The Cost of Opioid Use in High-Risk Hospitalized Infants.

INTRODUCTION: Hospitalizations of high-risk infants are among the most expensive in the United States, with many requiring surgery and months of intensive care. Healthcare costs and resource use associated with hospitalized infant opioid exposure are less well known. METHODS: A retrospective cohort of high-risk infants aged <1 y admitted from 47 children's hospitals from 2010 to 2020 was identified from Pediatric Healthcare Information System. High-risk infants were identified by International Classification of Diseases 9/10 codes for congenital heart disease procedures, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and gastrointestinal tract malformations. Healthcare resource utilization was estimated using standardized unit costs (SUCs). The impact of opioid use on SUC was examined using general linear models and an instrumental variable. RESULTS: Overall, 126,897 high-risk infants were identified. The cohort was majority White (57.1%), non-Hispanic (72.0%), and male (55.4%). Prematurity occurred in 26.4% and a majority underwent surgery (77.9%). Median SUC was $120,585 (interquartile range: $57,602-$276,562) per infant. On instrumental variable analysis, each day of opioid use was associated with an increase of $4406 in SUC. When adjusting for biologic sex, race, ethnicity, insurance type, diagnosis category, number of comorbidities, mechanical ventilation, and total parental nutrition use, each day of opioid use was associated with an increase of $2177 per infant. CONCLUSIONS: Prolonged opioid use is significantly associated with healthcare utilization and costs for high-risk infants, even when accounting for comorbidities, intensive care, ventilation, and total parental nutrition use. Future studies are needed to estimate the long-term complications and additional costs resulting from prolonged opioid exposures in high-risk infants.

Institutional and Regional Variation in Opioid Prescribing for Hospitalized Infants in the US.

Importance: High-risk infants, defined as newborns with substantial neonatal-perinatal morbidities, often undergo multiple procedures and require prolonged intubation, resulting in extended opioid exposure that is associated with poor outcomes. Understanding variation in opioid prescribing can inform quality improvement and best-practice initiatives. Objective: To examine regional and institutional variation in opioid prescribing, including short- and long-acting agents, in high-risk hospitalized infants. Design, Setting, and Participants: This retrospective cohort study assessed high-risk infants younger than 1 year from January 1, 2016, to December 31, 2022, at 47 children's hospitals participating in the Pediatric Health Information System (PHIS). The cohort was stratified by US Census region (Northeast, South, Midwest, and West). Variation in cumulative days of opioid exposure and methadone treatment was examined among institutions using a hierarchical generalized linear model. High-risk infants were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and other abdominal surgery. Infants with neonatal opioid withdrawal syndrome, in utero substance exposure, or malignant tumors were excluded. Exposure: Any opioid exposure and methadone treatment. Main Outcomes and Measures: Regional and institutional variations in opioid exposure. Results: Overall, 132 658 high-risk infants were identified (median [IQR] gestational age, 34 [28-38] weeks; 54.5% male). Prematurity occurred in 30.3%, and 55.3% underwent surgery. During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median (IQR) length of any opioid exposure was 5 (2-12) cumulative days, and median (IQR) length of methadone treatment was 19 (7-46) cumulative days. There was significant hospital-level variation in opioid and methadone exposure and cumulative days of exposure within each US region. The computed intraclass correlation coefficient estimated that 16% of the variability in overall opioid prescribing and 20% of the variability in methadone treatment was attributed to the individual hospital. Conclusions and Relevance: In this retrospective cohort study of high-risk hospitalized infants, institution-level variation in overall opioid exposure and methadone treatment persisted across the US. These findings highlight the need for standardization of opioid prescribing in this vulnerable population.

Immunostimulatory nanoparticles delivering cytokines as a novel cancer nanoadjuvant to empower glioblastoma immunotherapy.

