Race/ethnicity, socioeconomic status (SES), and geography have been associated with differential outcomes in congenital heart disease (CHD) mortality. In patients with hypoplastic left heart syndrome (HLHS), lower SES has been associated with increased complications and lower 1-year survival.[1]
No previous study has examined how sociodemographics impact neonatal mortality among prenatally diagnosed patients with HLHS. The study goal was to investigate infants with a prenatal diagnosis of HLHS to understand associations between maternal sociodemographics and patient characteristics with hospital discharge mortality.
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Study Design:
Data from the Fetal Heart Society Research Collaborative multicenter retrospective cohort study were used to identify relationships between sociodemographics and newborn hospital mortality among those prenatally diagnosed with HLHS among 19 sites in the US.[2] This study was approved by an institutional review committee and participant consent was not needed as the study was from a retrospective de-identified cohort.
Study Population:
Fetuses and infants <2 months of age with a prenatal diagnosis of HLHS from January 2012-December 2016 were included. Classic variants of HLHS and double outlet right ventricle with mitral atresia were included. Cardiac diagnoses were confirmed postnatally or at autopsy.
Study Variables:
Primary independent variables were: maternal race/ethnicity, insurance, and neighborhood factors including 1) SES (from maternal census tract, as described previously [3]), 2) neighborhood poverty level >20%, race/ethnicity distribution, and rural residence, and 3) driving distance and time to cardiac surgical center. Maternal variables (age at delivery and primary language) and infant characteristics known to be associated with worse HLHS outcomes (gestational age at birth, birthweight <2.5kg, restrictive or intact atrial septum, extracardiac birth defects (ECBD) and any genetic conditions) were treated as covariates. Earliest insurance type was recorded from the fetal or neonatal record. The primary outcome variable was death prior to newborn hospital discharge. Termination of pregnancy was a secondary outcome.
Statistical Analysis
For the primary analysis, associations between maternal sociodemographics and infant characteristics with hospital discharge mortality were evaluated using logistic regression. For this analysis, those with termination, fetal demise, comfort care, and unknown outcome were excluded. Multiple multivariable models were created accounting for clustering by site using generalized estimating equations. Causal mediation analysis was conducted to estimate direct and indirect effects in the fully adjusted models (CAUSALMED procedure). Secondary logistic regression analyses were conducted for associations between maternal sociodemographics and pregnancy termination. Analyses utilized SAS 9.4 (SAS Institute Inc, Cary, NC, USA); a p-value of 0.05 was statistically significant.
A total of 952 fetuses were identified, with 46.4% (n=369) diagnosed at >24 weeks gestation. Ninety-five (9.9%) died prior to birth, due to miscarriage or intrauterine fetal demise (n=20), pregnancy termination (n=74) or unknown causes (n=1). Among those diagnosed < 24 weeks, termination of pregnancy was 17.3%, and individuals with high SES and private insurance had higher percentages of termination compared to low SES (n= 58, 13.2% vs. n= 16, 3.5%, p<0.0001), and public insurance (n=50, 12.4% vs. n=9, 2.8%; p<0.0001). Excluding these and unknown pregnancy outcome cases (n=46), 811 live-born infants with HLHS underwent outcome analyses.
In multivariable analyses, prematurity, genetic disorder, restrictive atrial septum, presence of ECBD, and maternal Black race were associated with higher mortality (Table). No association between geography, SES, or low birth weight and mortality was noted. Clustering by site had no impact on findings. In a mediation analysis for the effect of Black race on death prior to hospital discharge, only 4% was explained by low birthweight, 3.2% by pre-term birth, and 9.2% by neighborhood SES.
