre;Sox11fl/fl, and Chd7Gt/+;Sox11+/- mice. Interestingly, we also observed delayed canal fusion plate formation and increased cell proliferation in Sox11 mutants. Expression of Sox11 was reduced in the otocyst with loss of Chd7, and Bmp4 expression in the presumptive lateral crista ampullaris was reduced with Sox11 loss. Conclusions: Our results indicate a Chd7-Sox11 gene regulatory network that is critical for mouse vestibular system development. Ongoing studies are designed to identify cis-regulatory elements that mediate Sox11 and Chd7 transcriptional regulation in the developing otocyst, with the long-term goal of designing interventions for alleviating vestibular dysfunction in humans.
Presented by
Jelka Cimerman
Institution
Departments of Pediatrics1, Human Genetics2, University of Michigan, Ann Arbor, MI. Otolaryngology – Head and Neck Surgery4, and Medical Scientist Training Program5, University of Michigan, Ann Arbor, MI.
Other Affiliations
Northwestern University Feinberg School of Medicine3, Chicago, IL.
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16: MATERNAL MEDITERRANEAN DIET ADHERENCE DURING BREASTFEEDING IS ASSOCIATED WITH INFANT ADIPOSITY

Aria Grabowski1, Lindsay Ellsworth2, Jacqueline Richardson3, Ana Baylin1,3, Alison Miller4, Ashley Gearhardt5, Katharine Rosenblum6, Julie Lumeng7, and Brigid Gregg8

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Background Human milk is optimal for infants, providing the ideal nutrition to promote infant health. The dynamic composition of human milk is influenced by maternal diet and nutrient stores. The Mediterranean diet (MedDiet) is considered a healthy eating pattern that is associated with better cardiovascular and cognitive health; however, the impact of the MedDiet during lactation on infant outcomes has not been studied.

Objectives (1) Evaluate the relationship between maternal MedDiet adherence and infant growth during lactation. (2) Determine associations between maternal diet and milk composition. (3) Determine associations between milk composition and infant growth.

Methods This study utilized data from the ABC mother-infant dyad cohort, a longitudinal study on maternal feeding practices. Dyads were enrolled at 2 weeks or 2 months of age and followed until 12 months. Mothers completed a validated food frequency questionnaire (FFQ) from which the MedDiet score was calculated, and energy-adjusted nutrient intake was calculated. Expressed human milk samples were collected and macronutrient analysis was completed using mid-infrared transmission spectroscopy (MIRIS Human Milk Analyzer). The following markers were measured for infant growth: weight, length, and flank skinfold thickness (ST) at each visit. Spearman correlations were calculated between maternal diet factors, infant growth, and milk composition. Correlations were then stratified by breastfeeding exclusivity (exclusive or mixed fed) based on breastfeeding intensity ratio calculated by the number of human milk feeds (average per week) divided by the total number of liquid feeds at 2 months. Infants were excluded from analysis if exclusively formula fed.

Results 161 dyads were included in the analysis. Maternal carbohydrate intake was negatively associated with weight-for-age Z score (WAZ) at 2 months (R:-0.14, p=0.08). MedDiet was negatively associated with ST at 2 months (R:-0.18, p=0.03) and 6 months (R:-0.160, p=0.07) and positively associated with WAZ at 2 months (R:0.13, p=0.09). When stratified by exclusively breastfed (n=125) or mixed-fed (n=36), MedDiet is negatively associated in only exclusively breastfed infants for ST at 2 months (R:-0.26, p: 0.005) and 6 months (R:-0.21, p=0.03). Further, at 2 months in exclusively breastfed infants, length-for-age Z score was positively associated with saturated fat intake (R:0.18, p=0.05) and WAZ was negatively associated with carbohydrate intake (R:-0.19, p=0.03). Evaluation of milk composition showed that maternal dietary fat types was negatively associated with milk protein content. There were no significant associations between milk composition and infant growth.

Conclusions Maternal dietary intake is associated with infant growth and human milk composition. Maternal Mediterranean diet adherence is associated with lower infant adiposity at 2 months and 6 months for exclusively breastfed infants.
Presented by
Aria Grabowski
Institution
1. University of Michigan, School of Public Health, Department of Nutritional Sciences, 2. University of Michigan, Department of Pediatrics, Division of Neonatal-Perinatal Medicine 3. University of Michigan, School of Public Health, Department of Epidemiology 4. University of Michigan, School of Public Health, Department of Health Behavior and Health Education 5. University of Michigan, College of Literature Science and the Arts, Department of Psychology 6. University of Michigan, School of Medicine, Department of Psychiatry 7. University of Michigan, Center for Human Growth and Development 8. University of Michigan, Department of Pediatrics, Division of Pediatric Endocrinology
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#humanmilk #infantgrowth #diet #mediterraneandiet
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Available May 24th, 12-1pm

19: Deep Mutagenesis Scan of SERPINC1 to inform variants affecting thrombosis risk.

Christopher Bidlack, Krista Golden, Mary Underwood, and Karl Desch

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Background Venous thromboembolism (VTE) includes both formation of pathogenic thrombi in the deep veins (deep vein thrombosis) and embolization of thrombi to the arterial circulation of the lungs (pulmonary embolism). VTE is a complex genetic disorder with an estimated heritability of 40-60% from family, sibling, and twin studies. Our lab recently conducted an exome sequencing study in ~400 VTE cases and found an excess of rare likely loss of function variants in three anticoagulant genes, PROC, PROS1 and SERPINC1. Antithrombin (AT), encoded by the SERPINC1 gene, is a critical anticoagulant protein that inactivates thrombin and factor Xa (FXa). Homozygosity for SERPINC1 deficiency is lethal, while partial absence leads to an increased risk of VTE. Damaging SERPINC1 variants can be categorized into two major types of antithrombin deficiencies: Type I deficiency due to decreased antithrombin concentrations in the bloodstream (quantitative deficiency), or Type II deficiency due to altered antithrombin function without necessarily affecting quantity (qualitative defects).

Objectives Since AT deficiency is a strong risk factor for VTE, a comprehensive functional database of SERPINC1 variants could guide the interpretation of sequencing results in VTE patients and lead to a better understanding of AT structure and function.

Design/Methods To perform a deep mutational scan, we will transfect the variant SERPINC1 cDNA library into cells bearing the Bxb1-based recombinase “landing pad” system described by Matreyek et al. To identify variants causing AT retention, we will tag our segmented SERPINC1 libraries with eGFP reporter genes (AT-eGFP), and subject our cells to fluorescence-activated cell sorting (FACS) followed by next gen sequencing to identify variants associated with poor AT secretion. To identify variants affecting antithrombin function we will add a transmembrane domain of glycophorin B (GYPB) instead of the c terminal eGFP tag (AT-GYPB). This will allow us to perform antithrombin functional screens using flow cytometry. Specifically, we will treat library cells with thrombin or factor Xa, two canonical ligands of antithrombin, to determine which variants disrupt AT function. Thrombin-Antithrombin (TAT) complex ELISA has confirmed the functionality of our SERPINC1-eGFP construct, and Sanger sequencing has confirmed successful mutagenesis of eight known SERPINC1 variants.

Results and Conclusions We have currently developed AT-eGFP which retains its functional inhibition of thrombin. We are also developing AT-GYPB and validating its ability to form inhibitory complexes. Efforts are underway to separate variants in SERPINC1 associated with poor secretion from reference and other functional variants. Our next steps also involve full library cloning and screens. Any variants found to affect AT secretion or function will be used to make a functional map to find mutational clustering patterns.
Presented by
Christopher Bidlack
Institution
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AIRWAY TUFT/BRUSH CELLS ARE REQUIRED FOR EXAGGERATED TYPE 2 INFLAMMATION AND MUCOUS METAPLASIA IN IMMATURE MICE UNDERGOING HETEROLOGOUS RHINOVIRUS INFECTION.

Haley A. Breckenridge, Mingyuan Han, Yiran Li, Daniel Sawicky, Adam M. Goldsmith, J. Kelley Bentley, Ichiro Matsumoto and Marc B. Hershenson

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Background. Wheezing-associated respiratory infections with rhinovirus (RV) have been associated with asthma development. We previously showed that sequential infection of immature mice with different RV strains induced a state of intensified type 2 eosinophilic inflammation and mucous metaplasia. At mucosal barriers, DCLK1- and TRPM5-expressing tuft/brush cells are the major source of IL-25 and TSLP, which in turn activate type 2 innate lymphoid cells. Objective. We wanted to examine the effect of viral infection on tuft/brush cell number and the requirement of these cells for innate cytokine expression, type 2 inflammation and mucous metaplasia in immature mice undergoing heterologous RV infection. Methods. Wild-type C57BL/6J and knockout mice deficient in the transcription factor SKN-1a, which is required for development of DCLK1- and TRPM5-expressing chemosensory cells, were treated as follows: (1) sham on day 6 of life plus sham on day 13 of life, (2) RV-A1B on day 6 plus sham on day 13, (3) sham on day 6 plus RV-A2 on day 13, and (4) RV-A1B on day 6 plus RV-A2 on day 13. Tuft/brush cells were indicated by double staining for either DCLK1 and IL-25 or TRPM5 and TSLP. Results. RV-A1B infection on day 6, but not RV-A2 infection on day 13 of life, increased the number of DCLK1+ IL-25+ airway epithelial cells, indicating an increase in tuft/brush cells. Heterologous infection with RV-A1B and RV-A2 caused a further increase in DCLK1+ IL-25+ and TRPM5+ TSLP+ cells. Skn-1a-deficient mice showed no increase DCLK1+ IL-25+ or TRPM5+ TSLP+ epithelial cells, indicating an absence of tuft/brush cell induction. Compared to wild-type mice, the Skn-1a KO failed to block IL-25, IL-13 or Muc5ac mRNA expression in mice infected with RV-A1B on day 6 of life. However, Skn-1a deficient mice infected with RV-A1B on day 6 and RV-A2 infection on day 13 showed significantly attenuated mRNA and/or protein expression of IL-25, TSLP, IL-4, IL-5, IL-13, Muc5ac and Clca1, as well as decreased airway epithelial cell PAS staining. IL-1β, TNF and IL-33 mRNA expression were unaffected. Conclusions. We conclude that airway tuft cells are required for the exaggerated asthma phenotype observed in immature mice undergoing repeated RV infections. Furthermore, viral infection increases tuft cell development, providing a mechanism by which early life viral infections could potentiate type 2 inflammatory responses to future infections. However, Skn-1a expression was not required for the RV-induced responses on day 6 of life, suggesting that, during early postnatal development, innate cytokine expression may be Skn1a-independent.

Supported by National Institutes of Health grants AI120526 and AI155444.
Presented by
Haley Breckenridge
Institution
Departments of Pediatrics and Molecular and Integrative Physiology, University of Michigan Medical School
Other Affiliations
Monell Chemical Senses Center, Philadelphia
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Available May 24 12-1pm

31: THERAPEUTIC TARGETING OF PRENATAL PONTINE ID1 SIGNALING IN DIFFUSE MIDLINE GLIOMA

Dana Messinger1^, Micah K. Harris1^, Jessica R. Cummings1, Chase Thomas1, Tao Yang1, Stefan R. Sweha1, Rinette Woo2, Robert Siddaway3, Martin Burkert4, Stefanie Stallard1,Tingting Qin1, Brendan Mullan1, Ruby Siada1, Ramya Ravindran1, Michael Niculcea1, Abigail Dowling1, Joshua Bradin1, Kevin F. Ginn6, Melissa A.H. Gener6, Kathleen Dorris7, Nicholas A. Vitanza8, Susanne V. Schmidt9, Jasper Spitzer9, Jiang Li10, Mariella G. Filbin10, Xuhong Cao1, Maria G. Castro1, Pedro R. Lowenstein1, Rajen Mody1, Arul Chinnaiyan1, Pierre-Yves Desprez2, Sean McAllister2, Matthew D. Dun11, Cynthia Hawkins3, Sebastian M. Waszak4,5, Sriram Venneti1, Carl Koschmann1*, and Viveka Nand Yadav1*

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Abstract
Background: Diffuse midline gliomas (DMG) are highly invasive brain tumors with rare survival beyond two years past diagnosis and limited understanding of the mechanism behind tumor invasion. Previous reports demonstrate upregulation of the protein ID1 with H3K27M and ACVR1 mutations in DMG, but this has not been confirmed in human tumors or therapeutically targeted.

Objective: This study aims to uncover the role ID1 plays in the invasive and migratory phenotypes of DMG, as well as determining its therapeutic targetability.

Methods: Whole exome, RNA, and ChIP-sequencing was performed on the ID1 locus in DMG tissue. Scratch-assay migration and transwell invasion assays of cultured cells were performed following shRNA-mediated ID1-knockdown. In vitro and in vivo genetic and pharmacologic [cannabidiol (CBD)] inhibition of ID1 on DMG tumor growth was assessed. Self-reported CBD dosing information was collected from DMG patients.

Results: Increased ID1 expression in human DMG and in utero electroporation (IUE) murine tumors is associated with H3K27M mutation and brainstem location. ChIP-sequencing indicates a similar epigenetically active state at ID1 regulatory regions in human H3K27M-DMG tumors and prenatal pontine cells. Higher ID1-expressing astrocyte-like DMG cells share a transcriptional program with oligo/astrocyte-precursor cells (OAPCs) from the developing human brain and demonstrate upregulation of the migration regulatory protein SPARCL1. Genetic and pharmacologic (CBD) suppression of ID1 decreases tumor cell invasion/migration and tumor growth in both murine IUE and multiple patient-derived (DIPG007 and DIPGXIIIP*) in vivo models of DMG. Finally, we analyzed the dose of self-reported CBD treatment in DMG patients.

Conclusions: Our study identifies that H3K27M-mediated re-activation of ID1 in DMG results in a SPARCL1+ migratory transcriptional program that is therapeutically targetable with CBD.
Presented by
Dana Messinger <dlmessin@umich.edu>
Institution
1University of Michigan Medical School; Ann Arbor, USA (UMMS). 2California Pacific Medical Center Research Institute; San Francisco, USA. 3Hospital for Sick Children, University of Toronto; Toronto, Canada. 4University of Oslo and Oslo University Hospital; Oslo, Norway. 5Rikshospitalet, Oslo University Hospital; Oslo, Norway. 6Children’s Mercy Kansas City; Kansas City, USA. 7University of Colorado School of Medicine; Aurora, USA. 8Department of Pediatrics, Seattle Children’s; Seattle, USA. 9Institute of Innate Immunity, AG Immunogenomics, University Bonn; Bonn, Germany.10Dana-Farber Boston Children’s Cancer and Blood Disorders Center; Boston, USA. 11University of Newcastle, School of Biomedical Sciences and Pharmacy, Australia.
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Available May 24, 2022 12-1:00 pm

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20: PEANUT-INDUCED FOOD PROTEIN INDUCED ENTEROCOLITIS

Kylie Jungles and Malika Gupta

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Abstract
Background: Food protein-induced enterocolitis (FPIES) is a non-IgE mediated food sensitivity that manifests as delayed repetitive emesis and pallor with or without lethargy 1 to 4 hours following ingestion of a food trigger. The most common reported triggers for FPIES are cow’s milk, soy, oat, and rice. However, peanut, which is typically associated with IgE-mediated food allergies, is now becoming a frequent trigger for FPIES. This increase in incidence seems to have correlated with the change in guidelines recommending early introduction of peanut in the diet of infants. Objectives: We aimed to better describe the characteristics of patients presenting with peanut (PN)-induced FPIES. We hypothesized that patients with peanut-induced FPIES would possess similar patient-specific characteristics and atopic risk factors. Methods: We identified 14 patients with a clinical diagnosis of FPIES with a peanut trigger, and retrospectively reviewed their charts. Patient specific characteristics including gender, age of onset of symptoms, presence of allergic comorbidities, skin-prick testing (SPT), and results of supervised oral food challenges (when available) were collected and analyzed. Results: Of 14 identified patients, 9 (64.2%) were male. Average age of symptom onset was 6 months (range, 5-8 months). 50% of patients demonstrated FPIES to PN only, while the other 50% had FPIES to additional foods, with oat (36%) being most prevalent. 21% of patients required an ER evaluation. 12 of 14 patients (86%) had negative SPT to PN. 5 of 12 patients (35.7%) had atopic comorbidities, with eczema (36%) being most common. 3 patients underwent an oral food challenge (OFC) to their FPIES trigger, and 1 of the 3 failed their challenge with FPIES symptoms. 1 patient had significant IgE sensitization on peanut skin testing, but passed an OFC to peanut. Conclusions: Our study is one of few case series describing PN-induced FPIES. It is important to better define this population, identify co-allergens, and risk factors. It is also important to recognize the risk of development of IgE sensitization to peanut when it is avoided initially due to FPIES.
Presented by
Kylie Jungles
Institution
Division of Allergy/Immunology, Department of Internal Medicine, The University of Michigan
Other Affiliations
Department of Pediatrics, The University of Michigan; Mary H. Weiser Food Allergy Center, Ann Arbor, MI
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#allergy #foodallergy #FPIES #peanutallergy
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21: CONTEMPORARY OUTCOMES OF TRACHEOSTOMY IN PATIENTS WITH SINGLE VENTRICLE HEART LESIONS

Dominic Zanaboni; Sunkyung Yu; Ray Lowery; Carolyn Vitale; Kurt R. Schumacher;

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Background Approximately 0.2% to 1.7% of children with congenital heart disease require a tracheostomy after congenital heart surgery with the majority having single ventricle (SV) congenital heart disease. Outcomes in SV patients undergoing tracheostomy are overall poor with reports of up to 44% in-hospital mortality in patients with hypoplastic heart syndrome (HLHS). We hypothesize, however, that mortality risk varies by tracheostomy indication in this population and that patients with anatomic airway abnormalities have better short and long term survival than those who required a tracheostomy for other indications. Methods We performed a single center, retrospective review of patients with SV heart disease who have undergone tracheostomy from January 2001 to December 2020. Demographics, pre and post-operative clinical information, surgical characteristics, Fontan completion, survival, and hospital follow up were collected from the electronic medical record. Survival was calculated using Kaplan-Meier curve. Standard univariate analyses were used to examine associations of different indications for tracheostomy with Fontan completion. Log-rank test was used to evaluate associations between indications for tracheostomy and survival. Results In total, 25 patients with SV heart disease underwent tracheostomy. The median age at tracheostomy was 2.9 months with a median weight of 3.5 kg. Most patients (64%) had HLHS. Tracheostomy occurred between stages I and II of SV palliation in 68% of patients. Median duration from most recent cardiac surgery to tracheostomy was 43 days (IQR 20-68 days). Indications for tracheostomy included: tracheobronchomalacia (32%), vocal cord paralysis (28%), tracheal/subglottic stenosis (24%), primary respiratory insufficiency (16%), diaphragm paralysis (12%), suboptimal hemodynamics (8%), and other upper airway issues (4%). Survival at 6 months, 1 year, 5 years, and 10 years was 76%, 68%, 63%, and 49%, respectively. Of the fourteen survivors, 12 (86%) patients were decannulated with median time to decannulation of 3 years (IQR 2.2-3.3 years). Most patients (64%) completed Fontan palliation. There was no significant association between tracheostomy indication and Fontan completion. Patients who underwent tracheostomy for suboptimal hemodynamics and/or respiratory insufficiency had an increased risk of mortality compared to those requiring tracheostomy for airway abnormalities (Hazard Ratio 4.1, p=0.02). Conclusions Tracheostomy for anatomic airway abnormalities in patients with SV heart lesions may represent a viable intervention for those unable to wean from a ventilator. Survival and completion of staged palliation in this select group is significantly better in comparison to currently reported outcomes of tracheostomy in SV patients. We suggest that patients with SV circulation may benefit from tracheostomy in select circumstances.
Presented by
Dominic Zanaboni
Institution
Division of Pediatric Cardiology, University of Michigan C.S. Mott Children’s Hospital
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Available May 24, 12-1pm

22: PARENT-REPORTED SLEEP PROFILE FOR CHILDREN WITH EARLY-LIFE EPILESIES

Gupta G1, Dang LT1, O’Brien LM1, Shellhaas RA1

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BACKGROUND: Sleep comorbidities are thought to be common and in some cases can be severe for children with early-life epilepsies (ELE). Yet, there is a paucity of data regarding the profile and most appropriate treatments of sleep disturbances for such children. Such information is needed to develop recommendations for management of sleep-related complications.

METHODS: Participants registered with the Rare Epilepsy Network (REN) were queried about sleep via online questionnaires. Descriptive statistics and logistic regression were performed.