Glioblastoma (GBM) stands as a highly aggressive and deadly malignant primary brain tumor with a median survival time of under 15 months upon disease diagnosis. While immunotherapies have shown promising results in solid cancers, brain cancers are still unresponsive to immunotherapy due to immunological dysfunction and the presence of a blood-brain barrier. Interleukin-12 (IL-12) emerges as a potent cytokine in fostering anti-tumor immunity by triggering interferon-gamma production in T and natural killer cells and changing macrophages to a tumoricidal phenotype. However, systemic administration of IL-12 toxicity in clinical trials often leads to significant toxicity, posing a critical hurdle. To overcome this major drawback, we have formulated a novel nanoadjuvant composed of immunostimulatory nanoparticles (ISN) loaded with IL-12 to decrease IL-12 toxicity and enhance the immune response by macrophages and GBM cancer cells. Our in vitro results reveal that ISN substantially increase the production of pro-inflammatory cytokines in GBM cancer cells (e.g. 2.6 × increase in IL-8 expression compared to free IL-12) and macrophages (e.g. 2 × increase in TNF-α expression and 6 × increase in IL-6 expression compared to the free IL-12). These findings suggest a potential modulation of the tumor microenvironment. Additionally, our study demonstrates the effective intracellular delivery of IL-12 by ISN, triggering alterations in the levels of pro-inflammatory cytokines at both transcriptional and protein expression levels. These results highlight the promise of the nanoadjuvant as a prospective platform for resharing the GBM microenvironment and empowering immunotherapy.

Insulin-like growth factor-1 receptor controls the function of CNS-resident macrophages and their contribution to neuroinflammation.

Signaling by insulin-like growth factor-1 (IGF-1) is essential for the development of the central nervous system (CNS) and regulates neuronal survival and myelination in the adult CNS. In neuroinflammatory conditions including multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), IGF-1 can regulate cellular survival and activation in a context-dependent and cell-specific manner. Notwithstanding its importance, the functional outcome of IGF-1 signaling in microglia/macrophages, which maintain CNS homeostasis and regulate neuroinflammation, remains undefined. As a result, contradictory reports on the disease-ameliorating efficacy of IGF-1 are difficult to interpret, together precluding its potential use as a therapeutic agent. To fill this gap, we here investigated the role of IGF-1 signaling in CNS-resident microglia and border associated macrophages (BAMs) by conditional genetic deletion of the receptor Igf1r in these cell types. Using a series of techniques including histology, bulk RNA sequencing, flow cytometry and intravital imaging, we show that absence of IGF-1R significantly impacted the morphology of both BAMs and microglia. RNA analysis revealed minor changes in microglia. In BAMs however, we detected an upregulation of functional pathways associated with cellular activation and a decreased expression of adhesion molecules. Notably, genetic deletion of Igf1r from CNS-resident macrophages led to a significant weight gain in mice, suggesting that absence of IGF-1R from CNS-resident myeloid cells indirectly impacts the somatotropic axis. Lastly, we observed a more severe EAE disease course upon Igf1r genetic ablation, thus highlighting an important immunomodulatory role of this signaling pathway in BAMs/microglia. Taken together, our work shows that IGF-1R signaling in CNS-resident macrophages regulates the morphology and transcriptome of these cells while significantly decreasing the severity of autoimmune CNS inflammation.

On the interdependence of ketone body oxidation, glycogen content, glycolysis and energy metabolism in the heart.

