Geospatial Distribution of Prenatally and Postnatally Diagnosed Congenital Heart Disease: Implications for Equitable Care from a Fetal Heart Society Research Collaborative Study.

OBJECTIVE: To characterize patterns in the geospatial distribution of pre- and postnatally diagnosed congenital heart disease (CHD) across 6 surgical centers. STUDY DESIGN: A retrospective, multicenter case series from the Fetal Heart Society identified patients at 6 centers from 2012 through 2016 with prenatally (PrND) or postnatally (PoND) diagnosed hypoplastic left heart syndrome (HLHS) or d-transposition of the great arteries (TGA). Geospatial analysis for clustering was done by the average nearest neighbor (ANN) tool or optimized hot spot tool, depending on spatial unit and data type. Both point location and county case rate per 10 000 live births were assessed for geographic clustering or dispersion. RESULTS: Of the 453 CHD cases, 26% were PoND (n = 117), and 74% were PrND (n = 336). PrND cases, in all but one center, displayed significant geographic clustering by the ANN. Conversely, PoND cases tended toward geographic dispersion. Dispersion of PoND HLHS occurred in 2 centers (ANN = 1.59, P < .001; and 1.47, P = .016), and PoND TGA occurred in 2 centers (ANN = 1.22, P < .05; and ANN = 1.73, P < .001). Hot spot analysis of all CHD cases (TGA and HLHS combined) revealed clustering near areas of high population density and the tertiary surgical center. Hot spot analysis of county-level case rate, accounting for population density, found variable clustering patterns. CONCLUSION: Geographic dispersion among postnatally detected CHD highlights the need for a wider reach of prenatal cardiac diagnosis tailored to the specific needs of a community. Geospatial analysis can support centers in improving the equitable delivery of prenatal care.

Early Clinical Outcomes in Infants with Prenatally Diagnosed Perimembranous and Muscular Ventricular Septal Defects (VSDs).

Isolated ventricular septal defect (VSD) is often associated with good clinical outcomes. However, infants prenatally diagnosed with VSD are often recommended for delivery at tertiary care centers. The aim of our study was to determine the odds of neonatal intensive care unit (NICU) admission in infants with persistent isolated VSD and complicated VSD, where an infant is affected by VSD and other genetic/structural abnormalities. We performed a retrospective cohort study, with data collected from a single academic institution from June 2018 to March 2023. Individuals with prenatally diagnosed VSD, in the absence of any other heart defects, were included in this study. The primary outcome was admission to the NICU. Multivariable logistic regression was used to assess associations. The association between persistence of VSD and NICU admission was adjusted for maternal age, fetal genetic abnormalities, fetal extracardiac abnormalities, and gestational age at the time of delivery. The association between complicated VSD and NICU admission was adjusted for maternal age and gestational age of the infant at the time of delivery. The odds of NICU admission were similar in infants with persistent isolated VSD and VSD that closed in utero (adjusted OR 1.31, 95% CI 0.30-5.61). However, infants with complicated VSD were at increased risk of NICU admission (adjusted OR 15.52, 95% CI 2.90-82.92). The risk of NICU admission was only increased in infants whose VSD was complicated by another genetic/major structural abnormalities. Therefore, women whose infants are prenatally diagnosed with VSD alone may not require delivery at tertiary care centers.

The Impact of Neighborhood Socioeconomic Status, Race and Ethnicity, and Language on Prenatal Diagnosis of CHD.

Congenital heart disease (CHD) is the most prevalent birth defect. This study aimed to assess whether prenatal diagnosis (PD) of CHD and time of the diagnosis are associated with maternal race, ethnicity, neighborhood SES, and language. In this retrospective cohort study, we analyzed data on 163 patients who underwent surgical intervention for CHD within 30 days of birth between 2011 and 2020 at the University of Maryland Children's Hospital. A neighborhood SES score was calculated using the mother's address at time of discharge and 6 SES variables from the US Census block group data with a previously published method by Diez Roux et al. Neighborhood SES did not impact the likelihood of receiving a PD of CHD; however, patients of Latino ethnicity were 3.2 times and non-English-preferred language patients were 5.1 times more likely to not receive a PD. Patients whose preferred language was a non-English language received a prenatal diagnosis 5.3 weeks later, resulting in the PD being made in the third trimester rather than the second. Patients from the highest quartile SES received an earlier prenatal diagnosis, although this association was less significant when controlling for insurance type and preferred language. Significant disparities in PD of CHD were seen in patients of Latino ethnicity and patients who prefer non-English language. Better understanding of the root causes of these disparities will be important to guide interventions to reduce these disparities.