RESULTS: Median age of the 356 children was 56 months (interquartile range 30 to 99), 56% were female, and 53% (188/356) endorsed a sleep concern. Frequent nighttime awakenings (157 of 350; 45%), difficulty falling asleep (133 of 350; 38%), and very restless sleep (118 of 345; 34%) were most endorsed. Nocturnal seizures were associated with sleep concerns and were reported in 75% (268 of 356) of children. Of the children with nocturnal seizures, 56% (118 of 268) had sleep concerns. Of the children without nocturnal seizures, 43% (38 of 88) had sleep concerns. Sleep concerns were most common in dup15q syndrome (16 of 19; 84%). Children aged 4 to ≤ 10 years (adjusted odds ratio [aOR] 16.1; 95% confidence interval [CI] 2.0,131.0) and 10 to <13 years (aOR 22.2; 95% CI 2.6, 188.6) had a greater odds of having a sleep concern compared with children aged ≤ 6 months. Female sex appeared protective for sleep concerns (aOR 0.6; 95% CI 0.4, 0.9). The association between sleep concerns and nocturnal seizures was weaker when adjusted for sex and age category in a logistic regression model. CONCLUSIONS: The most commonly reported sleep concerns for children with ELE were similar to those of healthy children. Restless sleep, prolonged sleep latency and frequent nocturnal awakenings persisted in children with ELE, in contrast to the natural progression of sleep consolidation expected in healthy children. This could reflect altered neurodevelopment or untreated sleep pathology in children with ELE. Nocturnal seizures may compound these sleep concerns.
Presented by
Gita Gupta
Institution
1 University of Michigan Medical School, Ann Arbor, MI 48109, USA
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#epilepsy #sleep
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Available May 24, 12pm-1pm

23: CHARACTERISTICS OF SPECIALTY PALLIATIVE CARE UTILIZATION IN CHILDREN WITH HIGH GRADE GLIOMA WHO ENROLL ON CLINICAL TRIALS VERSUS THOSE WHO DO NOT

Holly J. Roberts, Andrea Franson

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BACKGROUND: Palliative care (PC) has been shown to provide numerous benefits for pediatric patients with cancer, including less intense clinical care in the last month of life, improved symptom management, and dedicated family communication. Pediatric patients with high grade glioma (HGG) are particularly well suited for early involvement of PC given their high symptom burden and poor prognosis. Despite well-studied benefits, a recent study revealed that pediatric patients with primary malignant central nervous system (CNS) tumors missed multiple opportunities for appropriate PC involvement throughout their disease courses. We hypothesized that clinical trial enrollment may lead to a lack of or delay in involvement of PC in children and young adults with HGG, a population in which trial enrollment is especially prevalent. OBJECTIVES: Our primary aim was to evaluate the percentage of patients receiving PC and timing of PC involvement among pediatric and young adult patients with HGG who enroll in clinical trials versus those who do not. METHODS: After receiving IRB exemption, we identified a cohort of 43 deceased pediatric patients with HGG who received care at our institution. For each patient, the electronic medical record was reviewed to collect patient demographics, cancer diagnoses and outcomes, clinical trial enrollment, therapies, and PC involvement. Statistical analysis was performed comparing patients enrolled in trials to those not enrolled, employing Fisher’s exact tests for categorical data and t tests for numerical data. RESULTS: Overall, 72% (31/43) of patients had at least one visit with a specialty PC provider. 56% (24/43) of patients enrolled in a clinical trial with HGG-directed therapy. 71% (17/24) of patients who enrolled in a clinical trial received specialty PC compared to 74% (14/19) of non-trial participants (p = 1.000). Similarly, among patients who received PC, there was no statistically significant difference in the timing of PC involvement, measured from the date of first PC contact to date of death, for patients who enrolled in a clinical trial (mean = 177 days) compared to those who did not (mean = 113 days, p = 0.180). Of the 24 patients enrolled in clinical trials, only 7 (29%) had PC involvement prior to initiation of study treatment. CONCLUSIONS: As our understanding of the genomic landscape of pediatric brain tumors increases, it can be expected that patients enrolling in targeted therapy clinical trials will also increase. As such, it is reassuring that our data suggest that trial participation does not interfere with the receipt of specialty PC in children with HGG. While not statistically significant, initial PC involvement trended toward occurring in closer proximity to death in the patients who are not enrolled on a clinical trial. Overall, it is encouraging that enrollment in clinical trials does not appear to adversely impact specialty PC receipt in our cohort.
Presented by
Holly Roberts
Institution
Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI
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Available 5/24/22 12-1pm

24: MATERNAL METABOLIC HEALTH AND PERINATAL FACTORS INFLUENCING PRETERM INFANT BODY COMPOSITION AT HOSPITAL DISCHARGE

Lindsay Ellsworth1, Subramaniam Pennathur2

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Background: Preterm infants are at risk for long-term metabolic disease. Evaluating growth patterns including body composition measures are key to accurately assess nutritional status, quality of growth, and to identify modifiable perinatal factors. Objective: To characterize the relationship between maternal metabolic factors (overweight/obesity (OW/OB), gestational weight gain (GWG)), infant nutrition, and infant growth with preterm infant body composition. Methods: This pilot study utilizes an ongoing prospective, observational mother-infant cohort of neonates born ≤34 weeks gestational age or ≤1800 grams birth weight in the Brandon Neonatal Intensive Care Unit. Infants were excluded if fed exclusively formula or diagnosed with congenital anomalies or a genetic syndrome. Maternal data included pre-pregnancy body mass index (BMI), GWG, and calculated GWG Z-score. Infant weight and length were collected longitudinally from birth to hospital discharge with Z-scores calculated. At discharge or near term age, infant body composition was measured using air displacement plethysmography (PeaPod, Cosmed) to evaluate fat free mass, fat mass, and percent body fat for which Z-scores were calculated. Analyses were conducted with Pearson correlations to evaluate associations between maternal and perinatal factors with infant body composition. Results: For this pilot study, 19 infants (17 mothers, 2 sets of twins) able to complete PeaPod measurements were included in analysis. Infant gestational age ranged from 26 to 34 weeks with 47% female. Infants received on average 81% mother’s own milk over their hospitalization. 47% of mothers had an OW/OB BMI pre-pregnancy. Infant body composition by PeaPod showed a mean fat free mass (FFM) 2.02 kg (±0.36 kg) and body fat percentage 12.76% (±3.90%). FFM Z-score was less than the 10th percentile for 31% of infants. Maternal GWG Z-score was negatively correlated with infant FFM Z-score (r=-0.50, p=0.03) and discharge weight Z-score (r=-0.54, p=0.02); however maternal BMI showed no correlation with infant FFM. Infant FFM Z-score was positively correlated with birth weight Z-score (r=0.78, p=<0.0001) and discharge weight Z-score (r=0.95, p<0.0001). There were no correlations with percentage of mother’s milk intake versus donor milk or estimated early protein, caloric intake. There were no correlations with infant body fat percentage. Conclusions: Preterm infants are at risk for growth failure with suboptimal fat free mass accretion at the time of discharge. Maternal health status may impact body composition with negative correlations between GWG and infant FFM. Infant body composition provides a more complete assessment of adiposity development.

Funding Support & Acknowledgements: M-Diabetes Clinical/Translational Research Scholar, MNORC P30DK089503.
Presented by
Lindsay Ellsworth
Institution
1 Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Michigan 2 Division of Nephrology, Department of Medicine and Molecular and Integrative Physiology, University of Michigan
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Available May 24 12-12:30p

25: Neonatal Lung Mesenchymal Stromal Cells as Early-Life Predictors of Asthma in Survivors of Prematurity

VanBeckum, DR1, Kaciroti N2, Cui TX1, Popova AP1

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BACKGROUND: As survival of premature infants increases, so does the incidence of bronchopulmonary dysplasia (BPD) and associated chronic asthma-like symptoms and airflow obstruction. We have shown that tracheal aspirates from mechanically-ventilated premature infants contain mesenchymal stromal cells (MSCs) with properties of myofibroblast progenitors. OBJECTIVES: While isolation of MSCs predicts BPD development, little is known about their ability to predict development of asthma. We hypothesized that presence of MSCs in tracheal aspirates predicts development of asthma in the first 5 years of life of former preterm infants. METHODS: We collected tracheal aspirates from infants born at ≤ 32 weeks gestation, mechanically-ventilated for respiratory distress in the first week of life. MSCs were isolated by growing adherent cells to confluence. Chart review for chronic respiratory outcomes up to age 5 years was completed. Asthma was defined by clinical diagnosis including bronchial hyperreactivity and recurrent wheezing requiring inhaled medications or oral corticosteroids. BPD was defined as oxygen requirement at 36 weeks postmenstrual age. Logistic regression model assessed whether MSCs were independent predictors of asthma controlling for gestational age, birth weight, sex, race and BPD development. RESULTS: Eighty-six participants had complete records--of these, 53 (61%) developed asthma by 5 years of age. Logistic regression model revealed that presence of MSCs predicts asthma in early childhood (OR=3.7, 95% CI 1.3-10.4) controlling for gestational age, birth weight, sex and race. Furthermore, MSCs retained their association with asthma after controlling for BPD diagnosis (OR=2.6, 95% CI 0.91-7.2, p=0.062). The area under the ROC curve was 68.6 for MSCs and 66 for BPD indicating higher predictive power of MSCs compared to BPD on future development of asthma. MSCs were associated with increased risk of both hospitalization and inhaled corticosteroids use as a secondary outcome (RR=4.1, p=0.08) independent of BPD. CONCLUSIONS: In mechanically-ventilated premature infants, MSCs isolated from tracheal aspirates in the first week of life strongly predict development of asthma in early childhood in both a direct and indirect manner. MSCs present in developing lungs may increase risk of developing BPD through various mechanisms, and in turn BPD may predispose children to development of asthma. There is an additional direct effect of MSCs on development of asthma suggestive of pathways independent of BPD. Although marginally significant, the association between MSCs, hospitalization and inhaled corticosteroid use indicates that MSCs may also predict increased morbidity. Additional studies with larger cohorts are needed to validate these results.
Presented by
Danielle VanBeckum
Institution
1Department of Pediatrics, University of Michigan, Ann Arbor, MI; 2Department of Biostatistics, University of Michigan, Ann Arbor, MI
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26: Reproductive Counseling in Women with Congenital Heart Disease: A survey of primary care provider comfort and knowledge

Kristin N Andres, Mark D Norris, Justine Wu

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Background There are currently 1.4 million adults with congenital heart disease (CHD) living in the US. The majority of women born with CHD reach reproductive age, but over half do not receive family planning education. 75% of patients with CHD are lost to cardiology follow-up during their prime reproductive years, but the majority continue to see their primary care physician (PCP) making them uniquely poised to provide reproductive health education. There is no current literature assessing PCP comfort and competence in providing reproductive counselling to this unique population.

Objective A survey was performed to assess the current comfort of PCP managing reproductive health for women with CHD as well as their ability to provide evidence based contraceptive options and family planning counseling.

Methods A survey was distributed to a convenience sample of PCPs treating reproductive-aged women at the University of Michigan.

Results The final sample included 163 providers (response rate= 47%), 43% of whom reported currently caring for premenopausal women with CHD. Although half (46%) of respondents felt they should take primary responsibility for reproductive counseling in women with CHD the majority (86%) were uncomfortable discussing pregnancy risk, and only half (54%) felt comfortable providing basic contraceptive counseling to these patients. Few providers felt they had the knowledge necessary to provide individualized contraception (46%) or pregnancy risk (10%) counselling. Providers were more likely to prescribe a medically contraindicated form of contraception to a hypothetical patient with simple CHD (57%) compared to one with a complex cardiac lesion (30%) and few respondents identified all medically appropriate forms of contraception for these patients (15% and 25% respectively). Clinicians were also more likely to underestimate the risk of pregnancy in a patient with simple CHD compared to one with complex CHD (25% and 10% respectively).

Conclusion PCPs have low degrees of comfort addressing reproductive health concerns in women with CHD and knowledge gaps which are a barrier to providing medically appropriate care. Interestingly, women with simple CHD were more likely to receive medically inappropriate counselling. Further education of PCPs could enhance provider comfort and improve patient care.
Presented by
Kristin Andres
Institution
University of Michigan Department of Internal Medicine Pediatrics
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#ACHD #ReproductiveHealth #GrandRoundsPresentation #TopResidentAbstract
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Available Tuesday, May 24 (12-1:00 PM

27: INTESENSORY INTEGRATION IN INFANTS WITH AUTISM SPECTRUM DISORDER

Pooja Rao; Michael Lewis

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Background and Aims Audio-visual speech perception is a process that may be critical in infants for developing social cues and adaptive behavior. Previous studies have demonstrated developing infants rely on the synchrony between the visual aspect of lip movements and speech to facilitate language and social learning. Furthermore, studies have shown how children and adolescents with neurodevelopmental conditions such as Autism Spectrum disorder (ASD) are associated with socio-emotional and cognitive deficits that could hinder their audio-visual speech perception and, subsequently, their language and social development. This study examined two groups of infants' sensitivity to audiovisual synchrony when presented with social stimuli of a speaking face.

Methods To measure infants' sensitivity to audiovisual synchrony, subjects around 4-5 months of age, sat in front of two screens playing a video of a woman articulating the syllable /ba/. The experiment consisted of 20 trials that were each 20 seconds each. On one screen, the audio matched the women’s lip movement. On the other discrepant screen, the same events were presented at increasing levels of audio-visual asynchrony (333 ms, 500 ms, 666 ms, 833 ms, and 1000 ms), with the sound always preceding its corresponding visual event. To ensure there were no external variables, the matching, and discrepant videos were displayed on the left and right sides in a randomized order in each trial. Infants were also given one of two conditions that randomized the trial order in which the delay binding windows were displayed. Our lab developed a coding program to quantify the number of seconds the infant spent looking at the matching screen, discrepant screen, or looking away from the screen.

Analysis We first assessed whether individual subjects spent a more extended time looking at the matching screen or the discrepant screen. Typically developing subjects (n=56) spent an average of 6.33 seconds out of a 20 seconds trial looking at the matching screen. Subjects At-Risk for ASD (n=14) spent an average of 6.43 seconds out of 20 seconds of trials looking at the matching screen. Compared to the average time spent looking a the discrepant screen, both typically developing and at-risk subjects spent more time looking at the matching screen than the discrepant screen for all temporal binding windows. Next, we measured each subject’s preference of looking at the matching side versus the discrepant side for different delay windows. The delay window in which infants exhibited their most extended look duration indicates the individual sensitivity in their audio-visual temporal binding window. On average, typically developing subjects spent the most time looking at the matching screen at the 0.500 second Delay Binding Window. At-Risk spent more average time looking at the matching screen at the 1.000 second Delay Binding Window.
Presented by
Pooja Rao
Institution
Institute for the Study of Child Development, Robert Wood Johnson Medical School
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28: DESCRIBING SESAME SENSITIZATION PATTERNS IN INFANTS AND TODDLERS

Freigeh, George E1, Khokar, Dilawar2, Sanders, Georgina2,3, Gupta, Malika2,3

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Background: The prevalence of sesame allergy is increasing in the US population and is now considered the 9th most common food allergen. There are emerging but limited data on sesame epidemiology and co-sensitization trends within the US; thus, many questions regarding sesame allergy remain. While it is known peanut and tree nut allergies are associated with sesame sensitization, relationships between specific tree nuts have not been extensively studied. Demographic associations, specifically the impact of race/ethnicity, are also understudied. Objective: To investigate the associations of sesame sensitization as it relates to demographic, atopic, and other factors Design/Methods: A retrospective chart review was conducted identifying all patients in the age group of 0-3 years who had a sesame serum IgE level drawn over a 32-month period at a Michigan Medicine facility. Data was collected on demographics, clinical reactivity, skin prick testing, oral food challenges, co-morbid sensitizations and other atopic conditions. Descriptive analysis of frequencies and proportions was performed using IBM SPSS. Association testing performed using McNemar’s test. Study was reviewed and approved by the institutional IRB. Results: 169 charts were identified of which 166 were included. 3 charts were excluded due to there not being any other collectable data beyond serum IgE level and demographics. 119 patients had evidence of sesame sensitization through serum IgE levels and/or skin prick testing. Demographic data showed an overrepresentation of Asian, Middle Eastern and North African patients in the sesame sensitized population as compared to the general clinic population. Males showed higher rates of sesame sensitization compared to females at a ratio of almost 2:1. The majority of sesame sensitized patients had another atopic comorbidity, the most common being another food sensitization (82%) followed by eczema (75%). Most patients had sesame IgE levels drawn due to a history concerning for reaction rather than for screening purposes. The most common comorbid food sensitizations were tree nuts followed by peanut and then egg. Amongst the tree nuts, there was a statistically significant higher proportion of cashew/pistachio sensitization in the sesame sensitized population as compared to hazelnut, almond, and walnut/pecan (p < 0.001). Conclusions: Most patients with sesame sensitization have comorbid atopic conditions and are sensitized to another food. Sesame sensitization shows racial and ethnic differences. Sesame sensitization is significantly associated (p < 0.001) with cashew and/or pistachio sensitization compared to the other tree nuts.

Presented by
George Freigeh
Institution
1) Department of Pediatrics 2) Department of Internal Medicine, Division of Allergy and Clinical Immunology 3) Mary H Weiser Food Allergy Center
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29: Cutting Ties With an Old Friend: Omphalitis and Bacteremia With Umbilical Cord Nonseverance

Lydia Lannia, Katherine Panninga, Kimberly K. Monroeb, Maria Skoczylasb, Derek Spindlerb

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Initial Presentation: A 3 day old male presented for a well-newborn visit. Birth history was significant for term vaginal delivery and unremarkable maternal labs. Parents asked to have his umbilical cord cut, which remained attached to the placenta following requested umbilical nonseverance (UCNS), aka “lotus birth”, at the time of delivery. He was referred to the Emergency Department at this time. Physical Exam: The umbilical cord was intact at the base of the umbilicus and connected to the placenta. Erythema was present at the umbilicus with extension circumferentially. Trace yellow exudate was noted without crepitus nor induration. Abdomen was soft, nontender and nondistended. No other rashes, jaundice, or petechiae were appreciated. The infant was uncircumcised. The remainder of the exam was normal for a newborn. Vital signs remained age appropriate. Diagnostic Evaluation: Complete blood count and comprehensive metabolic panel were within normal limits. Procalcitonin was elevated to 0.43 ng/mL (reference range 0-0.25 ng/mL). Peripheral blood culture grew gram negative rods at 17 hours and resulted in Escherichia coli (resistant to ampicillin, ampicillin + sulbactam, and cefazolin). Urinalysis obtained by catheterization was significant for trace blood and bacteria on microscopy. Urine culture grew 1,000-10,000 CFU of Escherichia coli (resistant to ampicillin alone). Renal ultrasound was normal. Lumbar puncture was discussed with parents, who after counseling on risks and benefits of the procedure, declined. Diagnosis: A diagnosis of omphalitis was made on the basis of clinical presentation of erythema and purulent discharge from his umbilicus that resulted in E coli bacteremia, E coli bacteriuria, and presumed meningitis given his age and Gram-negative–rod bacteremia. Treatment was completed with a 21 day course of cefotaxime and 10 day course of clindamycin. Discussion At this time, limited case reports exist demonstrating adverse outcomes of UCNS, including idiopathic neonatal hepatitis, endocarditis, and hyperbilirubinemia1,2. At our institution, we previously reported a limited case series of 6 cases of UCNS, with no reported adverse outcomes3. Only one other published case of UCNS associated with omphalitis is reported; however, that case had negative blood cultures1. To our knowledge, our case is the first which demonstrates a case of omphalitis-associated UCNS, leading to culture positive bacteremia and bacteriuria. The severity of the associated complications demonstrate the need for further study and examination of cases of UCNS to better inform providers who care for patients in the newborn setting. Additionally, this would facilitate more informed anticipatory guidance for parents in the shared decision making medical model when UCNS is desired.

References 1. Ittleman, BR; German, KR; Scott, E; Walker, V; Flaherman, VJ; Szabo, J; Beavers, JB. “Umbilical Cord Nonseverance and Adverse Neonatal Outcomes.” Clinical Pediatrics. 2019. 58(2), 238–240. 2. Tricarico, A; Bianco, V; Di Biase, AR; Lughetti, L; Ferrari, F; Berardi, A. “Lotus birth associated with idiopathic neonatal hepatitis.” Pediatrics & Neonatology. 2016. 58(3), 281–282. Article, TAIPEI: Elsevier B.V. 3. Monroe, KK; Rubin, A; Mychaliska, KP; Skoczylas, M; Burrows, HL. “Lotus Birth: A Case Series Report on Umbilical Nonseverance.” Clinical Pediatrics. 2019. Vol. 58(1) 88–94

Presented by
Lydia Lanni
Institution
a Department of Pediatrics, C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan b Division of Pediatric Hospital Medicine, Pediatrics, University of Michigan, Ann Arbor, Michigan
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30: THE A-WORD, BLACK BOXES, AND LABYRINTHS: HOW PCPS THINK AND FEEL ABOUT AUTISM CARE IN THE MEDICAL HOME

Nicole Hamp (a), Sarah DeHaan (b), Celina Cerf (c), Jenny S. Radesky (a)

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Background: Early recognition of autism spectrum disorder (ASD) and referral to services leads to improved child outcomes, but the average age of ASD diagnosis in the United States remains between 4 and 5 years. Cultural and language barriers, lack of timely developmental screening, and long waitlists have been identified as sources of delay in ASD diagnosis. However, little research explores the cognitive and emotional experiences of pediatric primary care providers (PCPs) that influence medical decision-making, communication with families when ASD risk is identified, and the ability to provide adequate ASD care within the primary medical home.

Objective: We aimed to explore pediatric PCP experiences and needs around identification and management of ASD in toddlers as an initial phase of implementing a tiered ASD evaluation system at a large midwestern academic medical center.

Methods: We recruited 28 PCPs to take part in semi-structured interviews via Zoom. Probe questions elicited opinions about current screening and referral procedures; experiences obtaining services for patients; effective communication with parents; physician emotional experience when introducing ASD concerns; practice-based sources of disparities; and larger needs for ASD management in the primary care setting. All interested MM pediatric PCPs were eligible to take part. Interview transcripts were analyzed qualitatively by a multi-specialty research team for recurrent themes using grounded theory analysis.

Results: Participants were 89% female, ranging in clinical experience from <1 year to >27 years, representing all 8 pediatric primary care clinic sites at our institution. Dominant themes relating to the PCP’s cognitive, emotional, and relational experience of caring for patients with ASD were identified, which reflected the trajectory of ASD identification, management, and related medical decision making (Table 1).

Conclusions: Existing literature and results from this study suggest a need for targeted improvements in primary care to: (1) increase PCP capacity and confidence in communicating concerns of ASD with families, (2) refer for timely diagnostic evaluations in trusted and easy-to-navigate care systems, and (3) increase family activation and capacity to follow up on ASD evaluation and treatment services. Findings will inform the design of a tiered ASD evaluation pilot study at our institution.