In heart, glucose and glycolysis are important for anaplerosis and potentially therefore for d-ß-hydroxybutyrate (ßHB) oxidation. As a glucose store, glycogen may also furnish anaplerosis. We determined the effects of glycogen content on ßHB oxidation and glycolytic rates, and their downstream effects on energetics, in the isolated rat heart. High glycogen (HG) and low glycogen (LG) containing hearts were perfused with 11 mM [5-3 H]glucose and/or 4 mM [14 C]ßHB to measure glycolytic rates or ßHB oxidation, respectively, then freeze-clamped for glycogen and metabolomic analyses. Free cytosolic [NAD+ ]/[NADH] and mitochondrial [Q+ ]/[QH2 ] ratios were estimated using the lactate dehydrogenase and succinate dehydrogenase reaction, respectively. Phosphocreatine (PCr) and inorganic phosphate (Pi ) concentrations were measured using 31 P-nuclear magnetic resonance spectroscopy. Rates of ßHB oxidation in LG hearts were half that in HG hearts, with ßHB oxidation directly proportional to glycogen content. ßHB oxidation decreased glycolysis in all hearts. Glycogenolysis in glycogen-replete hearts perfused with ßHB alone was twice that of hearts perfused with ßHB and glucose, which had significantly higher levels of the glycolytic intermediates fructose 1,6-bisphosphate and 3-phosphoglycerate, and higher free cytosolic [NAD+ ]/[NADH]. ßHB oxidation increased the Krebs cycle intermediates citrate, 2-oxoglutarate and succinate, the total NADP/H pool, reduced mitochondrial [Q+ ]/[QH2 ], and increased the calculated free energy of ATP hydrolysis (∆GATP ). Although ßHB oxidation inhibited glycolysis, glycolytic intermediates were not depleted, and cytosolic free NAD remained oxidised. ßHB oxidation alone increased Krebs cycle intermediates, reduced mitochondrial Q and increased ∆GATP . We conclude that glycogen facilitates cardiac ßHB oxidation by anaplerosis. KEY POINTS: Ketone bodies (d-ß-hydroxybutyrate, acetoacetate) are increasingly recognised as important cardiac energetic substrates, in both healthy and diseased hearts. As 2-carbon equivalents they are cataplerotic, causing depletion of Krebs cycle intermediates; therefore their utilisation requires anaplerotic supplementation, and intra-myocardial glycogen has been suggested as a potential anaplerotic source during ketone oxidation. It is demonstrated here that cardiac glycogen does indeed provide anaplerotic substrate to facilitate ß-hydroxybutyrate oxidation in isolated perfused rat heart, and this contribution was quantified using a novel pulse-chase metabolic approach. Further, using metabolomics and 31 P-MR, it was shown that glycolytic flux from myocardial glycogen increased the heart's ability to oxidise ßHB, and ßHB oxidation increased the mitochondrial redox potential, ultimately increasing the free energy of ATP hydrolysis.

Linked birth cohort files for perinatal health research: California as a model for methodology and implementation.

PURPOSE: Rigorous perinatal epidemiologic research depends on population-based parental and neonatal sociodemographic and clinical data. Here we describe the creation of linked birth cohort files, an enriched data source that combines information from vital records with maternal delivery and infant hospital encounter records. METHODS: Probabilistic linkage techniques were used to link vital records (i.e., birth and fetal death certificates) from the California Department of Public Health with hospital inpatient, ambulatory surgery and emergency department encounter data for mothers and infants from the California Department of Health Care Access and Information. RESULTS: From 2012 to 2018, 95% of live birth records were successfully linked to maternal and newborn hospital records while 85% of fetal death records were linked to a maternal delivery record. Overall, 93% of postnatal hospital encounters of infants (i.e., <1 year old) were matched to a linked record. CONCLUSIONS: The linked birth cohort files is a rich resource opening many possibilities for understanding perinatal health outcomes and opportunities for linkage to longitudinal, social determinant, and environmental data. To optimally use this file for research, analysts should evaluate possible shortcomings or biases of the data sources being linked.

N-acetylcysteine treatment mitigates loss of cortical parvalbumin-positive interneuron and perineuronal net integrity resulting from persistent oxidative stress in a rat TBI model.

Traumatic brain injury (TBI) increases cerebral reactive oxygen species production, which leads to continuing secondary neuronal injury after the initial insult. Cortical parvalbumin-positive interneurons (PVIs; neurons responsible for maintaining cortical inhibitory tone) are particularly vulnerable to oxidative stress and are thus disproportionately affected by TBI. Systemic N-acetylcysteine (NAC) treatment may restore cerebral glutathione equilibrium, thus preventing post-traumatic cortical PVI loss. We therefore tested whether weeks-long post-traumatic NAC treatment mitigates cortical oxidative stress, and whether such treatment preserves PVI counts and related markers of PVI integrity and prevents pathologic electroencephalographic (EEG) changes, 3 and 6 weeks after fluid percussion injury in rats. We find that moderate TBI results in persistent oxidative stress for at least 6 weeks after injury and leads to the loss of PVIs and the perineuronal net (PNN) that surrounds them as well as of per-cell parvalbumin expression. Prolonged post-TBI NAC treatment normalizes the cortical redox state, mitigates PVI and PNN loss, and - in surviving PVIs - increases per-cell parvalbumin expression. NAC treatment also preserves normal spectral EEG measures after TBI. We cautiously conclude that weeks-long NAC treatment after TBI may be a practical and well-tolerated treatment strategy to preserve cortical inhibitory tone post-TBI.

Designed peptide-grafted hydrogels for human pluripotent stem cell culture and differentiation.

