Socioeconomic Mediators of Racial and Ethnic Disparities in Congenital Heart Disease Outcomes: A Population-Based Study in California.

Background Racial/ethnic and socioeconomic disparities exist in outcomes for children with congenital heart disease. We sought to determine the influence of race/ethnicity and mediating socioeconomic factors on 1-year outcomes for live-born infants with hypoplastic left heart syndrome and dextro-Transposition of the great arteries. Methods and Results The authors performed a population-based cohort study using the California Office of Statewide Health Planning and Development database. Live-born infants without chromosomal anomalies were included. The outcome was a composite measure of mortality or unexpected hospital readmissions within the first year of life defined as >3 (hypoplastic left heart syndrome) or >1 readmissions (dextro-Transposition of the great arteries). Hispanic ethnicity was compared with non-Hispanic white ethnicity. Mediation analyses determined the percent contribution to outcome for each mediator on the pathway between race/ethnicity and outcome. A total of 1796 patients comprised the cohort (n=964 [hypoplastic left heart syndrome], n=832 [dextro-Transposition of the great arteries]) and 1315 were included in the analysis (n=477 non-Hispanic white, n=838 Hispanic). Hispanic ethnicity was associated with a poor outcome (crude odds ratio, 1.72; 95% confidence interval [CI], 1.37-2.17). Higher maternal education (crude odds ratio 0.5; 95% CI , 0.38-0.65) and private insurance (crude odds ratio, 0.65; 95% CI , 0.45-0.71) were protective. In the mediation analysis, maternal education and insurance status explained 33.2% (95% CI , 7-66.4) and 27.6% (95% CI , 6.5-63.1) of the relationship between race/ethnicity and poor outcome, while infant characteristics played a minimal role. Conclusions Socioeconomic factors explain a significant portion of the association between Hispanic ethnicity and poor outcome in neonates with critical congenital heart disease. These findings identify vulnerable populations that would benefit from resources to lessen health disparities

Initial Metabolic Profiles Are Associated with 7-Day Survival among Infants Born at 22-25 Weeks of Gestation.

OBJECTIVE:To evaluate the association between early metabolic profiles combined with infant characteristics and survival past 7 days of age in infants born at 22-25 weeks of gestation. STUDY DESIGN:This nested case-control consisted of 465 singleton live births in California from 2005 to 2011 at 22-25 weeks of gestation. All infants had newborn metabolic screening data available. Data included linked birth certificate and mother and infant hospital discharge records. Mortality was derived from linked death certificates and death discharge information. Each death within 7 days was matched to 4 surviving controls by gestational age and birth weight z score category, leaving 93 cases and 372 controls. The association between explanatory variables and 7-day survival was modeled via stepwise logistic regression. Infant characteristics, 42 metabolites, and 12 metabolite ratios were considered for model inclusion. Model performance was assessed via area under the curve. RESULTS:The final model included 1 characteristic and 11 metabolites. The model demonstrated a strong association between metabolic patterns and infant survival (area under the curve [AUC] 0.885, 95% CI 0.851-0.920). Furthermore, a model with just the selected metabolites performed better (AUC 0.879, 95% CI 0.841-0.916) than a model with multiple clinical characteristics (AUC 0.685, 95% CI 0.627-0.742). CONCLUSIONS:Use of metabolomics significantly strengthens the association with 7-day survival in infants born extremely premature. Physicians may be able to use metabolic profiles at birth to refine mortality risks and inform postnatal counseling for infants born at <26 weeks of gestation

Resuscitation, survival and morbidity of extremely preterm infants in California 2011-2019.

OBJECTIVE: To describe changes over time in resuscitation, survival, and morbidity of extremely preterm infants in California. STUDY DESIGN: This population-based, retrospective cohort study includes infants born ≤28 weeks. Linked birth certificates and hospital discharge records were used to evaluate active resuscitation, survival, and morbidity across two epochs (2011-2014, 2015-2019). RESULTS: Of liveborn infants, 0.6% were born ≤28 weeks. Active resuscitation increased from 16.9% of 22-week infants to 98.1% of 25-week infants and increased over time in 22-, 23-, and 25-week infants (p-value ≤ 0.01). Among resuscitated infants, survival to discharge increased from 33.2% at 22 weeks to 96.1% at 28 weeks. Survival without major morbidity improved over time for 28-week infants (p-value < 0.01). CONCLUSION: Among infants ≤28 weeks, resuscitation and survival increased with gestational age and morbidity decreased. Over time, active resuscitation of periviable infants and morbidity-free survival of 28-week infants increased. These trends may inform counseling around extremely preterm birth

The Association of Gestational Age and Size with Management Strategies and Outcomes in Symptomatic Neonatal Tetralogy of Fallot.