Presented by
Sarah DeHaan
Institution
(a) Division of Developmental Behavioral Pediatrics, (b) Division of General Pediatrics, Michigan Medicine Department of Pediatrics, University of Michigan, Ann Arbor
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Available May 24 12-1:00 pm

32: Capacity for Regulation of Energy Intake in Infancy

Lyndsey AF. Reynoldsa, Harlan McCafferyb, Danielle Appugliesec, Niko A. Kacirotid, Alison L. Millere, Katherine L. Rosenblumf, Ashley N. Gearhardtg, Julie C. Lumengb,h

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Objective: To measure infant capacity for regulation of energy intake (REI).

Methods: Infant capacity for REI was measured at 2 wks, 2, 4, 6, 9, and 12 mos in healthy, full-term infants. For 6 hours, the caregiver fed the infant ad lib on day one (“typical”(TYP)), and hourly on day two (“increased frequency”(INC)). Intake was measured using pre- and post- bottle weights and maternal report of solids. Capacity for REI was indexed as the percent increase in intake and as the difference in intake in kilocalories per kilogram (kcal/kg) infant body weight, between the INC vs. TYP protocols; a value of zero in either index indicates perfect REI. Infant and caregiver characteristics were obtained by questionnaire and infant anthropometry measured. Trajectory analysis was used to determine: (1) if there are, on average, individual differences in the capacity for REI; (2) if the capacity for REI changes with age; and (3) if the capacity for REI differs by feeding type (milk only (MO), solids only (SO), or milk and solids combined (MS)).

Results: The sample (n=186 infants, 1184 feedings) was 50% male, 61% white, 15% black, 7% Hispanic; mean gestational age 39.5 wks (SD 1.1), birthweight 3.4 kg (SD 0.4), and 12 mo weight-for-age z-score 0.1 (SD 0.9). On average, an additional 2.2 to 2.7 feedings (across ages) were given in the INC vs. TYP protocols. Total kcal consumed from MS ranged from 165 (SD 74) at 2 wks to 336 (SD 225) at 12 mos (TYP) and 164 (SD 86) to 335 (SD 192) (INC). Trajectory analysis indicated a single trajectory for both indices (for MO, SO, and MS), indicating no evidence for individual differences. For the index that was the percent increase in intake in the INC vs. TYP protocols for MS, the estimate at 2 wks was 0.167% (95% CI [-0.005, 0.339], p = .057) and slope -0.185 (95% CI [-0.146, 0.516], p = .273). For the index that was the difference in intake in kcal/kg in the INC vs. TYP protocols for MS, the estimate at 2 wks was 2.76 kcal/kg (95% CI [0.166, 5.36], p = 0.037) and slope -0.299 (95% CI [-5.28, 4.68], p = 0.906). This indicates nearly perfect REI that did not change with age. The findings did not differ for MO, SO, or MS.

Conclusions: To our knowledge, this is the first study to objectively measure REI in healthy full-term infants across 6 age points in the first 12 mos of infancy. On average, infants have the capacity for precise energy regulation for both milk and solids from ages 2 wks to 12 mos.

Presented by
Lyndsey Reynolds
Institution
University of Michigan
Other Affiliations
aDivision of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI bDivision of Developmental and Behavioral Pediatrics, Department of Pediatrics, University of Michigan, Ann Arbor, MI cAppugliese Professional Advisors, North Easton, MA dDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI eDepartment of Health Behavior and Health Education, University of Michigan School of Public Health, Ann Arbor, MI fDepartment of Psychiatry, University of Michigan Medical School, Ann Arbor, MI gDepartment of Psychology, University of Michigan, Ann Arbor, MI h Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI
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Available May 24th, 2022 12-1 pm

34: IMPROVED RISK STRATIFICATION OF PEDIATRIC FEBRILE NEUTROPENIA EPISODES USING A NOVEL CLINICAL TOOL WITH PROCALCITONIN: INTERNAL ANALYSIS PRIOR TO IMPLEMENTATION

Nate Nessle DO1, Tom Braun PhD2, Sung Choi MD MS1, Rajen Mody MD MS1

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Background: Risk stratification of pediatric febrile neutropenia (FN) is an established concept, yet current clinical risk tools misclassify up to 5% of clinical standard-risk episodes with severe outcomes. The clinical discriminatory performance of a clinical risk tool observed in one region cannot be inferred to a different region and patient population. Few international groups documented improved performance of a clinical risk tool when inflammatory biomarkers are combined with clinical risk factors, but a combined clinical risk tool with procalcitonin has not been evaluated in a North American cohort. The internal evaluation of a clinical risk tool before implementation has not been well-described.

Primary Aim: The primary aim of this study was to describe our single institution experience of the non-interventional, internal evaluation of a recommended clinical risk tool alone and in combination with serial procalcitonin prior to local implementation: an important, “required” step recommended by the International Fever and Neutropenia Guideline Panel and Children’s Oncology Group (COG).

Methods: The evaluated novel risk tool, termed study decision rules (SDR), incorporated serial procalcitonin with a modified, more restrictive clinical risk tool (Alexander, et al.) recommended by the COG. The study standard-risk (SSR) group met clinical standard-risk criteria with two serial procalcitonin <0.4 ng/mL; median time from fever onset for each procalcitonin value was 2 and 16 hours, respectively. The study high-risk (SHR) group met clinical high-risk criteria or clinical standard-risk with a procalcitonin ≥0.4 ng/mL. Severe events were defined as blood stream infection (BSI), intensive care unit (ICU) admission, or death. Descriptive and bivariate statistics compared the groups and outcomes.

Results: In 608 FN episodes, the clinical risk tool alone identified 39.1% (238/608) clinical standard-risk episodes; 5.9% (14/238) had severe events. Prospectively using the SDR, the SHR group included 76.6% (92/120) of episodes; severe events occurred in 20% (3/15) of clinical standard-risk episodes included in the SHR group due to elevated procalcitonin ≥0.4 ng/mL. The SHR group had significantly more BSI [21.7% (20/92) vs. 0% (0/28); P= 0.007] and ICU admissions [13% (12/92) vs. 3.6% (1/28); P= 0.158]. This group also had significantly fewer short hospital stays < 3 days [17.4% (16/92) vs. 60.7% (17/28); P= <0.001].

Conclusion: The modified clinical risk tool in our institution has similar performance to prior validation studies. However, the novel SDR with serial procalcitonin aided in identifying severe events in clinical standard-risk episodes, but analysis was limited. Institutions may consider similar internal evaluation methodology before FN episode risk stratification.
Presented by
Nate Nessle
Institution
1 University of Michigan, Division of Pediatric Hematology Oncology, Department of Pediatrics 2 University of Michigan, School of Public Health, Department of Biostatistics Email: cnessle@med.umich.edu
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Available Tuesday May 24, 12pm-1pm EST

35: SUSPECTED MIS-C ADMISSIONS FROM EMERGENCY DEPARTMENT TO INPATIENT UNIT: A REVIEW

Budnik, Elizabeth,1 Chang, Y Katharine,2 Mikesell, Christine,2 Pomeranz, Elaine1,2

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Abstract
Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a newly identified condition associated with recent Coronavirus Disease 19 (COVID-19) infection that results in multi-organ dysfunction. While most patients will recover, some can become critically ill. Predicting who will develop life-threatening complications remains a challenge. Early reports of well-appearing children decompensating quickly prompted the development of guidelines with recommendations to obtain a wide array of tests and to admit children with abnormal lab values, regardless of clinical appearance. We hypothesized that hospitalizing patients based on laboratory criteria alone would result in unnecessary admission of children who could have been safely managed with close outpatient follow-up.

Objectives: To identify children undergoing MIS-C evaluation and to determine if using only laboratory criteria to make admission decisions resulted in the hospitalization of well-appearing children who could have been managed on an outpatient basis.

Design/Methods: We performed a retrospective chart review of patients 18 years and under who presented to Children’s Emergency Services between February 2020 and March 2021. Patients were included if they had a ferritin obtained in the Emergency Department (ED) and were admitted to the pediatric hospital medicine (PHM) service. Manual chart review was then conducted to determine if ferritin was obtained as part of a MIS-C workup, if patients met other admission criteria, if they were well-appearing based on clinical documentation, if they required further intervention for Kawasaki disease (KD) or MIS-C, or if they required escalation of care within 48 hours of admission. Final diagnoses were also recorded.

Results: We identified 59 well-appearing patients who underwent MIS-C evaluation and were admitted to the PHM service. Of those, 58 patients met at least one other criterion for admission (eg, inability to tolerate oral fluids, fever of unknown origin, concern for malignancy); 5 were treated for MIS-C or Kawasaki Disease (KD); and 4 patients required escalation of care (supplemental oxygen, transfer to the PICU, or rapid response team call) within 48 hours of admission. One patient with urinary tract infection could have been managed with outpatient antibiotics. The most common discharge diagnosis was viral illness.

Conclusions: While we hypothesized that well-appearing children were being admitted due to abnormal labs alone, our study did not find this to be the case. Only one patient who could have been discharged from the ED was admitted because of abnormal MIS-C labs. All other admitted patients undergoing MIS-C evaluation also met additional admission criteria and would not have been discharged regardless of the lab results. We conclude that abnormal MIS-C screening labs are correlated with clinical illness appropriate for hospitalization, and neither result in excess admissions nor facilitate disposition from the ED.
Presented by
Elizabeth Budnik
Institution
1. University of Michigan Department of Emergency Medicine 2. University of Michigan Department of Pediatrics
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Available May 24 12:00-1:00 pm

36: THE RELATIONSHIP BETWEEN ESTROGEN AND SUBSEQUENT GROWTH RESTRICTION AMONG ADOLESCENTS WITH HEAVY MENSTRUAL BLEEDING

Jessie M Hoxie1, Sarah D Compton1, Mina M Farahzad2, Olivia K Winfrey2, and Monica W Rosen2.

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Abstract
Background: Heavy menstrual bleeding (HMB) has an estimated prevalence of up to 40% among all healthy adolescent girls, with the majority presenting within the first year after menarche. While hormonal suppression is first-line treatment for HMB, some providers choose to postpone the use of estrogen-containing therapies for adolescent girls until at least a year after menarche given the largely theoretical concern for potential height restriction secondary to early growth plate fusion. Objectives: To evaluate the relationship between estrogen-containing treatments for HMB and subsequent growth restriction compared to progesterone-only or non-hormonal treatments among adolescent girls when initiated at menarche. Design/Methods: A retrospective chart review was performed of adolescent females aged 10-15 years who presented to an institution-affiliated outpatient, inpatient, or emergency department setting for management of HMB within 3 months of menarche. Heights (cm) at menarche, 6 months, 12 months, and 24 months were compared among patients treated with 1) estrogen-containing methods, 2) progesterone-only methods, and 3) non-hormonal methods (controls). The primary outcome measure was the difference in height between menarche and 24 months. Groups were compared using bivariate analysis with chi-square or Fisher’s exact test where appropriate and linear regressions. All statistics were performed in Stata v16 using an α-level of 0.05. Institutional Review Board approval was obtained. Results: At 24 months, the mean increase in height from menarche was 6.4 cm among the control group (n=54), 7.2 cm among the progesterone-only group (n=10), and 3.8 cm among the estrogen group (n=16). The increase in height for the estrogen group was significantly decreased compared to the control group (p=0.041). A significant difference was not observed when comparing the progesterone-only group to the control group (p=0.87). Adolescents receiving estrogen had an average of 1.8 fewer cm of growth (absolute change in height) compared to those receiving either progesterone-only or non-hormonal treatment. No significant differences existed between groups at the 6-month or 12-month timepoints. Additionally, for each year younger an adolescent was at menarche, she had 1 fewer cm of growth (change in height) at 24 months after menarche (p<0.002). Conclusions: Estrogen-containing treatments for HMB initiated within 3 months of menarche was associated with reduced height at 24 months compared to treatment with progesterone-only or non-hormonal methods. The clinical applicability of the 1.8 cm absolute reduction in height in the estrogen group may be of considerable significance for those who are shorter at baseline.
Presented by
Jessie Hoxie
Institution
1 Department of Obstetrics and Gynecology, University of Michigan Medical School 2 Department of Obstetrics and Gynecology, University of Michigan
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37: THE REPRODUCIBILITY AND RELIABILITY OF INSULIN RESISTANCE INDICES IN CHILDREN AND ADOLESCENTS

Nellie Said; Mary Ellen Vajravelu; Jennifer L. Meijer; Joyce Lee

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Abstract
Objective: To examine the reproducibility of measures of insulin sensitivity and secretion in obese youth compared to normal weight youth, and compare these indices based on the use of fasting measures, sex, and race.

Background: Insulin sensitivity and secretion indices can be useful tools to better understand insulin homeostasis in children and adolescents who are at risk for developing diabetes. There have been studies in the adult population comparing various indices against OGTT’s and insulin clamp testing, but there have not been studies examining the reproducibility and reliability of these measures in adolescents.

Methods: We performed two formal 2 oral glucose tolerance tests (OGTTs) in overweight (BMI ≥85th%, n=189) and normal weight (BMI <85th%, n=93) children within a 3-week period. We calculated multiple measures of insulin sensitivity - Homeostasis model assessment of insulin resistance (HOMA-IR; ((G_0*I_0 ))/22.5), WBISI Whole body sensitivity index (WBISI; 1000/√(〖(G_0*I_0 )*(G_mean*I_mean )〗^ )), Quantitative Insulin sensitivity Check Index (QUICKI) - 1/(log(I_0 )+) log(G_0 ), 1/fasting insulin levels, Fasting glucose to insulin ratio (FGIR). We also calculated measures of insulin secretion - Insulinogenic index (IGI; (ΔI_0,30)/Δ G_0,30), Homeostasis Model Assessment of beta cell function (HOMA-B; ((20*I_0 ))/((G_0-3.5) )) and disposition index (IGI x WBISI). We assessed the reproducibility of the indices between the first and second visits. We also compared the correlation coefficients of each fasting measure against each non-fasting measure overall, in the overweight/obese group, and in the normal weight group. Finally, we compared the correlation coefficients based on weight category, sex and race.

Analysis was done using R version 4.0.5 and the package cocor. Spearman correlations of first and second measurements were calculated for each sensitivity and secretion test. Fisher’s z-transformation was used to compare the correlation coefficients for the first and second measurements of overweight/obese to control, male to female, and white to black subsamples (Fisher 1925). Correlation coefficients of first and second measurements of the different tests were compared using the method of Dunn and Clark (1969).

Results: The non-fasting insulin sensitivity measurement (WBISI) was significantly more reproducible than all fasting measures overall and in the overweight/obese cohort. In the control group, WBISI was significantly more reproducible than HOMA-IR and QUICKI. However, there was no significant difference in reproducibility between WBISI and FGIR & 1/fasting insulin. Fasting insulin sensitivity measures were significantly more reproducible in the overweight & obese cohort compared to the normal weight cohort. There were no significant differences in the reproducibility of insulin secretion measures or non-fasting insulin sensitivity measures for overweight & obese vs. normal weight. There were no significant differences in the reproducibility of insulin secretion and insulin sensitivity measures for male vs. female groups and white vs. black individuals

Conclusions: Non-fasting insulin sensitivity measures are more reproducible than fasting insulin sensitivity measures, regardless of weight category. Insulin secretion measures have poor reproducibility overall and by weight category. Sex (male vs. female) and race (white vs. black) do not impact the reproducibility of insulin sensitivity and secretion measures.
Presented by
Nellie Said
Institution
Division of Pediatric Endocrinology, Department of Pediatrics, Michigan Medicine
Other Affiliations
Division of Pediatric Endocrinology, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh; Department of Pediatrics, Dartmouth Geisel School of Medicine
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Available May 24th 12-1 pm

38: INTEGRATIVE OMICS APPROACH TO INVESTIGATE MATERNAL BMI AND INFLAMMATION IN PREGNANT BLACK WOMEN

Nadia Saadat1, Todd A. Lydic2, Vasantha Padmanabhan1, Christopher G. Engeland3, Dawn Misra2, and Carmen Giurgescu4

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Background: African American (Black) women have a higher risk of pregnancy complications and adverse birth outcomes compared to non-Hispanic white women. According to National Health and Nutrition Examination Survey, 74.2% of Black women between 20 and 39 years of age (childbearing age) had body mass index (BMI) ≥25. Obesity during pregnancy is reported to be related to various pregnancy complications and increased risk for adverse birth outcomes, but the mechanisms are not yet well understood. Maternal obesity is related to higher systemic inflammation and dysregulation of lipid metabolism. Adipose tissues, in addition to synthesizing and storing fat, produce pro-inflammatory mediators, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. Objectives: We hypothesized that maternal BMI and inflammatory markers are related to lipidome profiles during pregnancy in Black women. Design/methods: Thirty-six women were recruited and plasma samples were collected between 9 to 25 weeks of gestation. Plasma Inflammatory markers were measured by multiplex assays and lipidome profiles were determined by “shotgun” Orbitrap high resolution/accurate mass spectrometry. The data were analyzed by multivariate analysis using SIMCA P+ software. Results: The Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) score plot showed good separation of the pre-pregnancy BMI groups (i.e., BMI ≥25 and BMI <25) in terms of their lipidome profiles. Higher levels of lipid species diglyceride(DG) DG(40:5), phosphatidylcholine(PC) PC 16:0, PC(O-47:2), PC(Ox26:0), triglyceride(TG) TG(49:1) TG(49:2), TG(55:6), TG(57:9), TG(64:7), and TG(66:9) were associated with the higher BMI group, whereas PC(O-37:3), PC(Ox22:00), fatty acid(FA) FA23:3, FA23:4, phosphatidylethanolamine(PE) PE(20:0), and PE(30:0) were associated with the lower BMI group. The concentration of lysophosphatidylcholine species PC (16:0), a biomarker of cardiovascular disease, diabetes, and cancer was found to be elevated in the higher compared to the lower BMI group. Inflammatory markers such as TNF-α, IL-6, IL-8, IL-10, and C-reactive protein (CRP) were positively correlated to lipidome profiles. Interestingly, CRP was highly correlated to the lipidome, but this association was independent of the BMI status in our cohort. Conclusions: Maternal BMI and inflammatory markers are related to lipidome profiles, and a detailed investigation of these markers may lead to the identification of the metabolic pathways associated with higher BMI and systemic inflammation among pregnant Black women. A strong association of CRP with lipidome was not found to be related to BMI status, and in a recent study, we reported higher levels of plasma CRP were related to depressive symptoms in pregnant Black women. Future integrative research is required to study associations of inflammatory markers with lipidome in relation to the social environment.
Presented by
Nadia Saadat
Institution
University of Michigan1, Michigan State University2, University of Michigan1, Pennsylvania State University3, Michigan State University2 and University of Central Florida4
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39: Code status variation through four surges of COVID-19 pandemic at University of Michigan

Lily Rodgers, Blair Lenhan, Katie Epler, Tom O’Callaghan, Natalia Painter, Allison Bloom, and Emily Jacobson.

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Intro: Through the past two years of the SARS-CoV2 pandemic (COVID-19), the medical field has seen a dynamic shift in treatment options and survival rates. During the first wave of the pandemic, patients were found to transition from full to restricted resuscitation preferences both from prior admissions and within their COVID-19 admission. Interestingly, these changes were made at the start of the admission, suggesting that perception of outcomes from COVID influenced change in code status more than a patient’s clinical course. As medical and public perspective of COVID-19 has changed over the past two years, our team was curious if there was a reflective shift in code status preference.

Methods: We reviewed the code status of adult patients (>18 years old) admitted to the University of Michigan with a positive COVID-19 test using electronic medical records. Data was retrospectively collected from March 2020 to December 2021 with patients separated into admission during 4 time periods correlating to COVID-19 surges (1st surge 3/1-9/31/2020, 2nd surge 10/1/20-2/28/22021, 3rd surge 3/1-7/30/2021, and 4th surge 8/1-12/31/2021). Patient characteristics and outcomes were collected along with code statuses during admission. Data was compared with sample t-test, ANOVA and Chi square tests.

Results: A total of 3187 patients met inclusion criteria. Patients admitted in the first two surges were more likely to be older than those in later surges and those admitted during the second surge had higher average comorbidity score. Similarly, those admitted during the first surge had longer length of stay along with ICU requirement compared to all other surges. Comparing initial code status preference between surges, over time there was a decreased percentage of those with DNAR/partial code status (16.6% vs 15.3% vs 8.3% vs 11.3%, p<0.001) along with increased percentage without a code status order (13.8% vs 18.6% vs 21.5% vs 23.0%, p<0.001). This same trend was observed with final code status at discharge, in addition to increased percentage with full code in the third surge (60.4% vs 60.9% vs 67.8% vs 61.5%, p=0.01).