Table:
Unadjusted and adjusted associations between socioeconomic status and mortality by logistic regression
| Variables in Model | Death Prior to Discharge | ||||
|---|---|---|---|---|---|
| Unadjusted | Model 1 | Model 2 | Model 3 | Model 4 | |
| OR† (95% CI) | aOR‡ (95% CI) | aOR (95% CI) | aOR (95% CI) | aOR (95% CI) | |
| Low SES* | 1.45 (1.03 – 2.05) | 1.24 (0.83 – 1.88) | 1.24 (0.83 – 1.86) | 1.22 (0.81 – 1.84) | 1.20 (0.76 – 1.89) |
| Native American/Alaskan/PI | 2.44 (0.57 – 10.43) | 3.56 (0.94 – 13.46) | 2.59 (0.61 – 11.08) | 1.03 (0.12 – 9.01) | |
| Low birthweight | -- | 1.51 (0.90 – 2.53) | -- | 1.18 (0.66 – 2.12) | 1.53 (0.84 – 2.79) |
| Preterm birth | -- | -- | 1.91 (1.16 – 3.16) | 1.76 (0.99 – 3.14) | 1.65 (0.89 – 3.01) |
| Restrictive atrial septum | -- | 2.59 (1.53 – 4.37) | 2.67 (1.60 – 4.46) | 2.64 (1.56 – 4.48) | -- ‖ |
| Extracardiac birth defect | -- | 3.57 (2.10 – 6.10) | 3.14 (1.86 – 5.29) | 3.40 (1.98 – 5.83) | 2.92 (1.63 – 5.23) |
| Any genetic defect | -- | 1.81 (0.81 – 4.07) | 2.01 (0.90 – 4.47) | 1.90 (0.85 – 4.29) | 2.38 (1.01 – 5.63) |
SES- Socioeconomic status;
OR- Odds Ratio;
aOR- Adjusted Odds Ratio;
Patients with restrictive atrial septum excluded
Our study demonstrated that while SES is associated with termination of pregnancy, SES and geography were not associated with hospital discharge mortality among liveborn infants. Prematurity, and presence of a genetic disorder and/or a restrictive atrial septum were associated with mortality. Geography may not be significantly associated as risks contributing to short-term mortality (distance to a cardiac care center, late presentation due to lack of prenatal diagnosis, etc.) are mitigated and largely “controlled” for with the patient being born at or near a tertiary cardiac care center. Perhaps most alarming was the finding that risk of death was 1.8 times higher in Black compared to White infants, and mediation analyses demonstrating that the majority of the association (>80%) was due to unexplained or unmeasured factors, or potentially structural racism described in prior studies of Black neonates.[4] This is particularly concerning as CHD studies have found that rates of mortality remain highest in Black patients compared to other races/ethnicities from birth until at least the age of 35.[5]
Limitations of the study included its retrospective design, inability to completely control for center characteristics or determine maternal health during pregnancy, and limited assessment of the social determinants of health potentially driving demonstrated disparities in birth outcomes. Nonetheless, our study represents a large cohort of prenatally diagnosed HLHS patients and factors associated with mortality. Future work is needed to identify modifiable factors that may contribute to worse outcomes in Black infants with HLHS to eliminate these disparities.
Acknowledgements:
This publication was developed with the support of the Fetal Heart Society sponsoring institutions, including the Children’s National Hospital, University of California, San Francisco Benioff, Children’s Hospital, The Hospital for Sick Children, The University of Utah School of Medicine / Intermountain Primary Children’s Hospital, Lucile Salter Packard Children’s Hospital at Stanford University, Texas Children’s Hospital, Columbia University Irving Medical, Center, Phoenix Children’s Hospital, Children’s Minnesota, University Hospitals Rainbow Babies & Children’s Hospital, Children’s Healthcare of Atlanta, Mount Sinai Hospital, Children’s Health System of Texas (Dallas), Ann and Robert H. Lurie Children’s Hospital of Chicago, Nemours Children’s Hospital & Foundation, Cincinnati Children’s Hospital Medical Center/UK Health Care Kentucky Children’s Hospital, Arkansas Children’s Hospital, The Children’s Mercy Hospital (Kansas), The Heart Institute at UPMC Children’s Hospital of Pittsburgh, Inova Health Care Services, Seattle Children’s Hospital, Nationwide Children’s Hospital, University of Virginia Children’s Hospital, University of California Davis Medical Center, Duke University, Monroe Carell Jr. Children’s Hospital at Vanderbilt, OSF Healthcare - Children’s Hospital of Illinois, Johns Hopkins All Children’s, Fairview Health Services, Children’s Hospital & Medical Center Omaha, Washington University School of Medicine, Cleveland Clinic Children’s Hospital. Without their contributions the evolution of the Fetal Heart Society and this and ongoing research would not be possible.
Funding Sources:
Supported by grant K23 HL127164 (principal investigator: Dr Lopez) from the National Institutes of Health/National Heart Lung and Blood Institute and by the National Institute on Minority Health Disparities under award P20MD000198. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funded by the National Institutes of Health (NIH).
Non-standard Abbreviations and Acronyms:
- SES
Socioeconomic status
- CHD
Congenital heart disease
- HLHS
Hypoplastic left heart syndrome
- ECBD
Extracardiac birth defects
Appendix:
Collaborators: Mary Craft1, Heather Gramse2, Anita Moon-Grady, MD3, Wes Lee, MD4, Dawn Park5, Alysia Wiener, MD6
1. Division of Cardiology, Columbia University, New York, NY. 2. University of Utah, Data Coordinating Center, Salt Lake City, UT. 3. Division of Cardiology, University of California, San Francisco, San Francisco, CA. 4. Department of Cardiology, Division of Cardiology, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX. 5. Division of Cardiology, The Heart Institute, Children’s Hospital of Colorado/University of Colorado, Aurora, CO. 6. Children’s National Heart Institute, Washington, DC
Footnotes
Conflict of Interest Disclosures: None
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