Cardiac Alterations in Children Born Extremely Preterm

Background: Extremely low gestational age neonates (ELGANs; born <28 weeks gestation) are at risk for significant morbidities, including bronchopulmonary dysplasia (BPD), the most common lung disease of infancy. While the impact of BPD on pulmonary function in survivors of preterm birth throughout life is well described, the effect of prematurity on the pulmonary vasculature and cardiac function remains understudied. Mounting data suggest that survivors of prematurity are at high risk to develop persistent right ventricular hypertrophy, dysfunction, and pulmonary hypertension. The risk of cardiopulmonary insufficiency may be amplified for individuals born at earlier gestational ages, and the ELGANs of the current era have not been studied beyond infancy. The objective of this study was to evaluate ELGANs in adolescence to determine whether cardiopulmonary changes are present at an earlier age.
We hypothesized that healthy former ELGANs have detectable cardiopulmonary alterations in mid-childhood.

Methods: A cohort study of former ELGANs underwent cardiac magnetic resonance imaging (CMR). The cases were defined as ELGANs between the ages of 9 and 17 years; controls were healthy subjects born at term age and gender matched. The primary endpoint was the ratio of right to left ventricular end diastolic volume (RVEDV:LVEDV), which is a surrogate marker for pulmonary vascular resistance by CMR. Additional cardiac metrics included right ventricular global longitudinal strain (RV GLS) analysis, right and left ventricular ejection fraction (RVEF, LVEF), right and left ventricular end diastolic and systolic volumes (RVEDVi, RVESVi, LVEDVi, and LVESVi), and right and left ventricular mass.

Results: 44 study subjects completed the study (22 cases and 22 controls). The RVEDV:LVEDV ratio was increased in cases but did not reach statistical significance (p=0.126). Average RV GLS and free wall RV GLS were significantly reduced in cases (-20.2+/-4.3% versus -23.5+/-4.0%, p<0.001; and -24.5+/-5.4% versus -28.6+/-5.0%, p<0.001, respectively, suggesting subclinical RV dysfunction (Figure 1). Although we found no difference in RVESVi or RVEDVi, the RVEF was also significantly reduced in cases (55.1+/-4.7 versus 59.36, p=0.005). The RV mass was not significantly different between cases and controls. There was no significant difference in LVEF, LVEDVi, LVESVi, or LV mass.

Conclusion: Occult pulmonary vascular disease characterized by elevated pulmonary vascular pressure, stiffness, and RV dysfunction is a concern for adults born premature. Our findings suggest that this process may be detectable in children, indicating dysfunction across the lifespan. Although the clinical implications for children remain unclear, enhanced susceptibility among former ELGANs requires vigilance among clinicians. Key opportunities remain including: (a) identify the timing of these changes relevant to the pediatric life course; and (b) identify specific, potentially modifiable targets for therapeutic interventions in mid-childhood or even younger (e.g., infancy) to prevent or treat morphologic and functional cardiopulmonary impairments before adulthood.