Discussion: As expected, there was a decrease in those electing DNAR or partial code status preference over time. Interestingly, providers were less likely to order code statuses over time. There may be multiple reasons for this including increasing community spread but decreased virulence resulting in increased admissions with COVID-19 but not secondary to it. This is a limitation of our study, as it is unknown how many of these patients would have preferred a code status other than full. Our next step will be to perform multi-variable analysis looking at how age, co-morbidities, and vaccine status may have affected code status.
Presented by
Lily Rodgers, Blair Lenhan
Institution
University of Michigan
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40: INFANTS WITH SEVERE CONGENITAL RENAL ANOMALIES ARE AT INCREASED RISK FOR DEVELOPMENTAL DYSPLASIA OF THE HIP

Gretchen Stepanovich1, Ashlee Smith2, Aunum Akhter1, Julie Sturza3, Rebecca Vartanian1, Matt Stepanovich4

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Abstract
Background: In the Neonatal Intensive Care Unit (NICU), multiple infants with congenital renal anomalies, especially severe anomalies necessitating peritoneal dialysis (PD), have been observed to have Developmental Dysplasia of the Hip (DDH). There are known risk factors for DDH in pediatric literature such as in utero breech presentation, immediate family history, and female sex, but orthopedic literature also supports oligohydramnios as such a risk factor. Consequently, as the fetal kidneys are the primary producers of amniotic fluid, infants with severe renal anomalies and resultant oligohydramnios should be at increased risk for DDH. However, as these infants often also have pulmonary hypoplasia and significant critical care needs, attention to their hips may be neglected or delayed. Objectives: 1) To evaluate the incidence of DDH in infants with severe renal anomalies and compare this to the reference incidence in liveborn infants, 2) to evaluate whether exposure to in utero oligohydramnios increased the risk of DDH development, and 3) to investigate whether earlier ultrasound screening resulted in a decreased need for surgical intervention. Methods: This was a retrospective case series involving infants admitted to the NICU from January 1, 2010-July 31, 2021 with severe renal anomalies as coded by the Vermont Oxford Network Manual of Operations. A total of 189 infants were reviewed; baseline patient characteristics were noted, including presence of risk factors for DDH. The primary outcome was development of DDH; in patients with DDH, timing of the first hip ultrasound and treatment details were recorded. Results: Compared to the published rate of DDH in liveborn infants (1-2/1,000 = 0.2%), infants with congenital renal anomalies had a greater rate of DDH (15/190 = 7.9%), especially those who required PD (7/30 = 23%). Among the 93 patients with a known prenatal Amniotic Fluid Index (AFI) , there was an association between normal or high AFI and a decreased risk of DDH, OR .91 (.83 -.99, p = .037). Documented exposure to oligohydramnios trended toward increasing the risk for DDH in a manner that was additive to other known risk factors, though this was not statistically significant (p = 0.10). Earlier screening hip ultrasound did not result in a decreased rate of hip surgery. Conclusions: Infants with severe renal anomalies, especially those exposed to low amniotic fluid levels, are at increased risk for DDH. While earlier hip ultrasounds in this study did not result in a decreased need for hip surgery, identification of DDH may influence the planning of other surgeries such as PD catheter and gastric tube insertions, as their location can directly confound the orthotic and/or casting care required for DDH treatment. Early screening and recognition of DDH in this vulnerable patient population leads to an overall improvement in their long-term care.
Presented by
Ashlee Smith and Gretchen Stepanovich
Institution
1 Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Michigan 2 Department of Pediatrics, University of Michigan 3 Biostatistics and Data Management Unit, University of Michigan 4 Division of Pediatric Orthopedic Surgery, Department of Orthopedic Surgery, University of Michigan
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#Neonatology #DDH #CongenitalRenalAnomaliesIncreaseDDHRisk #PDCatheterInsertionSiteMattersToTheHips
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Available 5/24/22 12:00-1:00pm
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41: Outcomes Following Biventricular Repair Of Atrioventricular Septal Defect With Single Left Ventricular Papillary Muscle

Scarlet Woodrick, Carlen Fifer, Jennifer Romano, Kellianne Kleeman, Ray Lowery, Sunkyung Yu

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Abstract
Background The goal of successful repair of atrioventricular septal defect (AVSD) is the creation of two separate atrioventricular (AV) valves that are competent but not stenotic. In patients with AVSD and single papillary muscle in the left ventricle (LV), the risk of creating a stenotic left AV valve (LAVV) is increased, as this anatomy may result in the formation of a “parachute mitral valve” after repair. Objectives The aim of this study was to evaluate outcomes following repair of AVSD with single LV papillary muscle attachments and to identify preoperative characteristics that might predict post-operative LAVV outcomes. Methods All patients with AVSD and anatomically or functionally single LV papillary muscle who underwent biventricular repair at C. S. Mott Children’s Hospital from 07/2000 – 07/2020 were retrospectively reviewed to obtain demographic details, operative technique, and rates of re-intervention at the left AV valve. Echocardiographic data including anatomic description, LV measurements and valve measurements were directly obtained from pre- and post-operative time points. Univariate analysis was used to identify associations between demographic details, pre-operative echocardiographic findings, and surgical characteristics with the need for re-intervention on the LAVV or the development of significant LAVV dysfunction postoperatively. Results The study population included 38 patients. Nearly all were repaired with no or partial closure of the LAVV cleft. Median duration of follow-up was 8.3 years; freedom from LAVV re-intervention was 91% and 84% at 1 and 3 years, respectively. A total of 5 patients (13%) required reintervention on the LAVV. Most common indication for reintervention was LAVV regurgitation (4/5 patients). The only preoperative factor that predicted need for reintervention on the LAVV was > mild LAVV regurgitation on preoperative echocardiogram (HR 6.04 [1.01-36.2], p= 0.02). At discharge, 63% (24/38) of patients had > mild LAVV regurgitation, only 5% (2/38) had > mild LAVV stenosis. At most recent follow-up, 32% (7/28) had > mild LAVV regurgitation, 8% (2/26; 2 unreported) had > mild stenosis. Younger age at repair and AV valve index <0.67 on preoperative echocardiogram was associated with increased risk of > mild LAVV regurgitation at discharge, however these were no longer associated with LAVV regurgitation at most recent follow-up. Conclusion Despite concern for creation of a stenotic valve following repair, few patients developed either early or late LAVV stenosis greater than mild, and only one patient required LAVV reintervention due to stenosis. Mitral regurgitation was the predominant issue following repair, with improvement in regurgitation over time. A significant portion of our cohort had unbalance of the AVSD and small left-sided structures pre-operatively, but these factors were not associated with significant LAVV stenosis or increased risk of re-intervention on the LAVV after repair. Surgical technique and anatomic valve characteristics were not associated with need for re-intervention or valve dysfunction at follow-up. Our study suggests that repair of AVSD in patients with a single LV papillary muscle is generally successful with low risk of LAVV stenosis or regurgitation significant enough to require repair or replacement, even in patients with anatomy concerning for inadequate LAVV size.
Presented by
Scarlet Woodrick
Institution
Departments of Internal Medicine and Pediatrics, Department of Pediatric Cardiac Surgery; Michigan Congenital Heart Outcomes Research and Discovery; C. S. Mott Children's Hospital, University of Michigan
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Available May 24, 2022 12-12:30 pm

42: A RETROSPECTIVE STUDY ON CAUSE OF DEATH DUE TO HIGH-GRADE GLIOMAS IN PEDIATRIC VS ADULT PATIENTS

Samantha Lyons, Larry Junck, Andrea Franson

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Background There is limited literature that describes the specific pathophysiologic mechanisms by which children, adolescents and adults die from high-grade gliomas (HGGs). Possible mechanisms include primary brain failure, hemorrhage, or herniation, which may differ between and within these populations.This study primarily aims to identify the likely specific cause of death in patients with HGGs. Secondary outcomes of interest included the use and timing of palliative care and hospice services, code status, and location of death.

Objectives We hypothesized that patients with midline tumors of the brainstem, which is primarily seen in the pediatric population, die through brain/brainstem failure. For adults, we hypothesized that patients with HGG would die from brain failure, with or without brainstem involvement. We predicted that cause of death for a subset of patients is related to hydrocephalus and subsequent herniation resulting from tumor growth. Lastly, we expected that there may be patients with HGG who die from causes not directly related to tumor progression, such as systemic infection or radiation necrosis.

Design/Method We conducted a retrospective review of pediatric patients with grade 4 glial tumors or adults (>18 years of age) with grade 2 glial tumors that transformed into grade 3 or grade 4 tumors, or grade 3 or grade 4 tumors at diagnosis at or after 1/1/2016 at Michigan Medicine (HUM00208443). We collected demographic information and analyzed medical records and brain imaging within 3 weeks of death to assess characteristics relevant tol impression of cause of death.

Results Fifty-one pediatric patients were identified; 26 of which met inclusion criteria. Adult patient review remains ongoing with 43 patients included thus far. Initial data analysis reveals that the majority of pediatric and adult patients with HGG died from tumor progression and subsequent neurologic failure as opposed to to brainstem herniation. Additionally, there appears to be a greater use of palliative care and hospice in the pediatric population, with adults minimally using or being referred to palliative care at any time following HGG diagnosis. Pediatric patients at Michigan Medicine are almost always supported by Child and Family Life services; however, psychological support services are rarely provided or even offered to adult patients. Hospice is also involved closer to time of death in adult patients compared to pediatric patients.

Conclusion Data analysis is ongoing, though current data trends indicate opportunities for changes in practice and culture to ease the suffering of all patients with HGG through patient and provider education for end-of-life preparations.
Presented by
Samantha Lyons <lyonssam@med.umich.edu>
Institution
University of Michigan Medical School, Departments of Neurology and Pediatric Hematology/Oncology, C.S. Mott Children's Hospital
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#oncology #hopsice #palliative
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Available May 24, 2022 12:00 - 12:30 PM

43: CHARACTERIZATION OF CODE STATUS ORDERS IN ADULT PATIENTS ADMITTED WITH COVID-19 INFECTION

homas O’Callaghan, Katharine Epler, Blair Lenhan. Natalia Painter, Julie Barrett, Emily Jacobson

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Background: Discussions surrounding advanced care planning were frequent early in the pandemic given concerns for provider safety, limited resources, and early data showing poor outcomes after CPR in patients with COVID-19. While past studies have demonstrated many factors impacting code status decisions for patients and limitations in provider skill and documentation of code status discussions, less is known about code status orders during hospitalizations for patients with COVID-19. Objectives: Our research aimed to characterize code status documentation for patients hospitalized with COVID-19 during the first peak of the pandemic, when prognosis, resource availability, and provider safety were uncertain. When applicable, code status orders for the COVID-19 admission were compared to that of prior admissions. Finally, we sought to understand how demographic variables (race, gender, age), socioeconomic variables, and in-hospital variables such as ICU admission correlated to documented code status. Design/Method: This was a retrospective cohort study of patients admitted between March 1, 2020 through October 31, 2020 who tested positive for COVID-19. We collected demographic information and hospital outcome data, along with the code status orders during the COVID-19 admission and prior admissions. Data were analyzed with multivariable analysis to identify predictors of code status choice. A total of 720 patients were included. Results: Most patients (86%) had a code status order placed during their COVID admission, with the majority (70%) as full code and 12% as do-not-attempt-resuscitation (DNAR) status on admission. By discharge, 20% of patients were DNAR. Of patients with a prior admission (n=227), 33.5% previously had no code status order and 44.5% had a different code status for their COVID-19 admission. Of those with a change, most transitioned to less aggressive resuscitation preferences Conclusions: Most patients elected to be full code. Almost half of patients with pre-pandemic admissions had a different code status during their COVID-19 admission, with a trend towards less aggressive resuscitation preferences. More investigation is needed to understand the factors that influenced these trends as well as understand how resuscitation preferences evolved as the pandemic progressed.
Presented by
Thomas O'Callaghan and Katharine Epler
Institution
IM-Peds Residency, Divisions of Hospital Medicine and Pediatric Hospital Medicine, MIchigan Medicine
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Available April 24, 12-1pm

44: FREQUENCY OF POUCHITIS AFTER COLECTOMY AMONG PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS

Seth Iskowitz, Samir K. Gadepalli, Anita Sharma, Jeremy Adler

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Background Patients with ulcerative colitis (UC) undergo colectomy for various reasons, most commonly medically refractory disease. After colectomy, typically an ileal pouch-anal anastomosis (IPAA) is created to restore fecal continence. Inflammation of the IPAA, called pouchitis, commonly occurs and has a major detrimental impact on quality of life. The annual incidence of pouchitis in studies of adults with UC who underwent IPAA are reported as occurring up to 40%. Little data is available on the incidence of pouchitis in children with UC who underwent IPAA.

Objectives We sought to evaluate the incidence and outcomes of pouchitis in pediatric patients with UC who underwent IPAA.

Design/Method We identified all patients at our institution with UC who underwent a proctocolectomy with IPAA from June 2013 through December 2020 via endoscopic software database and prospectively maintained patient registry. Inclusion began at ostomy take-down (or IPAA if no ostomy). We excluded patients with IPAA for reasons other than UC. The primary outcome was the development of pouchitis that was diagnosed clinically at any time after colectomy. The secondary outcome was endoscopically diagnosed or confirmed pouchitis. The study was granted waiver of consent from the IRB.

Results Among the 77 patients with UC who underwent an IPAA, 69% (53/77) were clinically diagnosed with pouchitis at least once during the study timeframe. In total, 61% (47/77) underwent endoscopic evaluation (for any indication). 85% (40/47) of those who underwent endoscopic evaluation were confirmed to have pouchitis. 13% (6/47) of those who underwent endoscopy were found to have Crohn’s disease (5/6 had pouchitis). In total, 62% (48/77) of patients were clinically or endoscopically diagnosed pouchitis. At least 6 more patients were found to have Crohn’s disease (8% of 77).

Conclusions In this study spanning 7 years, nearly 2 in 3 pediatric patients with UC and IPAA were diagnosed with pouchitis at least once. Of those, nearly 90% responded poorly to initial therapy leading to endoscopic evaluation. Larger studies in pediatrics are needed to corroborate these findings. Most importantly, evidence-based strategies are needed to predict and prevent pouchitis in order to improve quality of life for children with UC post-colectomy with IPAA.
Presented by
Seth Iskowitz
Institution
Department of Pediatric Gastroenterology; Department of Pediatric Surgery
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Available May 24, 2022 12-1:00 pm

45: INFANT SUCKING IN RESPONSE TO A CHALLENGING NIPPLE AND GROWTH OUTCOMES AT 12 AND 24 MONTHS OF AGE

Amanda K Crandall (1), Megan H Pesch (1), Ashley N Gearhardt (2), Allison L Miller (3), Katharine L Rosenblum (4, 5), Julie C Lumeng (1)

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Abstract
BACKGROUND Infant sucking behavior may be a risk factor for the development of childhood obesity. Past work has suggested that greater sucking pressure when presented with a challenging nipple indicates greater motivation to obtain food, a known risk factor for obesity development.

OBJECTIVES The current analysis sought to examine the extent to which sucking adaptations to a challenging nipple predict differences in growth at one year and two years of age. We hypothesized that infants who increased their sucking pressure, number of sucks in a feed, and mean suck duration in response to a challenging nipple would have greater weight for length z-scores (WLZ) across their first year. We further hypothesized that those who exhibited greater increases in sucking pressure, number of sucks in a feed, and suck duration in response to the challenging (vs. typical) nipple in early infancy would have a greater weight for length z-score (WLZ) across early infancy, 12 months (m) and 24m of age.

METHODS Healthy full-term infants (n=147, 51% male) were offered a bottle by their caregivers on two days, one with their typical nipple aperture size and another with a smaller nipple aperture size that made sucking more challenging. Sucking metrics (intraoral pressure, number of sucks, mean suck duration) were measured with a pressure transducer in the nipple. This task was completed at ages 2 weeks and 2, 4, 6, 9, and 12 months. A subset of infants (n=45) had anthropometric data at 24m. Multilevel modeling for longitudinal data was used to examine how sucking metric changes in response to the challenging (vs. typical) nipple were associated with WLZ concurrently at each age point across the first year. Multilevel models were also used to examine how sucking metrics in early infancy (“baseline”: 2 weeks, 2m or 4m) predicted WLZ across baseline, 12m and 24m.

RESULTS Infants who responded to the challenging nipple with greater sucking pressure had greater increase in WLZ over the first year of infancy (β = 0.0023, t(192.92) = 2.27, p = 0.024). Among infants with 24-month data, a greater increase in mean suck duration in response to a challenging nipple at baseline was associated with a greater WLZ across baseline, 12m, and 24m (β = 2.78, t(116.53) = 2.64, p = 0.009).

CONCLUSIONS This evidence suggests that a more vigorous response to a challenging nipple, even early in infancy, is predictive of greater weight for length z-scores across the first two years of life. Infants who increase their sucking pressure and mean suck duration in response to a challenging nipple may be more motivated to obtain milk than infants who maintain the same or decrease their sucking pressure and suck duration. Future research in this area should investigate the extent to which different nipple aperture sizes may be suited to different infants depending on their individual appetitive characteristics in early infancy.
Presented by
Amanda K Crandall <amkcrand@med.umich.edu>
Institution
University of Michigan, Medical School, Departments of Pediatrics (1), Psychiatry (4), and Obstetrics & Gynecology (5); College of Literature, Science, and the Arts, Department of Psychology (2); School of Public Health, Department of Health Behavior & Health Education (3)
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Available May 24, 2022 12-1:00 pm
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46: DISPARITIES IN HIGH-RISK NEONATAL DEVELOPMENTAL CLINIC FOLLOW-UP RATES: DATABASE CREATION, PROOF OF CONCEPT, AND PRELIMINARY RESULTS

Lilia Popova(1), Emman Dabaja(2), Cambrynne Dejong(1), Sanaya Irani(1), Caroline McGowan(1), Mohammad Attar(2)

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[Background] There are disparities in high-risk neonatal developmental follow-up rates by race, maternal smoking status, and distance from the hospital. Three additional potential risk factors that have not been studied in this population are maternal parity, multi-specialty follow-up, and previous no-show visits. But in order to conduct disparities research in this population, certain variables, such as previous insurance and maternal race and ethnicity, need to be consistently recorded in neonatal health records.

[Objectives] Our objectives were to determine how reliably prior insurance and maternal race and ethnicity were recorded in neonatal records, to assess how maternal parity affected compliance with follow-up recommendations, and to determine how multi-specialty follow-up and previous no-shows affected the odds of being lost to follow-up.

[Methods] Our cohort consisted of all patients who were born between January 1st, 2014 and December 31st, 2017, had NICU or PICU stays at Michigan Medicine within three months of life, and were referred to the high-risk neonatal developmental clinic. We generated two random samples of patients for the preliminary analysis, used manual chart review for data collection, and used SAS for data analysis.

[Results] Maternal race and ethnicity was missing from 94% of neonatal records. Insurance status during the initial admission was well-documented under “Benefits Inquiry” for 100% of patients. For each additional child, the odds of being compliant with follow-up visits in the high-risk neonatal developmental clinic were 48% lower (OR: 0.52, 95% CI: 0.30, 0.93; p=0.03), unadjusted, and 44% lower after adjusting for confounding covariates including multiple gestation and race (p=0.04). Public insurance and follow-up with three or more specialties were associated with higher odds of loss to follow-up but were not statistically significant. Patients who had at least one no-show visit had 4.8 times higher (95% CI = 1.1, 20.8) odds of being lost to follow-up (p=0.04).

[Conclusions] Self-reported maternal race and ethnicity was not consistently available in neonatal records. Families with more children and with a history of no-show visits may be at increased risk for not meeting developmental follow-up recommendations.
Presented by
Lilia Popova
Institution
(1) University of Michigan Medical School; (2) Michigan Medicine Department of Pediatrics, Division of Neonatal-Perinatal Medicine
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#disparities #development #pcp #neonatal #dei #nicu
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Available Tuesday, May 24, 12-1:00 PM
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47: IMPACT OF THE COVID-19 PANDEMIC ON CHILDREN AND ADOLESCENTS PRESENTING TO A PSYCHIATRIC EMERGENCY DEPARTMENT

Benjamin Erjavac, Alicia Rolin, Keerthi Gondi, James Cranford, Ahmad Shobassy, Bernard Biermann, Alexander Rogers, and Victor Hong

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Background: The COVID-19 pandemic has had widespread effects on the world’s economy and public health, and while COVID-19 can significantly impact the physical health of infected patients, the consequences of the pandemic have also significantly impacted mental well-being. Recent studies have highlighted the impact of the COVID-19 pandemic on mental health due to pandemic-related factors, such as isolation from loved ones, distressing media information, reduced financial income, and daily death counts. Children and adolescents have been particularly affected by societal changes, with evidence that younger individuals who are in social isolation or quarantine are more likely to experience stress, frustration, and suicidal ideation.

Objectives: This study aims to further describe the effects of the COVID-19 pandemic on children and adolescent mental health by surveying individuals specifically seeking psychiatric emergency care. We hypothesized that limited access to outpatient care would be a factor in why a significant number of individuals visited the emergency department, that various age groups would experience differences in symptom predominance, and that trends in mental health symptoms impacted by the COVID-19 pandemic would evolve over the months of the study.

Methods: A mixed methods survey study was conducted on a sample of 571 children and adolescents ages 0-21 that presented to a large Midwestern academic center psychiatric emergency department between July-October 2020. The 32-question survey could be filled out by the patient or their parent/guardian. Survey data was combined with demographic data from the hospital electronic medical record. All dependent variables were categorical and were analyzed with chi-squared tests. Qualitative data was analyzed using a grounded theory approach.

Results: Among the survey respondents, there were significant increases in mental health symptoms attributed to the COVID-19 pandemic, with anxiety (71% of respondents) as the most prevalent, followed by depression (66%), suicidal thoughts or behaviors (45%), and aggression (31%). There were significant differences in reported increases in symptoms by age and gender. Additionally, 38% of participants reported that the pandemic led to a change or closure of their health care treatment, including mental health providers, with 22% reporting that the alterations in treatment access led to their emergency visit.