 In neonatal, symptomatic tetralogy of Fallot (sTOF), data are lacking on whether high-risk groups would benefit from staged (SR) or complete repair (CR). We studied the association of gestational age (GA) at birth and z-score for birth weight (BWz), with management strategy and outcomes in sTOF. California population-based cohort study (2011-2017) of infants with sTOF (defined as catheter or surgical intervention prior to 44 weeks corrected GA) was performed, comparing management strategy and timing by GA and BWz categories. Multivariable models evaluated composite outcomes and days alive and out of hospital (DAOOH) in the first year of life. Among 345 patients (SR = 194; CR = 151), management strategy did not differ by GA or BWz with complete repair defined as prior to 44 weeks corrected gestational age; however, did differ by GA with regard to complete/timely repair (defined as complete repair within first 30 days of life). Full-term and early-term neonates underwent CR 20 (95%CI: - 27.1, - 14.1; p < 0.001) and 15 days (95%CI: - 22.1, - 8.2; p < 0.001) sooner than preterm neonates. Prematurity and major anomaly were associated with mortality or non-cardiac morbidity, while only major anomaly was associated with mortality or cardiac morbidity (OR = 3.5, 95%CI: 1.8,6.7, p < .0001). Full-term infants had greater DAOOH compared to preterm infants (35.2 days, 95%CI: 4.0, 66.5, p = 0.03). LGA infants and those with major anomaly had significantly lower DAOOH. In sTOF, patient specific risk factors such as prematurity and major anomaly were more associated with outcomes than management strategy

Developing a resiliency model for survival without major morbidity in preterm infants

ObjectiveDevelop and validate a resiliency score to predict survival and survival without neonatal morbidity in preterm neonates <32 weeks of gestation using machine learning.Study designModels using maternal, perinatal, and neonatal variables were developed using LASSO method in a population based Californian administrative dataset. Outcomes were survival and survival without severe neonatal morbidity. Discrimination was assessed in the derivation and an external dataset from a tertiary care center.ResultsDiscrimination in the internal validation dataset was excellent with a c-statistic of 0.895 (95% CI 0.882-0.908) for survival and 0.867 (95% CI 0.857-0.877) for survival without severe neonatal morbidity, respectively. Discrimination remained high in the external validation dataset (c-statistic 0.817, CI 0.741-0.893 and 0.804, CI 0.770-0.837, respectively).ConclusionOur successfully predicts survival and survival without major morbidity in preterm babies born at <32 weeks. This score can be used to adjust for multiple variables across administrative datasets

Cross-trienamines in Asymmetric Organocatalysis

Cross-conjugated trienamines are introduced as a new concept in asymmetric organocatalysis. These intermediates are applied in highly enantioselective Diels–Alder and addition reactions, providing functionalized bicyclo[2.2.2]­octane compounds and γ′-addition products, respectively. The nature of the transformations and the intermediates involved are investigated by computational calculations and NMR analysis

Cross-trienamines in Asymmetric Organocatalysis

Cross-conjugated trienamines are introduced as a new concept in asymmetric organocatalysis. These intermediates are applied in highly enantioselective Diels–Alder and addition reactions, providing functionalized bicyclo[2.2.2]­octane compounds and γ′-addition products, respectively. The nature of the transformations and the intermediates involved are investigated by computational calculations and NMR analysis

Newborn Metabolic Profile Associated with Hyperbilirubinemia With and Without Kernicterus

Abstract Our objective was to assess the relationship between hyperbilirubinemia with and without kernicterus and metabolic profile at newborn screening. Included were 1,693,658 infants divided into a training or testing subset in a ratio of 3:1. Forty‐two metabolites were analyzed using logistic regression (odds ratios (ORs), area under the receiver operating characteristic curve (AUC), 95% confidence intervals (CIs)). Several metabolite patterns remained consistent across gestational age groups for hyperbilirubinemia without kernicterus. Thyroid stimulating hormone (TSH) and C‐18:2 were decreased, whereas tyrosine and C‐3 were increased in infants across groupings. Increased C‐3 was also observed for kernicterus (OR: 3.17; 95% CI: 1.18–8.53). Thirty‐one metabolites were associated with hyperbilirubinemia without kernicterus in the training set. Phenylalanine (OR: 1.91; 95% CI: 1.85–1.97), ornithine (OR: 0.76; 95% 0.74–0.77), and isoleucine + leucine (OR: 0.63; 95% CI: 0.61–0.65) were the most strongly associated. This study showed that newborn metabolic function is associated with hyperbilirubinemia with and without kernicterus

Environmental and Socioeconomic Factors Influence the Live-Born Incidence of Congenital Heart Disease: A Population-Based Study in California.

BACKGROUND The development of congenital heart disease (CHD) is multifactorial with genetic and environmental influences. We sought to determine the relationship between socioeconomic and environmental factors with the incidence of CHD among live-born infants in California and to determine whether maternal comorbidities are in the causal pathway. METHODS AND RESULTS This was a population-based cohort study in California (2007-2012). The primary outcome was having significant CHD. Predictors included socioeconomic status and environmental exposure to pollutants determined by U.S. Census data. A social deprivation index and environmental exposure index was assigned based on neighborhood socioeconomic variables, categorized into 4 quartiles. Quartile 1 was the best with the least exposure to pollutants and social deprivation, and quartile 4 was the worst. Multivariate logistic regression and mediation analyses were performed. Among 2 419 651 live-born infants, the incidence of CHD was 3.2 per 1000 live births. The incidence of CHD was significantly higher among those in quartile 4 compared with quartile 1 (social deprivation index: 0.35% versus 0.29%; odds ratio [OR], 1.31; 95% CI, 1.21-1.41; environmental exposure index: 0.35% versus 0.29%; OR, 1.23; 95% CI, 1.15-1.31) after adjusting for maternal race/ethnicity and age and accounting for the relationship between the 2 primary predictors. Maternal comorbidities explained 13% (95% CI, 10%-20%) of the relationship between social deprivation index and environmental exposure index with the incidence of CHD. CONCLUSIONS Increased social deprivation and exposure to environmental pollutants are associated with the incidence of live-born CHD in California. Maternal comorbidities explain some, but not all, of this relationship. These findings identify targets for social policy initiatives to minimize health disparities