Human pluripotent stem cells (hPSCs) have the ability to differentiate into cells derived from three germ layers and are an attractive cell source for cell therapy in regenerative medicine. However, hPSCs cannot be cultured on conventional tissue culture flasks but can be cultured on biomaterials with specific hPSC integrin interaction sites. We designed hydrogels conjugated with several designed peptides that had laminin-ß4 active sites, optimal elasticities and different zeta potentials. A higher expansion fold of hPSCs cultured on the hydrogels was found with the increasing zeta potential of the hydrogels conjugated with designed peptides, where positive amino acid (lysine) insertion into the peptides promoted higher zeta potentials of the hydrogels and higher expansion folds of hPSCs when cultured on the hydrogels using xeno-free protocols. The hPSCs cultured on hydrogels conjugated with the optimal peptides showed a higher expansion fold than those on recombinant vitronectin-coated plates, which are the gold standard of hPSC cultivation dishes. The hPSCs could differentiate into specific cell lineages, such as mesenchymal stem cells (MSCs) and MSC-derived osteoblasts, even after being cultivated on hydrogels conjugated with optimal peptides for long periods of time, such as 10 passages.

Pulmonary Hypertension in Preterm Infants Treated With Laser vs Anti-Vascular Endothelial Growth Factor Therapy for Retinopathy of Prematurity.

Importance: Anti-vascular endothelial growth factor (VEGF) therapy for retinopathy of prematurity (ROP) has potential ocular and systemic advantages compared with laser, but we believe the systemic risks of anti-VEGF therapy in preterm infants are poorly quantified. Objective: To determine whether there was an association with increased risk of pulmonary hypertension (PH) in preterm infants with ROP following treatment with anti-VEGF therapy as compared with laser treatment. Design, Setting, and Participants: This multicenter retrospective cohort study took place at neonatal intensive care units of 48 children's hospitals in the US in the Pediatric Health Information System database from 2010 to 2020. Participants included preterm infants with gestational age at birth 22 0/7 to 31 6/7 weeks who had ROP treated with anti-VEGF therapy or laser photocoagulation. Exposures: Anti-VEGF therapy vs laser photocoagulation. Main Outcomes and Measures: New receipt of pulmonary vasodilators at least 7 days after ROP therapy was compared between exposure groups, matched using propensity scores generated from preexposure variables, and adjusted for birth year and hospital. The odds of receiving an echocardiogram after 30 days of age was also included to adjust for secular trends and interhospital variation in PH screening. Results: Among 1577 patients (55.9% male) meeting inclusion criteria, 689 received laser photocoagulation and 888 received anti-VEGF treatment (95% bevacizumab, 5% ranibizumab). Patients were first treated for ROP at median 36.4 weeks' postmenstrual age (IQR, 34.6-38.7). A total of 982 patients (491 in each group) were propensity score matched. Good covariate balance was achieved, as indicated by a model variance ratio of 1.15. More infants who received anti-VEGF therapy were treated for PH, but when adjusted for hospital and year, this was no longer statistically significant (6.7%; 95% CI, 2.6-6.9 vs 4.3% 95% CI, 4.4-10.2; adjusted odds ratio, 1.62; 95% CI, 0.90-2.89; P = .10). Conclusions and Relevance: Anti-VEGF therapy was not associated with greater use of pulmonary vasodilators after adjustment for hospital and year. Our findings suggest exposure to anti-VEGF may be associated with PH, although we cannot exclude the possibility of residual confounding based on systemic comorbidities or hospital variation in practice. Future studies investigating this possible adverse effect seem warranted.

Effect of extracellular matrix proteins on the differentiation of human pluripotent stem cells into mesenchymal stem cells.

The transplantation of human mesenchymal stem cells (hMSCs), such as bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs), has shown beneficial effects in protecting transplanted tissues and cells against graft-versus-host disease (GVHD). Human pluripotent stem cell (hPSC)-derived mesenchymal stem cells (MSCs) can also be used to generate hMSCs with stable characteristics without limitations. Therefore, we differentiated human induced pluripotent stem cells (hiPSCs, H-M5) and human embryonic stem cells (hESCs, H9) into hMSCs on dishes coated with different extracellular matrix (ECM) proteins to study the effect of cell culture biomaterials on hPSC differentiation into hMSCs. hPSC-derived MSCs cultured on Matrigel (MAT)-coated, collagen (COL)-coated and laminin-521 (LN-521)-coated tissue culture polystyrene (TCP) dishes showed excellent proliferation speed and reduced aging over 10 passages. High MSC surface marker (CD44, CD73, CD90 and CD105) expression was also observed on hPSC-derived MSCs cultured on MAT-coated, COL-coated and LN-521-coated TCP dishes as well as uncoated TCP dishes. Analysis of late osteogenic differentiation by evaluation of mineral deposition revealed that hPSC-derived MSCs cultured on fibronectin (FN)-coated and LN-521-coated TCP dishes showed high osteogenic differentiation. ECM proteins are effective as coating materials on cell culture biomaterials to regulate the proliferation and differentiation fate of hPSC-derived MSCs.