Conclusions: Significantly increased levels of mental health symptoms attributable to the COVID-19 pandemic were reported, with mental health impacts manifesting differently in distinct populations. Further research is indicated to assess other, more diverse populations, as well as the longer-term mental health impacts of the pandemic.
Presented by
Alicia Rolin
Institution
University of Michigan Department of Pediatrics
Other Affiliations
University of Michigan Department of Child and Adolescent Psychiatry
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Available May 24, 2022 12-1:00 pm

48: Physician Adherence of Otitis Media and Related Sequelae of Tympanostomy Surgeries for Pediatric Patients Admitted to the Emergency Department

Noor Sulieman, Rana Chouaib, Danny Majed, Mikaela Bradley, Mohamad Sulieman, Fatima Saad, Tami Hart-Johnson, Brandon Lucas, R. Alexander Blackwood

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Background: Otitis Media is one of the most common conditions for pediatric patients presenting at the Emergency Department. This condition is recurrent in children as it relates to their smaller eustachian tubes which are more likely to clog. Otitis Media presents with middle ear effusion and is normally reported by two categories: Acute Otitis Media (AOM) and Otitis Media with Effusion (OME). For effusion in the middle ear, detection with the combined use of otoscopy, pneumatic otoscopy, and tympanometry is commonly recommended. Interventional use involves tympanostomy tube insertion. By Rosenfeld et al. children by the age of 3 years, nearly 1 of every 15 children (6.8%) will have tympanostomy tubes increasing by more than 2-fold; each year, 667,000 children younger than 15 years receive tympanostomy tubes, accounting for more than 20% of all ambulatory surgery in this group. Objectives: Given the limited emergency medicine related data on Otitis Media and tympanostomy surgeries, this study aims to report the prevalence of overall adherence and related data regarding this ear condition and tympanostomies in the pediatric population of the Emergency Department. Design: Data collected via retrospective medical record abstraction from the Michigan Medicine University of Michigan Emergency Department suggests 8.8% (n = 66) of pediatric patients with Otitis Media had tympanostomy tube surgical intervention and presented to the Emergency Department in 2016. Results: From 770 patients analyzed, the overall adherence for Otitis Media guidelines was 76% (n = 585). This study also evaluates the adherence to the two types of OM and their associated laterality: 77.4% cases of Acute Otitis Media (n = 681) and 66.3% cases of Otitis Media with Effusion (n = 89) were adherent. For laterality purposes, 78.9% cases of Bilateral AOM, 75.8% cases of Unilateral AOM, 70.6% cases of Bilateral OME, and 70.9% cases of Unilateral OME were adherent. In terms of the relationship with age and physician adherence to Otitis Media guidelines, patients in the greater than 24 months age group had lower adherence (64%, n = 400) than the patients in the under 24 months age group (p < 0.001) with physician adherence being highest for patients 0-6 months (93%, n = 45). Conclusions: Many factors could influence such a significant change; one such factor is that guidelines for younger than 24 months old are more specified for physicians with regards to treatment guideline adherence and another can be explained by the sample size. The study also found that patients who visited their primary care physician prior to their emergency department visit received higher adherence rates (p = 0.002). Moving forwards, this project will provide data for future research to increase awareness and improve physician adherence to medical treatment guidelines in this pediatric population for Otitis Media in the Emergency Department.
Presented by
Noor Sulieman
Institution
Wayne State University School of Medicine, University of Michigan Office for Health, Equity, and Inclusion, Michigan Medicine University of Michigan Hospital
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Available May 24, 2022 12-1:00 pm

49: CASE REPORT: SEVERE MYCOPLASMA-INDUCED RASH AND MUCOSITIS TREATED WITH IVIG

Paris D. Rollins, BA, BSc, Andrew D. Prince, BA, Michelle Glick, MD, MA (presenting this), and Nora Biary, MD

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Abstract
Background: Mycoplasma pneumoniae is known to cause a variety of extrapulmonary complications, including many dermatologic manifestations. The mucocutaneous eruptions vary significantly but have historically been categorized within the syndromes of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). In their 2014 literature review, Canavan et al posited that such cases represented a new entity, distinct from previously described syndromes. It became known as M pneumoniae–induced rash and mucositis (MIRM). Diagnostic criteria for MIRM include the following: skin detachment of less than 10% of the total body surface area, involvement of at least 2 mucosal sites, few skin lesions (including vesiculobullous or atypical targets), and evidence of atypical pneumonia (clinical and laboratorial). The literature surrounding MIRM is relatively sparse. Most cases resolve with supportive care including antibiotics and systemic corticosteroids. To our knowledge, only 3 case reports describe treatment-resistance MIRM, in which the aforementioned therapies were insufficient for timely resolution of symptoms. In these cases, intravenous immunoglobulin (IVIG) was noted to be an effective additional treatment.

Purpose: We present here another case of rare treatment-refractory MIRM, defined by the aforementioned diagnostic criteria. In doing so, we endeavor to expand current literature on this uncommon diagnosis and the use of IVIG treatment for resistant disease.

Methods: A literature review was completed as well as patient chart review to summarize findings, signs/symptoms, treatment, and response to treatment.

Results: The most distressing symptoms of MIRM typically resolve with supportive care and antibiotics within 1 to 2 weeks. In contrast, our patient continued to require rigorous inpatient care despite a week of antibiotics, 18 days of systemic corticosteroids, 27 days of TPN, and supportive therapy from multiple care teams. Our decision to pursue IVIG therapy was driven by anecdotal evidence that demonstrates symptom relief in refractory cases of MIRM. The proposed pathophysiology of MIRM involves aberrant activation of the apoptotic ligand Fas (CD95L), resulting in apoptosis of keratinocytes and loss of mucosal barriers.5 It has been proposed that IVIG may work by blocking this ligand receptor interaction, thus inhibiting large-scale apoptosis of epithelial cells in patients with MIRM. Working alongside pharmacy colleagues, we administered a 2 g/kg dose of IVIG over 3 days based on excellent reports of this dosing used in severe mucositis from syndromes like paraneoplastic pemphigus.

Conclusion: In sharing this case, we hope to emphasize several important aspects of MIRM management. First, early recognition based on diagnostic criteria is critical, as it is often misclassified within the spectrum of EM, SJS, and TEN. Second, treatment-resistant MIRM is a rare presentation that can be successfully treated, preferably early, with IVIG therapy, but also treated even late in the course of the disease. Third, classification of MIRM is in its infancy and it is a subject that warrants more research into its clinical presentation, histopathology, and treatment. Of note, this specific case is important as it documents a rare dermatologic case in a child of color (underrepresented in literature).

Severe Mycoplasma-Induced Rash and Mucositis Treated With IVIG (sagepub.com)
Presented by
Michelle Glick
Institution
University of Michigan, Department of Pediatrics
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50: KEEPING CHILDREN HEALTHY AT SUMMER CAMP: A STUDY OF MEDICATIONS ADMINISTERED IN THE CAMP SETTING

Tara Funk, Leon Quach, Aditi Mahajan, Sarang Modi, Emily Supenia, Natalie Schellpfeffer, Michael Ambrose, Tracey Gaslin, Barry Garst, Andrew Hashikawa

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Background: The American Camp Association identified campers’ health and safety as the number one emerging issue facing camps. Studies show significant parental anxiety is associated with campers’ medical needs and parents’ medication inquiries are among the most frequent questions posed to camps. There is, however, a substantial knowledge gap concerning the types of medications being administered in camps to allow children with medical conditions – including chronic illnesses as well as mental, emotional, and social health concerns – to attend camps.

Objective: Use data from a national camp-specific electronic health record (EHR) program to categorize all medications administered in 870 camps in 2019.

Methods: We used a deidentified data set from CampDoc.com, an online EHR that allows parents and nurses to input campers’ medications. Medications were classified based on drug type, mechanism and indication following a coding book developed with a pediatric pharmacist (Table 1). Data on all available campers between the ages of five to seventeen years were analyzed using descriptive statistics.

Results: Data were available from 75,072 campers encompassing 163,853 medications from 870 camps, with camps represented from all U.S. census geographic regions including: Northeast (31%), Midwest (23%), South (24%), and West (21%).

Medications were classified into 26 primary classifications (Table 2). Within the primary classifications, Antihistamines/Allergy Agents represented the highest proportion of medications at 24.14% (n = 39,560), followed by Psychotropic Agents at 20.46% (n = 33,521), Emergency and Rescue 115 Agents at 12.05% (n = 19,740), Herbal, Supplement and Vitamin at 7.22% (n = 11,838), and Respiratory at 5.33% (n = 8,735). These five categories comprised nearly 70% of all camp medications.

In total, 98,268 medications were further organized into 52 distinct medication subcategories (Table 2). Notable medication subcategories included the following: Attention Deficit Hyperactivity Disorder Agents (11.37%; n = 18,634), Asthma Rescue (7.85%; n = 12,860), Anaphylaxis Rescue (3.80%; n = 6,234), Status Epilepticus Rescue Agents (0.31%; n = 506), and Prescription Pain Medications (0.51%; n = 836). There were also a substantial number of medications for mental health: Anti- Depressants (3.35%; n = 5,481), Anxiolytics (3.29%; n = 5,394), Anti-psychotics (1.41%; n = 2,314), and Bipolar Agents (0.17%; n = 283).

Conclusions: Our study is the first to describe the vast quantity and wide spectrum of medications used by campers nationally. Our data illustrate the immense effort required by camp healthcare staff to receive, store, dispense, and triage medications to ensure campers’ needs are met for routine health care and emergencies. Pediatricians should advocate for robust safety and quality improvement measures to provide appropriate safeguards against adverse medication events to optimize campers’ health and safety while attending camp.
Presented by
Tara Funk
Institution
Michigan Medicine, University of Michigan, Ann Arbor, MI
Other Affiliations
Oakland University William Beaumont, Royal Oak, MI; Lake Erie College of Osteopathic Medicine, Erie, PA; St. Joseph Mercy Hospital, Ypsilanti, MI; Association of Camp Nursing, Fisherville, KY; Clemson University, Clemson, SC
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#medicationsafety #medicationmanagement

51: PREDICTORS OF SEVERE SEPSIS IN PEDIATRIC INTESTINAL FAILURE (POSSIPIF) - RESEARCH IN PROGRESS

Helen Mulcahy, Alex Rogers

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Background Bacteremia leading to severe sepsis is prevalent in the pediatric intestinal failure population. Patient factors that contribute to this increased disease state include bacterial translocation from fragile intestinal mucosa as well as the common presence of long term central venous lines (CVL). Febrile patients with a history of intestinal failure present commonly to the pediatric emergency department due to this risk. Broad work up is often performed and most patients require inpatient admission for intravenous antibiotics and awaiting culture growth. Due to this, many intestinal failure patients with a viral illness or other, non-serious illness are admitted only to watch for decompensation. There are not well evidenced guidelines that guide pediatric emergency providers in risk stratifying these patients.

Objectives The POSSIPIF study was designed to test the hypothesis that there are objective factors that confer risk for poor outcomes in febrile intestinal failure patients. The first poor outcome is severe sepsis. The second poor outcome is patient death. The factors studied include age, race, type of CVL, initial vital signs, height of fever, subjectivity of fever, laboratory values (inflammatory markers, bilirubin, coagulation factors, glucose), blood culture results, urine culture results, antibiotics administered. The poor outcome of severe sepsis was measured based on need for intensive care unit admission, evidence of hypotension for age, bacteremia, lactic acid peaks, creatinine peaks, need for vasoactive support. The poor outcome of death was measured by patient death while admitted or within 30 days of discharge.

Methods A multi-center, retrospective study was conducted. Data was collected separately from each site’s electronic health record (EHR). Qualifying patient emergency department encounters were chosen for review within a five year date range (2014-2019). Patient encounters were included based on pediatric age, qualifying diagnosis of intestinal failure or enrollment in the intestinal failure program, presence of central venous line and presence of fever at home or in the emergency department (ED). Patients were excluded if they were transferred from an outside facility, had a history of solid organ transplant or had received parenteral antibiotics before the ED encounter. Data is being collected and inputted.

Results Results are not available as this study is ongoing across many sites. The results will hopefully provide odds ratios for predicting severe sepsis for the variables analyzed such as demographics, type of CVL in place, vital signs, antibiotic therapy. It will also predict mortality as a secondary outcome.

Conclusion Conclusions are not available as this study is ongoing across many sites. The conclusion will hopefully provide a summary findings and how to apply them clinically. This conclusion will hopefully fill an evidence gap.
Presented by
Helen Mulcahy
Institution
Department of Pediatrics, Children’s Emergency Services - University of Michigan
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Available May 24, 2022 12-1:00 pm

65: CAREGIVERS’ PERCEPTION OF UNIVERSAL TRAUMA SCREENING IN PEDIATRIC MEDICAL SETTINGS

Yi Tak (Daisy) Tsang, Cassie N. Ross, Katherine L. Rosenblum, Kristin A. Kullgren

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Background: Trauma exposure among children and their families before and during medical care is associated with increased health risks and issues with healthcare engagement. Universal trauma screening is often mentioned as a potential standard of care in healthcare settings. However, some argue that trauma screening can be harmful due to stigma and potential re-traumatization while completing the screener. Little is known about families’ acceptability and preferences around trauma screening as well as whether variability may be associated with demographic factors.

Objectives: The goal of the study is to assess parents’/caregivers’ acceptability, preference, and perceived utility of universal trauma screening in pediatric settings. This study also aims to highlight potentially differing perspectives from ethnic minority subgroups.

Design/Method: Caregivers of children with chronic illnesses were asked to rate their comfort level, perceived benefits and detriments, and preferences about trauma screening via a nationwide online survey. Caregivers were recruited through pediatric illness foundations, parent support groups, general social media advertisements, and the “UM Health Research” platform.

Results: Data collection is completed with 1236 responses received. Incomplete or fraudulent responses are being screened out. Data cleaning and analysis are in progress.

Conclusions: This study will lay critical groundwork for the implementation of trauma screening, which is an essential building block as the field continues to develop effective, person-centered, and culturally-sensitive trauma-informed care practices among pediatric healthcare settings.

Research supported by department intramural funding – Fall 2021 Department of Pediatrics Resident and Fellow Research Grant Program (Percy J Murphy, MD and Mary C Murphy, RN Endowed Children’s Research Fund)
Presented by
Yi Tak (Daisy) Tsang
Institution
Department of Pediatrics; Department of Psychiatry - Michigan Medicine, University of Michigan, Ann Arbor
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Available Zoom passcode is 1234. Primary presenter is out for maternity leave. Please see youtube link for oral presentation. Co-authors may be available to answer questions during parts of the 12-1:00PM hour.
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57: Adolescent and Young Adult Opinions on Transgender Athletes in Sports

Waselewski, Alexander C1; Kruger, Laura G2; Waselewski, Eric A3; Waselewski, Marika E2; Chang, Tammy2

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Background: Transgender individuals are a vulnerable population. These individuals have increased rates of suicide, depression, and anxiety. Both social and medical affirmation have shown to improve mental health in this population. One form of social affirmation is athletics. 27 states currently have proposed or passed laws banning transgender athletes from participating in sports based on their gender identity. These laws are being discussed, written, and voted upon by adults. Objectives: We sought to seek out the opinion and experiences of adolescents and young adults on the inclusion and impact of transgender athletes in sports. Design/Methods: An open-ended, five question survey about transgender individuals in sports was sent to the 1199 MyVoice participants. The national MyVoice cohort is a longitudinal text-message poll of youth that seeks to understand youth opinion on salient health and policy issues impacting them. MyVoice represents a diverse sample of youth, aged 14-24 years, from across the United States who are recruited via social media based on national benchmarks. Qualitative responses were coded using thematic analysis and data were summarized with descriptive statistics. IRB approval for MyVoice was obtained from the University of Michigan with a waiver of parental consent for minors Results: The average age of the 905 respondents (response rate 75%) was 20 years old (SD=2.4) with 53% identifying as male and 71% identifying as Caucasian. 34% of respondents participated in either high school and/or collegiate athletics. 95% of respondents did not personally know of anyone who was denied access to sports based on their gender identity. 47% of respondents stated transgender athletes should be able to participate based on their gender identity without any restriction while 35% of respondents said they should be restricted based on the sex assigned at birth. Another 10% said that participation should be dependent on things such as stage of transition, hormone levels, or what sport is being played. Fairness was a concern brought up in responses to several of the questions, specifically for transgender females’ participation in women’s sports. 59% of respondents felt that it would be affirming for transgender athletes to participate based on gender identity and 19% mention mental health may be improved. Conclusions: There are varying opinions among the MyVoice cohort on whether transgender individuals should be able to participate in sport based on their gender identity with no clear majority in favor or against participation. Respondents do feel that transgender athletes would benefit from participation based on gender identity as they would have their gender affirmed and may improve their mental health, but that sports will become unfair. Given two thirds of respondents were not athletes and unable to have participated with transgender athletes, it would be interesting to identify how opinions of transgender athletes were formed.
Presented by
Alexander Waselewski
Institution
1. University of Michigan, Department of Pediatrics 2. University of Michigan, Department of Family Medicine 3. University of Michigan, Department of Internal Medicine
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Available 5/24/2022 12-1PM

58: Variations in Prevalence of Newborn Drug Testing by Birth Parent Race and Ethnicity at Michigan Medicine

Melissa Plegue1,2, Sebastian Schoneich2, Tori Waidley3, Justine Wu2, Lauren Oshman2, P Paul Chandanabhumma2, Christopher Frank2

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Background: Newborn drug testing (NDT) is often performed in cases of known or suspected exposure to drug and/or alcohol use during pregnancy. At Michigan Medicine (MM) there is no formal policy regarding newborn drug testing often leaving the decision to the health care professional. The objective of this study was to characterize patterns of ordering NDT at Michigan Medicine and variations in ordering by birth parent race and ethnicity to explore potential inequities in NDT clinical practice.

Methods: Electronic Health Records were extracted for dyads of newborns and birth parents who received at least one prenatal care visit and delivered at MM between July 2014 and December 2020. Birth parent sociodemographics, delivery- and prenatal-related diagnosis codes, procedures and prenatal urine drug screening (UDS) data were analyzed. Associations between NDT and demographics, presence of specific diagnoses, prenatal UDS orders and results and delivery year were assessed using logistic regression with generalized estimating equations to account for individuals with multiple births in the study period.

Results: We identified a total of 26,366 deliveries across 21,648 birth parents that met study criteria. NDTs were ordered for 1,237 (4.7%) of these deliveries. Across all years, NDT ordering was significantly higher for newborns of Non-Hispanic (NH) Black birth parents (11.3%) compared to newborns of birth parents of all other races (4.2% NH White, 0.2% Asian, 3.5% Hispanic and 4.8% Other Race, p<0.001). Drug testing was more likely to be performed on newborns of birth parents with positive prenatal UDS (73.8%) than newborns of birth parents with negative prenatal UDS (31.3%) or birth parents who did not undergo prenatal UDS (2.4%) (2.4%) (p-values<0.001). This finding was not consistent across races; newborns of Black birth parents were more likely to undergo drug testing even when the birth parent had not undergone UDS during pregnancy (7.3%) compared with newborns of all other races (1.9% NH White, 1.8% Hispanic, 0.7% NH Other including Asian).

Conclusions: Newborns of Black birth parents were more likely to undergo drug testing than newborns of non-Black birth parents, irrespective of risk factors. Findings suggest racial bias in NDT and underscore the need for formal institutional guidelines to promote equitable practices in newborn drug testing.
Presented by
Melissa Plegue
Institution
1Susan B. Meister Child Health Evaluation and Research Center, Department of Pediatrics, Michigan Medicine 2Department of Family Medicine, Michigan Medicine 3University of Michigan School of Medicine, Michigan Medicine
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#AWARD #PlatformPresentation

59: ASSESSING THE IMPACT OF COVID-19 ON IMMUNIZATIONS IN MICHIGAN

Hannah K. Peng1, Ryan Malosh2, Sukhesh Sudan2, Hannah Forsythe2, Abhinav Nalla2, Pooja Patel1, Kevin J. Dombkowski1

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Abstract
Background: The COVID-19 pandemic has led to substantial decreases in outpatient services, with many individuals choosing to defer preventive services, including immunizations. Concerns about this led to the development of a surveillance report by the Michigan Department of Health and Human Services’ (MDHHS) Division of Immunizations.

Objective: The objective of the COVID-19 Impact Report is to monitor the potential influence of the COVID-19 pandemic on non-COVID immunizations reported to the Michigan Care Improvement Registry (MCIR).

Methods: MCIR was queried to assess trends in doses administered over time (2018-2021) and population-level immunization coverage. The Advisory Committee on Immunization Practices (ACIP)-recommended vaccine series coverage was assessed for children aged 19-35 months and for adolescents aged 13-17 years. Non-influenza/non-COVID doses administered were quantified by insurance eligibility (Medicaid enrollee vs. not), age group, vaccine type, and facility type.

Results: Between March 2020 and December 2021, immunization series coverage decreased by 4.4 percentage points for children aged 19-35 months, and 3.8 percentage points for adolescents aged 13-17 years. The pandemic exacerbated an existing disparity in series coverage by Medicaid status, with Medicaid-enrolled children 19-35 months of age having coverage 10.2 percentage points lower than those without Medicaid as of December 2021. The number of non-influenza/non-COVID immunization doses administered in January-December 2021 was 8.2% lower for children 0-8 years of age and 15.2% lower for adolescents 9-18 years of age, compared to the January-December 2018-2019 average. However, this was an improvement over the decreases in administrations seen in 2020, which were 10.8% lower for children and 23.4% lower for adolescents, compared to the January-December 2018-2019 average. While most childhood vaccines saw a consistent increase in administrations following 2020, Polio and Hib failed to rebound to pre-pandemic levels until the last quarter of 2021. For adolescents, Hepatitis A coverage failed to rebound throughout 2021. As of December 2021, vaccine administrations to children and adolescents were similar to pre-pandemic levels at pediatric and family practice sites, but still lagged pre-pandemic levels at local health departments.

