Congenital heart disease alters mortality and morbidity risks in preterm infants

Congenital heart disease was associated with substantially higher odds of death and several major neonatal complications among preterm infants, with the size of the mortality difference changing across gestational age. A secondary analysis of two North American neonatal registries found that infants born before 35 weeks’ gestation with congenital heart disease had four times the odds of in-hospital mortality compared with preterm infants without the condition. The estimate was adjusted odds ratio 4.0, with a 95% confidence interval of 3.76–4.21. The analysis included 11,221 infants with congenital heart disease from the Children’s Hospitals Neonatal Consortium and 720,846 without congenital heart disease from the Vermont Oxford Network, covering 2010–2022.

The pattern was not uniform across the preterm period. Mortality was similar between the groups at the earliest gestational ages, but the relative effect of congenital heart disease increased as gestational age advanced. The researchers therefore concluded that prematurity predominated as a driver of mortality at the lowest gestational ages, whereas congenital heart disease became increasingly influential as infants approached greater gestational maturity. This does not mean that the absolute number of deaths rose at every gestational age, nor does the registry comparison establish that congenital heart disease caused each death. Instead, it quantifies an additional association beyond prematurity itself in the studied population.

Several neonatal morbidities were also more frequent among preterm infants with congenital heart disease. The analysis identified significantly increased risks of severe bronchopulmonary dysplasia, intraventricular hemorrhage and necrotizing enterocolitis. These are major complications of preterm birth, and the findings indicate that the additional burden associated with congenital heart disease extended beyond survival. The analysis stratified neonatal outcomes and adjusted odds ratios by gestational age and compared both relative and absolute differences between infants with and without congenital heart disease. In-hospital mortality was the primary outcome, while major neonatal morbidities were secondary outcomes.

The study’s scale makes the gestational-age interaction a central feature rather than a secondary observation. More than 730,000 preterm infants were represented overall, including a comparatively small group with congenital heart disease but a very large comparison group without it. Even so, the work was a secondary analysis of registry data rather than a randomized trial, and the supplied summary does not provide information about the distribution of individual cardiac diagnoses, the severity of malformations, treatment decisions or other clinical and social factors that could affect outcomes. The results therefore support a population-level association between congenital heart disease and elevated mortality and morbidity risks in infants born before 35 weeks, while the changing magnitude of that association across gestational age remains the principal finding.

Subject of Research: Gestational-age-dependent mortality and neonatal morbidity risks associated with congenital heart disease in preterm infants

Article Title: Congenital heart disease confers gestational age–dependent risks of mortality and morbidity in preterm infants

Article References: Chaudhry, P. M., Sweeney, N., Zaniletti, I., Martin, L. J., Edwards, E. M., Gowda, S. H., Padula, M., Murthy, K., Grover, T. R., Morton, S. U., DiGeronimo, R., Shepherd, J. L., Levy, P. T., Ball, M. K., Piazza, A., Sysyn, G., Lucke, A., Pont, M., Black, A., … on behalf of Children’s Hospital Neonatal Consortium Cardiac Focus Group (2026). Congenital heart disease confers gestational age–dependent risks of mortality and morbidity in preterm infants. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02924-2

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02924-2

Keywords: congenital heart disease, preterm infants, neonatal mortality, gestational age, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, neonatal registries, major neonatal morbidity, North America, Congenital, heart