Jodie K. Votava-Smith

Pulmonary venous obstruction (PVO) is a major determinant of early morbidity and mortality in neonates with total anomalous pulmonary venous return (TAPVR). Accurate prenatal identification of obstructed TAPVR remains challenging due to low pulmonary blood flow in fetal circulation. Maternal hyperoxygenation (MHO) increases fetal pulmonary blood flow and may unmask clinically significant obstruction. We retrospectively reviewed three fetuses with prenatally diagnosed TAPVR who underwent late‑gestation fetal echocardiography with MHO testing. Doppler indices of pulmonary vasoreactivity and vertical vein (VV) flow were assessed at baseline and during MHO and correlated with postnatal clinical outcomes. All fetuses demonstrated preserved pulmonary vasoreactivity during MHO. One fetus had no Doppler evidence of PVO at rest or during MHO and had a stable postnatal course without emergent intervention. One fetus demonstrated elevated VV velocities at baseline that worsened during MHO and required emergent surgical repair shortly after birth. In the third fetus, VV Doppler findings were normal at baseline but became abnormal during MHO, accurately predicting postnatal clinical deterioration and the need for early catheter‑based intervention. These findings suggest that MHO testing can unmask occult pulmonary venous obstruction in fetal TAPVR and may improve prenatal risk stratification and perinatal planning.

Background: Neurodevelopmental outcome disparities, partially linked to socioeconomic status, race‐ethnicity, persist in congenital heart disease (CHD). Fetal brain development is a key predictor of subsequent neurocognitive outcomes. Methods: Magnetic resonance imaging was performed on fetuses with and without complex CHD at 2 sites. Childhood Opportunity Index (COI) and maternal race‐ethnicity were used to assess neighborhood and individual‐level maternal social determinants of health, respectively. The contributions of COI and race‐ethnicity on fetal brain volume, controlling for fetal gestational age and sex, were compared using multivariable regression between both groups. Results: Among 168 fetuses in this analysis, 106 (63.10%) were from non‐Hispanic White mothers, 43 (25.60%) were from Hispanic mothers, and 19 (11.31%) were from non‐Hispanic Black mothers. Total brain volume in the group with CHD (n=49) was significantly associated with the interaction of maternal race‐ethnicity and the COI Social and Economic subdomain Score (β=−0.74, P P =0.04). Maternal race‐ethnicity, COI Social and Economic subdomain Score, and their interaction accounted for 30% of the variance in total fetal brain volume in the group with CHD, although the same effect was not noted in the control group. Conclusions: Results indicate that maternal COI likely modifies the relationship between maternal race‐ethnicity and fetal brain development in CHD. The impact of maternal race‐ethnicity and COI on brain development differs between fetuses with and without CHD. Addressing maternal social determinants of health could reduce disparities in neurodevelopmental outcomes in CHD. Although limitations in sample size temper conclusions, initial analysis suggests that maternal social determinants of health and environment can contribute to neurodevelopmental outcome variance in individuals with CHD.

BACKGROUND: Neurodevelopmental and functional impairments are among the most consequential morbidities for survivors of hypoplastic left heart syndrome after staged single ventricle surgical palliation. The SVRIII trial (Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type) enrolled adolescents, who were randomized to different surgical shunt types at the time of Norwood procedure as neonates, for multifaceted in-person evaluation. This study reports their neurodevelopmental outcomes. METHODS: Transplant-free survivors from SVRIII were invited to complete an in-person comprehensive neurodevelopmental evaluation in early adolescence. Outcomes across domains of cognition, academics, learning, memory, and attention, as well as social, emotional, behavioral, adaptive, and executive function, were compared with those of normative populations. Associations with demographic and medical covariates, including Norwood shunt type, were also assessed. RESULTS: Among 549 participants enrolled in the SVR trial (Single Ventricle Reconstruction), 200 of the 237 SVRIII participants (84%) completed a neurodevelopmental evaluation at a mean age of 11 years (range, 10 to 14 years). SVRIII participants who did versus did not undergo evaluation were more likely to be male (63% versus 51%), to be White (87% versus 76%), and to have a higher Childhood Opportunity Index score (61±26 versus 46±39). Full-scale intelligence quotient (88±18) was significantly lower than in the normative population, with 39% >1 and 15% >2 SD below the normative mean. Similar patterns were seen for reading (38% >1 SD and 16% >2 SD below the normative mean) and math (38% >1 SD and 19% >2 SD below the normative mean) scores. Attention, executive functioning, social development, visual memory, and adaptive functioning were all more impaired than in the normative population. Measures of socioeconomic status, number of medical complications, and requirement for a gastrostomy tube were each independent predictors of neurodevelopment, with socioeconomic status the most consistently significant factor across models. Group differences by shunt type were inconsistent across neurodevelopmental domains without a clear benefit of one surgical strategy. CONCLUSIONS: In early adolescence, transplant-free survivors of surgical palliation for hypoplastic left heart syndrome show concerning impairments across all domains of neurodevelopment. The distribution of affected outcomes is broad and associated with demographic, medical, and, most frequently, socioeconomic factors. Our findings support recommendations for neurodevelopmental evaluation during adolescence to guide individualized interventions to promote educational success and psychosocial well-being. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02455531.