Conclusions: Widespread decreases in immunizations were observed throughout Michigan following the onset of the pandemic. While immunization rates are starting to improve, they have not yet reached pre-pandemic levels. Statewide immunization registries such as MCIR are an important tool to evaluate the impacts of the pandemic on immunization delivery and identify potential opportunities for improvement.
Presented by
Hannah Peng
Institution
1Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, Department of Pediatrics, University of Michigan; 2Michigan Department of Health and Human Services
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#HonorableMention #FeaturedPoster
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Available May 24, 12-1 pm

60: CYSTIC FIBROSIS RELATED DIABETES – ADHERENCE TO SCREENING AT A LARGE CLINICAL CENTER

Nellie Said, Jung Eun Lee, Emily Dhadphale, Joyce Lee, Samya Nasr

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Abstract
Background Cystic fibrosis-related diabetes (CFRD) is increasing in incidence among patients with cystic fibrosis as the life expectancy improves with the advent of CFTR modulator treatments. The current Cystic Fibrosis Foundation screening guidelines, last updated in 2010, recommend screening for CFRD with a 2-hour OGTT annually, starting at 10 years of age [1]. Prior studies have demonstrated that centers with higher rates of screening with OGTT’s diagnose CFRD earlier and have slower rates of pulmonary decline [2]. Questions remain as to the best way to screen for diabetes among patients with CF given their complexity. The aim of our study was to describe the adherence rates of ordering OGTT’s and rates of completion of OGTT’s at Michigan Medicine in CF populations. Methods The cohort was defined as patients with CF who were eligible for screening with an OGTT between 2010 and 2021. We excluded patients with a diagnosis code of CFRD. We defined screen eligible years as the number of years between 2010 and 2021 in which the CF patients should have been screened with an OGTT. We defined the number of OGTT tests ordered per patient by summing the number of OGTT orders per year that were performed over the period. We defined the number of OGTT tests completed per patient by summing the number of completed OGTT tests for the period. We defined order adherent as having a % ordered per patient that was >/= 75%. We defined test adherent as having a percent performed per patient that was >/= 75%. We analyzed the differences in these measures based on race, gender, and age. We examined the outcomes of screening (pre-diabetes or diabetes) based on OGTT results and HbA1c.

Results At Michigan Medicine, among all patients eligible for screening with an OGTT, there was a center-level rate of ordering OGTT’s of 16.5%, and a rate of screening with completed OGTT’s of 13.8 %. 83% OGTT’s ordered were completed by patients, while 100% of HbA1c’s ordered were completed. Of the OGTT’s completed, 24% screened positive for pre-diabetes and 3.4% screened positive for diabetes. Of the HbA1c performed, 31% screened positive for pre-diabetes, and 1.2% screened positive for diabetes. There were significant differences by age in rates of screening (p<0.01) and rates of completion (p<0.01) with higher rates of screening in younger vs older patients, but not by gender or race (Table 1).

Conclusions Overall, rates of adherence to OGTT ordering and completion were suboptimal. Patients had a higher rate of adherence to diabetes screening with HbA1c compared to OGTT and ordering adherence was higher for pediatric vs adult patients. While current CFF guidelines recommend the OGTT as the standard of screening for CFRD, OGTT testing is more burdensome, and takes more time to complete among a patient population that already has high healthcare utilization. Continued analysis of our data is needed to further determine outcomes of screening, specifically trends in BMI, pulmonary function tests (FEV-1 and FEF25-75), number of hospitalizations and variations in insulin use.
Presented by
Nellie Said
Institution
Division of Pediatric Endocrinology, Department of Pediatrics, Michigan Medicine; Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan; Division of Pediatric Pulmonology, Department of Pediatrics, Michigan Medicine
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61: Hydroxyurea Utilization Patterns Among People Living with Sickle Cell Disease

M. Rushing1, S. Horiuchi2, M. Kayle3, S. Reeves1, S. Paulukonis2

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Abstract
Background: Hydroxyurea is the primary pharmaceutical intervention for sickle cell disease (SCD) because it effectively reduces the risk of SCD complications, including pain crises. Despite much evidence of the short- and long-term effectiveness of hydroxyurea, adherence is low, and little is known about hydroxyurea adherence over time.

Objectives: Identify hydroxyurea utilization patterns among Californians living with SCD who receive Medicaid benefits.

Design/Method: The analysis was completed using the California Sickle Cell Data Collection (SCDC) program data. The SCDC is a CDC funded public health surveillance at the population level. Californians living with SCD enrolled in Medicaid with at least one filled hydroxyurea prescription between 2010-2018 were included in the analysis. The observation period for each participant began following the first filled hydroxyurea prescription between 2010 and 2017 and ended 365 days later. The medication possession ratio (MPR) was used as a proxy measure of utilization. The monthly MPR was calculated by summing the total number of days of filled hydroxyurea prescriptions divided by the total number of days in the month, while accounting for days admitted inpatient. Group based trajectory modeling was used to identify distinct MPR trajectory groups. Model selection was based on BIC, significance of group membership, and clinical relevance. A chi-squared test was conducted to determine the association between age and trajectory group membership.

Results: There were 713 Medicaid enrollees with SCD included in the analysis: 57% were under 21 years old and 50% were males. Three distinct groups of hydroxyurea possession patterns were identified: persistently high (n=263, 37%), moderate decreasing to low utilization (n=253, 35%), and low decreasing to no utilization (n=197, 28%). The distribution across the three groups were similar between sexes. The association between age and trajectory group membership was significant (χ2=23.56, p<.01). Among the pediatric population, 44% had persistently high hydroxyurea utilization (n=178) and 22% had low decreasing to no utilization (n=89). In contrast, among adults, 28% had persistently high hydroxyurea utilization (n=85) and 36% had low dropping to no compliance (n=108).

Conclusions: Despite the evidence of hydroxyurea in reducing pain crises, the majority of people with SCD that filled hydroxyurea prescriptions did not remain adherent. A more adherent utilization pattern was observed among the pediatric population, suggesting there are specific factors among the pediatric population promoting higher adherence that are not present among adults. Interventions are urgently needed to increase adherence to hydroxyurea among people with sickle cell disease.
Presented by
Melinda Rushing <rushingm@med.umich.edu>
Institution
1 Susan B. Meister Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan, Ann Arbor, MI 2 Tracking California Public Health Institute, Richmond, CA 3 Duke University School of Nursing, Durham, NC
Hashtags
#groupbasedtrajectorymodeling #GBTM #SCD #sicklecell
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Available May 24, 2022 12-1:00 pm
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62: DISPARITIES IN HEIGHT AT THE TIME OF INFLAMMATORY BOWEL DISEASE DIAGNOSIS

Joann M. Samalik1, Jeremy Adler1,2

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Abstract
Background Severe inflammatory bowel disease (IBD) is associated with poor growth. Diagnostic delay is associated with prolonged untreated disease and resultant short stature. Growth patterns of healthy children are similar between racial and ethnic groups in US society (Centers for Disease Control & NHANES data). We therefore propose that height Z-score at IBD diagnosis may serve as a surrogate for diagnostic delay. We hypothesize that stunted growth at diagnosis will be found more often among individuals of low socioeconomic status (public insurance, racial and ethnic minorities).

Objectives We aimed to determine if patients with lower socioeconomic status are disproportionately shorter at time of diagnosis.

Methods This is a retrospective evaluation of prospectively collected data from patients with IBD in the ImproveCareNow (ICN) Network (2007-2018). Patients in the ICN registry were included if enrolled <3 months from IBD diagnosis; excluded if age >18 yr, or missing height at diagnosis. Our primary outcome was height Z-score at diagnosis. Height Z-score <-1 was considered short, and <-2 very short. Insurance at ICN enrollment was categorized as private insurance or no private insurance, regardless of Medicaid or supplemental insurance. Bivariate comparisons were made using Student’s t-test, and chi-squared analyses. Multivariate logistic regression used patient and disease characteristics, race, ethnicity, gender, and insurance status to predict short or very short stature as independent variables. The Institutional Review Board granted a waiver of consent.

Results Among the 2867 patients included, 1268 were female (44%), median age 14.2yr (interquartile range 11.3-16.2). Diagnoses were 62% Crohn’s disease, 30% ulcerative colitis, and 8% IBD unclassified. Demographics: 278 (12%) Black, 1,866 (80%) White, 186 (8%) other race, 150 (5%) Hispanic, and 2141 (75%) non-Hispanic (20% ethnicity missing). Insurance: 2015 (70%) private insurance, 610 (21%) no private insurance, (8% missing).

More patients without private insurance (26%) were short at enrollment than those with private insurance (18%; 0<0.001; Figure 1). There were no differences in short stature by race (p=0.37). However, 27% of Hispanic patients were short, compared to 20% non-Hispanic (p=0.03). There was an interaction between ethnicity and insurance, where more Hispanic patients without private insurance were short (31%) compared to all other groups (p=0.007).

Conclusions Patients without private insurance are more likely to be short at IBD diagnosis than those with private insurance. There is no plausible biological explanation for differences in height by insurance status. This difference may relate to diagnostic delay and duration of untreated disease. However, food insecurity may also contribute. Qualitative studies are needed. Efforts are needed to minimize diagnostic delay and address food insecurity among low-income families.

Figure 1. Incidence of Short Stature at diagnosis of inflammatory bowel disease by insurance type
Presented by
Joann Samalik
Institution
1Division of Pediatric Gastroenterology, Michigan Medicine 2Susan B. Meister Child Health Center and Research Center, Michigan Medicine
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63: ACUTE HEALTHCARE UTILIZATION FOR INDIVIDUALS WITH SICKLE CELL DISEASE IN MICHIGAN

Pooja N Patel1, Krista Latta1, Hannah K Peng1, Kevin J Dombkowski1, Sarah L Reeves1

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Abstract
Background: Sickle cell disease (SCD) is a rare, genetic disorder in the United States associated with significant morbidity and early mortality. However, population-level information regarding SCD is unknown in part due to highly fragmented care and the lack of a centralized registry. The Michigan Sickle Cell Data Collection (SCDC) Program is a CDC-funded, population-based surveillance system that aims to longitudinally collect data from multiple sources to better understand the prevalence, healthcare utilization, and health outcomes among persons living with SCD. Objectives: Identify all individuals living with SCD in Michigan and characterize their acute healthcare utilization (i.e., emergency department (ED) visits and inpatient admissions). Design/Methods: The Michigan SCDC program identifies people living with SCD and their healthcare utilization through combining longitudinal, individual-level data from a wide range of sources, including newborn screening, vital records, Medicaid claims, hospital and emergency discharge data, and clinic data. Demographics (age group, sex, geographic location) were assessed for anyone living in the state with SCD in 2017. To evaluate healthcare utilization, ED visits and inpatient admissions for each person were identified from Michigan Medicaid and statewide discharge data, then deduplicated by visit date. Number of visits for each healthcare utilization measure, as well as visit rate per person, were assessed by age group across the lifespan, with a focus on the following three age groups: <10, 10-19, and 20-29 years of age. Results: Overall, there were 3,331 individuals with SCD living in Michigan during 2017. Although the majority (80%) of individuals lived in six counties (Wayne, Oakland, Macomb, Genesee, Saginaw, and Kent), over half of Michigan’s 83 counties were home to at least one individual with SCD. Of those living with SCD, 2,104 (63%) were under 30 years of age. Those under the age of 30 comprised 55% of the total ED visits and 62% of the total inpatient admissions. The ED admission rate for each of the three age groups (<10, 10-19, and 20-29 years) was 0.93, 1.24, and 4.58 visits per person, respectively. The inpatient admission rate for each of the respective age groups was 0.76, 0.88, and 1.36 visits per person. Conclusions: The SCDC program presents an innovative approach to assess population-level data for SCD in Michigan. Our findings show increased healthcare utilization for the 20-29 year age group, suggesting a need for better understanding of transition from pediatric to adult care settings within this population.
Presented by
Pooja Patel
Institution
1Susan B Meister Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan, Ann Arbor, MI
Hashtags
#sicklecell #surveillance #healthservicesresearch
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Available May 24, 2022 12-1:00 pm

64: THERAPY AND MEDICAL APPOINTMENT UTILIZATION AMONG MEDICAL STUDENTS

Keats Ewing and Sarah Thilges

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Abstract
Medical student wellness has increasingly become an area of focus and intervention among medical schools to help combat concerning trends of burnout, depression, and suicide.

Objective: Despite these well-studied trends, more work is needed in the utilization of mental health resources by medical students.

Design/Methods: The authors measured outpatient mental health resource (OMHR) utilization trends among medical students by administering a questionnaire to students at one medical school in December 2020. The primary outcome measure was defined as the use of outpatient mental health services with subgroup analyses of preclinical versus clinical years of medical school and comparison to utilization of other medical appointments.

Results: Of 699 medical students available for participation, 27.9% (n = 193) completed the questionnaire, 49% (n = 94) stated they had utilized OMHR at some point during their time in medical school. Of those, 57% (n = 50) reported canceling their OMHR appointments due to mandatory medical school requirements and 79% (n = 70) avoided making OMHR appointments. In comparison, 80% (n = 148) attended a medical appointment after starting medical school while 57% (n = 83) had to cancel their medical appointments and 80% (n = 119) avoided making medical appointments. In our subgroup analysis, there was no significant difference in OMHR utilization between students in preclinical versus clinical years, but those in their clinical years were significantly more likely to cancel their OMHR appointment than those in preclinical years. There was not a significant difference in canceling medical appointments during preclinical versus clinical years. Women were significantly more likely to attend OMHR appointments than men, but there was no significant difference between men and women in attending medical appointments.

Conclusion: The authors’ findings support the need for further medical school administrative support of students as they attempt to receive the mental health and medical care they deserve.
Presented by
Keats Ewing
Institution
Department of Pediatrics, University of Michigan, Ann Arbor, MI
Other Affiliations
Department of Psychiatry and Behavioral Neurosciences, Loyola University of Chicago, Maywood, IL.
Hashtags
#meded #medicalstudent #mentalhealth #therapyutilization
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Available May 24, 2022 12-1:00 pm

66: EXPERIENCE OF STIGMA AND ITS RELATIONSHIP TO IDENTIFICATION WITH THE NEURODIVERSITY MODEL FOR INDIAN PARENTS OF CHILDREN WITH AUTISM SPECTRUM DISORDER

Sahita Manda1, Elizabeth Buvinger2, Shichi Dhar3, Harika Veldanda4

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Abstract
Background: It is widely recognized that individuals with autism spectrum disorder (ASD) and their families continue to face extensive stigma and that much of the current research on ASD is deficit-focused. Diversity and inclusion perspectives are emerging, but there is less of a focus on how stigma affects the adoption of these approaches.

Objectives: In collaboration with the University of Michigan Department of Psychology and the national Indian organization Action For Autism, our research aims to understand the experience of stigma and its relationship to identification with the neurodiversity model for Indian parents of children with ASD. The neurodiversity model proposes that ASD is a natural variation of human behavior that should be celebrated (Jaarsma & Welin, 2011). This study explores the extent to which Asian value adherence, child functioning, and perceived ASD stigma contribute to parental alignment with the neurodiversity model. It also investigates the ways in which alignment with the model affects parental stress, isolation from family and friends, parenting goals, identification of child’s strengths, and positive perceptions about raising a child with ASD.

Method: The study was carried out by administering anonymous online surveys through the platform of Qualtrics to Indian parents residing in India (N=82; full data n=56) with children aged 17 or younger diagnosed with ASD.

Results: Statistically significant correlations between a child’s ASD behaviors, perceived ASD stigma, parental stress, and isolation from family and friends were found. Neurodiversity alignment was also identified as a mediator in the relationship between perceived ASD stigma and parental stress.

Conclusion: Findings demonstrate that perceived stigma from ASD-related behaviors can compel parents to isolate themselves from family and friends to avoid possible rejection or exclusion. Results also support the idea that social surroundings, of which stigma is a part, must be conducive for parents to adopt a strength-based approach. More complex mediation analyses incorporating the neurodiversity alignment variable as well as Asian value adherence will be conducted and will have implications for the adoption of strength-based practices and the reduction of stigma associated with ASD within different cultural contexts.
Presented by
Sahita Manda
Institution
1School of Public Health, University of Michigan; 2Department of Psychology, University of Michigan; 3School of Public Health, University of Michigan; 4College of Literature, Science, and the Arts, University of Michigan
Hashtags
#autism#india
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67: HOSPITALIZATION AND MORTALITY DUE TO COVID-19 AMONG PEOPLE BORN 1987-2019 WITH SICKLE CELL DISEASE OR SICKLE CELL TRAIT IN MICHIGAN

Krista Latta1, Susan Paulukonis2, Isabel Hurden3, Sarah Reeves1

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Abstract
Background: Sickle cell disease (SCD) is a rare, genetic hemoglobinopathy considered to be a risk factor for severe COVID-19 outcomes. Some evidence suggests that individuals with sickle cell trait (trait), the carrier state of SCD, may also be at risk for severe COVID-19 outcomes. To date, there have been no studies that assess COVID-19 outcomes in those living with SCD and trait at the population level.

Objective: Assess COVID-19 related hospitalization and mortality among those living with SCD or trait using population-based cohorts in the state of Michigan.

Methods: We linked all COVID-19 infections in the Michigan Disease Surveillance System from March 2020-November 2021 to births in newborn screening records (NBS) from 1987-2019 in the state of Michigan. Individuals that did not link, had an unknown NBS hemoglobin result, or had an abnormal, non-sickle cell hemoglobinopathy were excluded from analysis. Race, sex, and age were obtained from NBS; COVID-19 hospitalization and mortality were obtained from the Michigan Disease Surveillance System. We used logistic regression models with generalized estimating equations (GEE) to assess the relationship between hemoglobin status (normal hemoglobin, SCD, trait), COVID-19 hospitalization, and COVID-19 mortality. GEE was used to account for individuals with multiple infections. We limited models to those identified as Black race due to missing race data concerns across all hemoglobin groups. Models were adjusted for sex and age.

Results: We linked 329,552 infections among individuals ages 0 to 33 from the COVID-19 registry to NBS records (98.7% normal hemoglobin, 0.1% SCD, 1.2% trait). Of those that linked, 14.0% (n=45,630) were identified as Black race. For those identified as Black race, the adjusted odds of hospitalization for SCD was 15.4 (95% CI: 10.4, 22.9) times greater than the normal hemoglobin group. The adjusted odds of death due to COVID-19 in those with SCD was 15.9 (95% CI: 4.8, 52.5) times greater than the normal hemoglobin group. We did not find a significant difference in odds of hospitalization or death between the trait and normal hemoglobin groups.

Conclusions: Individuals with SCD are at a higher risk of severe COVID-19 outcomes compared to individuals with normal hemoglobin; however, trait does not appear to be a significant risk factor. These results demonstrate that vaccinations and access to early COVID-19 treatments are important to promote among populations living with SCD.
Presented by
Krista Latta
Institution
1 Susan B. Meister Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan, Ann Arbor, MI
Other Affiliations
2 Tracking California Public Health Institute, Richmond, CA 3 Lifecourse Epidemiology and Genomics Division, Michigan Department of Health and Human Services, Lansing, MI
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Available May 24, 2022 12-1:00 pm

68: MULTICENTER EVALUATION OF PATTERNS OF AND REASONS FOR BIOLOGIC DISCONTINUATION AMONG CHILDREN WITH CROHN’S DISEASE

Jana Creps1, Dianne C Singer2, Michaella K Baker2, Sabina Ali3, Jess L Kaplan4, Jonathan Moses5, Brad A Pasternak6, Charles M Samson7, David L Suskind8, Jeremy Adler2,9

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Abstract
Background Crohn’s disease (CD) causes progressive bowel damage, poor quality of life, and is incurable. Monoclonal antibody medications (biologics) have dramatically improved outcomes for children with CD. However, few biologics are available, and many patients discontinue one biologic after another, sometimes exhausting the limited treatment options before reaching adulthood. The frequency of, and reasons for biologic discontinuation have not been evaluated, nor is it known how often stopping biologics may be preventable. We conducted a multicenter study to determine patterns of biologic use and discontinuation. This preliminary report is already the largest study (adult or pediatric) to evaluate this important topic for patient care.

Objectives To determine how often children with CD discontinue biologics, the reasons for, and evaluations performed prior to discontinuation.

Methods Clinician and patient parents were involved in creating and conducting this study. We identified all patients with CD at 6 Pediatric Inflammatory Bowel Disease Centers in the US (2010-2021) from the ImproveCareNow (ICN) Network registry. Inclusion criteria required enrollment in ICN within 30 days of diagnosis and age at diagnosis <18 yr. Biologics included infliximab, adalimumab, certolizumab pegol, ustekinumab, vedolizumab, and their available biosimilars. Medical record abstraction supplemented the prospectively collected ICN registry data. Patient characteristics and treatment patterns, evaluations prior to biologic discontinuation, and reasons for discontinuation were classified. Changes in biologics were visualized with Alluvial plots. Bivariate comparisons were performed using Student t-test and chi-square with Stata 17.0. The study was approved by each institution’s Institutional Review Board.

Results To date, data from 358 of 1,009 (35%) patients were analyzed. In total, 305 (85%) started at least one biologic. Of those, 132 (44%) switched to a 2nd biologic (including 45 who switched to a biosimilar). Of all biologic starters, 31 (9%) went on to a 3rd or 4th biologic during pediatric care. Reasons for biologic discontinuation included primary non-response (8%), secondary loss of response (23%), developing anti-drug antibodies (6%), adverse event (18%; 3 considered serious), non-adherence or choice (6%), and insurance problems (15%). Among all who discontinued their 1st biologic for inadequate efficacy, 90% underwent at least some pre-discontinuation evaluation, including checking serum level (81%), fecal calprotectin (21%), endoscopy (36%), or MR/CT imaging (55%).

Conclusions In this multicenter study of pediatric CD, we found 44% of those who started their 1st biologic eventually discontinued it. Ultimately nearly 10% discontinued 3 or more biologics. Medical reasons dominated, but 15% of patients discontinued due to insurance problems. Strategies are needed to reduce the rate of biologic discontinuation to improve outcomes and preserve long-term treatment options.