Arch intervention following stage 1 palliation in hypoplastic left heart syndrome is associated with slower feed advancement: a report from the National Pediatric Quality Cardiology Improvement Collaborative.

INTRODUCTION: Infants undergoing stage 1 palliation for hypoplastic left heart syndrome may have post-operative feeding difficulties. Although the cause of feeding difficulties in these patients is multi-factorial, residual arch obstruction may affect gut perfusion, contributing to feeding intolerance. We hypothesised that undergoing arch reintervention following stage 1 palliation would be associated with post-operative feeding difficulties. METHODS: This was a retrospective cohort study. We analysed data from the National Pediatric Cardiology Quality Improvement Collaborative, which maintains a multicentre registry for infants with hypoplastic left heart syndrome discharged home following stage 1 palliation. Patients who underwent arch reintervention (percutaneous or surgical) prior to discharge following stage 1 palliation were compared with those who underwent non-aortic arch interventions after stage 1 palliation and those who underwent no intervention. Median post-operative days to full enteral feeds and weight for age z-scores were compared. Predictors of post-operative days to full feeds were identified. RESULTS: Among patients who underwent arch reintervention, post-operative days to full enteral feeds were greater than for those who underwent non-aortic arch interventions (25 versus 16, p = 0.003) or no intervention (median days 25 versus 12, p < 0.001). Arch intervention, multiple interventions, gestational age, and the presence of a gastrointestinal anomaly were predictors of days to full feeds. CONCLUSIONS: Repeat arch intervention is associated with a longer time to achieve full enteral feeding in patients with hypoplastic left heart syndrome after stage 1 palliation. Further investigation of this association is needed to understand the role of arch obstruction in feeding problems in these patients.

Infant cardiac magnetic resonance imaging using oscillatory ventilation: safe and effective.

Cardiac magnetic resonance imaging (CMR) for infants and young children typically requires sedation. General anesthesia with controlled ventilation can eliminate motion artifact with breath-holds during imaging to limit respiratory artifact, but these may lead to atelectasis or other complications. High-frequency oscillatory ventilation (HFOV) provides ventilation with near-constant mean airway pressure and minimal movement of chest wall and diaphragm, thus obviating the need for breath-holding. Clinical data were collected for 8 infants who underwent CMR with HFOV and 8 controls who underwent CMR with conventional ventilator and breath-hold technique. Data included demographic information, adverse events, and scan-acquisition time. Studies were reviewed for image quality by two cardiologists who were blinded to type of ventilation. There were no significant differences in patient characteristics between the two groups. There was no significant difference in average image quality for cine short-axis or black blood imaging. Total CMR scan time was not significantly different between groups, but the short-axis cine stack was acquired more quickly in the HFOV group (1.8 ± 0.8 vs. 5.0 ± 3.6 min). There were no adverse events in the HFOV group, but scans were terminated early for two patients in the conventional ventilator group. HFOV during CMR is feasible and well tolerated. Image quality is equivalent to that obtained with conventional ventilation with breath-holding technique and allows shorter cine scan times for some sequences.

Neighborhood socioeconomic status and length of stay after congenital heart disease surgery.

Background and Objectives: Socioeconomic factors are associated with health outcomes and can affect postoperative length of stay after congenital heart disease (CHD) surgery. The hypothesis of this study is that patients from neighborhoods with a disadvantaged socioeconomic status (SES) have a prolonged length of hospital stay after CHD surgery. Methods: Pre- and postoperative data were collected on patients who underwent CHD surgery at the University of Maryland Medical Center between 2011 and 2019. A neighborhood SES score was calculated for each patient using data from the United States Census Bureau and patients were grouped by high vs. low SES neighborhoods. The difference of patient length of stay (LOS) from the Society for Thoracic Surgeons median LOS for that surgery was the primary outcome measure. Linear regression was performed to examine the association between the difference from the median LOS and SES, as well as other third variables. Results: The difference from the median LOS was -4.8 vs. -2.2 days in high vs. low SES groups (p = 0.003). SES category was a significant predictor of LOS in unadjusted and adjusted regression analyses. There was a significant interaction between Norwood operation and SES-patients with a low neighborhood SES who underwent Norwood operation had a longer LOS, but there was no difference in LOS by SES in patients who underwent other operations. Conclusions: Neighborhood SES is a significant predictor of the LOS after congenital heart disease surgery. This effect was seen primarily in patients undergoing Norwood operation.