BACKGROUND: 2D-speckle tracking echocardiography may help detect subclinical ventricular dysfunction, but data in multisystem inflammatory syndrome in children (MIS-C) are scarce. We investigated left ventricular (LV) strain parameters in MIS-C and their association with outcomes. METHODS: We performed an ambi-directional, 32-center cohort study on hospitalized MIS-C patients (March 2020–November 2021) with at least 1 echocardiogram read by the Core Lab. Generalized estimating equation modeling was used to test associations between LV strain and a composite in-hospital adverse cardiovascular outcome (vasoactive support, arrhythmias, cardiac arrest, extracorporeal support, death, or heart transplant). RESULTS: Of 349 patients (median age, 8.7 years [interquartile range, 5.3–12.9]), 35% had decreased LV ejection fraction during hospitalization, and 45% had depressed LV strain (either 4-chamber LV longitudinal strain [4CH-LVLS] or mid-ventricular LV circumferential strain [mid-LVCS]). The worst 4CH-LVLS and mid-LVCS occurred at ≈5 days of illness; 50% of abnormal LV strain normalized within 1 week, and 95% within 50 days. In-hospital adverse outcomes occurred in 35% of patients; these patients were older ( P =0.003) and, at admission, had more likely abnormal troponin ( P P P P =0.015), worse LV ejection fraction ( P P =0.002; mid-LVCS, P =0.001). Covariate-adjusted individual models for each strain parameter showed that 4CH-LVLS (adjusted odds ratio, 1.09 [95% CI, 1.07–1.12]), mid-LVCS (adjusted odds ratio, 1.06 [95% CI, 1.04–1.09]), worst LV strain Z score between 4CH-LVLS and mid-LVCS (adjusted odds ratio, 1.30 [95% CI, 1.21–1.41]), and early diastolic longitudinal strain rate (EDLSR; adjusted odds ratio, 1.68 [95% CI, 1.26–2.23]) at admission were found to be associated with adverse outcomes. CONCLUSIONS: About half of MIS-C patients had abnormal LV strain during hospitalization. 4CH-LVLS, mid-LVCS, the most abnormal strain Z score, and early diastolic longitudinal strain rate at admission were independently associated with in-hospital adverse cardiovascular outcome. These data may help early characterization and prognostication in MIS-C.

Infants with congenital heart disease (CHD) may have impaired cerebral autoregulation (CA) associated with cerebral fractional tissue oxygen extraction (FTOE). We conducted a pilot study in nine CHD neonates to validate a noninvasive CA measure, cerebrovascular stability index (CSI), by eliciting responses to postural tilts. We compared CSI to an invasive measure of CA and to FTOE collected during tilts (FTOE_Spot). FTOE_Spot correlated with CSI, as did the change in FTOE during tilts, but CSI’s correlation with impaired CA did not reach significance. Larger trials are indicated to validate CSI, allowing for noninvasive CA measurements and measurements in outpatient settings.

Congenital heart disease (CHD) is a common birth defect in the United States. CHD infants are more likely to have smaller head circumference and neurodevelopmental delays; however, the cause is unknown. Altered cerebrovascular hemodynamics may contribute to neurologic abnormalities, such as smaller head circumference, thus we created a novel Cerebrovascular Stability Index (CSI), as a surrogate for cerebral autoregulation. We hypothesized that CHD infants would have an association between CSI and head circumference. We performed a prospective, longitudinal study in CHD infants and healthy controls. We measured CSI and head circumference at 4 time points (newborn, 3, 6, 9 months). We calculated CSI by subtracting the average 2-min sitting from supine cerebral oxygenation (rcSO₂) over three consecutive tilts (0–90°), then averaged the change score for each age. Linear regressions quantified the relationship between CSI and head circumference. We performed 177 assessments in total (80 healthy controls, 97 CHD infants). The average head circumference was smaller in CHD infants (39.2 cm) compared to healthy controls (41.6 cm) (p < 0.001) and head circumference increased by 0.27 cm as CSI improved in the sample (p = 0.04) overall when combining all time points. Similarly, head circumference increased by 0.32 cm as CSI improved among CHD infants (p = 0.04). We found CSI significantly associated with head circumference in our sample overall and CHD infants alone, which suggests that impaired CSI may affect brain size in CHD infants. Future studies are needed to better understand the mechanism of interaction between CSI and brain growth.