Quality Improvement for Neonatal Resuscitation and Delivery Room Care.

Quality improvement has become a foundation of neonatal care. Structured approaches to improvement can standardize practices, improve teamwork, engage families, and improve outcomes. The delivery room presents a unique environment for quality improvement; optimal delivery room care requires advanced preparation, adequately trained providers, and carefully coordinated team dynamics. In this article, we examine quality improvement for neonatal resuscitation. We review the published literature, focusing on reports targeting admission hypothermia, delayed cord clamping, and initial respiratory support. We discuss specific challenges related to delivery room quality improvement, including small numbers, data collection, and lack of benchmarking, and potential strategies to address them including simulation, checklists, and state and national collaboratives. We examine how quality improvement can target equity in delivery room outcomes, and explore the impact of the COVID-19 pandemic on delivery room quality of care.

Evaluation of Trends in Bronchopulmonary Dysplasia and Respiratory Support Practice for Very Low Birth Weight Infants: A Population-Based Cohort Study.

OBJECTIVES: To characterize the incidence of bronchopulmonary dysplasia (BPD) over time and to test the association of multilevel factors, including respiratory support, with the diagnosis of BPD. STUDY DESIGN: This population-based cohort study included 40 268 infants born between 22 and 32 weeks of gestation at hospitals in California between 2008 and 2017. The diagnosis of BPD was based on respiratory support at 36 weeks postmenstrual age. Tests for linear trend and multivariable logistic regression analyses were performed. RESULTS: The rate of BPD was consistent year to year, and the mortality rate declined. The incidence of BPD was 23.5% for the overall cohort, 44.9% for infants born at <28 weeks of gestational age, and 45.2% for extremely low birth weight infants. For infants born at >26 weeks of gestational age, the incidence of BPD was significantly decreased in the most recent 3-year period compared with the earlier 3 years (OR, 0.91). Invasive ventilation during delivery room resuscitation (OR, 2.64) and after leaving the delivery room (OR, 10.02) conferred the highest risk of BPD compared with oxygen or no respiratory support. Noninvasive ventilation as maximum respiratory support at 36 weeks increased by 20% over time. CONCLUSIONS: Marked changes in noninvasive support care have occurred without an overall decline in BPD rate. Further research, quality improvement, and strategies, along with noninvasive respiratory support, are needed for a reduction in the incidence of BPD.

Purification of Colon Carcinoma Cells from Primary Colon Tumor Using a Filtration Method via Porous Polymeric Filters.

Cancer stem cells (CSCs) or cancer-initiating cells (CICs) are key factors for tumor generation and metastasis. We investigated a filtration method to enhance CSCs (CICs) from colon carcinoma HT-29 cells and primary colon carcinoma cells derived from patient colon tumors using poly(lactide-co-glycolic acid)/silk screen (PLGA/SK) filters. The colon carcinoma cell solutions were permeated via porous filters to obtain a permeation solution. Then, the cell cultivation media were permeated via the filters to obtain the recovered solution, where the colon carcinoma cells that adhered to the filters were washed off into the recovered solution. Subsequently, the filters were incubated in the culture media to obtain the migrated cells via the filters. Colon carcinoma HT-29 cells with high tumorigenicity, which might be CSCs (CICs), were enhanced in the cells in the recovered solution and in the migrated cells based on the CSC (CIC) marker expression, colony-forming unit assay, and carcinoembryonic antigen (CEA) production. Although primary colon carcinoma cells isolated from colon tumor tissues contained fibroblast-like cells, the primary colon carcinoma cells were purified from fibroblast-like cells by filtration through PLGA/SK filters, indicating that the filtration method is effective in purifying primary colon carcinoma cells.