The S1P2 sphingosine 1-phosphate receptor is essential for auditory and vestibular function.

Sphingosine 1-phosphate (S1P) is an endogenous growth factor with potent effects on many different cell types. Most of these effects are produced by activation of one or more of a family of G-protein coupled receptors. The S1P2 receptor can mediate S1P-induced proliferation, differentiation and survival in a wide variety of cells in culture. However, identifying essential in vivo functions for S1P2 has been hampered by its ubiquitous expression and the failure to detect any anatomical abnormalities in initial analyses of S1P2 knockout mice. We report here that all S1P2 knockout mice are profoundly deaf from postnatal day 22 and approximately half display a progressive loss of vestibular function with aging. Anatomically, both the auditory and vestibular systems appear to develop normally but then degrade. Morphological defects associated with hearing are first detected at 3 weeks postnatal as deformations of the organ of Corti/Nuel's space. By one year of age structures within the scala media are dramatically altered. The S1P2 knockout mice also display a loss of otoconia consistent with the vestibular impairment. The present data are the first to indicate that S1P signaling plays critical roles, in vivo, in auditory and vestibular functions. The data further establish that the S1P signaling occurs through the S1P2 receptor and makes an essential contribution to the structural maintenance of these systems, raising the possibility that properly targeted enhancement of this signaling may prove to be clinically beneficial.

The Effect of a Quality Improvement Intervention on Variability of Measurements of Left Ventricular Dimensions in a Pediatric Echocardiography Laboratory.

OBJECTIVE: To assess the effect of a multifaceted quality improvement intervention on variability of left ventricular dimensions as measured on pediatric echocardiograms. METHODS: Variability of measurements of left ventricular dimensions was assessed using percent error before a multifaceted educational intervention. Sonographers attended group sessions, used visual prompts and received individual feedback regarding the proper technique for measuring the left ventricle. Variability was reassessed following the intervention. RESULTS: Sonographers were more likely to use proper measurement technique (38% vs. 62%, P = .017) after the educational intervention. The percent error of the left ventricular end systolic measurement decreased significantly (12.4% to 8.8%, P = .002). The percent error of the left ventricular end diastolic measurement showed a trend toward a decrease (7.7% to 5.8%, P = .067). There was no significant improvement in percent error for other measurements. Use of correct technique and sonographer experience of less than 5 years predicted decreased percent error. CONCLUSION: A multifaceted educational intervention can be used to improve measurement variability in pediatric echocardiography laboratories.

Targeted disruption of the S1P2 sphingosine 1-phosphate receptor gene leads to diffuse large B-cell lymphoma formation.

S1P(2) sphingosine 1-phosphate receptor signaling can regulate proliferation, survival, morphology, and migration in many cell types in vitro. Here, we report that S1P(2)(-/-) mice develop clonal B-cell lymphomas with age, such that approximately half of the animals display this neoplasm by 1.5 to 2 years of age. Histologic, immunophenotypic, and molecular analyses revealed a uniform tumor phenotype with features of germinal center (GC)-derived diffuse large B-cell lymphoma (DLBCL). Tumor formation was preceded by increases in GC B cells and CD69(+) T cells, as well as an increased formation of spontaneous GCs, suggesting that S1P(2) loss may promote lymphomagenesis in part by disrupting GC B-cells homeostasis. With the sole exception of rare lung tumors, the effect of S1P(2) gene disruption is remarkably restricted to DLBCL. In humans, 28 of 106 (26%) DLBCL samples were found to harbor multiple somatic mutations in the 5' sequences of the S1P(2) gene. Mutations displayed features resembling those generated by the IgV-associated somatic hypermutation mechanism, but were not detected at significant levels in normal GC B cells, indicating a tumor-associated aberrant function. Collectively, our data suggest that S1P(2) signaling may play a critical role in suppressing DLBCL formation in vivo. The high incidence of DLBCL in S1P(2)(-/-) mice, its onset at old age, and the relative lack of other neoplasms identify these mice as a novel, and potentially valuable, model for this highly prevalent and aggressive human malignancy.