Kawasaki disease (KD) is a childhood vasculitis of unknown aetiology. It is the leading cause of acquired paediatric heart disease in developed countries, with coronary artery aneurysms (CAAs) occu...

Advanced brain imaging of neonatal macrostructure and microstructure, which has prognosticating importance, is more frequently being incorporated into multi-center trials of neonatal neuroprotection. Multicenter neuroimaging studies, designed to overcome small sample sized clinical cohorts, are essential but lead to increased technical variability. Few harmonization techniques have been developed for neonatal brain microstructural (diffusion tensor) analysis. The work presented here aims to remedy two common problems that exist with the current state of the art approaches: 1) variance in scanner and protocol in data collection can limit the researcher's ability to harmonize data acquired under different conditions or using different clinical populations. 2) The general lack of objective guidelines for dealing with anatomically abnormal anatomy and pathology. Often, subjects are excluded due to subjective criteria, or due to pathology that could be informative to the final analysis, leading to the loss of reproducibility and statistical power. This proves to be a barrier in the analysis of large multi-center studies and is a particularly salient problem given the relative scarcity of neonatal imaging data. We provide an objective, data-driven, and semi-automated neonatal processing pipeline designed to harmonize compartmentalized variant data acquired under different parameters. This is done by first implementing a search space reduction step of extracting the along-tract diffusivity values along each tract of interest, rather than performing whole-brain harmonization. This is followed by a data-driven outlier detection step, with the purpose of removing unwanted noise and outliers from the final harmonization. We then use an empirical Bayes harmonization algorithm performed at the along-tract level, with the output being a lower dimensional space but still spatially informative. After applying our pipeline to this large multi-site dataset of neonates and infants with congenital heart disease (n= 398 subjects recruited across 4 centers, with a total of n=763 MRI pre-operative/post-operative time points), we show that infants with single ventricle cardiac physiology demonstrate greater white matter microstructural alterations compared to infants with bi-ventricular heart disease, supporting what has previously been shown in literature. Our method is an open-source pipeline for delineating white matter tracts in subject space but provides the necessary modular components for performing atlas space analysis. As such, we validate and introduce Diffusion Imaging of Neonates by Group Organization (DINGO), a high-level, semi-automated framework that can facilitate harmonization of subject-space tractography generated from diffusion tensor imaging acquired across varying scanners, institutions, and clinical populations. Datasets acquired using varying protocols or cohorts are compartmentalized into subsets, where a cohort-specific template is generated, allowing for the propagation of the tractography mask set with higher spatial specificity. Taken together, this pipeline can reduce multi-scanner technical variability which can confound important biological variability in relation to neonatal brain microstructure.

In this review, we describe the near-infrared spectroscopy (NIRS) technology and its clinical use in high-risk neonates in critical care settings. We searched databases (e.g., PubMed, Google Scholar, EBSCOhost) to find studies describing the use of NIRS on critically ill and high-risk neonates. Near-infrared spectroscopy provides continuous noninvasive monitoring of venous oxygen saturation. It uses technology similar to pulse oximetry to measure the oxygen saturation of hemoglobin in a tissue bed to describe the relative delivery and extraction of oxygen. Near-infrared spectroscopy can be a valuable bedside tool to provide clinicians indirect evidence of perfusion. It may prompt early interventions that promote oxygen delivery, which can improve high-risk neonatal outcomes.

We present a case of the successful use of bosentan for increased pulmonary vascular resistance (PVR) in a 10-year-old male who underwent late single ventricle surgical palliation for double-inlet left ventricle with pulmonary artery banding and a bidirectional Glenn shunt. The patient was treated with bosentan for 16 weeks, with decreases in mean pulmonary artery pressure from 23 to 16 mmHg on the right and from 31 to 21 mmHg on the left, and a decrease of the transpulmonary gradient by 7–8 mmHg. Cardiopulmonary exercise testing demonstrated an increase in peak oxygen consumption (VO₂) by 8% and peak work rate by 10%. Bosentan is a relatively new oral therapy option for increased PVR in patients with single ventricle physiology and bidirectional Glenn shunts.