  Figure 1. Alluvial plot of changes in medication use. Those who never changed remain in the same category.
Presented by
Jeremy Adler
Institution
1Division of Pediatric Surgery, Michigan Medicine; 9Division of Pediatric Gastroenterology, Michigan Medicine 2Susan B. Meister Child Health Evaluation and Research Center, Michigan Medicine
Other Affiliations
3Division of Pediatric Gastroenterology, University of California San Francisco 4Division of Pediatric Gastroenterology, MassGeneral Hospital for Children 5Division of Pediatric Nutrition and Gastroenterology, Rainbow Babies & Children’s Hospital 6Division of Pediatric Gastroenterology, Phoenix Children’s Hospital 7Division of Pediatric Gastroenterology, St. Louis Children's Hospital 8Division of Pediatric Gastroenterology, Seattle Children’s Hospital
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Available May 24, 2022 12-1:00 pm

69: Use of Recommended Antiviral Medications for Children Hospitalized with Influenza 2010-2020

Kavita Warrier1, Harlan McCaffery2, Richard Eikstadt2, Sarah Reeves3, Emily Martin4, Alison Tribble1

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Abstract
Antiviral medications improve outcomes and reduce hospitalization length in children with influenza, and CDC/AAP recommend their use for children hospitalized with influenza since the 2009-2010 pandemic season. Five years after the pandemic, antiviral use at children’s hospitals increased to only 73%, leaving a sizable proportion of children, including those at high risk for severe illness, without antiviral therapy. What factors drive antiviral use, and if uptake has improved, are unknown. We sought to describe current antiviral use for children hospitalized with influenza, identify patient characteristics associated with receipt of recommended antivirals, and assess trends in use and variability by hospital. Using Pediatric Health Information System data, we conducted a retrospective analysis of children 0-17 years with ICD-9/10 codes of influenza discharged from children’s hospitals between 10/2010 and 6/2020. We excluded those with influenza discharges in the prior 30 days or stay <1 day. Receipt of antivirals was modeled using mixed effects logistic regression to account for hospital clustering and adjust for risk factors for severe influenza illness, illness severity (need for vasopressors, mechanical ventilation, or ECMO) and influenza season. We used descriptive statistics and X2 to assess receipt of recommended antivirals over time and by hospital for the 2019-20 influenza season. We identified 83034 influenza discharges (56% male; median age 3 years [IQR 1-8 years]) at 49 hospitals. 11% had severe illness, 72% had ≥1 risk factor, and 71% received recommended antivirals. Receipt of recommended antivirals was associated with influenza risk factors (OR 1.8 [CI 1.7-1.9]) and severe illness (OR 1.35 [CI 1.2-1.5]) (Fig 1). Overall antiviral use was unchanged over the past 5 years (2019 vs 2014: OR 1.029[CI 0.8-1.3]). Although use for severe disease was highest in 2019 (87%), receipt among low-risk patients declined (62%) [X2 p<0.001]. The proportion of antiviral receipt by hospital ranged from 0.52 (SE 0.02) to 0.90 (SE 0.02) (Fig 2); only 27% of hospitals provided antivirals to >80% of patients. Despite longstanding national recommendation for antiviral use in children hospitalized with influenza, a substantial proportion do not receive antiviral therapy, including 30% in the 2019-2020 influenza season. Overall use has remained static, with declining use in low-risk children. Antiviral use also varies considerably across pediatric hospitals. To provide optimal care for children hospitalized with influenza, children’s hospitals should address these gaps.
Presented by
Kavita Warrier
Institution
1University of Michigan Department of Pediatrics, Division of Pediatric Infectious Diseases 2University of Michigan Department of Pediatrics Biostats Core 3University of Michigan Department of Pediatrics, CHEAR 4School of Public Health, University of Michigan
Hashtags
#AWARD #PlatformPresentation

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52: ADULT VERSUS PEDIATRIC CARE SETTING DIFFERENCES IN ‘REASON FOR ETHICS CONSULT’ FOR PATIENTS 18 TO 26 YEARS OLD

Janice Firn, Samantha Lyons, George Freigeh, Kelly Matula

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Abstract
Background The liminal space between childhood and adulthood is distinctive for medical care as decision-making authority shifts from the parent to the young adult, and the patient’s responsibility shifts from assent to consent. Patients aged 18 to 26 can be cared for by pediatric or adult clinicians or both. Either group might work limitedly and be unfamiliar with the ethical issues that arise for this population. Although the evolution of ethical concerns across this continuum is commonplace, characterization of ethical issues encountered in this group and if they differ depending on whether care is provided in the adult or pediatric setting is lacking.

Objectives We hypothesized that there would be differences between ethics consultation requests and primary contextual features based on the setting (adult vs. pediatric) where the consult originated.

Design/Method We conducted a retrospective review of 613 ethics consultation notes to identify patients 18-26 years old seen by either the Adult or Pediatric Ethics Committees at Michigan Medicine from 1/1/2016 - 12/31/2020 (HUM00197110). We collected demographic information and coded consultation notes using a classification schema for ethics consultation adapted from Nilson et al. and Johnson et al. and analyzed these using descriptive statistics.

Results Forty-six notes (14 pediatric, 32 adult) were identified; 43 of which were unique patients. The median age was 24 in the adult setting and 19 in the pediatric setting. All patients spoke English with 50% female; 96% were non-Hispanic, 65% were White, and 78% were inpatient. The primary ethical issue in the adult setting was refusal of recommended treatment (17%), while the principal contextual issue was communication disputes between the staff and the patient (12%). The leading ethical issue for the pediatric setting was goals of care (11%), and the dominant contextual issue was tied (8%) between communication conflicts between the staff and family and quality of life.

Conclusion The ethical dilemmas and related contextual features experienced by this population are different based on setting. Regardless of setting, improved patient-provider communication may ameliorate some of these challenges, and certain demographics (age, race, language, inpatient) from this study raise concerns for utilization of ethics services for some patients. Further education on communication, implicit bias, and ethics services may be needed.
Presented by
Janice Firn
Institution
Department of Learning Health Sciences, and Center for Bioethics and Social Sciences in Medicine; Department of Pediatrics University of Michigan Medical School
Other Affiliations
James M. Anderson Center for Health Systems Excellence, Cincinnati’s Children Hospital Medical Center
Hashtags
#bioethics
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Available May 24, 2022 1-2:00 pm

53: Perspectives of Language Barriers and Interpretive Services Use in the Neonatal Intensive Care Unit Among House Officers and Clinicians

Aunum Akhter, Michael Redmond, Kate Stanley

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Abstract
Background: Language barriers are associated with unequal access to healthcare and poor patient outcomes. Despite the availability of interpretive services, patients and families with limited English proficiency (LEP) are more likely to experience medical errors, poor patient comprehension and diminished patient satisfaction. Language barriers are especially challenging in the Neonatal Intensive Care Unit (NICU) given the acuity, chronic illnesses, and long-term follow-up associated with prematurity. Currently, there is no standard curriculum that educates neonatology medical learners about these barriers and how to address them.

Objective: We aimed to assess the knowledge, skills, and attitudes of current neonatology fellows and early career neonatologist regarding language barriers among LEP families and best practices using interpretive services (IS) in the NICU.

Methods: An anonymous needs assessment was created using Michigan Medicine’s Qualtrics software. It consisted of 32 questions grouped into demographic, knowledge, confidence, and attitude sections. Specific scores were created for each section and then compared across various demographics. The needs assessment was distributed electronically using the American Academy of Pediatrics (AAP) Training and Early Career Neonatologists (TECaN) listserv to neonatology house officers and early career neonatologists. Aggregated data was analyzed using descriptive statistics and comparative analysis.

Results: One hundred and nineteen questionnaires were completed and analyzed. Most respondents were female, Caucasian, and native English speakers who did not speak a second language. Neonatology fellows accounted for 49% of respondents with even representation across all three years of fellowship. Fifty-one percent of respondents were early career neonatologists with an even distribution of clinicians who graduated one to seven years from fellowship. Most respondents (88%) frequently used phone and video IS. However, 87% of respondents preferred in-person IS. While respondents almost always used IS when obtaining consent or breaking bad news, only 28% of respondents used IS half the time or less when providing families with daily patient updates. Mean confidence scores in using IS across different clinical encounters were significantly higher among respondents who received post-graduate education about IS (p=0.04) and specific training on cultural norms/sensitivities of ethnic minorities (p=0.004) compared to those who did not receive education.

Conclusion: Training in cultural sensitivity and IS skills that specifically addresses daily patient communication for LEP families are two areas to target when designing a health disparities educational curriculum for neonatology medical learners.
Presented by
Aunum Akhter
Institution
Department of Pediatrics Neonatal-Perinatal Medicine; Industrial and Operations Engineering - University of Michigan
Other Affiliations
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Available May 24, 2022 12-12:30 pm

54: Pediatric Continuous Renal Replacement Therapy Curriculum for Pediatric Critical Care Medicine Fellows

Brooke Blazius, Rebecca Lombel, Debbie Gipson, Vivian Shih, Deborah Rooney

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Abstract
Background: Acute kidney injury (AKI) is common in the intensive care unit (ICU) setting with associated morbidity and mortality. As many as 27% of pediatric ICU patients develop AKI, with up to 1.5% requiring renal replacement therapy (RRT). Though pediatric nephrologists typically manage pediatric RRT, at some institutions, intensivists prescribe and manage RRT. It is important for the ICU physicians to be familiar with indications and management of RRT.

Objectives: Our institution has twice yearly one-hour long lectures in pediatric Continuous Renal Replacement Therapy (CRRT) management for the Pediatric Critical Care Medicine (PCCM) fellows. We developed a formalized, virtual pediatric CRRT curriculum to train PCCM fellows on indications to start and stop pediatric CRRT, prescription writing, electrolyte management, nutrition management, and CRRT machine review. The aim was to improve cognitive and confidence skills in pediatric CRRT management in the PCCM fellows.

Methods: A general needs assessment was distributed to the PCCM fellows, CRRT nurse initiators, and PICU attending physicians. Three modules were created to teach pediatric CRRT prescription writing, management of pediatric patients on CRRT, and CRRT machine navigation. The format of educational modules was recorded videos on a virtual learning platform. This allowed PCCM fellows to complete the educational content at their own pace. The PCCM fellow completed pre- and post-module assessments to measure for cognitive and confidence improvements, and a final anonymous evaluation of the curriculum was administered.

Results: Seven of nine PCCM fellows completed the curriculum. There was a statistically significant improvement in pre- and post-module scores, with p-value less than 0.05 for Modules 1 and 3, and Cohen’s d of 2.00 and 1.07, respectively. There was statistically significant improvement in confidence for all three modules, Cohen’s d ranging from 0.49 to 1.16. All fellows that completed the curriculum recommended it be offered to trainees in subsequent years.

Conclusion: This curriculum resulted in improved confidence and knowledge in pediatric CRRT management. In facing barriers with limited in person interaction due to the COVID-19 pandemic, a flexible virtual curriculum has been shown to be successful. Next steps include application of the curriculum to other centers that perform pediatric CRRT and development of in-person simulation cases to enhance the educational experience.
Presented by
Brooke Blazius
Institution
Department of Pediatric Nephrology; Clinical Simulation Center, University of Michigan
Other Affiliations
Department of Pediatric Nephrology, University of Colorado
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Available May 24, 2022 12-1:00 pm

55: DEVELOPING A SUMMER CAMP TO EXPOSE YOUTH IN UNDER-RESOURCED AREAS TO PSYCHOLOGY

Haggerty, D. 1, Birnbaum, R. 1, Bourchtein, E. 1, & Harris, S. D.1

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Background Advocacy and outreach are essential to diversifying psychology training programs. Diverse students often experience systems-level barriers in recruitment which leads to disproportionate representation in the field of psychology. To address barriers in psychology recruitment of diverse students, the University of Michigan Health, Division of Pediatric Psychology, in partnership with Wolverine Pathways (WP), piloted a psychology summer camp. WP is a college-readiness program for 7th- 12th grade students (“scholars”) from under-resourced urban areas. Objectives The purpose of this study was to (a) document the development and implementation of a pilot summer camp that exposed scholars to psychology learning and (b) assess scholar perception of changes in their psychology knowledge and interest. Design/Method Twenty-three, 10th grade WP scholars registered for the seven-day, virtual, Psychology Summer Camp in July 2021. The camp was led by three pediatric psychology fellows. Psychology topics, including Memory and Attention, Development, Health Behaviors, Neurodiversity, and Positive Psychology were taught through group activities, videos, and guest speakers. Program evaluation data were collected using pre-post surveys, with 10 Likert items rated on a 10-point scale (strongly disagree to strongly agree), to assess interest in pursuing psychology learning and knowledge about each of the camp psychology topics. A t-test was used to analyze changes from pre to postsurvey. Open-ended questions were included to evaluate motivation for selecting the psychology camp and to elicit feedback for future camp improvement. Qualitative data were reviewed to identify common themes. Results The results from the presurvey (M = 4.73, SD = 1.38) and postsurvey (M = 6.79, SD = 0.69) indicate scholars’ aggregate interest and knowledge about psychology increased significantly (p = .001) by the end of camp. Scholar knowledge in each content area increased by the end of camp. Twenty (86.96%) scholars endorsed they would recommend the camp to fellow scholars. Scholars’ feedback about improvements for camp included more guest speakers, a wider range of psychology topics, and further information about psychology career paths. Conclusions Pilot camp data suggest initial acceptability of psychology camp for scholars interested in learning about psychology as a field and career. Our initial findings will inform the next step in our advocacy and outreach goals, including collecting more robust data overtime and partnering with other divisions and universities to replicate the camp model with the intent of increasing diversity in psychology training programs through early exposure and mentorship.
Presented by
Danielle Haggerty
Institution
1Division of Pediatric Psychology, 2Biostatistics and Data Management Unit Department of Pediatrics, University of Michigan, Ann Arbor, MI.
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56: Evaluation of Gender Bias in Pediatric Faculty Assessments by Residents at a Tertiary Care Children’s Hospital

Alexandra Blumer, Rebekah Shaw, Katrina Foo, Leah Rappaport

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Introduction Women are under-represented in leadership positions. Evaluations play an important role in physician advancement.Few studies have investigated gender bias in learner evaluations of faculty. In a recent study of a male-dominated field,general internal medicine male physicians were rated more favorably than their female counterparts. Other studies ofgender balanced programs have not demonstrated evaluation bias. It is not known if gender bias exists in the field ofPediatrics. Objective We sought to investigate gender differences in evaluation within our Department of Pediatrics. Additionally, we soughtto investigate whether these differences vary across sub-specialties and practice setting. Methods Faculty evaluations from January 1, 2015 – March 9, 2020 for general inpatient services, subspecialty inpatient services,PICU, NICU, general outpatient continuity clinics and subspecialty outpatient clinics were obtained. The evaluation formutilizes a 5-point Likert scale to answer 17 prompts, including a global assessment of overall teaching ability. Meanratings of faculty performance were then compared by gender using a Wilcoxon two-sample test. Results 5,091 evaluations of male faculty and 10,051 of female faculty were included in our study. Female faculty were rated ashaving higher overall teaching ability compared to their male colleagues (female=4.7 vs male=4.6; p=0.004) and wererated higher in 12 of the remaining 16 prompts. In the inpatient setting, there was no statistical difference in the meanratings of male and female faculty. In the outpatient setting, female faculty were rated as having higher overall teachingability (female=4.79 vs male=4.73; p=0.005) and were rated higher than male faculty in 3 of the remaining 16 prompts.For general pediatric faculty, females received higher ratings for overall teaching ability and for each of the prompts. Bycontrast, there was no difference in ratings of subspecialty pediatric male and female faculty. Discussion/Conclusion In a female predominate field, Pediatric female faculty were rated higher than their male colleagues in overall teachingability. This trend was replicated in the outpatient setting and for general pediatrics however no difference was seen inthe inpatient setting or for subspecialty faculty evaluations. This study is the first of its kind in Pediatrics which adds tothe continued investigation of gender disparities in academic medicine.
Presented by
Alexandra (Alex) D Blumer
Institution
University of Michigan, Department of Pediatrics
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Available May 24, 2022 12-1:00 pm

70: ED Boarding: Inpatient Provider Perception of Safety Concerns and Gaps in Knowledge of Policies

Jessica Hoffman, Blair Lenhan, Kyle Yoo, Shoshana Rudin, Genevieve Allen, Maria Pliakas, Samiksha Tarun PI’s: Emily Jacobson, Julie Barrett

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BACKGROUND: ED boarding continues to be a complex issue affecting both the pediatric and adult hospitals at the University of Michigan, with several ongoing institutional efforts to reduce the number of patients boarding and improve patient safety when care is escalated. The inpatient provider perspective thus far has not been formally assessed. The primary aim of this study is to better understand the perceived challenges and safety concerns of ED boarding from inpatient providers to identify areas for improvement.

METHODS: This project was done as part of the ED Boarding Initiative through the House Officer Quality and Safety Committee (HOQSC). We first met with leadership in AES (Adult Emergency Services) and CES (Children’s Emergency Services) in 2019-2020 to better understand current policies and procedures with regards to ED boarding. We also reviewed house officer and nursing safety reports. We surveyed all house officers in March 2020 on perceived safety concerns with the care provided to boarding patients compared to non-boarding patients. We attempted chart review to identify potential delays in care but ultimately chose to defer further analyses given the complexities and changes because of the COVID-19 pandemic. We performed focus groups with nurses in both CES (2021) and AES (2021-2022), along with a “go and see” with an AES nurse (2021), to better understand the nursing perspective. We then performed root cause analyses through which we highlighted communication barriers between nursing and inpatient providers along with a lack of inpatient provider knowledge of boarding procedures, which we assessed further through surveys sent in January 2022 to Internal Medicine/Med-Peds house officers and MFH providers.

RESULTS: On the initial survey sent to all house officers in March 2020, we had 171 responses and the vast majority (>85%) felt that the care provided to boarding patients is less safe than the care provided to non-boarding patients, with the most common reported issues being the release and completion of orders, communication with nursing, physical distance, and perceived delays in care. Focus groups with AES and CES nursing revealed similar concerns, along with particular concern with inpatient providers releasing orders which is against current policy. We surveyed 112 Internal Medicine/Med-Peds house officers (63%) and MFH providers (37%) on practices for placing and releasing orders for patients who are boarding in the ED, which revealed that 93% have incorrectly released orders themselves, 68% currently place orders in the incorrect location in Michart when patients are boarding, and 88% are not aware of a protocol for how orders are supposed to be placed and released when patients are boarding.

CONCLUSION: The work of this study has been primarily focused on describing the current state of ED boarding, which has changed and become even more complex during this project a result of the COVID-19 pandemic. We have shown that many inpatient providers have concerns with the safety of patients who are boarding in the ED. There are many challenges and areas for improvement in communication, the process of boarding procedures, and education to providers. We provided a brief education intervention to Internal Medicine/Med-Peds house officers and MFH providers in February-March 2022 to inform them of current protocols with regards to releasing orders along with suggested communication strategies to improve teamwork with AES nursing. We plan to assess the effectiveness of this intervention, distribute this education to other specialties, and continue working on additional interventions for quality improvement.
Presented by
Jessica Hoffman
Institution
University of Michigan / Internal Medicine - Pediatrics
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71: IMPROVING CONTINUITY IN RESIDENT PRIMARY CARE CLINIC: RESIDENT AS PCP TRIAL

S. DiBattista1; G. Freigeh1; L. Helms1

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Background: Despite primary care being a common career choice for University of Michigan Pediatrics residents, continuity of care in resident clinics is limited. Previous study data noted that most residents and faculty strongly agreed resident continuity is important for education and patient care. However, data over an 18-month period noted residents saw only 9% of patients at least twice compared to 41% for faculty. In comparison, Med-Peds residents were twice as likely as Pediatric residents to see their pediatric patients for return visits in the same period. Identifying Med-Peds residents as the primary care provider (PCP) was hypothesized to contribute to increased continuity.

Purpose: The purpose of our study was to establish a pilot program identifying Pediatric residents as the PCP to assess impact on continuity. We hypothesized that residents listed as PCP would increase continuity compared to those not listed as PCP.

Methods: This study was conducted over an 18-month period. A cross-sectional analysis of EHR data was performed on patient visits between July 1, 2020 - December 31, 2021 at two continuity clinic sites from 4 residents identified as PCPs and compared to 20 peers (non-PCPs). Survey data was also collected from resident PCPs and supporting faculty during this time. The primary outcome was the percent of patients seen at least twice. A two-tailed t-test compared the percentage between the resident PCPs to non-PCPs from this time period and to all Pediatric residents from the prior data set. Percent of patients seen at least twice by all Pediatric residents during the two time periods was also compared using two-tailed t-test. Survey data was reviewed for trends and subjective comments; no statistical analysis was completed given small sample.

Results: The percent of patients seen at least twice did not differ significantly between groups. Resident PCPs saw 7.4% of patients at least twice compared with 4.5% for non-PCPs (p=0.14). Overall percent of return visit patients decreased from 6% to 5% (p=0.10). Based on survey data, resident PCPs increased their patient panel to 5-20 patients by 18 months. They reported answering inbasket messages rarely to a few times per month. Resident PCP autonomy and clinic satisfaction slightly to greatly increased at 18 months. Faculty reported their time managing inbasket messages was unchanged to slightly decreased, with no faculty concerns or significant issues noted.