Poly(vinyl alcohol-co-itaconic acid) hydrogels grafted with several designed peptides for human pluripotent stem cell culture and differentiation into cardiomyocytes.

We developed poly(vinyl alcohol-co-itaconic acid) (PV) hydrogels grafted with laminin-derived peptides that had different joint segments and several specific designs, including dual chain motifs. PV hydrogels grafted with a peptide derived from laminin-ß4 (PMQKMRGDVFSP) containing a joint segment, dual chain motif and cationic amino acid insertion could attach human pluripotent stem (hPS) cells and promoted high expansion folds in long-term culture (over 10 passages) with low differentiation rates, whereas hPS cells attached poorly on PV hydrogels grafted with laminin-α5 peptides that had joint segments with and without a cationic amino acid or on PV hydrogels grafted with laminin-ß4 peptides containing the joint segment only. The inclusion of a cationic amino acid in the laminin-ß4 peptide was critical for hPS cell attachment on PV hydrogels, which contributed to the zeta potential shifting to higher values (3-4 mV enhancement). The novel peptide segment-grafted PV hydrogels developed in this study supported hPS cell proliferation, which induced better hPS cell expansion than recombinant vitronectin-coated dishes (gold standard of hPS cell culture dishes) in xeno-free culture conditions. After long-term culture on peptide-grafted hydrogels, hPS cells could be induced to differentiate into specific lineages of cells, such as cardiomyocytes, with high efficiency.

Correction: Weng et al. New International Association for the Study of Lung Cancer (IASLC) Pathology Committee Grading System for the Prognostic Outcome of Advanced Lung Adenocarcinoma. Cancers 2020, 12, 3426.

The authors would like to make a correction to their published paper [...].

A validated model for prediction of survival to 6 months in patients with trisomy 13 and 18.

Congenital heart disease is exceedingly prevalent in trisomy 13 and 18. Improved survival following congenital heart surgery has been reported, however, mortality remains significantly elevated. Utilizing inpatient data on trisomy 13 and 18 from the 2003-2016 Pediatric Health Information System database, a survival model was developed and validated using data from the California Perinatal Quality Care Collaborative and the California Office of Statewide Health Planning and Development. The study cohort included 1,761 infants with trisomy 13 and 18. Two models predicting survival to 6 months of age were developed and tested. The initial model performed excellently, with a c-statistic of 0.87 and a c-statistic of 0.76 in the validation cohort. After excluding procedures performed on the day of death, the revised model's c-statistic was 0.76. Certain variables, including cardiac surgery, gastrostomy, parenteral nutrition, and mechanical ventilation, are predictive of survival to 6 months of age. This study presents a model, which potentially can inform decision-making regarding congenital heart surgery.

Factors Associated with Early Neonatal and First-Year Mortality in Infants with Myelomeningocele in California from 2006 to 2011.

OBJECTIVE: The aim of this study is to examine factors associated with early neonatal (death within first 7 days of birth) and infant (death during the first year of life) mortality among infants born with myelomeningocele. STUDY DESIGN: We examined linked data from the California Perinatal Quality Care Collaborative, vital records, and hospital discharge records for infants born with myelomeningocele from 2006 to 2011. Survival probability was calculated using Kaplan-Meier Product Limit method and 95% confidence intervals (CI) using Greenwood's method; Cox proportional hazard models were used to estimate unadjusted and adjusted hazard ratios (HR) and 95% CI. RESULTS: Early neonatal and first-year survival probabilities among infants born with myelomeningocele were 96.0% (95% CI: 94.1-97.3%) and 94.5% (95% CI: 92.4-96.1%), respectively. Low birthweight and having multiple co-occurring birth defects were associated with increased HRs ranging between 5 and 20, while having congenital hydrocephalus and receiving hospital transfer from the birth hospital to another hospital for myelomeningocele surgery were associated with HRs indicating a protective association with early neonatal and infant mortality. CONCLUSION: Maternal race/ethnicity and social disadvantage did not predict early neonatal and infant mortality among infants with myelomeningocele; presence of congenital hydrocephalus and the role of hospital transfer for myelomeningocele repair should be further examined. KEY POINTS: · Mortality in myelomeningocele is a concern. · Social disadvantage was not associated with death. · Hospital-based factors should be further examined.