Conclusion: Our data show a trend toward greater continuity among resident PCPs. It also shows greater satisfaction among resident PCPs without changing overall work burden. There were several limitations to our study. The trial group included a small number of residents and represented those likely motivated to take on an increased role in continuity clinic. The COVID-19 pandemic also impacted the study period. We hope this data can encourage residents and program administration to augment the continuity clinic experience.
Presented by
Suzie DiBattista
Institution
1Department of Pediatrics, University of Michigan
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Available May 24, 2022 12-1:00 pm

72: ADDRESSING THE TIME TO INITIATION OF PHOTOTHERAPY IN THE NEWBORN NURSERY

Matthew Wolf, Elise Gross, Emily Jacobson, Mayya Malakh

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Background: The need for phototherapy is a common medical issue that arises on the well newborn floor. At Michigan Medicine, over a three-month period (August through October of 2019), over 70 newborns were started on phototherapy in the newborn nursery. The average length of stay of these infants was 3.3 days. Given a consistently high census, 34% of these infants were transferred off the well newborn floor for care. In the newborn nursery, there is a delay in starting phototherapy in jaundiced infants with the largest delay from order to initiation of phototherapy. We hypothesized that the implementation of a standardized and automated process may reduce the time to initiation of phototherapy and thus the total length of stay for jaundiced infants requiring management.

Objectives: This project aimed to reduce the time from order to initiation of phototherapy by 25% in order to subsequently reduce the length of stay of jaundiced infants. Secondary outcomes included an effort to reduce the number of total blood draws while under phototherapy as well as the percent of first re-checks under 6 hours from initiation.

Design/method: A “Phototherapy Quick Tips” information card was generated and placed in the resident workroom on the newborn floor for use. This card outlined the need for a serum bilirubin level based on recent Northern California Neonatal Consortium guidelines. This card also provided instructions to help residents time their subsequent serum bilirubin levels appropriately, based on the time of initiation of phototherapy. Lastly, an automatic page was incorporated into the phototherapy order set to alert nursing of the placed order, so as to eliminate potential delays in communication between members of the care team regarding this order. Data was collected via retrospective chart review for three months prior to and three months after implementation of these interventions. Analysis was performed using independent two-sample t-test and two proportion z-test.

Results: Time from order to initiation of phototherapy, overall length of stay, and percentage of first bilirubin re-checks less than six hours from starting phototherapy remained unchanged despite implementation of interventions. However, the number of bilirubin lab draws while undergoing phototherapy did reduce with statistical significance.

Conclusions: While the primary objective of reduction time time from order to initiation of phototherapy was not achieved, the number of lab draws while under phototherapy was reduced. However, the clinical significant of this reduction is arguable. Overall, there remains numerous intervention points to help reach the goal of a 25% reduction in time from order to initiation of phototherapy.

Presented by
Matthew Wolf
Institution
University of Michigan Department of Pediatrics
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Available May 24, 2022 12-1:00 pm

73: IMPLEMENTATION OF A COMMUNITY PARTNERSHIP ADVOCACY CURRICULUM

E. Hovel1; S. DiBattista1; M. Naughton1; J. Sturza2

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Background: Pediatricians have the potential for tremendous impact in advocacy for children, and pediatricians’ role as advocates is well supported by the American Academy of Pediatrics. Child advocacy training is a requirement of pediatric residences, but there are limited guidelines and curricula available. We designed and implemented a hands-on, community-based advocacy curriculum to augment advocacy training for pediatric residents at a major children’s hospital. This was embedded into an existent community health rotation starting in July 2021.

Methods: This is an ongoing prospective pre- and post-intervention study of a new community-based advocacy curriculum for pediatric residents (N= 31) at a large academic children’s hospital. Our curriculum began with self-directed exploration of an online bank of resources relating to local youth justice reform, legislative advocacy, social media advocacy, and writing Op-eds. Residents then worked with a local nonprofit organization to learn about the youth justice system and exercise concrete advocacy skills. We distributed an anonymous survey to residents before and after their participation in the curriculum. The survey assessed comfort in advocacy-related skills and attitudes towards advocacy using Likert-type 5-point scales. To analyze the data, paired t-tests or McNemar tests were used to assess change.

Results: Comfort in various areas was assessed on a scale from 1 (extremely uncomfortable) to 5 (extremely comfortable). Comfort in working with community organizations increased from an average of 3 to 3.8 (p = 0.0004). Comfort in exercising legislative advocacy, social media advocacy, and writing Op-eds all increased significantly (2.5 vs 3.5, 1.9 vs 3, and 2.3 vs 3.7 respectively, p <0.0001). Residents’ perceived importance in highlighting disparities while advocating for children increased, though the change was not significant (p = 0.06). Perceived awareness of local youth justice reform more than doubled on a 5-point scale (1.5 to 3.3, p <0.0001). Lack of knowledge as a barrier to advocacy decreased from 53% to 10% (p = 0.0005), but lack of time remained a barrier (73% vs 87%).

Discussion: This curriculum was easily nested into an existing community health rotation month, which is required by the ACGME for pediatric residency programs. After participating in this curriculum, residents’ comfort with advocacy in general, working with community organizations, and exercising the three skills our curriculum focused on all increased to a statistically significant degree. Additionally, far fewer residents cited lack of knowledge on how to advocate as a barrier to advocacy. As this is an ongoing pilot, our sample size was small at the time of statistical analysis. It will be important to continue analysis with a larger sample size, and to integrate resident feedback in improving this curriculum.
Presented by
Suzie DiBattista and Liz Hovel
Institution
1Department of Pediatrics, University of Michigan; 2University of Michigan Charles Woodson Biostatistics Consultation Program
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Available May 24, 2022 12-1:00 pm

74: EXAMINING FOLLOW-UP CARE FOR CHILDREN AT-RISK OF DEVELOPMENTAL DELAY TO REDUCE HEALTH DISPARITIES

Sharnita D. Harris, Teryn Bruni, Jennifer Radesky, Layla Mohammed, Danielle Haggerty, Tiffany Munzer, Elizabeth Koval

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Background Developmental screening is recommended at every health maintenance visit beginning at 9 months. Disparities in developmental screening, surveillance, and provider responses among children from underserved backgrounds result in undetected developmental and behavioral concerns, delayed diagnoses, increased risk for future behavior problems, and missed opportunities for early intervention.

Objective The aim of this project was to better understand barriers in developmental follow-up care by assessing current provider responses to abnormal development screeners, provider and caregiver acceptability of those responses, and subsequent engagement with follow-up resources.

Design/Methods Mixed methods, multi-informant interviews were used to evaluate developmental services at an underserved primary care clinic affiliated with an academic institution. Of 111 eligible participants (aged 4 to 60 months, determined at-risk for developmental delay during a health maintenance appointment between Aug 2019 -Mar 2020), we completed brief phone interviews with 51 caregivers to assess acceptability of provider referral practices, response to developmental concerns, and access to follow-up resources. Participants were average 37 months old, 63% male, 88% spoke English, 57% African American, and 67% had Medicaid insurance. Three pediatric and 2 family medicine providers who practiced at the clinic were interviewed about developmental screening, referral, and barriers to care. Parent and provider interview data were analyzed qualitatively and coded (κ ranging from .71 to 1 and .55 to 1, respectively) using the Consolidated Framework for Implementation Research (CFIR) to identify themes regarding the acceptability, accessibility, and sources of disparities in current developmental care practices.

Results Caregiver data revealed receiving clear instructions, ease of scheduling, and provider follow-up were components of effective referrals, while long wait times, difficulty getting connected to referrals, and the inability follow through with referrals were barriers. Caregivers reported preferring in-depth conversations with provider about delays, handouts, and follow-up appointments with a specialist. Providers identified challenges related to patient needs and resources, networks and communications for both internal and external referrals.

Conclusion(s) Systems-level interventions are necessary to meet the needs of patients and families from diverse backgrounds to ensure developmental concerns are detected early and appropriate resources are provided.
Presented by
Sharnita Harris
Institution
Divisions of Pediatric Psychology, Developmental Behavioral Pediatrics, General Pediatrics - Department of Pediatrics, Michigan Medicine
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76: Improving Safe Sleep in the Newborn Nursery

Megan Zakerski, Kristen Unsicker, Elise Gross, Maria Skoczylas, Derek Spindler

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Background: Approximately 3,500 infants die of SUID annually. The AAP provides evidence-based Safe Sleep recommendations. The newborn hospitalization is a critical period to provide education and guidance about safe sleep. However, newborns are often found in unsafe sleep conditions during the newborn hospitalization. Currently, at C.S. Mott Children’s Hospital, safe sleep education is reviewed and monitored by nursing throughout the newborn admission, with education re-iterated by pediatric providers upon discharge.

Purpose: The purpose of this QI project was to conduct a baseline assessment of how often safe sleep was documented and observed by nursing and how frequently safe sleep is reviewed during the newborn hospitalization and then develop interventions for improving frequency of safe sleep. During our assessment, a transition to a specialized nursing postpartum model occurred in October 2021. As part of this staffing reconfiguration, nurses received a refresher on infant safe sleep.

Methods: Providers met with nursing leadership in VVWH to understand the nursing workflow and process regarding documenting infant safe sleep. Safe sleep is documented by nursing during assessments as part of the infant drop risk assessment within flowsheets in MiChart. This data was extracted and analyzed for babies admitted to the newborn nursery from April 2021 to February 2022 (n=4,381). The frequency that safe sleep was documented and whether safe sleep was reviewed by nursing staff during their newborn hospitalization was calculated for each month. The introduction of the specialized postpartum nursing model was considered during the review.

Results: Safe sleep was observed in approximately 85% of nursing assessments between April 2021-February 2022. Safe sleep was reviewed by nursing staff during 74% of newborn hospitalizations during that same time period. There was no difference following the transition to the specialized postpartum nursing model in October 2021.

Conclusion: Based on this baseline needs assessment, safe sleep is being reviewed 74% of the time during the newborn hospitalization, with room for improvement. Observation of adherence to safe sleep best practices during the newborn admission suggest that increased review of safe sleep is needed. We plan to meet with nursing leadership to discuss these results and develop a multidisciplinary intervention. We aim to improve safe sleep review from 74% to 90% over a 6-month period following our next intervention.
Presented by
Megan Zakerski
Institution
University of Michigan, Department of Pediatrics
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77: Expediting Discharge for Infants Acquiring Oral Feeding Skills and Tube Weaning from the Comfort of Home with Telehealth Home NG Clinic

Natalie Morris,1 Catherine Joppich,3 Megan Schmuckel,1 Christine Ndagije,1 Kimberly Monroe,2 Melissa Andersen1

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Background: Infants born prematurely and with medical illness experience delays and disruptions to oral feeding skill acquisition resulting in prolonged hospitalization and parental stress. When this occurs, providers and parents feel pressure to speed up the oral feeding process using volume-driven strategies that lead to unsafe and uncomfortable feeding experiences. This can result in feeding problems that prolong admission, persist and worsen after discharge, and long-term feeding tube dependency. Our institution established a comprehensive Cue-Based Feeding quality improvement program designed to support cue-based feeding for infants hospitalized after birth and provide coordinated, multidisciplinary telehealth outpatient care after discharge.

Objectives: The objectives of the outpatient clinic are to 1) decrease hospital length of stay, 2) support parents to use evidence-based feeding practices, 3) facilitate safe, efficient oral feeding skill acquisition and tube weaning from home, 4) promote adequate growth and weight gain, 5) prevent long-term feeding tube dependency and feeding disorders, and 6) increase access to specialized feeding support statewide through telehealth services.

Design/Method: The Cue-Based Feeding team screened infants admitted after birth to identify eligible patients to discharge to the Home NG Follow-Up Clinic once they have achieved at least 30% PO and were medically ready for discharge. All patients were followed via telehealth within 1 week of discharge and weekly until weaned from the NG tube. The main outcomes gathered included number of bed days saved (decreased length of stay), number of tubes weaned, weight, g-tube placement, feeding-related readmissions, and parent satisfaction. Outcome data were collected via chart review and parent satisfaction surveys administered at discharge. This project was supported by funds from the Center of Medicare and Medicaid Services through the Michigan Department of Health and Human Services and from Michigan Health Endowment Fund.

Results: Pilot data demonstrate clinical efficacy, feasibility and high levels of parent satisfaction. Thirty-nine patients have been discharged to the outpatient Home NG Follow-Up clinic, resulting in 193 days decreased length of stay (average of 5 bed days per patient). Average weight gain was 29.7 grams/day, with 100% of tubes weaned by a median of 1 month of age. All patients at risk of g-tube placement were weaned from their NG tubes. Fifteen percent of the patients lived over 50 miles from the institution.

Conclusion: This model of care provides increased access to effective and specialized multidisciplinary care which promotes efficient, successful tube weaning, prevention of long-term feeding problems, and high levels of parent satisfaction.
Presented by
Melissa Andersen <melandrs@med.umich.edu>
Institution
1. Pediatric Psychology, 2. Pediatric Hospitalist Medicine, 3. Nutrition Services - C.S. Mott Children’s Hospital, Michigan Medicine
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#AWARD #infantfeeding #NGclinic #tubeweaning #careathome #telehealth #cuebasedfeeding
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Available May 24 12-1pm

78: PHARYNGITIS GUIDELINES IN THE AMBULATORY SETTING; A REVIEW OF COMPLIANCE

Kendra Brown #1, Courtney Nugent #1, Heather Burrows1 (#Equal Authorship)

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Objective: In the ambulatory care setting, pharyngitis is a common presenting symptom, however only 10% of patients have a bacterial etiology despite the frequent use of antibiotics. Our research retrospectively assessed the use of SmartSets in the EPIC EMR to evaluate if physicians using SmartSets were more compliant with the Michigan Medicine pharyngitis guidelines, ultimately looking back five years from an initial study asking the same question.

Methods: A retrospective chart review was conducted which looked at patient encounters from the eight different Primary Care facilities within Michigan Medicine Pediatrics between October 2019 - December 2019 for patients presenting with a chief complaint of pharyngitis. Our initial query identified 1,793 encounters which were stratified to separate the encounters in which the SmartSet was used, which was found to be 407 of these encounters and 1,386 encounters in which the SmartSet was not used. In discussion with an institutional statistician, it was determined that to detect a difference of approximately 10% of appropriate antibiotic use in SmartSet vs non-SmartSet users, a total of at least 504 charts would need to be reviewed. The Michigan Medicine Ambulatory Adult and Pediatric Pharyngitis Guidelines was reviewed, and qualifying patient encounters were assessed based on their compliance with these guidelines.

Results: SmartSet users were compliant with University of Michigan guidelines 91.7% of the time (n=233) compared to non-SmartSet users who were compliant only 85.8% of the time (n=217). A chi-square analysis was performed, which demonstrated there was no statistical difference in compliance between those using SmartSets vs those not using SmartSets (p=0.336).

Discussion: While SmartSet users were more compliant than non-SmartSet users, there was no statistical difference between these two groups. There were limitations to our research including small sample size and time since initial study leading to physician turnover and not knowing there is a smart set. Our research did however reveal that there are common areas between both SmartSet and non-SmartSet users where non-compliance with guidelines is the highest including sending PCRs for patients > 16 years old and inappropriate dosing of antibiotics. Thus, our study revealed particular areas for improvement moving forward, and opportunities for further education.

Presented by
Courtney Nugent and Kendra Brown
Institution
1Department of Pediatrics, University of Michigan, Ann Arbor, Michigan
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Available May 24 12-1pm

79: RESIDENT-PREPARED CHALK TALKS FOR MEDICAL STUDENT EDUCATION- A QUALITY IMPROVEMENT STUDY

K. Ramos1; E. Boulger1; M. Neelakantan1; E. Jacobson1

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Background: Medical student education is an important resident responsibility. Our initial PDSA cycle included a literature review that showed studies have not focused on the utility of scripts and chalk talks for medical student education in a high volume inpatient pediatric setting so an initial library of chalk talks was created. The aim of this quality improvement study was to improve and increase utilization of this library of chalk talks and in doing so, improve medical student education by pediatric residents.

Methods: A pre-assessment survey from 2020 was utilized in order to improve and create new chalk talks for medical student education in Jan 2021. Feedback encouraged more visual aids and case-based teaching. Post-survey was distributed to all students who had completed their pediatrics rotation Feb-Dec 2021. Feedback obtained focused on the methods in which residents taught students, and whether or not chalk talks were useful for these educational sessions. A post-assessment survey was also distributed to all categorical pediatrics and med-peds residents focusing on comfort level teaching medical students and beneficial adjustments to chalk talks. A two proportion Z-test was performed to assess for statistical significance.

Results: Of the 38 medical student respondents, approximately 76% received formal teaching overall during their pediatric rotation, with chalk talks being incorporated into 71% of these sessions. This was an increase in utilization of chalk talks from the pre-assessment survey (51% from a sample size of 45 medical students), which was found to be significant with a p = 0.019. 66% of students found chalk talks to be the most helpful form of teaching, citing a combination of elements including pictures, flowcharts, case presentations, and brainstorming sessions as useful techniques. While the percent increased to 56%, this result was not significant (p = 0.41). Of the 18 resident respondents, approximately 37% had used the prepared chalk talks. This was increased from the prior PDSA cycle (32%) but was not found to be a significant difference (p=0.72). 68% of residents agreed or strongly agreed that having available prepared chalk talks increased willingness to teach students, and 55% of residents believed having chalk talks increased teaching skills.

Conclusions: In continued attempts to improve the methods of teaching students during their pediatrics rotation, this study demonstrated the utility of chalk talks along with the large stride of improvements that are yet to be made. The limited responses from residents (18 respondents out of 105 categorical, med-peds, pediatric genetics, and pediatric neurology residents) made it difficult to ascertain the overall opinion of chalk talks from the resident perspective. In regards to the medical students, survey results demonstrate an increase in utility and application of chalk talks as an educational tool; this should continue to be improved upon in future PDSA cycles.
Presented by
Katie Ramos
Institution
1Department of Pediatrics, University of Michigan, Ann Arbor, MI
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Available May 24, 2022 12-1 PM

80: EVALUATING THE IMPACT OF VIDEO-BASED SUMMARIES FOR CLINICAL PRACTICE GUIDELINES IN PEDIATRICS

Emile Muallem; David A. Stewart

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Background: Video based learning has become an effective modality for delivering information to learners in both an efficient and easy manner. It allows learners to follow along more clearly and create a visual framework for which to digest larger evidence based practices. Videos can help students by visualizing how something works and show information and details difficult to explain by text or static photos. In addition, videos can attract students’ attention, thus motivating them and engaging them to increase their collaboration. Using videos thus can lead to better learning outcomes.

Objective: Translating Pediatric clinical practice guidelines (CPGs) to video based format may lead to increased utilization of guidelines and perhaps improved clinical practices in our institution.

Design/Method: The project incorporates a pre-video survey with three components including a needs assessment, current understanding of current CPG information, content review, and demographic information. Two pediatric CPG’s were utilized based on perceived resident need, difficulty of topic, and expected utilization in clinical practice. The videos were completed using digital software and include introduction information, review of flowsheets and management guidelines. The pediatric CPGs are both 5-7 minutes in length and in the process of being reviewed by faculty, including relevant stakeholders and CPG authors before being distributed to house officers this upcoming academic year.

Results: A total of 73 responses were obtained from house officers via a Qualtrics survey in October 2021 and indicate that 93% surveyed had managed neonatal hyperbilirubinemia and 86% surveyed had managed bronchiolitis. Of those who indicated they had managed hyperbilirubinemia, 82% of them had referred to the CPG and of the house officers who managed bronchiolitis, 87% of them had referred to the corresponding CPG. The most helpful sections of the CPGs were noted to be figures and graphics (45%), management (text) (36%) and diagnostic information (10%). When asked which barriers most prevented utilizing CPG’s in clinical practice 46% of respondents stated locating CPG was the largest barrier followed by length of CPG and lack of time (36% each). When asked how likely residents would be to watch a 5-7 minute video with n=66, responses indicated a mean of 3.29, STD 1.25, variance 1.57 with nearly 56% of house officers (37/66) indicating they are somewhat or extremely likely to watch.

Conclusion: Data suggests that house officers find both locating CPG and time constraints as leading limitations to utilizing CPGs, as well as length of CPGs. House Officers state that the most helpful part of CPG is images/charts/flowsheets and majority would be interested in video CPG (56%). Clinical practice guidelines change frequently so videos can become outdated soon after release which was a limitation of the study.

Presented by
Emile Muallem
Institution
Department of Pediatrics, Hospital Medicine, University of Michigan Health System
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Available May 24 12-1:00 pm

REVISION OF THE PARENT ACCEPTANCE OF PEDIATRIC INTEGRATED CARE SURVEY

R. Birnbaum, A. Cook, D. Haggerty, L. Turnier, H. McCaffery, T. Tope-Banjoko

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Abstract
Background: The onset of the Covid-19 pandemic and the subsequent change in integrated behavioral health (IBH) service delivery in pediatric primary care from in-person to virtual compelled a revision to the original Parent Acceptance of Pediatric Integrated Care Survey (PAPICS).

Objectives: The primary objectives of the project were to update the PAPICS by including questions regarding virtual behavioral health service delivery, revise existing questions to improve internal consistency estimates, and validate the newly designed, chosen survey model.

Design/Method: The PAPICS was revised (PAPICS-R) with a team of experts in IBH pediatric primary care. The Qualtrics Online Panels Service was used to distribute the PAPICS-R to a diverse sample (n = 834) of parents with children under 18-years old. Exploratory and confirmatory factor analyses were then performed with independent samples.

Results: The resulting chosen factor model for the PAPICS-R consisted of 42 items and 5 factors with higher internal consistency estimates than the original version (α = .845 to .923).

Conclusions: The PAPICS-R offers IBH pediatric primary clinics at the University of Michigan Health and other medical systems a tool to better serve parents and children in their community. Gaining insights into parent perspectives on IBH and appropriately addressing their concerns and misperceptions could result in a much needed increase in children, adolescents, and their families accessing behavioral health care.
Presented by
Richard Birnbaum <birnba@med.umich.edu>
Institution
Division of Pediatric Psychology; Biostatistics and Data Management Unit Department of Pediatrics, University of Michigan/University of Michigan Health
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#pediatricpsychology #ibh #primarycare
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Available May 24, 2022 12-1:00 pm